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ABSTRACT: OBJECTIVES: To establish the value of MRI in targeting re-biopsy for undiagnosed prostate cancer despite multiple negative biopsies and determine clinical relevance of detected tumors. MATERIALS AND METHODS: Thirty-eight patients who underwent MRI after 2 or more negative biopsies due to continued clinical suspicion and later underwent TRUS-guided biopsy supplemented by biopsy of suspicious areas depicted by MRI were identified. Diagnostic performance of endorectal 3T MRI in diagnosing missed cancer foci was assessed using biopsy results as the standard of reference. Ratio of positive biopsies using systematic versus MRI-prompted approaches was compared. Gleason scores of detected cancers were used as surrogate for clinical relevance. RESULTS: Thirty-four percent of patients who underwent MRI before re-biopsy had prostate cancer on subsequent biopsy. The positive biopsy yield with systematic sampling was 23% versus 92% with MRI-prompted biopsies(p<0.0001). Seventy-seven percent of tumors were detected exclusively in the MRI-prompted zones. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRI to provide a positive biopsy were 92%, 60%, 55%, 94% and 71%, respectively. The anterior gland and apical regions contained most tumors; 75% of cancers detected by MRI-prompted biopsy had Gleason score≥7. CONCLUSIONS: Clinically relevant tumors missed by multiple TRUS-guided biopsies can be detected by a MRI-prompted approach.
Magnetic Resonance Imaging 04/2013; · 1.99 Impact Factor
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Daniel A Hamstra,
Anna S C Conlon,
Stephanie Daignault,
Rodney L Dunn,
Howard M Sandler,
A Larry Hembroff,
Anthony L Zietman,
Irving Kaplan,
Jay Ciezki,
Deborah A Kuban,
John T Wei, Martin G Sanda,
Jeff M Michalski
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ABSTRACT: PURPOSE: To evaluate patients treated with external beam radiation therapy as part of the multicenter Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA), to identify factors associated with posttreatment patient-reported bowel health-related quality of life (HRQOL). METHODS AND MATERIALS: Pretreatment characteristics and treatment details among 292 men were evaluated using a general linear mixed model for their association with measured HRQOL by the Expanded Prostate Cancer Index Composite instrument through 2 years after enrollment. RESULTS: Bowel HRQOL had a median score of 100 (interquartile range 91.7-100) pretreatment and 95.8 (interquartile range 83.3-100) at 2 years, representing new moderate/big problems in 11% for urgency, 7% for frequency, 4% for bloody stools, and 8% for an overall bowel problems. Baseline bowel score was the strongest predictor for all 2-year endpoints. In multivariable models, a volume of rectum ≥25% treated to 70 Gy (V70) yielded a clinically significant 9.3-point lower bowel score (95% confidence interval [CI] 16.8-1.7, P=.015) and predicted increased risks for moderate to big fecal incontinence (P=.0008). No other radiation therapy treatment-related variables influenced moderate to big changes in rectal HRQOL. However, on multivariate analyses V70 ≥25% was associated with increases in small, moderate, or big problems with the following: incontinence (3.9-fold; 95% CI 1.1-13.4, P=.03), rectal bleeding (3.6-fold; 95% CI 1.3-10.2, P=.018), and bowel urgency (2.9-fold; 95% CI 1.1-7.6, P=.026). Aspirin use correlated with a clinically significant 4.7-point lower bowel summary score (95% CI 9.0-0.4, P=.03) and an increase in small, moderate, or big problems with bloody stools (2.8-fold; 95% CI 1.2-6.4, P=.018). Intensity modulated radiation therapy was associated with higher radiation therapy doses to the prostate and lower doses to the rectum but did not independently correlate with bowel HRQOL. CONCLUSION: After contemporary dose-escalated external beam radiation therapy up to 11% of patients have newly identified moderate/big problems with bowel HRQOL 2 years after treatment. Bowel HRQOL is related to baseline function, rectal V70, and aspirin use. Finally, our findings validate the commonly utilized cut-point of rectal V70 ≥25% as having significant impact on patient-reported outcomes.
