Article

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer

September 2016
The New-England Medical Review and Journal 375(15)

DOI:10.1056/NEJMoa1606220

Authors:

Freddie Hamdy

University of Oxford

Athene Lane

University of Bristol

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Background The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain. Methods We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. Results There were 17 prostate-cancer–specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). Conclusions At a median of 10 years, prostate-cancer–specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. (Funded by the National Institute for Health Research; Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)

The RECONCILE study protocol: Exploiting image-based risk stratification in early prostate cancer to discriminate progressors from non-progressors (RECONCILE)

Article

Full-text available

Oct 2024
PLOS ONE

Introduction RECONCILE (ClinicalTrials.gov:NCT04340245) will identify molecular and radiomic markers associated with clinical progression and radiological progression events in a cohort of localised, newly diagnosed Gleason 3 + 4 tumours. Molecular markers will be correlated against standard of care MRI-targeted histology and oncological outcomes. Methods RECONCILE is an ethics approved (20/LO/0366) single centre, prospective, longitudinal, observational cohort study of recently diagnosed (within 12 months), organ-confined Gleason 3 + 4 cancers (MCCL ≤10mm) currently under active surveillance. 60 treatment-naïve participants with a concordant MRI lesion (Likert score 4 or 5) and PSA ≤ 15 ng/ml will be recruited. Blood, urine and targeted prostate tissue cores will be subject to next generation sequencing at baseline and one year in all participants. Semen will be collected from a specified sub-population. Baseline and interval MR images will be extracted from standard of care prostate MRI ahead of radiomic analysis. Data extracted from radiological and biological samples will be used to derive the association of molecular change and radiological progression, the primary outcome of the study. To compensate for spatial intratumoral heterogeneity and inherent sampling bias, a molecular index will be derived for each participant using the molecular profile of tumour tissue at both baseline (MolBL) and one year (MolFU). We will extract a ΔMolBL:MolFU score for each participant. Molecular progression will be defined as a MolBL:MolFU score >95% CI of the combined ΔMolBL scores. Radiological progression is defined as a PRECISE score of 4 or 5. The study is powered to detect an association with a statistical power of 80%. Results Recruitment began in July 2020 (n = 62). To date, 37 participants have donated tissue for analysis. Conclusion We have designed and implemented a prospective, longitudinal study to evaluate the underlying molecular landscape of intermediate risk, MR-visible prostate tumours. Recruitment is ongoing.

Active surveillance follow-up for prostate cancer: from guidelines to real-world clinical practice

Article

Full-text available

Nov 2024
WORLD J UROL

Purpose To assess active surveillance (AS) adherence for prostate cancer (PCa) in a “real-world” clinical practice. Materials and methods We utilized our institutional database which was built by interrogating electronic medical records for all men who got diagnosed with PCa from 1995 to 2022. Our cohort included all patients aged < 76 years, with PCa Gleason Grade (GG) 1 or 2, ≤ cT2c, PSA ≤ 20 ng/ml at diagnosis, enrolled on AS, and with at least one biopsy after diagnosis. Patients were separated into two groups based on the monitoring intensity. Patients with at least 1 PSA/year and at least 1 biopsy every 4 years were categorized as adherent to guidelines. Univariable and Multivariable logistic regression analyses were used to examine the impact of covariates on non-adherence to guidelines. Competing risks cumulative incidence was used to depict prostate cancer-specific mortality (PCSM). Results A total of 546 men met the inclusion criteria. Overall, 63 (11%) patients were adherent to guidelines (Group 1), while 483 (89%) were not (Group 2). Median PSAs/year and median biopsies/year were 2.3 (2.0-2.7) and 0.4 (0.3–0.6) for Group 1, and 1.2 (0.7–1.8) and 0.2 (0.1–0.2) for Group 2, respectively (both p < 0.0001). At multivariable analysis, Black men had a 2.20-fold higher risk of being in Group 2 than White men (p < 0.05). Patients with cT2 (OR:0.24, CI:0.11–0.52) and those with CCI ≥2 (OR:0.40, CCI:0.19–0.82) were less likely to be in Group 2, when compared to cT1 stage and CCI = 0, respectively (both p < 0.05). At 10 years, the cumulative incidence estimate of PCSM for the entire cohort was 2.1%. Conclusion We found substantial deviations from AS monitoring guidelines, particularly in biopsy frequency, which did not seem to compromise PCSM in patients with stable PSA. Notably, our findings suggest that strict adherence to guidelines, especially in patients with cT2 at diagnosis, remains crucial.

Weight Loss, Pathological Changes, and Inflammatory Effects from a Short-Term Ketogenic Diet in Overweight and Obese Men with Untreated Prostate Cancer on Active Surveillance

Article

Full-text available

Oct 2024

Background and Aims: Active Surveillance (AS) is a favored strategy for the management of indolent prostate cancers (PCs). Overweight and obese men harbor an increased risk of cancer progression during AS. We aim to prospectively evaluate the feasibility and outcomes of a ketogenic diet (KD) weight-loss intervention in overweight men with PC. Materials and Methods: Men with PC and a BMI > 25 kg/m² undergoing AS were placed on an 8-week ad libitum KD program before a scheduled surveillance biopsy to assess the impact on clinical grade group (CGG). Blood ketone levels were tracked to ensure compliance. BMI, PSA, and inflammatory marker data (TNF-α, TNFR1, TNFR2, sICAM-1, sVCAM-1, IL-6, IL1-RA, CRP, and SAA) were collected before and after the KD intervention. A Shapiro–Wilk test was performed to assess the normality of all continuous study variables. Paired t-tests and Wilcoxon rank sum tests were utilized to compare normally and non-normally distributed study outcomes, respectively. Results: Ten AS patients aged 62.1 (±5.4) years were enrolled with an average BMI of 31.7 kg/m² (±11.8). Post-KD intervention mean blood ketone levels were 0.32 (±0.12) mmol/L with a mean BMI reduction of 7.4% (p < 0.0003). There were no meaningful changes in PSA or inflammatory biomarkers (p > 0.05). Nine patients completed re-biopsy following a KD with four patients showing no evidence of cancer; one downgraded to a lower CGG; two had unchanged CGG scores; and two had higher CGG scores compared to baseline. Conclusions: Short-term KD interventions for BMI reduction are feasible in men undergoing AS for PC and may result in favorable pathological effects without inflammatory marker changes. Larger studies with longer follow-up are needed to explore whether KD-induced weight loss can improve clinical outcomes with AS in PC.

Active Surveillance Follow-Up for Prostate Cancer: From Guidelines to Real-World Clinical Practice

Preprint

Full-text available

Aug 2024

Purpose To assess active surveillance (AS) adherence for prostate cancer (PCa) in a “real-world” clinical practice. Materials and Methods We utilized our institutional database which was built by interrogating electronic medical records for all men who got diagnosed with PCa from 1995 to 2022. Our cohort included all patients aged < 76 years, with PCa Gleason Grade (GG) 1 or 2, ≤ cT2c, PSA ≤ 20 ng/ml at diagnosis, enrolled on AS, and with at least one biopsy after diagnosis. Patients were separated into two groups based on the monitoring intensity.Patients with at least 1 PSA/year and at least 1 biopsy every 4 years were categorized as adherent to guidelines. Univariable and Multivariable logistic regression analyses were used to examine the impact of covariates on non-adherence to guidelines. Competing risks cumulative incidence was used to depict PCSM. Results A total of 546 men met the inclusion criteria. Overall, 63 (11%) patients were adherent to guidelines (Group 1), while 483 (89%) were not (Group 2). Median PSAs/year and median biopsies/year were 2.3 (2.0-2.7) and 0.4 (0.3-0.6) for Group 1, and 1.2 (0.7-1.8) and 0.2 (0.1-0.2) for Group 2, respectively (both p<0.0001). At multivariable analysis, Black men had a 2.20-fold higher risk of being in Group 2 than White men (p<0.05). Patients with cT2 (OR:0.24, CI:0.11-0.52) and those with CCI ³2(OR:0.40, CCI:0.19-0.82) were less likely to be in Group 2, when compared to cT1 stage and CCI=0, respectively (both p< 0.05). At 10 years, the cumulative incidence estimate of prostate cancer-specific mortality (PCSM) for the entire cohort was 2.1%. Conclusion We found substantial deviations from AS monitoring guidelines, particularly in biopsy frequency, which did not seem to compromise PCSM in patients with stable PSA. Notably, our findings suggest that strict adherence to guidelines, especially in patients with cT2 at diagnosis, remains crucial.

Trends in focal therapy for localized prostate cancer: a bibliometric analysis from 2014 to 2023

Article

Full-text available

Sep 2024

Focal therapy, a minimally invasive strategy for localized prostate cancer, has been widely employed in the targeted treatment of localized prostate cancer in recent years. We analyzed 1312 relevant papers from the last decade using Web of Science Core Collection data. Our analysis covered countries, institutions, journals, authors, keywords, and references to offer a multifaceted perspective on the development of this field. The U.S. led in publications, contributing over half of the top 10 institutions. Emberton, M from University College London was the most published and cited author. “EUROPEAN UROLOGY” was the top journal by impact factor in 2022. Analysis of references and keywords suggests the prevalence of brachytherapy-related research, while high-intensity focused ultrasound (HIFU), cryotherapy, and irreversible electroporation (IRE) are emerging as new research focuses. Consequently, more high-quality evidence is necessary to evaluate the long-term effectiveness and safety of these novel therapeutic methods.

Prognostic Testing for Prostate Cancer—A Cost-Effectiveness Analysis Comparing a Prostatype P-Score Biomarker Approach to Standard Clinical Practice

Article

Full-text available

Jan 2025
PHARMACOECONOMICS

The Prostatype score (P-score) is a prognostic biomarker that integrates a three-gene (IGFBP3, F3, and VGLL3) signature derived from prostate biopsy samples, with key clinical parameters, including prostate-specific antigen (PSA) levels, Gleason grade, and tumor stage at diagnosis. The test has demonstrated superior predictive accuracy for prostate cancer outcomes compared with traditional risk categorization systems such as D’Amico. Notably, it reclassifies a higher proportion of patients into the low-risk category, making them eligible for active surveillance. This study assessed the cost-effectiveness of the P-score in comparison with D’Amico and the Swedish National Prostate Cancer Register (NPCR) risk categorization systems. A two-step decision analytic model was developed. The model consisted of a decision tree-informed Markov structure estimating the lifetime outcomes of 60-year-old men with diagnosed prostate cancer. Prostate cancer was classified as low-risk, intermediate-risk, or high-risk using either the P-score or D’Amico. Initial therapy was based on observed treatment patterns from the Swedish NPCR. Costs (SEK, year 2022) and quality-adjusted life years (QALYs) were estimated from a healthcare perspective and discounted at 3% per year; incremental cost-effectiveness ratio (ICER) was the primary outcome. The P-score led to cost savings and generated an additional 0.19 QALYs compared with D’Amico. The added costs of the genetic test and higher costs of active surveillance and radiotherapy were counterbalanced by savings from reduced costs of surgery, treatment-related side-effects, and metastatic disease. The gain in QALYs was primarily due to the avoidance of metastatic disease and a reduction in treatment-related side-effects. The results of this study suggest that the P-score is likely to be a cost-effective alternative to D’Amico for prognostic evaluation of newly diagnosed prostate cancer in Sweden and compared with NPCR when health-related quality of life was included.

Prostate Cancer: A Journey Through Its History and Recent Developments

Article

Full-text available

Jan 2025

Prostate cancer is one of the most common diseases among men worldwide and continues to pose a serious threat to health. This review shows the history and the new developments in the management of prostate cancer, with an emphasis on a range of therapeutic approaches, such as hormone therapy, radiation therapy, surgery, and innovative targeted therapeutics. The evolution of these treatments is examined in light of clinical outcomes, patient quality of life, and emerging resistance mechanisms, such as the recently shown vitamin D-based strategies. New developments that have the potential to increase survival rates and reduce side effects are also discussed, including PARP inhibitors (PARPis), immunotherapy, and tailored medication. Additionally, the use of biomarkers and sophisticated imaging methods in therapeutic decision-making is explored, with a focus on how these tools might improve patient care. The absolute necessity for a multidisciplinary approach for improving treatment strategies is becoming more and more apparent as our understanding of the biology of prostate cancer deepens. This approach ensures that patients receive customized medicines that fit their unique profiles. Future avenues of investigation will focus on resolving issues dealing with treatment efficacy and resistance to improve treatment results, ultimately leading to disease cure for prostate cancer patients.

