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Gleason scores of prostate biopsy and radical prostatectomy specimens over the past 10 years: Is there evidence for systematic upgrading?
Abstract
With the advent of the prostate specific antigen (PSA) assay, an increased detection rate of prostate carcinoma has ensued. This has been associated with a downward stage migration. In contrast, grade has shifted heavily toward moderate differentiation. The authors sought to test the hypothesis that such changes in grade in part may be because of trends among pathologists to upgrade similar specimens over time.
Two expert genitourinary pathologists regraded 23 prostate biopsies and 15 radical prostatectomy specimens during a 3-year period (1989-1991). Each pathologist then regraded 32 prostate biopsies and 15 radical prostatectomies from 1998 to 2000. For both time periods, each pathologist regraded only specimens that they personally had graded initially. All specimens were scored using the Gleason system, the predominant system used in describing prostate carcinoma grade. In evaluating original and regraded scores, the authors classified score changes between less than or equal to 6 and greater than or equal to 7 or between 7 and greater than or equal to 8 as significant because such changes have a high probability of altering clinical management. The results were analyzed using the two-tailed Fisher exact test.
Of 23 prostate biopsies from 1989 to 1991, 10 of 23 (44%) had a clinically significant Gleason score change when regraded, whereas 2 of 15 (13%) radical prostatectomy specimens from the same period had a clinically significant Gleason score change. A significant change in the distribution of biopsy Gleason scores on regrading was observed (P < 0.04). In comparison, when the prostate biopsies from 1998-2000 were regraded, 10 of 32 (31%) had a clinically significant grade change. Radical prostatectomy specimens from the same period revealed 3 of 15 (20%) with a clinically significant grade change. After regrading the biopsies from 1989-1991, 8 of 23 (35%) of were upgraded, whereas 2 of 23 (9%) were downgraded. In comparison, of the biopsies with significant changes from 1998 to 2000, 3 of 32 (9%) were upgraded, whereas 7 of 32 (22%) were downgraded. Of the radical prostatectomy specimens with significant change, only 2 of 15 from each period were upgraded. Significant upgrading (P < 0.005) occurred only in the biopsy specimens from 1989 to 1991.
The authors' data suggest that rates of upgrading and downgrading of biopsy specimens differ between the 1989-1991 cases and the 1998-2000 cases, with the 1989-1991 samples exhibiting a significant change toward higher grades. Although not excluding the possibility of a change in the biology of prostate carcinoma over time, these findings suggest that the apparent trend toward higher biopsy grades in part may be because of how pathologists interpret these specimens today as compared with 10 years ago. Therefore, outcome studies including a biopsy Gleason score from older specimens as a risk variable have a significant chance of being vulnerable to this phenomenon. Based on the authors' data, all such specimens should undergo rereview.
... En el curso del estudio hemos asistido a una migración del score de Gleason hacia valores más altos (figura 1). Este hecho es conocido y ya ha sido descrito por otros autores (10,11) . Puede introducir confusión cuando se comparan grupos de pacientes tratados en diferentes épocas. ...
... Naturalmente, una comparación con los resultados quirúrgicos tampoco es posible pues los pacientes sometidos a prostatectomía son seleccionados en forma diferente, normalmente se excluyen los estadios T3 y PSA iniciales muy elevados. La cirugía, además, se beneficia de la frecuente sobrepuntuación del score Gleason de la pieza de prostatectomía comparando con la biopsia transrectal obtenida antes de la operación (11) . A fines solamente comparativos señalamos los resultados de cuatro series quirúrgicas estadounidenses en la tabla 5. ...
A sample of 560 patients with localized prostate cancer were analyzed from 1993 to 2001. All patients were treated with tridimensional conformal radiotherapy. Global survival after 9 years was 71%, while specific cause survival was 88%. Mortality due to prostate cancer was 4,8% compared to 8,3% observed in other causes mortality. Survival without biochemical fallen again according to risk-group was 83%, 68% and 41% after 9 years, respectively for groups at low, medium and high risk in 504 patients (p
... All of these changes have the potential to cause a shift towards higher grading. Several investigators have observed a trend towards increasing prostate cancer grades over recent decades [10,10,11,11,12,12,14,16]. It is unclear how much the ISUP revision has contributed to this process. ...