International journal of radiation oncology, biology, physics 04/2013; · 4.59 Impact Factor
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Daniel W Lin,
Lisa F Newcomb,
Elissa C Brown,
James D Brooks,
Peter R Carroll,
Ziding Feng,
Martin Gleave,
Raymond D Lance, Martin G Sanda,
Ian M Thompson,
John T Wei,
Peter S Nelson
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ABSTRACT: PURPOSE: Active surveillance is used to manage low risk prostate cancer. Both PCA3 and TMRPSS2-ERG are promising biomarkers that may be associated with aggressive disease. This study examines the correlation of these biomarkers with higher cancer volume and grade determined at the time of biopsy in an active surveillance cohort. EXPERIMENTAL DESIGN: Post-DRE urine was collected prospectively as part of the multi-institutional Canary Prostate Active Surveillance Study (PASS). PCA3 and TMPRSS2-ERG levels were analyzed in urine collected at study entry. Biomarker scores were correlated to clinical and pathologic variables. RESULTS: In 387 men, both PCA3 and TMPRSS2-ERG scores were significantly associated with higher volume disease. For a negative repeat biopsy, and 1-10%, 11-33%, ≥34% positive cores, median PCA3 and TMPRSS2-ERG scores increased incrementally (P < 0.005). Both PCA3 and TMPRSS2-ERG scores were also significantly associated with presence of high grade disease. For a negative repeat biopsy, Gleason 6 and Gleason ≥7 cancers, the median PCA3 and TMPRSS2-ERG scores also increased incrementally (P = 0.02 and P = 0.001, respectively). Using the marker scores as a continuous variables, the odds ratio for a biopsy in which cancer was detected versus a negative repeat biopsy (ref) on modeling was 1.41 (95% CI 1.07-1.85), P = 0.01 for PCA3 and 1.28 (95% CI 1.10-1.49), P = 0.001 for TMPRSS2-ERG. CONCLUSIONS: For men on active surveillance both PCA3 and TMPRSS2-ERG appear to stratify risk of having aggressive cancer as defined by tumor volume or Gleason score.
Clinical Cancer Research 03/2013; · 7.74 Impact Factor
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Stacy Loeb,
Lori J Sokoll,
Dennis L Broyles,
Chris H Bangma,
Ron H N van Schaik,
George G Klee,
John T Wei, Martin G Sanda,
Alan W Partin,
Kevin M Slawin,
Leonard S Marks,
Isaac A Mizrahi,
Sanghyuk S Shin,
Amabelle B Cruz,
Daniel W Chan,
William L Roberts,
William J Catalona
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ABSTRACT: PURPOSE: Reported prostate-specific antigen (PSA) values may differ substantially between assays with the Hybritech and World Health Organization (WHO) standardization. [-2]proPSA (p2PSA) and the Beckman Coulter prostate health index (phi) are newly approved serum markers, which are associated with prostate cancer risk and aggressiveness. Our objective was to study the influence of assay standardization on these markers. MATERIALS AND METHODS: PSA, % free PSA (%fPSA), and p2PSA were measured using the Hybritech calibration in 892 men undergoing prostate biopsy from a prospective multicenter study. Phi was calculated as: [p2PSA/ fPSA) x (square root of PSA)]. Performance characteristics of phi for prostate cancer detection were then determined using re-calculated WHO calibration PSA values. RESULTS: The median phi was significantly higher in men with prostate cancer compared to those with negative biopsies using the WHO values (47.4 vs 39.8, p<0.001). Phi offered improved discrimination of prostate cancer detection on biopsy (AUC 0.704) compared to %fPSA or total PSA using the WHO calibration. CONCLUSIONS: Phi can be calculated using Hybritech or WHO standardized assays, and significantly improved the prediction of biopsy outcome over %fPSA or PSA alone.
The Journal of urology 11/2012; · 4.02 Impact Factor
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ABSTRACT: Study Type - Therapy (attitude prevalence) Level of Evidence 2a What's known on the subject? and What does the study add? Marked differences in uncertainty among patients have been found relating to race and social environment indicating that as uncertainty increases, social functioning declines. Correlations have been found between uncertainty and patients' coping, psychological adjustment and perceptions of their health and illness. Studies suggest the detrimental effect of uncertainty among patients with prostate cancer in the perception of their quality of life. These studies underline the potential benefit of targeted intervention. The study provides a unique insight into the impact of uncertainty and perception of danger on overall satisfaction with treatment outcomes in men with prostate cancer. Its results suggest that possible disparities related to patient racial background and education may exist in the perception of cancer-related uncertainty. Racial and educational disparities, coupled with a mild to moderate association of uncertainty or danger perception and overall outcome satisfaction, suggest an unmet need for healthcare and nursing services for men undergoing treatment for prostate cancer. OBJECTIVES: • To investigate patient uncertainty and perception of danger regarding prospects for clinical prostate cancer control. • To determine the impact of these factors on satisfaction with overall prostate cancer treatment outcome. PATIENTS AND METHODS: • Men who had undergone primary treatment for early stage prostate cancer and who were participants in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) prospective cohort study of prostate cancer outcomes (the parent study) were offered the opportunity to participate in the present study. • Centralized phone interviews were conducted to determine patient-reported uncertainty regarding cancer status (measured by the Mishel Uncertainty in Illness Scale-Community Form), perception of danger (measured by Folkman and Lazarus' Appraisal Scale) and satisfaction with treatment outcome (measured by the Service Satisfaction Scale for Cancer Care). The study used the same centralized telephone interview centre as was used in the parent study. • Data were collected at 48, 60 or 72 months after the completion of prostate cancer treatment. • Relationships among measures were characterized by Spearman rank correlation coefficients (r). RESULTS: • A total of 338 agreed to participate, representing 76% of those who were invited. • Younger patients experienced less uncertainty (r= 0.20, P < 0.001), yet reported greater perception of danger (r=-0.12; P= 0.03) concerning their previously treated prostate cancer. • African-American patients showed greater uncertainty than other ethnic groups (P= 0.005) but did not have a greater perception of danger (P= 0.36). • Education played a major role in uncertainty; patients with lower levels of education tended to report higher degrees of uncertainty (r=-0.25; P < 0.001). • There was a mild to moderate general association between the three outcomes. A greater sense of uncertainty was associated with a greater perception of danger (r= 0.34, P < 0.001), and as danger and uncertainty increased, satisfaction with treatment outcome tended to decrease (r was between -0.30 and -0.34, P < 0.001). CONCLUSIONS: • Results suggest that possible disparities related to patient racial background and education may exist in the perception of cancer-related uncertainty. • Racial and educational disparities, coupled with a mild to moderate association of uncertainty or danger perception and overall outcome satisfaction, suggest an unmet need for healthcare and nursing services for men undergoing treatment for prostate cancer.