Impacto Da Biópsia De Próstata No Diagnóstico Precoce Do Câncer De Próstata

Article

Jan 2025

Adriana Maria Lamego Rezende

O câncer de próstata é o segundo tipo de câncer mais comum em homens em todo o mundo, representando uma significativa causa de morbidade e mortalidade masculina, especialmente em populações acima de 50 anos. A biópsia de próstata surge como um método essencial para o diagnóstico precoce e preciso, sendo um recurso central no manejo clínico dessa doença. Embora exames como o PSA (antígeno prostático específico) e o toque retal sejam amplamente utilizados na triagem inicial, suas limitações em termos de sensibilidade e especificidade frequentemente levam a resultados falso-positivos ou falso-negativos, subestimando ou superestimando a presença de câncer. A biópsia, considerada o padrão-ouro para confirmação do diagnóstico, permite a coleta direta de tecido prostático para análise histopatológica, diferenciando neoplasias malignas de condições benignas, como hiperplasia prostática benigna ou prostatite. Técnicas modernas, como a biópsia transretal e a biópsia perineal guiadas por ultrassonografia ou ressonância magnética multiparamétrica, têm aprimorado a detecção de tumores clinicamente significativos, minimizando os riscos associados ao sobrediagnóstico e ao sobretratamento. Estudos demonstram que a combinação de biópsia guiada por ultrassom com ressonância magnética multiparamétrica aumenta a precisão diagnóstica, identificando lesões relevantes em estágio inicial e reduzindo a probabilidade de identificar tumores indolentes que não requerem intervenção imediata. Epstein et al. (2012) enfatizam que essa abordagem integrada oferece maior eficiência no rastreamento de tumores agressivos, sendo fundamental na classificação do escore de Gleason, que orienta o planejamento terapêutico. A avaliação histopatológica detalhada, obtida a partir do tecido coletado, é indispensável para determinar o grau de diferenciação tumoral, auxiliando na decisão entre monitoramento ativo, terapias menos invasivas ou intervenções mais agressivas, como prostatectomia radical ou radioterapia. Apesar de sua relevância, a biópsia de próstata não é isenta de limitações e riscos. Complicações como infecção, sangramento, retenção urinária aguda e dor são preocupações frequentes, embora tecnologias modernas tenham reduzido significativamente esses eventos adversos. Além disso, o impacto psicológico do procedimento, associado à ansiedade e ao estresse, pode comprometer a adesão dos pacientes ao diagnóstico. Estudos recentes têm explorado estratégias para melhorar a experiência do paciente, incluindo a utilização de sedação leve, profilaxia com antibióticos e técnicas minimamente invasivas, como biópsias por fusão de imagens, que combinam ultrassonografia em tempo real com ressonância magnética para aumentar a precisão e reduzir desconfortos. A detecção precoce do câncer de próstata por meio da biópsia está intimamente associada a melhores prognósticos. Pacientes diagnosticados em estágios iniciais têm acesso a opções terapêuticas menos agressivas e maior chance de sobrevida a longo prazo. Além disso, a diferenciação entre tumores agressivos e indolentes, proporcionada pela análise histopatológica, é crucial para evitar tratamentos desnecessários, que podem causar efeitos colaterais significativos, como disfunção erétil e incontinência urinária. O manejo clínico baseado em dados objetivos da biópsia também permite maior personalização do tratamento, alinhando-se às diretrizes modernas de medicina de precisão. O avanço das tecnologias diagnósticas tem sido determinante na evolução da biópsia de próstata. A introdução de métodos como a biópsia perineal minimamente invasiva e a biópsia por fusão de imagens representa um marco no aumento da precisão e redução das complicações associadas ao procedimento. Segundo Ahmed et al. (2017), essas técnicas têm se mostrado superiores em comparação às abordagens convencionais, especialmente em pacientes com histórico de biópsias anteriores negativas e níveis persistentes de PSA elevados. Além disso, o uso de biomarcadores específicos para direcionar as biópsias é uma área emergente que promete revolucionar o diagnóstico do câncer de próstata, fornecendo uma abordagem ainda mais direcionada e eficiente. No Brasil, o acesso desigual aos recursos diagnósticos e terapêuticos para o câncer de próstata é uma preocupação significativa. Em regiões com menor disponibilidade de ressonância magnética multiparamétrica ou ultrassonografia avançada, a realização de biópsias eficazes pode ser limitada, impactando diretamente os índices de diagnóstico precoce. Políticas públicas voltadas à ampliação do acesso a tecnologias e à capacitação de profissionais de saúde são indispensáveis para garantir que os benefícios da biópsia de próstata sejam amplamente disponíveis. Em conclusão, a biópsia de próstata desempenha um papel central no diagnóstico precoce do câncer de próstata, sendo uma ferramenta indispensável para a identificação e o manejo eficaz da doença. Apesar dos desafios associados ao procedimento, os avanços tecnológicos e a integração de métodos inovadores têm ampliado sua precisão e segurança, promovendo melhores desfechos para os pacientes

Analysis of the predictive value of the prostate-specific antigen-to-neutrophil ratio for the diagnosis of prostate cancer

Article

Full-text available

Jan 2025

Currently, serum PSA is the most commonly used screening tool in clinical practice. However, PSA levels in the range of 4–10 ng/ml are considered the ‘grey zone’ of prostate cancer screening. Patients within this range need to be further evaluated using additional parameters such as PSA ratio, PSA density, and other indices to determine the necessity of prostate biopsy (PBx). Despite this, patients in the ‘grey zone’ still have a low rate of positive biopsy results. Neutrophils have been found to be associated with tumor development and inflammation. Based on this, we combined PSA and absolute neutrophil counts to calculate the total PSA to absolute neutrophil ratio (PNR), which is higher in patients with prostate cancer and lower in those with benign conditions. PNR is elevated in prostate cancer patients compared to those with prostate enlargement. Therefore, the aim of this study is to explore the diagnostic efficacy of PNR for prostate cancer across different PSA intervals and to provide new insights into the diagnosis, treatment, and screening strategies for prostate cancer. In this study, we explored the predictive value of prostate-specific antigen-to-neutrophil ratio (PNR) for the diagnosis of prostate cancer, with a view to further improving the diagnostic accuracy of prostate cancer. Patients were grouped in three different divisions of PSA 4–10 ng/ml, 10–20 ng/ml, > 20 ng/ml, We grouped the patients and compared the test data such as age, PSA, PSA-density (PSAD), and prostate-specific antigen-to-neutrophil ratio (PNR) between the two groups of patients who had puncture results of prostate cancer and non-prostate cancer at the same time using Log regression test to verify the diagnostic value of PNR. When PSA levels are in the range of 4–10 ng/ml, an elevated PNR is an independent risk factor for prostate cancer. In this range, the diagnostic value of f/t PSA and PSAD for prostate cancer is limited. However, the use of PNR can significantly enhance the diagnostic efficacy for prostate cancer and thereby effectively reduce the incidence of unnecessary prostate biopsies.

Biparametric MRI-based radiomics for noninvastive discrimination of benign prostatic hyperplasia nodules (BPH) and prostate cancer nodules: a bio-centric retrospective cohort study

Article

Full-text available

Jan 2025

To investigate the potential of an MRI-based radiomic model in distinguishing malignant prostate cancer (PCa) nodules from benign prostatic hyperplasia (BPH)-, as well as determining the incremental value of radiomic features to clinical variables, such as prostate-specific antigen (PSA) level and Prostate Imaging Reporting and Data System (PI-RADS) score. A restrospective analysis was performed on a total of 251 patients (training cohort, n = 119; internal validation cohort, n = 52; and external validation cohort, n = 80) with prostatic nodules who underwent biparametric MRI at two hospitals between January 2018 and December 2020. A total of 1130 radiomic features were extracted from each MRI sequence, including shape-based features, gray-level histogram-based features, texture features, and wavelet features. The clinical model was constructed using logistic regression analysis. Radiomic models were created by comparing seven machine learning classifiers. The useful clinical variables and radiomic signature were integrated to develop the combined model. Model performance was assessed by receiver operating characteristic curve, calibration curve, decision curve, and clinical impact curve. The ratio of free PSA to total PSA, PSA density, peripheral zone volume, and PI-RADS score were independent determinants of malignancy. The clinical model based on these factors achieved an AUC of 0.814 (95% CI: 0.763–0.865) and 0.791 (95% CI: 0.742–840) in the internal and external validation cohorts, respectively. The clinical-radiomic nomogram yielded the highest accuracy, with an AUC of 0.925 (95% CI: 0.894–0.956) and 0.872 (95% CI: 0.837–0.907) in the internal and external validation cohorts, respectively. DCA and CIC further confirmed the clinical usefulness of the nomogram. Biparametric MRI-based radiomics has the potential to noninvasively discriminate between—BPH and malignant PCa nodules, which outperforms screening strategies based on PSA and PI-RADS.

Alternate definitions of adverse pathology to predict a very high risk of metastasis in men with intermediate‐ and low‐risk prostate cancer

Article

Full-text available

Jan 2025
CANCER-AM CANCER SOC

Background Adverse pathology (AP) is often used as an intermediate end point for long‐term outcomes in men with prostate cancer (PCa) who are active surveillance candidates. The association between a commonly used AP definition and long‐term outcomes was tested, which identified definitions more strongly linked to a high risk of metastasis. Methods Data were reviewed from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing radical prostatectomy (RP) from 1988 to 2020 at nine Veterans Affairs hospitals. Men meeting National Comprehensive Cancer Network low‐risk and favorable intermediate‐risk criteria were included. Men with and without AP were compared; men with AP were defined as having grade groups 3–5 or pathological stage ≥pT3a or pN1 at RP (definition 1). Sensitivity analyses were performed for six alternative definitions (definitions 2–7) and their association with biochemical recurrence (BCR), metastasis, PCa‐specific mortality (PCSM), and castrate‐resistant PCa (CRPC). Results A total of 2175 men were included: 711 had AP by definition 1. In univariable analyses, all AP definitions were associated with the risk of BCR, metastasis, and PCSM. All but one definition were associated with CRPC. In definitions 1–6, the 10‐year event rate for metastasis in those with AP ranged from 3.0% (definition 1) to 7.9% (definition 5). Only in definition 7 was the 10‐year event rate for metastasis >10%. However, only 0.5% of patients (11 of 2175) met definition 7. Conclusions AP was statistically associated with relatively worse outcomes. However, in all but the most stringent definitions, met by <1% of patients, the absolute event rate of metastasis in men with AP was low. This challenges the clinical usefulness of AP as an intermediate end point in men with intermediate‐ to low‐risk PCa.