... All of these changes have the potential to cause a shift towards higher grading. Several investigators have observed a trend towards increasing prostate cancer grades over recent decades [10,10,11,11,12,12,14,16]. It is unclear how much the ISUP revision has contributed to this process. ...
WHAT'S KNOWN ON THE SUBJECT?: In recent years there has been a shift upwards of how Gleason grading of prostate cancer is applied. At an International Society of Urological Pathology (ISUP) consensus meeting in 2005 recommendations were issued that might have contributed to this trend.
To study long-term trends in Gleason grading in a nation-wide population. To assess the impact of the ISUP revision of the Gleason system on grading practices.
All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998-2011, Gleason score (GS), clinical T stage (cT) and S-PSA (S-PSA) at diagnosis were analyzed.
A GS, cT and S-PSA was reported to NPCR in 97%, 99% and 99% of cases. Before and after 2005, GS 7-10 was diagnosed in 52% and 57%, respectively (p <0.001). After standardization for cT and S-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage T1c and S-PSA 4-10 ng/ml) GS 7-10 increased from 16% 1998 to 40% 2011 (ptrend <0.001), mean 19% and 33% before and after 2005 (p <0.001). Among high-risk tumours (stage T3 and S-PSA 20-50 ng/ml) GS 7-10 increased from 65% 1998 to 94% 2011 (ptrend <0.001), mean 78% and 90% before and after 2005 (p <0.001). A GS 2-5 was reported in 27% 1998 and 1% 2011. GS 5 decreased sharply after 2005 and GS 2-4 was almost abandoned.
There has been a gradual shift towards higher Gleason grading that started early but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of GS 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable the last decade. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.
... La relación entre los hallazgos al tacto rectal y los ecográficos en los pacientes con cáncer se detalla en la Tabla 3. (20,9) Los pacientes diagnosticados de cáncer con tacto rectal no sospechoso y sin nódulo ecográfico identificable representaron el 23,7% (276) del total de los casos. ...
... La práctica desaparición en la reclasificación de los grados 2-4 es debido a que es preciso la existencia de un patrón de arquitectura nodular, lo cual es un hallazgo muy infrecuente en los especimenes de biopsia prostática. Este sesgo de interpretación lo atribuyen los autores a la experiencia acumulada por los patólogos y a la actualización cada vez con criterios más específicos de asignación del grado, pero no pueden excluir que se esté produciendo un cambio en la biología del tumor en el tiempo 19,20 . ...
EVOLUTION OF THE CLINICAL, ECHOGRAPHIC AND PATHOLOGICAL CHARACTERISTICS OF PATIENTS WITH INDICATION OF TRANSRECTAL ULTRASOUND AND PROSTATE BIOPSY BETWEEN 1994 AND 2003 Objective: The aim of this paper is to evaluate the evolution in the clinical, echographic and pathological characteristics of patients undergoing transrectal ultrasound and prostate biopsy over a 10 year period (1994-2003). Material and methods: Patients undergoing a first biopsy of the prostate between 1994-2003 were studied retrospectively. Since the biopsy criteria have changed several times over this period, results were analysed for four different periods: 1994-1997, 1998, 1999-2003 (the latter was further divided into two periods - 1999-2001 and 2002-2003 - to observe the temporal evolution with the same biopsy criteria). Patients were assigned to risk groups according to DAmico. Results: We observed that individuals referred for biopsy and those diagnosed with prostate cancer (PC) had a lower mean age (p=0.0001 and p=0.01), there were more patients with a PSA from 4.1-10 ng/ml (p=0.0001 and p=0.0001), more patients had no significant DRE findings (p=0.0001 and p=0.0001) or ultrasound findings (p=0.0001 and p=0.0001). The incidence of cancer diag- nosis has decreased from 39.4% to 34.3% (p=0,03). There was an increased incidence of score 7, at the expense of a decline in scores 5-6 and 8-10 and disappearance of score 2-4 (p=0.0001). Patients assigned to the low risk group increased from 9% to 18.1%, those assigned to the intermediate risk group from 20.2% to 43.1% and there was a reduction in those assigned to the high risk group from 70.7% to 38.7% (p=0.0001). Analysis of the final two time periods revealed that the evolution of the series remained the same except for a decrease in age at biopsy and diagnosis of cancer. Conclusions: Nowadays, the risk factors of patients with an indication of biopsy have less weight than ten years ago. We currently diagnose patients with PC with more favourable prognostic factors. However, the price we pay for this earlier diagnosis is reflected in a less effective biopsy, a larger proportion of the population without PC having to experience the physical complications and psy- chological stress of a biopsy, a greater number of patients having to undergo a second biopsy and, therefore, a greater and more costly use of resources to diagnose PC.