BJU International 09/2012; · 2.84 Impact Factor
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ABSTRACT: BACKGROUND:: Partners of men treated for prostate cancer report more emotional distress associated with a diagnosis of prostate cancer than the men report; the duration of distress for partners is seldom examined. OBJECTIVES:: The purpose of this study was to determine the long-term effects of prostate cancer treatment on partners' appraisal of their caregiving experience, marital satisfaction, sexual satisfaction, and quality of life (QOL) and factors related to these variables. METHODS:: This exploratory study evaluated QOL among spouses of prostate cancer survivors at 24 months after treatment. Partners completed a battery of self-report questionnaires in a computer-assisted telephone interview. RESULTS:: The sample consisted of 121 partners with average age of 60 years. There was a significant relationship between partners' perceptions of bother about the man's treatment outcomes and negative appraisal of their caregiving experience and poorer QOL. Younger partners who had a more negative appraisal of caregiving also had significantly worse QOL. CONCLUSIONS:: Men's treatment outcomes continued to bother the partner and resulted in more negative appraisal and lower QOL 2 years after initial prostate cancer treatment. Younger partners may be at greater risk of poorer QOL outcomes especially if they have a more negative view of their caregiving experience. IMPLICATIONS FOR PRACTICE:: Findings support prior research indicating that prostate cancer affects not only the person diagnosed with the disease but also his partner. Partners may benefit from tailored interventions designed to decrease negative appraisal and improve symptom management and QOL during the survivorship period.
Cancer nursing 06/2012; · 1.88 Impact Factor
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ABSTRACT: To assess the value of dynamic contrast-enhanced (DCE) combined with T2-weighted (T2W) endorectal coil (ERC) magnetic resonance imaging (MRI) at 3 T for determining extracapsular extension (ECE) of prostate cancer.
In this IRB-approved study, ERC 3-T MRI of the prostate was performed in 108 patients before radical prostatectomy. T2W fast spin-echo and DCE 3D gradient echo images were acquired. The interpretations of readers with varied experience were analysed. MRI-based staging results were compared with radical prostatectomy histology. Descriptive statistics were generated for prediction of ECE and staging accuracies were determined by the area under the receiver-operating characteristic curve.
The overall sensitivity, specificity, positive predictive value and negative predictive value for ECE were 75 %, 92 %, 79 % and 91 %, respectively. Diagnostic accuracy for staging was 86 %, 80 % and 91 % for all readers, experienced and less experienced readers, respectively.
ERC 3-T MRI of the prostate combining DCE and T2W imaging is an accurate pretherapeutic staging tool for assessment of ECE in clinical practice across varying levels of reader experience. KEY POINTS : • Endorectal coil (ERC) magnetic resonance imaging is widely used for imaging prostatic disease. • ERC 3-T MRI is reasonably accurate for local prostate cancer staging. • High diagnostic accuracy is achievable across different levels of reader experience. • MRI facilitates therapeutic decisions in patients with prostate cancer.
European Radiology 06/2012; 22(10):2201-10. · 3.22 Impact Factor
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ABSTRACT: To assess the feasibility of 2 patient-reported health-related quality of life (HRQOL) instruments, Convalescence and Recovery Evaluation (CARE), and SF-12, as tools for evaluating HRQOL outcome consequences after renal surgery, and to determine which domains of these HRQOL instruments are most sensitive to HRQOL outcome effects of renal surgery.
Patients completed CARE and SF-12 preoperatively (baseline) and at 2, 4, 12, and 24 weeks after surgery. Clinical data, patient response rate, HRQOL changes over time, and likelihood of patient return to baseline HRQOL were evaluated.