Interpretable machine learning model for predicting clinically significant prostate cancer: integrating intratumoral and peritumoral radiomics with clinical and metabolic features

Article

Full-text available

Dec 2024
BMC Med Imag

Background To develop and validate an interpretable machine learning model based on intratumoral and peritumoral radiomics combined with clinicoradiological features and metabolic information from magnetic resonance spectroscopy (MRS), to predict clinically significant prostate cancer (csPCa, Gleason score ≥ 3 + 4) and avoid unnecessary biopsies. Methods This study retrospectively analyzed 350 patients with suspicious prostate lesions from our institution who underwent 3.0 Tesla multiparametric magnetic resonance imaging (mpMRI) prior to biopsy (training set, n = 191, testing set, n = 83, and a temporal validation set, n = 76). Intratumoral and peritumoral volumes of interest (VOIintra, VOIperi)) were manually segmented by experienced radiologists on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps. Radiomic features were extracted separately from the VOIintra and VOIperi. After feature selection via the recursive feature elimination (RFE) algorithm, intratumoral radiomic score (intra-rad-score) and peritumoral radiomic score (peri-rad-score) were constructed. The clinical model, MRS model, and combined model integrating radiomic, clinicoradiological and metabolic features were constructed via the eXtreme Gradient Boosting (XGBoost) algorithm. The predictive performance of the models was evaluated in both the training and testing sets using receiver operating characteristic (ROC) curve analysis. SHapley Additive exPlanations (SHAP) analysis was applied to the combined model to visualize and interpret the prediction process. Results A total of 350 patients were included, comprising 173 patients with csPCa (49.4%) and 177 patients with non-csPCa (50.6%). The intra-rad-score and peri-rad-score were constructed via 10 and 16 radiomic features. The combined model demonstrated the highest AUC, accuracy, F1 score, sensitivity, and specificity in the testing set (0.968, 0.928, 0.927, 0.932, and 0.923, respectively) and in the temporal validation set (0.940, 0.895, 0.890, 0.923, and 0.875, respectively). SHAP analysis revealed that the intra-rad-score, PSAD, peri-rad-score, and PI-RADS score were the most important predictors of the combined model. Conclusion We developed and validated a robust machine learning model incorporating intratumoral and peritumoral radiomic features, along with clinicoradiological and metabolic parameters, to accurately identify csPCa. The prediction process was visualized via SHAP analysis to facilitate clinical decision- making.

Comparison of Da Vinci XI and Da Vinci SI Surgical Systems in Robot-Assisted Radical Prostatectomy

Article

Dec 2024

Introduction . Robot-assisted radical prostatectomy is considered to be the “gold standard” for the radical treatment of prostate cancer, achieving excellent oncological outcomes with a low incidence of complications. Aim . To analyze and compare the efficiency of Da Vinci Xi and Da Vinci Si surgical systems applied in performing robot-assisted radical prostatectomy. Materials and methods. 165 patients were divided into two groups: Xi-group ( n = 77) and Si-group ( n = 88). The perioperative characteristics and oncological outcomes were analyzed and compared. Results . The demographic, clinical, and oncological characteristics of the two patient groups appeared similar and comparable. Interventions involving the preservation of the neurovascular bundle, the pelvic fascia, and the puboprostatic ligament were performed using Xi system significantly more often. The surgery duration was significantly shorter in the Xi-group. The postoperative recovery time and the incidence of postoperative complications appeared to be identical across both groups. No differences were revealed in the rates of positive surgical margins or biochemical recurrence. Discussion . Reasons behind the reduced operative time were considered as follows: first, the docking of the Xi system is more user-friendly, resulting in decreased docking time; second, the operational efficiency of the Xi system had been enhanced, thereby leading to reduced workflow times; third, a number of collisions between robotic arms was significantly lower during the procedure, which accelerates the surgical process. Conclusion . A robot-assisted radical prostatectomy performed by an experienced professional, using the Da Vinci Xi or Da Vinci Si surgical systems, appears to be safe and feasible without an increased risk of serious complications. However, the Xi system ensures better perioperative outcomes with comparable oncological results.

Stereotactic radiotherapy with five fractions vs. robot-assisted prostatectomy: first results of the PACE-A study

Article

Full-text available

Dec 2024
STRAHLENTHER ONKOL

Evaluation of a Clinical Acceptability of Deep Learning-Based Autocontouring: An Example of The Use of Artificial Intelligence in Prostate Radiotherapy

Article

Full-text available

Nov 2024

This study aimed to evaluate the usability and benefit of a new generation of auto segmentation, that automatically identifies organs and auto-contours them directly at CT simulator before creating prostate radiotherapy plans. The prostates of 10 patients were automatically contoured using the DirectORGANS auto-segmentation algorithm at the CT simulator. The CT scans were imported into the Eclipse treatment planning system for contouring. On the same CT image sets, the prostate was manually contoured by a group of five experienced physicians. MR-guided prostate contours were delineated using MRI images and used as a reference structure. The volumes of the prostate were measured, and the Overlap index (OI), Dice similarity index (DSC), and Volume difference (Dv) were calculated based on contours. The Kruskal-Wallis H test was performed with SPSS (P<0.05). MR-based contouring was used as a reference, and the OI, DSC, Dv, and contouring time results of users and artificial intelligence were analyzed accordingly. There was a significant difference in OI, DSC, and Dv between the results of users and artificial intelligence. The most significant difference between users, artificial intelligence, and MR-based contouring was contouring time (p <0.001). MR- based contouring was time-consuming. Artificial Intelligence’s automatic contouring of the prostate required minimal modification.

Outcomes and predictors of clinically significant prostate cancer detection by transperineal computer fusion biopsy during active surveillance

Article

Full-text available

Oct 2024
Urol Pol

Organ-confined prostate cancer with negative surgical margins in an entirely-embedded radical prostatectomy is essentially non-lethal—a retrospective single-institutional study of 520 patients

Article

Full-text available

Nov 2024
INT UROL NEPHROL

Purpose There is no risk-based stratification in serum PSA monitoring in prostate cancer (PCa) patients following radical prostatectomy (RP). Those patients with minimal risk of recurrence may be subjected to unnecessarily rigorous monitoring as well as to increased anxiety disproportionate to their actual prognosis. This study aimed to investigate outcomes in PCa patients with favorable pathologic parameters to see whether they can be followed less rigorously than current practice recommendations dictate. Methods 520 consecutive entirely embedded organ-confined RPs with negative margins and undetectable initial postoperative serum PSA at the University of Chicago Medical Center between 2005 and 2017 were retrospectively identified. Clinicopathologic parameters and follow-up data including serum PSA were analyzed. Results No patients, regardless of their grade group (GG), developed metastasis or succumbed to a PCa-specific death. These patients had a median postoperative follow-up of 109 months. 2.2% (22/520) of the patients developed biochemical recurrence (BCR). There were 163, 279, 69, 4, and 5 RPs from GG 1 to 5, respectively. Of these, 0% (0/163), 1.8% (5/279), 18.8% (13/69), 0% (0/4), and 60% (3/5) developed BCR, sequentially. Conclusion In this study, organ-confined PCa with negative margins in an entirely embedded RP carried no mortality risk. In particular, the patients with GG 1–2 disease may have benefited from less rigorous monitoring. Additionally, enhanced patient reassurance could play a role in reducing anxiety in this subset of patients.

Efficacy and safety of neoadjuvant chemohormonal therapy for high-risk prostate cancer treated with robot-assisted laparoscopic radical prostatectomy: a propensity score-matched analysis (the MSUG94 group)

Article

Full-text available

Nov 2024
INT UROL NEPHROL

Purpose The optimal neoadjuvant regimen before radical prostatectomy (RP) in patients with high-risk (HR) prostate cancer (PCa) remains to be determined. This retrospective multicenter cohort study assessed the effectiveness and safety of neoadjuvant chemohormonal therapy (NCHT) in patients with HR-PCa undergoing robot-assisted laparoscopic radical prostatectomy (RALP). Methods We reviewed the datasets of 1023 subjects who underwent RALP at nine Japanese facilities between September 2012 and October 2023. The enrolled patients were divided into two groups using propensity score matching: a RALP-alone group and those who underwent NCHT followed by RALP (NCHT group). The NCHT regimen consisted of a luteinizing hormone-releasing hormone antagonist and tegafur-uracil for at least 3 months before RALP. The primary endpoint was biochemical recurrence (BCR) after RALP. The secondary endpoint was the surgical specimen pathology findings. Results Propensity score matching identified 139 individuals for each group. Median follow-up was 18.2 months. During follow-up, BCR was observed in 41 patients (29.5%) in the RALP-alone group and 22 patients (15.8%) in the NCHT group (p = 0.010). Pathological results showed significantly more organ-confined PCa and significantly fewer positive surgical margins or lymphovascular invasion in the NCHT group than in the RALP-alone group. The 2-yr biochemical recurrence-free survival (BRFS) was 72.7% and 74.7% in the RALP-alone and NCHT groups, respectively (p = 0.086). Two patients (1.4%) experienced grade 3 liver disorder as an NCHT-related adverse event. Conclusion The results suggest that NCHT can safely treat HR-PCa and may reduce the incidence of BCR when combined with RALP.

Oncological Outcomes of Partial Gland Ablation Using High-Intensity Focused Ultrasound After Additional Confirmatory Transperineal Mapping Biopsy in Men with Prostate Cancer

Article

Full-text available

Oct 2024

Background/Objectives: To evaluate whether additional confirmatory transperineal mapping biopsy (TPMB) in men with localized prostate cancer (PCa) alters the treatment plan and outcome of partial gland ablation (PGA) using high-intensity focused ultrasound (HIFU). Methods: We retrospectively reviewed data from 96 patients who underwent PGA using HIFU between January 2020 and June 2022. After multiparametric magnetic resonance imaging (mpMRI), all men underwent transrectal ultrasound (TRUS)-guided, cognitive-targeted biopsy and systematic biopsy. Men eligible for PGA using HIFU first underwent confirmatory TPMB. Any changes in the treatment plan after TPMB were analyzed. Follow-up TRUS-guided biopsy was performed 1 year post-operatively to evaluate oncological outcomes. Clinically significant PCa (csPCa) was defined as Gleason grade (GG) ≥ 2. Results: Among all subjects, the median age (IQR) was 65.0 (60.0–72.0) years and the prostate-specific antigen level was 5.20 (3.71–7.81) ng/mL. The results of both TRUS-guided biopsy and TPMB led to a change in the treatment plan (from unilateral to bilateral PGA) for 13 (13.5%) patients. The 1-year follow-up TRUS-guided biopsy identified PCa in 13 (13.5%) patients, and csPCa in 7 (7.3%) patients. The infield- and outfield-positive rates were 8.3% (8/96) and 3.1% (3/96), respectively, for any PCa, and 3.1% (3/96) and 2.1% (2/96), respectively, for csPCa. Conclusions: Confirmatory TPMB results in better disease identification and localization, thereby affecting the treatment plan and improving oncological outcomes. Therefore, confirmatory TPMB should be considered to establish an appropriate strategy for patients with localized PCa eligible for PGA using HIFU.

Immunological facets of prostate cancer and the potential of immune checkpoint inhibition in disease management

Article

Full-text available

Oct 2024
thno

Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a major cause of cancer-related deaths. Whereas localized PCa can be cured by surgery and radiotherapy, metastatic disease can be treated, but is not curable. Inhibition of androgen signaling remains the main therapeutic intervention for treatment of metastatic PCa, in addition to chemotherapy, radionuclide therapy and emerging targeted therapies. Although initial responses are favorable, resistance to these therapies invariably arise with development of castration resistant PCa (CRPC) and lethal phenotypes. Recent findings have implicated the crosstalk between PCa cells and the tumor microenvironment (TME) as a key factor for disease progression and metastasis, and the immune system is becoming an increasingly attractive target for therapy. Given the striking success of immune checkpoint inhibitors (ICIs) in various cancer types, preclinical and clinical studies have begun to explore their potential in PCa. It has become clear that the PCa TME is largely immunosuppressive, and ICI therapy does not have efficacy for PCa. Intense effort is therefore being made in the field to understand the mechanisms of suppression and to turn the immunosuppressive TME into an immune active one that would enable ICI efficacy. Herein we examine this recent body of knowledge and how the mutational landscape of PCa integrates with an immunosuppressive TME to circumvent ICI-mediated T-cell activity and tumor killing. We then review the emerging potential success of combinatorial ICI approaches, utility of careful patient selection, and potential novel strategies to improve the efficacy of ICI for PCa therapy.