... Several international pathology guidelines including the International Collaboration on Cancer Reporting datasets and the widely applied ISUP reporting guidelines provide pathologists with rules for assessing tumour Gleason grade, standardize the way of reporting results, and, therefore, can be used for QA purposes 56,146 . However, the Gleason scoring system is hampered by substantial inter-observer and intra-observer variability and depends on pathologist's experience, tissue volume and quality of the sampled tissue [147][148][149][150][151] . Gleason score takes into account the two most common cell subtypes rather than the worst pattern, which can lead to underestimation of the aggressiveness of the tumour. ...
Multiparametric MRI of the prostate is now recommended as the initial diagnostic test for men presenting with suspected prostate cancer, with a negative MRI enabling safe avoidance of biopsy and a positive result enabling MRI-directed sampling of lesions. The diagnostic pathway consists of several steps, from initial patient presentation and preparation to performing and interpreting MRI, communicating the imaging findings, outlining the prostate and intra-prostatic target lesions, performing the biopsy and assessing the cores. Each component of this pathway requires experienced clinicians, optimized equipment, good inter-disciplinary communication between specialists, and standardized workflows in order to achieve the expected outcomes. Assessment of quality and mitigation measures are essential for the success of the MRI-directed prostate cancer diagnostic pathway. Quality assurance processes including Prostate Imaging-Reporting and Data System, template biopsy, and pathology guidelines help to minimize variation and ensure optimization of the diagnostic pathway. Quality control systems including the Prostate Imaging Quality scoring system, patient-level outcomes (such as Prostate Imaging-Reporting and Data System MRI score assignment and cancer detection rates), multidisciplinary meeting review and audits might also be used to provide consistency of outcomes and ensure that all the benefits of the MRI-directed pathway are achieved.
... However, in the more recent years, eight or more core biopsies were taken in 48% of cases, fewer than eight in 26%, and not known for 26%. The changes in Gleason scores can be largely attributed to an artefact on account of changes over time in the pathology grading system [12]. ...
Introduction:
The incidence of prostate cancer is on the rise in many industrialised countries, including Italy, most likely because of the spread of PSA testing. In Italy, prostate cancer mortality has been dropping since 2000, but it is difficult to understand whether PSA testing is the main reason, considering the role of treatment in prognosis. The objectives of this study were: (1) to describe Italian trends of prostate cancer risk categories and corresponding changes in treatment patterns and (2) to interpret changes in survival over time.
Methods:
We made a retrospective observational study using population-based cancer registries. We examined two periods, 1996-1999 and 2005-2007, analysing the distribution of patients among risk groups and treatment changes in those intervals. We estimated 7- and 15-year relative survival with the cohort approach, Ederer II method. We analysed 4635 cases.
Results:
There was downward risk migration from the first to the second period. In patients younger than 75 years, there was an increase in radical prostatectomy but not radiotherapy; patients older than 75 years rarely had treatment with radical intent. We noted an improvement of prostate cancer survival in the high-risk group.
Conclusion:
These findings raise several questions: the possible overtreatment of low-risk patients undergoing radical treatment; the utility of more aggressive treatment for elderly patients with high-risk disease; and the importance of a multidisciplinary clinical approach to ensure multiple and alternative treatment options. The increase in survival, with the decrease in mortality, suggests an effect of radical treatments on prognosis.
... It is true that contemporary pathologic review of prostate cancer has shifted to a predilection towards assigning higher Gleason grades. Multiple studies have confirmed that on re-grading of prostate biopsies, there is significant upgrading in recent years [22]- [24]. In an editorial, Epstein suggested that Gleason 2 -4 grades are not reliably reproducible among experts and should therefore be avoided altogether to avoid a false sense of indolent disease [25]. ...