Seventy-one patients were enrolled. Sixty patients completed the baseline and at least 1 follow-up set of questionnaires. The CARE pain, gastrointestinal (GI), and activity domain scores and the SF-12 physical composite score (PCS) were sensitive to changes in HRQOL (all P<.05), whereas other domain subscores of these instruments did not change from presurgical baseline to postsurgical follow-up. Postsurgical HRQOL effects detected by the CARE pain, GI, and activity domains, and SF-12 PCS were most evident at 2 weeks (all P<.001). The CARE composite score demonstrated that 74% and 50% of patients returned to within 90% of baseline 4 weeks after radical and partial nephrectomy, respectively.
Evaluation of patient-reported HRQOL outcomes after renal surgery is feasible; our findings suggest that the activity, pain, and GI domains of CARE and PCS subscores of the SF-12 are sensitive measures of HRQOL outcome consequences of renal surgery and represent appropriate measures of either care quality or comparative effectiveness analyses of robotic, laparoscopic, and open renal surgery.
Urology 04/2012; 79(6):1268-73. · 2.43 Impact Factor
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Donna P Ankerst,
Tim Koniarski,
Yuanyuan Liang,
Robin J Leach,
Ziding Feng, Martin G Sanda,
Alan W Partin,
Daniel W Chan,
Jacob Kagan,
Lori Sokoll,
John T Wei,
Ian M Thompson
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ABSTRACT: Online risk prediction tools for common cancers are now easily accessible and widely used by patients and doctors for informed decision-making concerning screening and diagnosis. A practical problem is as cancer research moves forward and new biomarkers and risk factors are discovered, there is a need to update the risk algorithms to include them. Typically, the new markers and risk factors cannot be retrospectively measured on the same study participants used to develop the original prediction tool, necessitating the merging of a separate study of different participants, which may be much smaller in sample size and of a different design. Validation of the updated tool on a third independent data set is warranted before the updated tool can go online. This article reports on the application of Bayes rule for updating risk prediction tools to include a set of biomarkers measured in an external study to the original study used to develop the risk prediction tool. The procedure is illustrated in the context of updating the online Prostate Cancer Prevention Trial Risk Calculator to incorporate the new markers %freePSA and [-2]proPSA measured on an external case-control study performed in Texas, U.S.. Recent state-of-the art methods in validation of risk prediction tools and evaluation of the improvement of updated to original tools are implemented using an external validation set provided by the U.S. Early Detection Research Network.
Biometrical Journal 11/2011; 54(1):127-42. · 1.25 Impact Factor
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ABSTRACT: Limited survival benefit and excess treatment because of prostate-specific antigen (PSA) screening in randomized trials suggests a need for more restricted selection of prostate biopsy candidates by discerning risk of histologically aggressive versus indolent cancer before biopsy.
Subjects undergoing first prostate biopsy enrolled in a multicenter, prospective cohort of the National Cancer Institute Early Detection Research Network (N = 635) were analyzed to develop a model for predicting histologically aggressive prostate cancers. The control arm of the Prostate Cancer Prevention Trial (N = 3833) was used to validate the generalization of the predictive model.
The Early Detection Research Network cohort was comprised of men among whom 57% had no cancer, 14% had indolent cancer, and 29% had aggressive cancer. Age, body mass index, family history of prostate cancer, abnormal digital rectal examination (DRE), and PSA density (PSAD) were associated with aggressive cancer (all P < .001). The Early Detection Research Network model outperformed PSA alone in predicting aggressive cancer (area under the curve [AUC] = 0.81 vs 0.71, P < .01). Model validation in the Prostate Cancer Prevention Trial cohort accurately identified men at low (<10%) risk of aggressive cancer for whom biopsy could be averted (AUC = 0.78; 95% confidence interval, 0.75-0.80). Under criteria from the Early Detection Research Network model, prostate biopsy can be restricted to men with PSAD >0.1 ng/mL/cc or abnormal DRE. When PSAD is <0.1 ng/mL/cc, family history or obesity can identify biopsy candidates.
A predictive model incorporating age, family history, obesity, PSAD, and DRE elucidates criteria whereby ¼ of prostate biopsies can be averted while retaining high sensitivity in detecting aggressive prostate cancer.
Cancer 10/2011; 118(10):2651-8. · 4.77 Impact Factor
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ABSTRACT: We examined patient reported outcomes among patients with prostate cancer treated with watchful waiting in a nationwide cohort.
We collected treatment information and patient reported outcomes from 1,230 patients with prostate cancer diagnosed with T1-T2 prostate cancer in the Physicians' Health Study, of whom 125 were initially treated with watchful waiting. Cox proportional hazards regression was used to identify predictors of treatment initiation among patients on watchful waiting. Logistic regression was used to calculate the OR and 95% CI to assess disease targeted quality of life by initial treatment or watchful waiting.
At a mean 7.3-year followup 41% of patients on watchful waiting remained free of treatment while 34% had received radiotherapy or brachytherapy, 16% had received primary hormonal therapy and 10% had undergone prostatectomy. Younger age, higher clinical stage, higher Gleason score and higher prostate specific antigen at diagnosis predicted progression to treatment. Watchful waiting compared to immediate treatment was associated with less urinary incontinence (3.5% vs 10%) and impotence (68% vs 78%) but more common obstructive urinary symptoms (22% vs 13%) on univariate analysis (each p <0.05). Incontinence and impotence differences remained significant after adjusting for age, comorbidity and time after cancer diagnosis. Quality of life outcomes in men who underwent delayed treatment after initially waiting were not worse than in men who underwent immediate treatment.