The hidden costs: a qualitative analysis exploring the experience of prostate cancer treatment-related side effects on sexual function and urinary incontinence among Black survivors and their caregivers

Article

Full-text available

Oct 2024

Purpose Prostate cancer (PCa) disproportionately affects Black men in the U.S., leading to high incidence and mortality rates. Post-treatment challenges, such as sexual dysfunction and urinary incontinence, significantly impact quality of life yet are frequently overlooked. The purpose of this study was to characterize the experience of treatment-related side effects around sexual function and urinary incontinence among Black survivors of PCa and their caregivers. Methods We conducted semi-structured virtual interviews with 11 Black survivors of PCa and 11 caregivers (22 total participants). Survivors were eligible if they were diagnosed and treated for PCa within the last decade and caregivers were eligible if they self-identified as a caregiver for a Black survivor. Interviews were transcribed verbatim and analyzed using a qualitative descriptive approach. Results During interviews, participants spontaneously discussed topics covering sexual dysfunction and urinary incontinence. Key themes identified from interview discussions included the physical experience of PCa treatment, knowledge of the impact of PCa treatment on life quality, and the process of navigating survivorship care. Although they received peer and familial support, survivors expressed a desire for clinicians to initiate discussions on sexual dysfunction and urinary incontinence. Caregivers recounted their experiences while providing support to the survivor. Conclusions The findings underscore the need for clinicians to prioritize discussions on sexual dysfunction and urinary incontinence with patients, and for enhancement of care pathways and resources for these issues in survivorship care. Implications for Cancer Survivors Trained professionals, such as occupational and physical therapists, social workers, genetic counselors, and psychologists, have the potential to fill this survivorship care gap.

Identifying the best candidate for focal therapy: a comprehensive review

Article

Full-text available

Oct 2024

Background Despite the evidence supporting the use of focal therapy (FT) in patients with localized prostate cancer (PCa), considerable variability exists in the patient selection criteria across current studies. This study aims to review the most recent evidence concerning the optimal approach to patient selection for FT in PCa. Methods PubMed database was systematically queried for studies reporting patient selection criteria in FT for PCa before December 31, 2023. After excluding non-relevant articles and a quality assessment, data were extracted, and results were described qualitatively. Results There is no level I evidence regarding the best patient selection approach for FT in patients with PCa. Current international multidisciplinary consensus statements recommend multiparametric magnetic resonance imaging (mpMRI) followed by MRI-targeted and systematic biopsy for all candidates. FT may be considered in clinically localized, intermediate risk (Gleason 3 + 4 and 4 + 3), and preferably unifocal disease. Patients should have an acceptable life expectancy. Those with prostate volume >50 ml and erectile dysfunction should not be excluded from FT. Prostate-specific antigen (PSA) level of < 20 (ideally < 10) ng/mL is recommended. However, the utility of other molecular and genomic biomarkers in patient selection for FT remains unknown. Conclusions FT may be considered in well-selected patients with localized PCa. This review provides a comprehensive insight regarding the optimal approach for patient selection in FT.

Analysis of early diagnostic pathway for prostate cancer in Slovenia

Article

Full-text available

Oct 2024
Radiol Oncol

Background Prostate cancer (PCa) is a prevalent male malignancy globally. Prolonged diagnostic intervals are associated with poorer outcomes, emphasizing the need to optimize this process. This study aimed to evaluate the doctor and primary care interval, research their impact on patient survival and explore opportunities to improve PCa diagnostic pathway in primary care. Patients and methods A retrospective cohort study using cancer patients' anonymised primary care data and data of the Slovenian Cancer Registry. Results The study found that the doctor interval had a median duration of 0 days (interquartile range ([IQR] 0–6) and primary care interval a median duration of 5 days (IQR 0–58). Longer intervals were observed in patients with more than two comorbidities, where general practitioners didn't have access to laboratory diagnostic tests within their primary health care centre and when patients first presented with symptoms (reported symptoms at first presentation: dysuria, lower urinary tract symptoms [LUTS], abdominal pain). The analysis also revealed a statistically significant association between lower 5-year survival rate and the accessibility of laboratory and ultrasound diagnostics in primary healthcare centres and a shorter 5-year survival of symptomatic patients in comparison to patients who were identified by elevated levels of prostate specific antigen (PSA). Conclusions This study shows that treating suspected PCa in primary care has a significant impact on 5-year survival. Several factors contribute to better survival, including easy access to laboratory and abdominal ultrasound in primary care centres. The study highlights the complex array of factors shaping PCa diagnosis, beyond individual clinicians' skills, encompassing test and service availability.

High-frequency irreversible electroporation ablation for the prostate in Beagle dogs

Article

Full-text available

Sep 2024

Background: Ablation procedures have garnered significant attention as a minimally invasive treatment of prostate diseases. However, the feasibility and safety of applying high-frequency irreversible electroporation (H-FIRE) to ablate the Beagle prostate for benign prostatic hyperplasia (BPH) treatment have not been thoroughly explored, the appropriate range of parameters has not been determined. In order to ensure the feasibility and safety of prostate ablation surgery, we conducted a study using Beagle dogs as subjects to investigate prostate tissue. Methods: We utilized a composite steep pulse therapy device to perform ablations on 26 lateral lobes of the prostate in 13 Beagles, employing various parameters for different needle distances. The effectiveness of this device was assessed through the observation of the ablation area, intraoperative muscle tremors, postoperative hematological examination, and gross inspection. Results: The findings of our study revealed that 1,000 to 2,000 v/cm in electric field strength, combined with 5 µs pulse width and pulse number 100, is a safe parameter range for ablation of prostate tissue. At the same time, the large electric field strength (2,000 v/cm) has the best ablation effect with the biggest continuous and thorough ablation area. All parameters of H-FIRE were safe for Beagles. Conclusions: H-FIRE ablation for prostate is safe and effective in dogs, which has the potential to be a useful addition to the range of minimally invasive treatments available for the treatment of BPH against this backdrop of increasing surgical practice.

Efficacy of brachytherapy versus radical prostatectomy for localized prostate cancer–propensity score-matched comparison

Article

Full-text available

Sep 2024
BMC CANCER

Objective The brachytherapy (BT) and radical prostatectomy (RP) are two methods recommended in current guidelines for the treatment of localized prostate cancer (PCa). It is difficult to compare the oncological results of these two treatments because of differences in baseline characteristics and treatment selection.we sought to compare the efficacy of BT and RP after propensity score matching(PSM)analysis. Methods Between January 2009 and December 2021, our institution treated 657 patients with localized PCa (BT: n = 198; RP: n = 459)and followed up for > 2 years. Biochemical recurrence was defined as prostate-specific antigen (PSA) levels of nadir plus 2 ng/ml or higher (Phoenix definition) for BT, and as PSA0.2 ng/ml or greater for RP. PSM was applied based on the age, body mass index, PSA, prostate volume, clinical T-stage, Gleason grade, percentage of positive puncture needles ≥ 1/2, maximum tumor diameter ≥ 5 mm, and follow-up period. Results Median follow-up was 63 months for BT and 52 months for RP. After propensity score adjustment, a total of 294 (147 each) patients remained for further analysis.Kaplan–Meier curves showed no statistically significant difference in clinical relapse-free survivals (cRFS) (p = 0.637),overall survival (OS) (p = 0.726),and cancer-specific survival (CSS) (p = 0.505).BT was associated with improved biochemical relapse-free survivals (bRFS) compared to RP (p = 0.022), Logistic multivariate analysis based on the whole cohort revealed that clinical T stage ≥ T2b (p = 0.043) and tumor maximum diameter ≥ 5 mm (p = 0.044) were associated with significantly bRFS. Conclusion The BT and RP group patients exhibited similar cRFS, OS, and CSS. However, patients in the BT groups exhibited better bRFS than those in the RP group.Clinical T stage ≥ T2b and a maximum tumor diameter ≥ 5 mm were independent prognostic factors.

Salvage lymphadenectomy or radiation therapy in prostate cancer patients with biochemical recurrence and PET positive lymph nodes after radical prostatectomy: A systematic review and pooled analysis

Article

Sep 2024
EJSO-EUR J SURG ONC

Risk of Biochemical Recurrence and Metastasis in Prostate Cancer Patients Treated with Radical Prostatectomy After a 10-year Disease-free Interval

Article

Sep 2024

Development and validation of nomograms for predicting pentafecta outcomes before and after robot-assisted radical prostatectomy: a retrospective study

Article

Full-text available

Jan 2025

Prostate cancer (PCa) is one of the most common cancers among men worldwide, and robot-assisted radical prostatectomy (RARP) is a widely used treatment for localized PCa. Achieving pentafecta outcomes, which include continence, potency, cancer control, free surgical margins, and no major complications, is a critical measure of surgical success and long-term prognosis. However, predicting these outcomes remains challenging. In this retrospective, single-center study, we analyzed data from 1,752 patients who underwent RARP for localized prostate adenocarcinoma between August 2009 and April 2023. The pentafecta outcome was achieved in 290 patients (16.6%). Multivariate analysis revealed that bilateral nerve sparing significantly increased the likelihood of achieving the pentafecta outcome (odds ratio 10.36, 95% CI: 5.75–18.66; p < 0.001). Preoperative potency and bilateral nerve sparing were also identified as key predictors. Nomograms were developed using preoperative and postoperative variables, including age, PSA level, biopsy Gleason score, clinical stage, pathological tumor stage, tumor grade, nerve sparing, and preoperative potency. Internal validation of the nomograms was performed using bootstrapping methods, demonstrating robust predictive performance. These nomograms provide valuable tools for personalized surgical planning and patient counseling and may be applicable to broader populations, given the inclusion of universally recognized predictive factors and rigorous validation. This study presents the development and validation of nomograms to predict pentafecta outcomes before and after RARP. These nomograms provide valuable tools for clinicians to estimate the likelihood of achieving postoperative pentafecta outcomes. Incorporating these nomograms into clinical practice may improve patient counseling and shared decision-making.

Effectiveness of Exercise Therapy for Patients with Prostate Cancer Focusing on High-intensity Interval Training: A Narrative Review

Article

Dec 2024

Shigenori Ito

Prostate cancer (PC) is the most frequently diagnosed cancer in men, and the population of survivors continues to increase. Although PC has a slower progression rate and a relatively favorable prognosis compared to other cancers, new strategies are needed to enhance outcomes after diagnosis and treatment. The effectiveness of exercise therapy in the prevention and treatment of PC is well documented. The significance of exercise for patients with PC includes prevention of disease progression, maintenance of physical fitness, and enhancement of muscle strength before surgery, as well as during chemotherapy and radiotherapy, all of which contribute to improving prognosis after treatment. High-intensity interval training (HIIT) is a well-established training protocol for long-distance runners that has also been applied to cardiovascular and metabolic diseases as a relatively novel and promising approach. HIIT, which involves high-intensity aerobic exercise, is known to enhance cardiorespiratory fitness, cardiac function, and insulin resistance to a greater extent than moderate-intensity training. Recent studies have demonstrated that HIIT effectively improves cancer cell growth inhibition and decreases prostate-specific antigen levels in both localized PC under active surveillance and metastatic castrate-resistant PC. However, the HIIT protocol should be tailored to each patient's condition and physical fitness level upon implementation. If accumulating evidence confirms the ability of HIIT to enhance physical fitness and suppress PC growth, the benefits to patients with PC would be substantial, and expected to be widespread.

Subject adherence

Chapter

Jan 2025

Hunter Wessells

Qualitative and mixed methods in urology

Chapter

Jan 2025

A controlled study of use and effectiveness of phosphodiesterase-5 inhibitors in long-term survivors after curative radiotherapy for prostate cancer (PCa)

Article

Dec 2024
RADIOTHER ONCOL

Investigation of the clinical significance of localized prostate cancer tissue expression of the immunohistochemical biomarkers enhancer of zeste homolog 2 and Forkhead box M1: A Greek retrospective study

Article

Dec 2024

Partial or Focal Brachytherapy for Prostate Cancer: A Systematic Review and Meta-Analysis

Article

Full-text available

Dec 2024
BRIT J RADIOL

Introduction Recent advances in image-guided brachytherapy have allowed for treatment volume reduction in the treatment of prostate cancer, with the aim to optimize disease control and reduce toxicities. This systematic review reports on the efficacy and safety of focal brachytherapy for treatment of patients with localized prostate cancer. Methods Medline, Embase, Web of Science and Cochrane were searched from inception to July 2023. Studies were included if they reported on focal brachytherapy, and described either dosimetry or clinical outcomes in the monotherapy or salvage setting. Meta-analysis was conducted to estimate biochemical control (BC) at 12-60 months. The review protocol was registered on PROSPERO (CRD42022320921). Results 26 studies reporting on 1492 patients were included in this review. 14 studies reported on monotherapy, 10 on salvage and 2 on boost. The majority of studies used MRI and/or biopsy or PET for target identification, and MRI fusion and transrectal ultrasound (TRUS) for image guidance technique. BC for monotherapy was 97% (95%CI: 86-99%) at 24 months, and 82% (95%CI: 65-92%) at 60 months. BC for salvage was 67% (95%CI: 62-72%) at 24 months, and 35% (95%CI: 17-58%) at 60 months. Low rates of toxicity were reported across studies. Conclusion Focal brachytherapy has promising efficacy and safety profiles. Future studies may compare focal brachytherapy to whole-gland treatments, to investigate relative efficacy and safety. Advances in knowledge In well-selected patients, partial or focal brachytherapy represents an evidence-based option with acceptable BC rates and a favourable toxicity profile.

Impact of prostate volume on the active surveillance in prostate cancer

Article

Dec 2024

Objective To determine the influence of the prostate volume (PVo) in the management of patients in active surveillance (AS) for prostate cancer. Materials and methods A retrospective analysis of clinical, biological, histological and radiological data collected between 2010 and 2021 was performed for patients included in an AS protocol in a university hospital. The impact of initial PVo on the subsequent risk of exiting AS was evaluated. Results In total, 109 patients were included in this analysis with a mean follow-up period of 52.74 ± 31 months, 50% were out of AS by the end of the follow-up period. The risk of exiting the AS protocol was significantly associated to the PVo: patients with smaller PVo had an increased risk of exiting AS ( p = 0.025). The maximal percentage of core invasion was the only initial predictive parameter for exiting the AS protocol on multivariate analysis of the global cohort ( p = 0.010) and in the sub-group of patients having PVo ⩽ 45 mL ( p = 0.013). In the group having a PVo > 45 mL, no single initial parameter was significantly associated to a risk of exiting AS. Conclusion Patients having small-sized prostate seemed to be at higher risk of exiting AS during follow-up. Level of evidence 4

Recent Advancement In Treatment of Prostate Cancer

Article

Full-text available

Dec 2024

Triveni Khurana

Radiotherapy is an appealing treatment option for prostate cancer and has a definite role in all stages of the disease. Over the last decade, breakthroughs in technology, imaging capabilities, and greater radiobiological understanding have profoundly revolutionized prostate cancer radiation, permitting dose escalation and widespread use of hypofractionation. Furthermore, the incorporation of magnetic resonance imaging (MRI) and enhanced physical accuracy of dose administration have offered an impetus to target intraprostatic tumor lesions, which were previously agnostic to the standard radiation target definition concept. The accumulating results from randomised clinical trials and observational studies demonstrate that ultra-hypofractionation is a safe strategy, but further study is needed to evaluate its efficacy to normal fractionation. Since hypofractionation has yet to produce the theoretically envisioned enhanced biochemical control outcomes, there is continuous uncertainty about the correct alpha/beta ratio for prostate cancer. Finally, a newly published randomised experiment resolved an ongoing debate on the role of elective pelvic lymph node radiotherapy in patients with high-risk prostate cancer, demonstrating a definite advantage when pelvic nodes were treated to 50 Gy. The significance of partial gland dosage escalation/tumor boosting is developing, and additional data is required before this strategy can be used in routine clinical care. In the future, molecular imaging will be critical for assessing disease biology, potentially predicting response, and optimally personalising radiation treatment decisions. We critically reviewed the published literature and offered a practical summary of current prostate radiation advances for busy doctors in this narrative review.

Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial

Article

Dec 2024
J Am Med Assoc

Importance Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown. Objective To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care. Design, Setting, and Participants Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor–positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023. Interventions Participants were randomized to receive active monitoring (follow-up every 6 months with breast imaging and physical examination; n = 484) or guideline-concordant care (surgery with or without radiation therapy; n = 473). Main Outcomes and Measures The primary outcome was 2-year cumulative risk of ipsilateral invasive cancer diagnosis, according to planned intention-to-treat and per-protocol analyses, with a noninferiority bound of 0.05%. Results The median age of the 957 participants analyzed was 63.6 (95% CI, 55.5-70.5) years in the guideline-concordant care group and 63.7 (95% CI, 60.0-71.6) years in the active monitoring group. Overall, 15.7% of participants were Black and 75.0% were White. In this prespecified primary analysis, median follow-up was 36.9 months; 346 patients had surgery for DCIS, 264 in the guideline-concordant care group and 82 in the active monitoring group. Forty-six women were diagnosed with invasive cancer, 19 in the active monitoring group and 27 in the guideline-concordant care group. The 2-year Kaplan-Meier cumulative rate of ipsilateral invasive cancer was 4.2% in the active monitoring group vs 5.9% in the guideline-concordant care group, a difference of −1.7% (upper limit of the 95% CI, 0.95%), indicating that active monitoring is not inferior to guideline-concordant care. Invasive tumor characteristics did not differ significantly between groups. Conclusions and Relevance Women with low-risk DCIS randomized to active monitoring did not have a higher rate of invasive cancer in the same breast at 2 years compared with those randomized to guideline-concordant care. Trial Registration ClinicalTrials.gov Identifier: NCT02926911

Diagnostic Imaging Advances

Chapter

Nov 2024

Safe and efficient high-dose radiation delivery to target tissue, while minimizing the exposure and toxicity of adjacent non-target organs, is considered the paramount goal of stereotactic radiosurgery. With the expanding applications of stereotactic radiosurgery, the requirement for imaging tools to precisely and accurately guide treatment planning and posttreatment disease monitoring has also grown. As radiosurgery pioneers many frontiers in non-invasive personalized medicine, the need for reliable imaging biomarkers is particularly evident in oncologic practice where differentiation of treatment-related changes from tumor recurrence is of critical importance. This chapter reviews entity-specific and technical considerations of advanced imaging in the planning and follow-up of a variety of benign and malignant intracranial lesions, as well as lung, liver, pancreatic, and prostate tumors.

French AFU Cancer Committee Guidelines - Update 2024-2026: Prostate cancer - Diagnosis and management of localised disease

Article

Nov 2024

Prevalence of clinical symptoms and their effect on quality of life among patients with benign prostatic hyperplasia at a tertiary health facility in Minna, North central Nigeria

Article

Full-text available

Nov 2024

Background: Benign prostate hyperplasia (BPH) is increasingly common among older adult males and its treatment has highly variable effect on patient's quality of life. The persistence of clinical symptoms varies widely and also frequently changes in the course of therapy. The severity of symptoms, side effect(s) of drugs, emotional distress and demographic factors have unpredictable impact on patient's quality of life. Furthermore, the persistence of residual clinical symptoms and abnormally high PSA levels remain an ongoing clinical challenge in the management of the disease. This study therefore aims to assess prevalence and severity of symptoms and quality of life of patients with benign prostate hyperplasia. Methods: The study was carried out at Ibrahim Badamosi Babangida specialized hospital Minna, Niger State. The hospital's electronic patient's records were used to identify prospective respondents. The medical information of 443 eligible patients were extracted for analysis. The selected patients were followed up during physician appointments and then administered the EPIC-CP and SF-12questionnaires to determine prevalence and severity of symptoms as well as quality of life respectively. Data was entered into Microsoft excel and scores calculated according to standard procedures. Asubscale score of ≤4 implied absence or mild symptoms, 5 – 8 (moderate symptom) and 9 – 12 severe symptoms (EPIC-CP), while physical and mental components of quality of life score higher than 50 was satisfactory (SF-12). Results: The mean age of respondents was 65 years and they had been on therapy for 4.9 years. Majority of patients were on Tamulosin monotherapy (63.1%) and Tamulosin / Dutasteride combination therapy (36.9%). The most reported symptoms included sexual dysfunction (96.1%), urinary incontinence (37.6%), urinary obstruction (34.5%) and hormonal symptoms (36%).The quality of life was generally poor and significantly associated with age (p=0.042) and PSA level (p<0.001).There was significant difference in quality of life based on demographic variables (p<0.001). Conclusion: The persistence of high level of sexual dysfunction and urinary symptoms among patients remains a major medical challenge. Quality of life was generally poor and affected by residual symptoms and side effect of drugs.

Recommandations françaises du comité de cancérologie de l’AFU – Actualisation 2024–2026 : cancer de la prostate – diagnostic et prise en charge de la maladie localisée

Article

Nov 2024
Prog Urol

Biochemical outcome of prostate cancer patients treated with hypofractionated external radiation and a single high-dose-rate brachytherapy boost

Article

Nov 2024
BRACHYTHERAPY

Imaging in Diagnosis and Active Surveillance for Prostate Cancer: A Review

Article

Nov 2024

Importance Active surveillance (AS) has become an increasingly important option for managing low-risk and select intermediate-risk prostate cancer. Although imaging, particularly multiparametric magnetic resonance imaging (mpMRI), has emerged in the prebiopsy pathway for the diagnosis of prostate cancer, the role of mpMRI in patient selection for AS and the necessity of prostate biopsies during AS remain poorly defined. Despite well-founded biopsy schedules, there has been substantial investigation into whether imaging may supplant the need for prostate biopsies during AS. This review aimed to summarize the contemporary role of imaging in the diagnosis and surveillance of prostate cancer. Observations Multiparametric MRI is the most established form of imaging in prostate cancer, with routine prebiopsy use being shown to help urologists distinguish between clinically significant and clinically insignificant disease. The visibility of these lesions on mpMRI closely correlates with their behavior, with visible disease portending a worse prognosis. Combined with other clinical data, risk calculators may better delineate patients with higher-risk disease and exclude them from undergoing AS. While current evidence suggests that mpMRI cannot replace the need for prostate biopsy during AS due to the possibility of missing higher-risk disease, the addition of prostate biomarkers may help to reduce the frequency of these biopsies. The role of prostate-specific antigen positron emission tomography/computed tomography is still emerging but has shown promising early results as an adjunct to mpMRI in initial diagnosis. Conclusions and Relevance Imaging in prostate cancer helps to better select patients appropriate for AS, and future studies may strengthen the predictive capabilities of risk calculators. Multiparametric MRI has been shown to be imperative to rationalizing biopsies for patients enrolled in AS. However, heterogeneity in the evidence of mpMRI during AS has suggested that further prospective studies and randomized clinical trials, particularly in homogenizing reporting standards, may reveal a more defined role in monitoring disease progression.

Update on PSMA-based Prostate Cancer Imaging

Article

Oct 2024
SEMIN NUCL MED

Decision regret after curative treatment and its association with the decision-making process and quality of life for prostate cancer patients

Article

Oct 2024
INT J UROL

Objectives To determine how the treatment decision‐making process and posttreatment health‐related quality of life (HRQOL) are related to regret about treatment choice for prostate cancer patients in Japan. Methods We invited a total of 614 patients who were treated with radiation therapy (RT), radical prostatectomy (RP), or active surveillance/watchful waiting (AS/WW) from April 2007 to March 2021. Posttreatment regret was evaluated by the Decision Regret Scale. HRQOL was evaluated by the Expanded Prostate Cancer Index Composite and the 12‐item Short Form Survey. The decision‐making process was assessed by patient evaluation of the decision‐making process. We compared the decision regret scale scores across treatment types, HRQOL, and decision‐making processes. Results Data from 371 patients were analyzed (RT: 202, RP: 149, AS/WW: 20). The median length of time since treatment was 64 (IQR: 43–93) months. The decision regret scale scores were not significantly different among the treatment groups but were significantly greater (strong regret) in patients with poor urinary summary scores, bowel summary scores, and hormonal summary scores. The decision regret scale scores were significantly lower (less regret) for patients who reported being adequately informed at the time of the treatment decision and who had adequately communicated their questions and concerns to physicians than for patients who reported less adequate communication. This result was also observed among patients who reported low HRQOL scores. Conclusions These findings underline the important influence of posttreatment HRQOL and decision‐making as an interactive process between physicians and their patients on posttreatment regret in prostate cancer patients.