Findings suggest quality of life benefits after watchful waiting in select patients with early stage prostate cancer compared to men treated immediately after diagnosis. Younger age and greater cancer severity at diagnosis predicted progression to treatment.
The Journal of urology 09/2011; 186(5):1862-7. · 4.02 Impact Factor
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Mehrdad Alemozaffar,
Meredith M Regan,
Matthew R Cooperberg,
John T Wei,
Jeff M Michalski,
Howard M Sandler,
Larry Hembroff,
Natalia Sadetsky,
Christopher S Saigal,
Mark S Litwin, [......],
Adam S Kibel,
Daniel A Hamstra,
Louis L Pisters,
Deborah A Kuban,
Irving D Kaplan,
David P Wood,
Jay Ciezki,
Rodney L Dunn,
Peter R Carroll, Martin G Sanda
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ABSTRACT: Sexual function is the health-related quality of life (HRQOL) domain most commonly impaired after prostate cancer treatment; however, validated tools to enable personalized prediction of erectile dysfunction after prostate cancer treatment are lacking.
To predict long-term erectile function following prostate cancer treatment based on individual patient and treatment characteristics.
Pretreatment patient characteristics, sexual HRQOL, and treatment details measured in a longitudinal academic multicenter cohort (Prostate Cancer Outcomes and Satisfaction With Treatment Quality Assessment; enrolled from 2003 through 2006), were used to develop models predicting erectile function 2 years after treatment. A community-based cohort (community-based Cancer of the Prostate Strategic Urologic Research Endeavor [CaPSURE]; enrolled 1995 through 2007) externally validated model performance. Patients in US academic and community-based practices whose HRQOL was measured pretreatment (N = 1201) underwent follow-up after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. Sexual outcomes among men completing 2 years' follow-up (n = 1027) were used to develop models predicting erectile function that were externally validated among 1913 patients in a community-based cohort.
Patient-reported functional erections suitable for intercourse 2 years following prostate cancer treatment.
Two years after prostate cancer treatment, 368 (37% [95% CI, 34%-40%]) of all patients and 335 (48% [95% CI, 45%-52%]) of those with functional erections prior to treatment reported functional erections; 531 (53% [95% CI, 50%-56%]) of patients without penile prostheses reported use of medications or other devices for erectile dysfunction. Pretreatment sexual HRQOL score, age, serum prostate-specific antigen level, race/ethnicity, body mass index, and intended treatment details were associated with functional erections 2 years after treatment. Multivariable logistic regression models predicting erectile function estimated 2-year function probabilities from as low as 10% or less to as high as 70% or greater depending on the individual's pretreatment patient characteristics and treatment details. The models performed well in predicting erections in external validation among CaPSURE cohort patients (areas under the receiver operating characteristic curve, 0.77 [95% CI, 0.74-0.80] for prostatectomy; 0.87 [95% CI, 0.80-0.94] for external radiotherapy; and 0.90 [95% CI, 0.85-0.95] for brachytherapy).
Stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer.
JAMA The Journal of the American Medical Association 09/2011; 306(11):1205-14. · 30.03 Impact Factor
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Peter Chang,
Konrad M Szymanski,
Rodney L Dunn,
Jonathan J Chipman,
Mark S Litwin,
Paul L Nguyen,
Christopher J Sweeney,
Robert Cook,
Andrew A Wagner,
William C DeWolf,
Glenn J Bubley,
Renee Funches,
Joseph A Aronovitz,
John T Wei, Martin G Sanda
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ABSTRACT: Measuring the health related quality of life of patients with prostate cancer in routine clinical practice is hindered by the lack of instruments enabling efficient, real-time, point of care scoring of multiple health related quality of life domains. Thus, we developed an instrument for this purpose.
The Expanded Prostate Cancer Index Composite for Clinical Practice is a 1-page, 16-item questionnaire that we constructed to measure urinary incontinence, urinary irritation, and the bowel, sexual and hormonal health related quality of life domains. We eliminated conceptually overlapping items from the 3-page Expanded Prostate Cancer Index Composite-26 and revised the questionnaire format to mirror the AUA symptom index, thereby enabling practitioners to calculate health related quality of life scores at the point of care. We administered the Expanded Prostate Cancer Index Composite for Clinical Practice to a new cohort of patients with prostate cancer in community based and academic oncology, radiation, and urology practices to evaluate instrument validity as well as ease of use in clinical practice.