CACA guidelines for holistic integrative management of prostate cancer

Article

Full-text available

Oct 2024

Prostate cancer (PC) is an epithelial malignancy occurring in the prostate. PC ranks second in incidence among all male malignancies globally by the latest statistics from the World Health Organization. Notably, China has seen a more rapid increase in PC incidence compared to developed European and American nations. By 2022, the newly reported cases and deaths due to PC in China increased to 134,200 and 47,500, respectively. Thus, early diagnosis and standardized treatment for prostate cancer in China remain far-reaching objectives. Burgeoning research on advanced PC and castration-resistant prostate cancer in recent years have paved the way for a new era of integrated treatment methods including novel endocrine drugs, chemotherapy, targeted therapy, and immunotherapy. Future therapies involve precision treatment guided by genetic testing and individualized integrated treatment as part of a multidisciplinary integrated diagnosis and treatment model for PC. The Genitourinary Oncology Committee of the China Anti-Cancer Association (CACA-GU) has invited multidisciplinary experts across fields including surgery, oncology, pathology, radiology, herbal medicine, physiatry, and psychology to collaboratively write, discuss, and revise guidelines on managing PC. The CACA Guidelines for Holistic Integrative Management of Prostate Cancer includes epidemiology, screening and diagnosis, treatment for localized PC, diagnosis and treatment of PC recurrence after radical prostatectomy, management of metastatic PC, traditional Chinese medicine diagnosis and treatment of PC, and rehabilitation from PC. This guideline aims to standardize the clinical diagnosis and treatment management of PC in China. It is more aligned with China’s clinical practice, highlights Chinese characteristics, and bears significant clinical importance.

MRI software and cognitive fusion biopsies in people with suspected prostate cancer: a systematic review, network meta-analysis and cost-effectiveness analysis

Article

Oct 2024
HEALTH TECHNOL ASSES

Background Magnetic resonance imaging localises cancer in the prostate, allowing for a targeted biopsy with or without transrectal ultrasound-guided systematic biopsy. Targeted biopsy methods include cognitive fusion, where prostate lesions suspicious on magnetic resonance imaging are targeted visually during live ultrasound, and software fusion, where computer software overlays the magnetic resonance imaging image onto the ultrasound in real time. The effectiveness and cost-effectiveness of software fusion technologies compared with cognitive fusion biopsy are uncertain. Objectives To assess the clinical and cost-effectiveness of software fusion biopsy technologies in people with suspected localised and locally advanced prostate cancer. A systematic review was conducted to evaluate the diagnostic accuracy, clinical efficacy and practical implementation of nine software fusion devices compared to cognitive fusion biopsies, and with each other, in people with suspected prostate cancer. Comprehensive searches including MEDLINE, and Embase were conducted up to August 2022 to identify studies which compared software fusion and cognitive fusion biopsies in people with suspected prostate cancer. Risk of bias was assessed with quality assessment of diagnostic accuracy studies-comparative tool. A network meta-analysis comparing software and cognitive fusion with or without concomitant systematic biopsy, and systematic biopsy alone was conducted. Additional outcomes, including safety and usability, were synthesised narratively. A de novo decision model was developed to estimate the cost-effectiveness of targeted software fusion biopsy relative to cognitive fusion biopsy with or without concomitant systematic biopsy for prostate cancer identification in biopsy-naive people. Scenario analyses were undertaken to explore the robustness of the results to variation in the model data sources and alternative assumptions. Results Twenty-three studies (3773 patients with software fusion, 2154 cognitive fusion) were included, of which 13 informed the main meta-analyses. Evidence was available for seven of the nine fusion devices specified in the protocol and at high risk of bias. The meta-analyses show that patients undergoing software fusion biopsy may have: (1) a lower probability of being classified as not having cancer, (2) similar probability of being classified as having non-clinically significant cancer (International Society of Urological Pathology grade 1) and (3) higher probability of being classified at higher International Society of Urological Pathology grades, particularly International Society of Urological Pathology 2. Similar results were obtained when comparing between same biopsy methods where both were combined with systematic biopsy. Evidence was insufficient to conclude whether any individual devices were superior to cognitive fusion, or whether some software fusion technologies were superior to others. Uncertainty in the relative diagnostic accuracy of software fusion versus cognitive fusion reduce the strength of any statements on its cost-effectiveness. The economic analysis suggests incremental cost-effectiveness ratios for software fusion biopsy versus cognitive fusion are within the bounds of cost-effectiveness (£1826 and £5623 per additional quality-adjusted life-year with or with concomitant systematic biopsy, respectively), but this finding needs cautious interpretation. Limitations There was insufficient evidence to explore the impact of effect modifiers. Conclusions Software fusion biopsies may be associated with increased cancer detection in relation to cognitive fusion biopsies, but the evidence is at high risk of bias. Sufficiently powered, high-quality studies are required. Cost-effectiveness results should be interpreted with caution given the limitations of the diagnostic accuracy evidence. Study registration This trial is registered as PROSPERO CRD42022329259. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135477) and is published in full in Health Technology Assessment ; Vol. 28, No. 61. See the NIHR Funding and Awards website for further information.

Radiotherapy As a Local Therapy in the Management of Patient with Oligometastatic Prostate Cancer

Chapter

Jun 2024

In an age characterized by an influx of information, access to comprehensive volumes on uro-oncology is becoming increasingly practical. This publication endeavors to present contemporary insights into the management of metastatic prostate cancer. The integration of new imaging methodolo-gies and therapeutic interventions signifies a transformative phase in prostate cancer management. Authored with contributions from esteemed professionals possessing both national and international expertise, this text offers a com-prehensive discourse on the holistic management of meta-static prostate cancer. By facilitating interdisciplinary collab-oration among fields such as urology, radiology, pathology, nuclear medicine and oncology, it serves as a guiding beacon amidst the complexities of contemporary clinical practice and scholarly pursuits.

Optical functional nanomaterials for cancer photoimmunotherapy

Article

Oct 2024
COORDIN CHEM REV

Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy vs. IMRT for Localized Prostate Cancer

Article

Sep 2024
INT J RADIAT ONCOL

Radiotherapy for Prostate Cancer: is it ‘what you do’ or ‘the way that you do it’? A UK Perspective on Technique and Quality Assurance

Article

Full-text available

Jul 2016

Aims: The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history of prostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial. Materials and methods: The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localised prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n = 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era. Results: There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outlining review showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of the prostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints in ProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent. Conclusion: The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials.

Patient-reported outcomes in the ProtecT randomised trial of clinically localised prostate cancer treatments: design and baseline urinary, bowel and sexual function and quality of life

Article

Full-text available

Jul 2016
BJU INT

Objectives: To present the baseline patient-reported outcome measures (PROMs) in the ProtecT (Prostate testing for cancer and Treatment) randomised trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localised prostate cancer and to compare results with other populations. Materials and methods: 1,643 randomised men aged 50-69 years in nine UK cities diagnosed with clinically localised disease identified by prostate-specific antigen (PSA) testing (1999-2009). Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific quality of life impacts (EPIC: 2005 onwards, ICIQ-UI: 2001 onwards, ICSmaleSF), anxiety and depression (HADS), generic mental and physical health (SF-12, EQ-5D-3L) were completed at prostate biopsy clinics before randomisation. Descriptive statistics presented by treatment allocation and by men's age and at biopsy and PSA testing time points for selected measures. Results: 1,438 participants completed biopsy questionnaires (88%) and between 77-88% were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms (LUTS) were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65-70 years), whilst urinary bother and physical health was somewhat worse than in younger men (49-54 years, all p<0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (p<0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments. Conclusion: ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were comparable to populations screened for prostate cancer and non-cancer controls. This article is protected by copyright. All rights reserved.

Contemporary accuracy of death certificates for coding prostate cancer as a cause of death: Is reliance on death certification good enough? A comparison with blinded review by an independent cause of death evaluation committee

Article

Full-text available

Jun 2016
BRIT J CANCER

Background: Accurate cause of death assignment is crucial for prostate cancer epidemiology and trials reporting prostate cancer-specific mortality outcomes. Methods: We compared death certificate information with independent cause of death evaluation by an expert committee within a prostate cancer trial (2002-2015). Results: Of 1236 deaths assessed, expert committee evaluation attributed 523 (42%) to prostate cancer, agreeing with death certificate cause of death in 1134 cases (92%, 95% CI: 90%, 93%). The sensitivity of death certificates in identifying prostate cancer deaths as classified by the committee was 91% (95% CI: 89%, 94%); specificity was 92% (95% CI: 90%, 94%). Sensitivity and specificity were lower where death occurred within 1 year of diagnosis, and where there was another primary cancer diagnosis. Conclusions: UK death certificates accurately identify cause of death in men with prostate cancer, supporting their use in routine statistics. Possible differential misattribution by trial arm supports independent evaluation in randomised trials.British Journal of Canceradvance online publication, 2 June 2016; doi:10.1038/bjc.2016.162 www.bjcancer.com.

Standardisation of information submitted to an endpoint committee for cause of death assignment in a cancer screening trial - Lessons learnt from CAP (Cluster randomised triAl of PSA testing for Prostate cancer) Data collection, quality, and reporting

Article

Full-text available

Jan 2015
BMC MED RES METHODOL

In cancer screening trials where the primary outcome is target cancer-specific mortality, the unbiased determination of underlying cause of death (UCD) is crucial. To minimise bias, the UCD should be independently verified by expert reviewers, blinded to death certificate data and trial arm. We investigated whether standardising the information submitted for UCD assignment in a population-based randomised controlled trial of prostate-specific antigen (PSA) testing for prostate cancer reduced the reviewers' ability to correctly guess the trial arm. Over 550 General Practitioner (GP) practices (>415,000 men aged 50-69 years) were cluster-randomised to PSA testing (intervention arm) or the National Health Service (NHS) prostate cancer risk management programme (control arm) between 2001 and 2007. Assignment of UCD was by independent reviews of researcher-written clinical vignettes that masked trial arm and death certificate information. A period of time after the process began (the initial phase), we analysed whether the reviewers could correctly identify trial arm from the vignettes, and the reasons for their choice. This feedback led to further standardisation of information (second phase), after which we re-assessed the extent of correct identification of trial arm. 1099 assessments of 509 vignettes were completed by January 2014. In the initial phase (n = 510 assessments), reviewers were unsure of trial arm in 33% of intervention and 30% of control arm assessments and were influenced by symptoms at diagnosis, PSA test result and study-specific criteria. In the second phase (n = 589), the respective proportions of uncertainty were 45% and 48%. The percentage of cases whereby reviewers were unable to determine the trial arm was greater following the standardisation of information provided in the vignettes. The chances of a correct guess and an incorrect guess were equalised in each arm, following further standardisation. It is possible to mask trial arm from cause of death reviewers, by using their feedback to standardise the information submitted to them.Trial registration: ISRCTN92187251.

Cost-effectiveness of Prostate Cancer Screening: A Simulation Study Based on ERSPC Data

Article

Full-text available

Jan 2015
J NATL CANCER I

The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, overdiagnosis, and costs. Based on data of the ERSPC trial, we predicted the numbers of prostate cancers diagnosed, prostate cancer deaths averted, life-years and quality-adjusted life-years (QALY) gained, and cost-effectiveness of 68 screening strategies starting at age 55 years, with a PSA threshold of 3, using microsimulation modeling. The screening strategies varied by age to stop screening and screening interval (one to 14 years or once in a lifetime screens), and therefore number of tests. Screening at short intervals of three years or less was more cost-effective than using longer intervals. Screening at ages 55 to 59 years with two-year intervals had an incremental cost-effectiveness ratio of $73000 per QALY gained and was considered optimal. With this strategy, lifetime prostate cancer mortality reduction was predicted as 13%, and 33% of the screen-detected cancers were overdiagnosed. When better quality of life for the post-treatment period could be achieved, an older age of 65 to 72 years for ending screening was obtained. Prostate cancer screening can be cost-effective when it is limited to two or three screens between ages 55 to 59 years. Screening above age 63 years is less cost-effective because of loss of QALYs because of overdiagnosis. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: Study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial

Article

Full-text available

Sep 2014
LANCET ONCOL

Background Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options. We report the study design, participant sociodemographic and clinical characteristics, and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment (ProtecT) trial, which aims to investigate the effectiveness of treatments for localised prostate cancer. Methods In this randomised phase 3 trial, men aged 50–69 years registered at 337 primary care centres in nine UK cities were invited to attend a specialist nurse appointment for a serum prostate-specific antigen (PSA) test. Prostate biopsies were offered to men with a PSA concentration of 3·0 μg/L or higher. Consenting participants with clinically localised prostate cancer were randomly assigned to active monitoring (surveillance strategy), radical prostatectomy, or three-dimensional conformal external-beam radiotherapy by a computer-generated allocation system. Randomisation was stratified by site (minimised for differences in participant age, PSA results, and Gleason score). The primary endpoint is prostate cancer mortality at a median 10-year follow-up, ascertained by an independent committee, which will be analysed by intention to treat in 2016. This trial is registered with ClinicalTrials.gov, number NCT02044172, and as an International Standard Randomised Controlled Trial, number ISRCTN20141297. Findings Between Oct 1, 2001, and Jan 20, 2009, 228 966 men were invited to attend an appointment with a specialist nurse. Of the invited men, 100 444 (44%) attended their initial appointment and 82 429 (82%) of attenders had a PSA test. PSA concentration was below the biopsy threshold in 73 538 (89%) men. Of the 8566 men with a PSA concentration of 3·0–19·9 μg/L, 7414 (87%) underwent biopsies. 2896 men were diagnosed with prostate cancer (4% of tested men and 39% of those who had a biopsy), of whom 2417 (83%) had clinically localised disease (mostly T1c, Gleason score 6). With the addition of 247 pilot study participants recruited between 1999 and 2001, 2664 men were eligible for the treatment trial and 1643 (62%) agreed to be randomly assigned (545 to active monitoring, 545 to radiotherapy, and 553 to radical prostatectomy). Clinical and sociodemographic characteristics of randomly assigned participants were balanced across treatment groups. Interpretation The ProtecT trial randomly assigned 1643 men with localised prostate cancer to active monitoring, radiotherapy, or surgery. Participant clinicopathological features are more consistent with contemporary patient characteristics than in previous prostate cancer treatment trials. Funding UK National Institute for Health Research Health Technology Assessment Programme.

Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)

Article

Full-text available

May 2014

Background: Screening for prostate cancer continues to generate controversy because of concerns about over-diagnosis and unnecessary treatment. We describe the rationale, design and recruitment of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP) trial, a UK-wide cluster randomised controlled trial investigating the effectiveness and cost-effectiveness of prostate-specific antigen (PSA) testing. Methods: Seven hundred and eighty-five general practitioner (GP) practices in England and Wales were randomised to a population-based PSA testing or standard care and then approached for consent to participate. In the intervention arm, men aged 50–69 years were invited to undergo PSA testing, and those diagnosed with localised prostate cancer were invited into a treatment trial. Control arm practices undertook standard UK management. All men were flagged with the Health and Social Care Information Centre for deaths and cancer registrations. The primary outcome is prostate cancer mortality at a median 10-year-follow-up. Results: Among randomised practices, 271 (68%) in the intervention arm (198 114 men) and 302 (78%) in the control arm (221 929 men) consented to participate, meeting pre-specified power requirements. There was little evidence of differences between trial arms in measured baseline characteristics of the consenting GP practices (or men within those practices). Conclusions: The CAP trial successfully met its recruitment targets and will make an important contribution to international understanding of PSA-based prostate cancer screening.

Prostate cancer: Summary of updated NICE guidance

Article

Full-text available

Jan 2014
Br Med J

Prostate cancer poses a major health problem in many countries and is the commonest cancer in men in the UK.1 Its incidence and mortality rate are higher in men of African-Caribbean origin. Since publication of the original NICE guideline in 2008,2 there have been several changes in diagnosis and management of prostate cancer. Great improvements in the treatment of hormone relapsed metastatic disease with the introduction of several new treatments (cabazitaxel, abiraterone, enzalutamide, and radium-223) have been assessed by NICE's Technology Appraisal Programme3 4 and are not covered by this guidance. This article summarises recently updated recommendations from the National Institute for Health and Care Excellence (NICE) on the diagnosis and care of men with prostate cancer.5 Many recommendations have not been updated from the previous guidance and can be found in a previous BMJ summary.

Radical Prostatectomy versus Observation for Localized Prostate Cancer

Article

Full-text available

Jul 2012
NEW ENGL J MED

The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known. From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality. During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

Prostate-Cancer Mortality at 11 Years of Follow-up

Article

Full-text available

Mar 2012
NEW ENGL J MED

Several trials evaluating the effect of prostate-specific antigen (PSA) testing on prostate-cancer mortality have shown conflicting results. We updated prostate-cancer mortality in the European Randomized Study of Screening for Prostate Cancer with 2 additional years of follow-up. The study involved 182,160 men between the ages of 50 and 74 years at entry, with a predefined core age group of 162,388 men 55 to 69 years of age. The trial was conducted in eight European countries. Men who were randomly assigned to the screening group were offered PSA-based screening, whereas those in the control group were not offered such screening. The primary outcome was mortality from prostate cancer. After a median follow-up of 11 years in the core age group, the relative reduction in the risk of death from prostate cancer in the screening group was 21% (rate ratio, 0.79; 95% confidence interval [CI], 0.68 to 0.91; P=0.001), and 29% after adjustment for noncompliance. The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent randomization. The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 (95% CI, 0.45 to 0.85; P=0.003). To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected. There was no significant between-group difference in all-cause mortality. Analyses after 2 additional years of follow-up consolidated our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality. (Current Controlled Trials number, ISRCTN49127736.).

Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after 13 Years of Follow-up

Article

Full-text available

Jan 2012
J NATL CANCER I

The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7-10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial. A total of 76 685 men, aged 55-74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided. Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (P(interaction) = .81), pretrial PSA testing (P(interaction) = .52), and comorbidity (P(interaction) = .68). After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.

Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer

Article

Full-text available

May 2011
NEW ENGL J MED

In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results. From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model. During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4). Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment. (Funded by the Swedish Cancer Society and the National Institutes of Health.).

Screening and Prostate-Cancer Mortality in a Randomized European Study

Article

Full-text available

Apr 2009
NEW ENGL J MED

The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer. We identified 182,000 men between the ages of 50 and 74 years through registries in seven European countries for inclusion in our study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006. In the screening group, 82% of men accepted at least one offer of screening. During a median follow-up of 9 years, the cumulative incidence of prostate cancer was 8.2% in the screening group and 4.8% in the control group. The rate ratio for death from prostate cancer in the screening group, as compared with the control group, was 0.80 (95% confidence interval [CI], 0.65 to 0.98; adjusted P=0.04). The absolute risk difference was 0.71 death per 1000 men. This means that 1410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer. The analysis of men who were actually screened during the first round (excluding subjects with noncompliance) provided a rate ratio for death from prostate cancer of 0.73 (95% CI, 0.56 to 0.90). PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of overdiagnosis. (Current Controlled Trials number, ISRCTN49127736.)

Mortality Results from a Randomized Prostate-Cancer Screening Trial

Article

Full-text available

Apr 2009
NEW ENGL J MED

The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.)

Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Haggman M, Andersson SO, Spangberg A, Busch C, Nordling S, Palmgren J, Adami HO, Johansson JE, Norlen BJA randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 347: 781-789

Article

Full-text available

Oct 2002
NEW ENGL J MED

Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression. During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96). In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.

Implementing the UK Medical Research Council (MRC) RT01 trial (ISRCTN 47772397): Methods and practicalities of a randomised controlled trial of conformal radiotherapy in men with localised prostate cancer

Article

Full-text available

Sep 2004
RADIOTHER ONCOL

Radiotherapy is the most frequently used treatment for men with localised prostate cancer. Conformal radiotherapy (CFRT) is a relatively new development. MRC RT01 was set-up to explore optimum CFRT dose. RT01 was an international multi-centre randomised controlled trial for men with T1b-T3a, N0, M0 prostate cancer that evolved from a single-centre pilot trial of similar design. All men received at least 3 months of pre-radiotherapy hormone treatment, before randomisation to standard (64 Gy) or high dose (74 Gy) radical CFRT. Accrual was completed in December 2001 with 843 men randomised from 25 centres in less than 4 years. RT01 has been a catalyst for implementing CFRT across UK. In addition to the Trial Management Group, independent Data Monitoring and Ethics Committee and independent Trial Steering Committee, a Quality of Life and Health Economics (QL/HE) group, a radiotherapy Quality Assurance (QA) Group and a Radiography Trial Implementation Group were set up. The QL/HE group ensured implementation, compliance, analysis and interpretation of the QL and HE data in the trial. The inauguration of QA and Radiography groups facilitated inter-centre collaboration. The QA Group ensured procedures were in place before and during trial participation, and monitored quality and consistency with systems including a physics questionnaire, a clinical examples exercise, a standard operating procedure document, designing and building a phantom, and convening a complications modelling subgroup. The Radiography group agreed and implemented technique improvements. More centres participated than initially predicted, enabling recruitment better than scheduled. The trial expedited the implementation of CFRT in many UK radiotherapy centres. Additionally, the QA and Radiography groups helped ensure smooth initiation and established consistency in planning, dosimetry and delivery of prostate CFRT services at participating UK centres. Considerable data has been collected; a series of papers will be produced, although mature clinical trial results are not anticipated until 2006-2008.

A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer

Article

Jan 2003
J UROLOGY

Long-term follow-up of a large active surveillance cohort of patients with prostate cancer

Article

Jan 2014

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer

Article

Sep 2016
NEW ENGL J MED

Background Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. Methods We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. Results The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. Conclusions In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)

Reevaluating PSA testing rates in the PLCO trial

Article

May 2016

The PLCO trial generated data that argue against PSA screening. However, participants in the control group also reported being screened. An analysis of health questionnaires suggests that more than 80% of controls had been tested within the previous 3 years.

Radical prostatectomy versus watchful waiting in early prostate cancer

Article

May 2005

Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities

Article

Feb 2016

In this article, the American Cancer Society provides the estimated number of new cancer cases and deaths for blacks in the United States and the most recent data on cancer incidence, mortality, survival, screening, and risk factors for cancer. Incidence data are from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries, and mortality data are from the National Center for Health Statistics. Approximately 189,910 new cases of cancer and 69,410 cancer deaths will occur among blacks in 2016. Although blacks continue to have higher cancer death rates than whites, the disparity has narrowed for all cancers combined in men and women and for lung and prostate cancers in men. In contrast, the racial gap in death rates has widened for breast cancer in women and remained level for colorectal cancer in men. The reduction in overall cancer death rates since the early 1990s translates to the avoidance of more than 300,000 deaths among blacks. In men, incidence rates from 2003 to 2012 decreased for all cancers combined (by 2.0% per year) as well as for the top 3 cancer sites (prostate, lung, and colorectal). In women, overall rates during the corresponding time period remained unchanged, reflecting increasing trends in breast cancer combined with decreasing trends in lung and colorectal cancer rates. Five-year relative survival is lower for blacks than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Progress in reducing cancer death rates could be accelerated by ensuring equitable access to prevention, early detection, and high-quality treatment. CA Cancer J Clin 2016. © 2016 American Cancer Society.

Mortality results from a randomized prostate-cancer screening trial (New England Journal of Medicine (2009) 360, (1310-9))

Article

Apr 2009

E.D. Crawford

Cancer Statistics 2016

Article

Jan 2016
CA-CANCER J CLIN

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2016, 1,685,210 new cancer cases and 595,690 cancer deaths are projected to occur in the United States. Overall cancer incidence trends (13 oldest SEER registries) are stable in women, but declining by 3.1% per year in men (from 2009-2012), much of which is because of recent rapid declines in prostate cancer diagnoses. The cancer death rate has dropped by 23% since 1991, translating to more than 1.7 million deaths averted through 2012. Despite this progress, death rates are increasing for cancers of the liver, pancreas, and uterine corpus, and cancer is now the leading cause of death in 21 states, primarily due to exceptionally large reductions in death from heart disease. Among children and adolescents (aged birth-19 years), brain cancer has surpassed leukemia as the leading cause of cancer death because of the dramatic therapeutic advances against leukemia. Accelerating progress against cancer requires both increased national investment in cancer research and the application of existing cancer control knowledge across all segments of the population. CA Cancer J Clin 2016. © 2016 American Cancer Society.