A total of 175 treated and 132 untreated subjects with prostate cancer completed the Expanded Prostate Cancer Index Composite for Clinical Practice. The domain scores of the Expanded Prostate Cancer Index Composite for Clinical Practice correlated highly with the respective domain scores from longer versions of the Expanded Prostate Cancer Index Composite (r≥0.93 for all domains). The Expanded Prostate Cancer Index Composite for Clinical Practice showed high internal consistency (Cronbach's α 0.64-0.84) and sensitivity to prostate cancer treatment related effects (p<0.05 in each of 5 health related quality of life domains). Patients completed the Expanded Prostate Cancer Index Composite for Clinical Practice efficiently (96% in less than 10 minutes and with 11% missing items). It was deemed very convenient by clinicians in 87% of routine clinical encounters and clinicians accurately scored completed questionnaires 94% of the time.
The Expanded Prostate Cancer Index Composite for Clinical Practice is a valid instrument that enables patient reported, health related quality of life to be measured efficiently and accurately at the point of care, and thereby facilitates improved emphasis and management of patient reported outcomes.
The Journal of urology 09/2011; 186(3):865-72. · 4.02 Impact Factor
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Scott A Tomlins,
Sheila M J Aubin,
Javed Siddiqui,
Robert J Lonigro,
Laurie Sefton-Miller,
Siobhan Miick,
Sarah Williamsen,
Petrea Hodge,
Jessica Meinke,
Amy Blase, [......],
Kyoko Sakamoto,
Jonathan L Silberstein,
Yves Fradet,
James B Amberson,
Stephanie Meyers,
Nallasivam Palanisamy,
Harry Rittenhouse,
John T Wei,
Jack Groskopf,
Arul M Chinnaiyan
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ABSTRACT: More than 1,000,000 men undergo prostate biopsy each year in the United States, most for "elevated" serum prostate-specific antigen (PSA). Given the lack of specificity and unclear mortality benefit of PSA testing, methods to individualize management of elevated PSA are needed. Greater than 50% of PSA-screened prostate cancers harbor fusions between the transmembrane protease, serine 2 (TMPRSS2) and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) genes. Here, we report a clinical-grade, transcription-mediated amplification assay to risk stratify and detect prostate cancer noninvasively in urine. The TMPRSS2:ERG fusion transcript was quantitatively measured in prospectively collected whole urine from 1312 men at multiple centers. Urine TMPRSS2:ERG was associated with indicators of clinically significant cancer at biopsy and prostatectomy, including tumor size, high Gleason score at prostatectomy, and upgrading of Gleason grade at prostatectomy. TMPRSS2:ERG, in combination with urine prostate cancer antigen 3 (PCA3), improved the performance of the multivariate Prostate Cancer Prevention Trial risk calculator in predicting cancer on biopsy. In the biopsy cohorts, men in the highest and lowest of three TMPRSS2:ERG+PCA3 score groups had markedly different rates of cancer, clinically significant cancer by Epstein criteria, and high-grade cancer on biopsy. Our results demonstrate that urine TMPRSS2:ERG, in combination with urine PCA3, enhances the utility of serum PSA for predicting prostate cancer risk and clinically relevant cancer on biopsy.
Science translational medicine 08/2011; 3(94):94ra72. · 7.80 Impact Factor
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Simpa S Salami,
Folke Schmidt,
Bharathi Laxman,
Meredith M Regan,
David S Rickman,
Douglas Scherr,
Gerardina Bueti,
Javed Siddiqui,
Scott A Tomlins,
John T Wei,
Arul M Chinnaiyan,
Mark A Rubin, Martin G Sanda
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ABSTRACT: OBJECTIVES: We sought to develop a clinical algorithm combining serum PSA with detection of TMPRSS2:ERG fusion and PCA3 in urine collected after digital rectal exam (post-DRE urine) to predict prostate cancer on subsequent biopsy. MATERIALS AND METHODS: Post-DRE urine was collected in 48 consecutive patients before prostate biopsy at 2 centers; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect PCA3 and TMPRSS2:ERG fusion transcript expression. Serum PSA was measured by clinical assay. The performance of TMPRSS2:ERG fusion, PCA3, and serum PSA as biomarkers predicting prostate cancer at biopsy was measured; a clinically practical algorithm combining serum PSA with TMPRSS2:ERG and PCA3 in post-DRE urine to predict prostate cancer was developed. RESULTS: Post-DRE urine sediment provided informative RNA in 45 patients; prostate cancer was present on subsequent biopsy in 15. TMPRSS2:ERG in post-DRE urine was associated with prostate cancer (OR = 12.02; P < 0.001). PCA3 had the highest sensitivity in predicting prostate cancer diagnosis (93%), whereas TMPRSS2:ERG had the highest specificity (87%). TMPRSS2:ERG had the greatest discriminatory value in predicting prostate cancer (AUC = 0.77 compared with 0.65 for PCA3 and 0.72 for serum PSA alone). Combining serum PSA, PCA3, and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction (AUC = 0.88; specificity = 90% at 80% sensitivity). CONCLUSIONS: A clinical algorithm specifying biopsy for all patients with PSA ≥ 10 ng/ml, while restricting biopsy among those with PSA <10 ng/ml to only those with detectable PCA3 or TMPRSS2:ERG in post-DRE urine, performed better than the individual biomarkers alone in predicting prostate cancer.