Intermediate and Longer-Term Outcomes From a Prospective Active-Surveillance Program for Favorable-Risk Prostate Cancer

Article

Aug 2015
J CLIN ONCOL

Compliance Rates with the Prostate Cancer Research International Active Surveillance (PRIAS) Protocol and Disease Reclassification in Noncompliers

Article

Jun 2015

Men with prostate cancer on active surveillance (AS) are advised to follow strict follow-up schedules and switch to definitive treatment on risk reclassification. However, some men might not adhere to these strict protocols. To determine the number of noncompliers and disease reclassification rates in men not complying with the follow-up protocol of the Prostate Cancer Research International Active Surveillance (PRIAS) study. A total of 4547 men with low-risk prostate cancer were included and prospectively followed on AS. Men were regularly examined using prostate-specific antigen (PSA), digital rectal examination, and repeat biopsies, and were advised to switch to definitive treatment on disease reclassification (>cT2c, Gleason score > 3+3, >2 cores positive, or PSA doubling time [PSA-DT] 0-3 yr). Rates of men not complying with follow-up visits or a recommendation to discontinue AS are reported. Biopsy outcome (Gleason ≥7 or >2 cores positive) was compared between compliers and noncompliers using Cox proportional hazards analysis. The compliance rate for PSA visits was 91%. By contrast, the compliance rate for standard repeat biopsies decreased over time (81%, 60%, 53%, and 33% at 1, 4, 7, and 10 yr after diagnosis, respectively). Yearly repeat biopsies in men with faster rising PSA (PSA-DT 3-10 yr) was low at <30%, although these men had higher upgrading rates at repeat biopsy (25-30% vs 16%). PSA-DT of 0-3 yr was the most common recommendation for discontinuation, but 71% continued on AS. Men with PSA-DT of 0-3 yr were at higher risk of upgrading on repeat biopsy (hazard ratio 2.02, 95% confidence interval 1.36-3.00) compared to men without fast rising PSA. Some men and their physicians do not comply with AS follow-up protocols. In particular, yearly repeat biopsies in men with fast rising PSA are often ignored, as is the recommendation to discontinue AS because of very fast rising PSA. Although these men are at greater risk of higher Gleason scores on repeat biopsy, the majority still exhibit favorable tumor characteristics. Fast rising PSA should therefore not trigger a recommendation to receive active treatment, but should rather serve as a criterion for stricter follow-up. In addition, we should aim to find ways of safely reducing the number of biopsies to increase adherence to AS protocols. We looked at compliance with an active surveillance protocol for low-risk prostate cancer in a large active surveillance study. We observed reluctance to undergo yearly biopsies because of fast rising prostate-specific antigen, despite a higher risk of disease progression. Further research should aim to safely reduce the number of repeat biopsies in men on active surveillance to increase protocol adherence. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Systematic Review and Meta-analysis of Factors Determining Change to Radical Treatment in Active Surveillance for Localized Prostate Cancer

Article

Jan 2015

Many men with clinically localized prostate cancer are being monitored as part of active surveillance (AS) programs, but little is known about reasons for receiving radical treatment. A systematic review of the evidence about AS was undertaken, with a meta-analysis to identify predictors of radical treatment. A comprehensive search of the Embase, MEDLINE and Web of Knowledge databases to March 2014 was performed. Studies reporting on men with localized prostate cancer followed by AS or monitoring were included. AS was defined where objective eligibility criteria, management strategies, and triggers for clinical review or radical treatment were reported. The 26 AS cohorts included 7627 men, with a median follow-up of 3.5 yr (range of medians 1.5-7.5 yr). The cohorts had a wide range of inclusion criteria, monitoring protocols, and triggers for radical treatment. There were eight prostate cancer deaths and five cases of metastases in 24 981 person-years of follow-up. Each year, 8.8% of men (95% confidence interval 6.7-11.0%) received radical treatment, most commonly because of biopsy findings, prostate-specific antigen triggers, or patient choice driven by anxiety. Studies in which most men changed treatment were those including only low-risk Gleason score 6 disease and scheduled rebiopsies. The wide variety of AS protocols and lack of robust evidence make firm conclusions difficult. Currently, patients and clinicians have to make judgments about the balance of risks and benefits in AS protocols. The publication of robust evidence from randomized trials and longer-term follow-up of cohorts is urgently required. We reviewed 26 studies of men on active surveillance for prostate cancer. There was evidence that studies including men with the lowest risk disease and scheduled rebiopsy had higher rates of radical treatment. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after 13Years of Follow-up

Article

Dec 2012
Year Bk Urol

Gerald L Andriole

Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients With Prostate Cancer

Article

Dec 2014

Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer. Long-term follow-up has been lacking. In this study, we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer. In a prospective single-arm cohort study carried out at a single academic health sciences center, 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach. Intervention was offered for a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression, or unequivocal clinical progression. Main outcome measures were overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients. Among the 819 survivors, the median follow-up time from the first biopsy is 6.4 years (range, 0.2 to 19.8 years). One hundred forty-nine (15%) of 993 patients died, and 844 patients are alive (censored rate, 85.0%). There were 15 deaths (1.5%) from prostate cancer. The 10- and 15-year actuarial cause-specific survival rates were 98.1% and 94.3%, respectively. An additional 13 patients (1.3%) developed metastatic disease and are alive with confirmed metastases (n = 9) or have died of other causes (n = 4). At 5, 10, and 15 years, 75.7%, 63.5%, and 55.0% of patients remained untreated and on surveillance. The cumulative hazard ratio for nonprostate-to-prostate cancer mortality was 9.2:1. Active surveillance for favorable-risk prostate cancer is feasible and seems safe in the 15-year time frame. In our cohort, 2.8% of patients have developed metastatic disease, and 1.5% have died of prostate cancer. This mortality rate is consistent with expected mortality in favorable-risk patients managed with initial definitive intervention. © 2014 by American Society of Clinical Oncology.

Screening and prostate cancer mortality: Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up

Article

Aug 2014

Background The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. Methods ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55–69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50–74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years’ follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. Findings With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83–1·99) after 9 years (1·64 [1·58–1·69] including France), 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for screening or one per 27 (17–66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61–0·88). Interpretation In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. Funding Each centre had its own funding responsibility.

Grading the New US Preventive Services Task Force Prostate Cancer Screening Recommendation

Article

Dec 2011
J Am Med Assoc

On October 11, 2011, the US Preventive Services Task Force (USPSTF) issued for public comment a draft recommendation statement regarding screening for prostate cancer.1 The public comment period is a new step taken by the USPSTF prior to finalizing its recommendation statements to help make its recommendations clearer and more useful to primary care providers. In taking this step, the task force signaled its intention to change its 2008 recommendation from a grade I statement (the current evidence is insufficient to assess the balance of the benefits and harms of the service) to a grade D recommendation—“The US Preventive Services Task Force . . . recommends against prostate-specific antigen (PSA)-based screening for prostate cancer.” Following an updated review of the evidence, the USPSTF concluded that there is moderate certainty that the harms of PSA-based screening for prostate cancer outweigh the benefits. The reaction from the media to the impending change has been swift, and organizations that support screening for prostate cancer in general have criticized the new recommendation. Is this reaction justified?

Multiple testing in clinical trials

Article

Jun 1991

Peter Bauer

The basic ideas of multiple testing are outlined and the problem of how to control the probability of erroneous decisions is discussed. The main emphasis is on the concept of the multiple level of significance (controlling the experiment, or family error in the strong sense) which can be achieved by applying the principle of closed tests. Various practical situations encountered in multiple testing in clinical trials are considered: more than one end point; more than two treatments, such as comparisons with a single control, comparisons using ordered alternatives, all pairwise comparisons and contrast methods; and more than one trial. Tests based on global statistics, the union intersection principle and other criteria are discussed. The application of the multiple test concept in sequential sampling is investigated. Finally some comments are made on multiple power, multiple confidence intervals and directed decisions.

Questionnaire based quality assurance for the RT01 trial of dose escalation in conformal radiotherapy for prostate cancer (ISRCTN 47772397)

Article

Dec 2004
RADIOTHER ONCOL

In order to ensure the validity of the outcome of the Medical Research Council's 'RTO1 trial' of dose escalation in conformal radiotherapy for prostate cancer it was considered important that the quality of treatment delivery should meet an adequate standard across all contributing centres. A questionnaire was therefore devised to ensure that all aspects of the planning and delivery process were adequately covered. The questionnaire considered each step in the planning and delivery process and drew the attention of the participants to the specific requirements of the trial. Before entering patients into the trial each participating centre had to complete the questionnaire and an outlining exercise (reported elsewhere). It was not practicable to define a detailed universally acceptable protocol for the whole process of delivery of conformal radiotherapy, not least because of the different equipment available for planning and treatment in different centres. The questionnaire identified some areas of difference in practice between centres where there may be a need for the development of a consensus as to best practice, particularly in the area of patient set-up. Occasionally it was necessary to follow up responses to questions that had been misunderstood or inadequately answered, but in most cases these issues proved to be easily resolved. The questionnaire proved to be a useful self-assessment tool as well as enabling the quality assurance group to ensure that the standards of the trial were being met. Subsequent follow-up visits confirmed the usefulness and validity of this self assessment process.

Roach M III, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler HDefining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 65(4): 965-974

Article

Aug 2006
INT J RADIAT ONCOL

In 1996 the American Society for Therapeutic Radiology and Oncology (ASTRO) sponsored a Consensus Conference to establish a definition of biochemical failure after external beam radiotherapy (EBRT). The ASTRO definition defined prostate specific antigen (PSA) failure as occurring after three consecutive PSA rises after a nadir with the date of failure as the point halfway between the nadir date and the first rise or any rise great enough to provoke initiation of therapy. This definition was not linked to clinical progression or survival; it performed poorly in patients undergoing hormonal therapy (HT), and backdating biased the Kaplan-Meier estimates of event-free survival. A second Consensus Conference was sponsored by ASTRO and the Radiation Therapy Oncology Group in Phoenix, Arizona, on January 21, 2005, to revise the ASTRO definition. The panel recommended: (1) a rise by 2 ng/mL or more above the nadir PSA be considered the standard definition for biochemical failure after EBRT with or without HT; (2) the date of failure be determined "at call" (not backdated). They recommended that investigators be allowed to use the ASTRO Consensus Definition after EBRT alone (no hormonal therapy) with strict adherence to guidelines as to "adequate follow-up." To avoid the artifacts resulting from short follow-up, the reported date of control should be listed as 2 years short of the median follow-up. For example, if the median follow-up is 5 years, control rates at 3 years should be cited. Retaining a strict version of the ASTRO definition would allow comparisons with a large existing body of literature.

dicine cer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial

Jan 2014
LANCET ONCOL
1109-1118

T h e ne w e ngl a nd jou r na l o f m e dicine cer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial. Lancet Oncol 2014; 15: 1109-18.

Grading the new US Preventive Services Task Force prostate cancer screening recommendation Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP)

Jan 2011
2715-2721

Rj Volk
Am Wolf
El Turner
C Metcalfe
Jl Donovan

Volk RJ, Wolf AM. Grading the new US Preventive Services Task Force prostate cancer screening recommendation. JAMA 2011; 306: 2715-6. 23. Turner EL, Metcalfe C, Donovan JL, et al. Design and preliminary recruitment results of the Cluster randomised triAl of PSA testing for Prostate cancer (CAP). Br J Cancer 2014; 110: 2829-36.

Jan 2014
1109-1118

J A Lane
J L Donovan
M Davis

Lane JA, Donovan JL, Davis M, et al. Oncol 2014; 15: 1109-18.

Jan 2016
90-94

E L Turner
C Metcalfe
J L Donovan

10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer

Abstract

No full-text available