Urologic Oncology 05/2011; · 3.22 Impact Factor
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ABSTRACT: Black and Hispanic men have a lower prostate cancer (PCa) survival rate than white men. This racial/ethnic survival gap has been explained in part by differences in tumor characteristics, stage at diagnosis, and disparities in receipt of definitive treatment. Another potential contributing factor is racial/ethnic differences in the timely and accurate detection of lymph node metastases. The current study was conducted to examine the association between race/ethnicity and the receipt of pelvic lymph node dissection (PLND) among men with localized/regional PCa.
Logistic regression was used to estimate the adjusted odds of undergoing PLND among men who were diagnosed during 2000 to 2002 with PCa, who underwent radical prostatectomy or PLND without radical prostatectomy, and who were diagnosed in regions covered by the Surveillance, Epidemiology, and End Results database (n = 40,848).
Black men were less likely to undergo PLND than white men (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84-0.98). When the analysis was stratified by PCa grade, black men with well differentiated PCa (OR, 0.48; 95% CI, 0.27-0.84) and poorly differentiated PCa (OR, 0.73; 95% CI, 0.60-0.89) were less likely to undergo PLND than their white counterparts, but racial differences were not observed among men with moderately differentiated PCa (OR, 0.96; 95% CI, 0.88-1.05).
Among men with poorly differentiated PCa, failure to undergo PLND was associated with worse survival. Racial disparities in the receipt of PLND, especially among men with poorly differentiated PCa, may contribute to racial differences in prostate cancer survival. Cancer 2011;. © 2011 American Cancer Society.
Cancer 03/2011; 117(20):4651-8. · 4.77 Impact Factor
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William J Catalona,
Alan W Partin, Martin G Sanda,
John T Wei,
George G Klee,
Chris H Bangma,
Kevin M Slawin,
Leonard S Marks,
Stacy Loeb,
Dennis L Broyles,
Sanghyuk S Shin,
Amabelle B Cruz,
Daniel W Chan,
Lori J Sokoll,
William L Roberts,
Ron H N van Schaik,
Isaac A Mizrahi
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ABSTRACT: Prostate specific antigen and free prostate specific antigen have limited specificity to detect clinically significant, curable prostate cancer, leading to unnecessary biopsy, and detection and treatment of some indolent tumors. Specificity to detect clinically significant prostate cancer may be improved by [-2]pro-prostate specific antigen. We evaluated [-2]pro-prostate specific antigen, free prostate specific antigen and prostate specific antigen using the formula, ([-2]pro-prostate specific antigen/free prostate specific antigen × prostate specific antigen(1/2)) to enhance specificity to detect overall and high grade prostate cancer.
We enrolled 892 men with no history of prostate cancer, normal rectal examination, prostate specific antigen 2 to 10 ng/ml and 6-core or greater prostate biopsy in a prospective multi-institutional trial. We examined the relationship of serum prostate specific antigen, free-to-total prostate specific antigen and the prostate health index with biopsy results. Primary end points were specificity and AUC using the prostate health index to detect overall and Gleason 7 or greater prostate cancer on biopsy compared with those of free-to-total prostate specific antigen.
In the 2 to 10 ng/ml prostate specific antigen range at 80% to 95% sensitivity the specificity and AUC (0.703) of the prostate health index exceeded those of prostate specific antigen and free-to-total prostate specific antigen. An increasing prostate health index was associated with a 4.7-fold increased risk of prostate cancer and a 1.61-fold increased risk of Gleason score greater than or equal to 4 + 3 = 7 disease on biopsy. The AUC of the index exceeded that of free-to-total prostate specific antigen (0.724 vs 0.670) to discriminate prostate cancer with Gleason 4 or greater + 3 from lower grade disease or negative biopsy. Prostate health index results were not associated with age and prostate volume.
The prostate health index may be useful in prostate cancer screening to decrease unnecessary biopsy in men 50 years old or older with prostate specific antigen 2 to 10 ng/ml and negative digital rectal examination with minimal loss in sensitivity.
The Journal of urology 03/2011; 185(5):1650-5. · 4.02 Impact Factor
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ABSTRACT: Recent reports have suggested a possible involvement of Single-minded homolog 2 (SIM2) in human solid cancers, including prostate cancer. However, the exact role of SIM2 in cancer in general, and in prostate cancer in particular, remains largely unknown. This study was designed to elucidate the role of SIM2 in prostate cancer using a shRNA-based approach in the PC3 prostate cancer cell line.
Lentiviral shRNAs were used to inhibit SIM2 gene and protein levels in PC3 cells. Quantitative RT-PCR and branched DNA were performed to evaluate transcript expression. SIM2 protein expression level was measured by western blot. Profiling of gene expression spanning the whole genome, as well as polar metabolomics of several major metabolic pathways was performed to identify major pathway dysregulations.
SIM2 gene and protein products were significantly downregulated by lenti-shRNA in PC3 cell line. This low expression of SIM2 affected gene expression profile, revealing significant changes in major signaling pathways, networks and functions. In addition, major metabolic pathways were affected.
Taken together, our results suggest an involvement of SIM2 in key traits of prostate tumor cell biology and might underlie a contribution of this transcription factor to prostate cancer onset and progression.
PLoS ONE 01/2011; 6(12):e28837. · 4.09 Impact Factor
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ABSTRACT: There is no universally accepted instrument to measure sexual function (SF) in men. We compare validated SF measures in a single cohort.
We compare the Sexual Health Inventory for Men (SHIM), Expanded Prostate Cancer Index Composite SF domain (EPIC-SF), and a reconstructed University of California Los Angeles Prostate Cancer Index SF domain (PCI-SF) in 856 men scheduled for radical prostatectomy. We define potency thresholds for the PCI-SF and EPIC-SF.
Mean age, body mass index, Gleason sum, and PSA were 57 years, 26.7 kg/m(2), 6.3, and 5.9 ng/mL, respectively. Mean instrument scores were as follows: SHIM 20.1; EPIC-SF 65; PCI-SF 71. All instruments were significantly intercorrelated (r = 0.99 for EPIC-SF vs PCI-SF, r = 0.75 for SHIM vs EPIC-SF, r = 0.77 for SHIM vs PCI-SF, all P < .001). The SHIM had the greatest negative skew and ceiling effect (P < .001). Although high scores on either the EPIC-SF or PCI-SF translated reliably to high SHIM scores, the reverse was not true. Subjects who reported no erectile dysfunction (ED) on the SHIM (>or=22) had diverse overall SF, whereas those who scored highly on the EPIC-SF or PCI-SF had both excellent erectile function (potency) and overall SF (including orgasmic function, erectile function, and sexual desire). EPIC-SF scores >or=65 and PCI-SF scores >or=75 define men that are both potent and have good SF.
The SHIM is intended as an instrument to assess ED. It is, however, inadequate as a measure of overall SF. The EPIC-SF and PCI-SF capture gradations of both sexual and erectile function and may also be used to define potency more comprehensively.
Urology 08/2010; 76(2):380-6. · 2.43 Impact Factor
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Lori J Sokoll, Martin G Sanda,
Ziding Feng,
Jacob Kagan,
Isaac A Mizrahi,
Dennis L Broyles,
Alan W Partin,
Sudhir Srivastava,
Ian M Thompson,
John T Wei,
Zhen Zhang,
Daniel W Chan
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ABSTRACT: The free prostate-specific antigen (PSA) isoform, [-2]proPSA, has been shown to be associated with prostate cancer. The study objective was to characterize the clinical utility of serum [-2]proPSA for prostate cancer detection and assess its association with aggressive disease.
From among 669 subjects in a prospective prostate cancer detection study at four National Cancer Institute Early Detection Research Network clinical validation centers, 566 were eligible. Serum PSA, free PSA, and [-2]proPSA were measured (Beckman Coulter Access 2 Analyzer).
Two hundred and forty-five (43%) of the 566 participants had prostate cancer on biopsy. At 70% specificity, the sensitivity of %[-2]proPSA ([-2]proPSA/fPSA) was 54% [95% confidence interval (CI), 48-61%; null hypothesis, 40%]. Including %[-2]proPSA in a multivariate prediction model incorporating PSA and %fPSA improved the performance (P<0.01). In the 2 to 4 ng/mL PSA range, %[-2]proPSA outperformed %fPSA (receiver operator characteristic-areas under the curve, 0.73 versus 0.61; P=0.01). At 80% sensitivity, %[-2]proPSA had significantly higher specificity (51.6%; 95% CI, 41.2-61.8%) than PSA (29.9%; 95% CI, 21.0-40.0%) and %fPSA (28.9%; 95% CI, 20.1-39.0%). In the 2 to 10 ng/mL PSA range, a multivariate model had significant improvement (area under the curve, 0.76) over individual PSA forms (P<0.01 to <0.0001). At 80% sensitivity, the specificity of %[-2]proPSA (44.9%; 95% CI, 38.4-51.5%) was significantly higher than PSA (30.8%; 95% CI, 24.9-37.1%) and relatively higher than %fPSA (34.6%; 95% CI, 28.5-41.4%). %[-2]proPSA increased with increasing Gleason score (P<0.001) and was higher in aggressive cancers (P=0.03).
In this prospective study, %[-2]proPSA showed potential clinical utility for improving prostate cancer detection and was related to the risk of aggressive disease.
The addition of %[-2]proPSA could affect the early detection of prostate cancer.
Cancer Epidemiology Biomarkers & Prevention 05/2010; 19(5):1193-200. · 4.12 Impact Factor