... 15 The recommendations of the 2005 ISUP Consensus Conference may potentially have the effect of grade migration towards higher Gleason scores, as has been shown in population-based studies. 16,17 As observed by Smith et al., 18 the change in distribution of Gleason score may be also largely attributed to the pathologist's interpretation of grading. In this study, prostate biopsies from 1989-1991 and 1998-2000 were re-evaluated by the same pathologists, resulting in downgrading of 9% and 22%, respectively, for the two time periods, and upgrading of 35% and 9%. ...
Objectives: Our aim was to evaluate changes in prostate cancer diagnosis and management and to examine changes in the stage and grade of newly diagnosed prostate cancer in the North West of England over a 10-year period.
Materials and methods: Data was collected concerning the diagnosis (including stage and grade) and management of newly diagnosed prostate cancer in the North West of England. There were three time points: 2003, 2007 and 2011 including a total of 648 patients. For assessment of median time changes Spearman’s Rank correlation test was used, for the assessment of changes in Gleason grade and clinical stage Mann–Whitney U test was used, and assessment of positive margin rates was done with Fisher’s test.
Results: Median time from management decision to surgery has reduced from 46 (2003), 34 (2007) to 27 days (2011) (p=0.074). The proportion of patients managed with active surveillance has remained relatively constant over time (18%, 16% and 21% respectively). More minimally invasive, nerve-sparing prostatectomies are now performed, and positive margin rates have significantly reduced from 53% (2003) to 23% (2011) (p<0.001). Gleason grade significantly increased over time (p<0.001); Gleason 7 disease was diagnosed in 23% of patients in 2003, 32% in 2007 and 49% in 2011 (p<0.001). There was an increase in Gleason 8 disease; 6% (2003) to 8.6% (2011), but this was not significant (p=0.27). Increase in clinical stage was also noted over time; identification of T3 disease rose from 2% (2003 and 2007) to 5% (2011) (p=0.045) (excluding cases with non-recorded stage).
Conclusion: Prostate cancer management in the North West of England has evolved over the last decade, with overall improvements in management quality. We have demonstrated an increase in the presenting stage and grade of prostate cancer over a 10-year period.
... From CR to death, although a Gleason score 8-10 was a factor of influence in the univariate study, contrary to other published papers, it was not influential in the multivariate study. Perhaps this was the case because of the evolution in the type of patient candidate to radical prostatectomy in 20 years, 35 or because of the changes in the pathological qualification criteria with a tendency to upgrade the Gleason score, 36 or because of the clinic-pathological stage migration of this disease. 37,38 The only death survival independent predictor factor was the Ki-67 value. ...
Introduction:
We evaluate the prognosis of patients with biochemical recurrence (BCR) treated with androgen deprivation therapy (ADT) and to determine the influential factors to castration resistance (CR) and death.
Methods:
From a series of 1310 patients with T1-T2 prostate cancer treated with radical prostatectomy between 1989 and 2012, 371 had BCR. Patients with lymph node involvement were excluded. We analyzed only the 159 treated with salvage ADT. At the end of the study, 77 (48%) had developed CR.
Results:
The median follow-up to CR was 9.2 years. The CR-resistant free survival (RFS) was 76 ± 3%, 62 ± 3% and 43 ± 9% in 5, 10 and 15 years, respectively. The RFS median time was 14 years. In the multivariate study, the prostate-specific antigen (PSA) doubling time (PSA-DT) was <6 months (p = 0.01) (hazard ratio [HR] 3; 95% confidence interval [CI] 1.4-6.8, p = 0.007); seminal vesicle involvement (HR 3.1; 95% CI 1.5-6.2, p = 0.01) and PSA velocity in ng/mL/year (HR 1.3; 95% CI 1.1-1.5, p = 0.002) with better cut-off points of 0.84 ng/mL/year (p = 0.04) (HR 4; 95% CI 1.7-9.4, p = 0.001) were influential variables. Specific survival (SS) at 5, 10 and 15 years since surgery was 96 ± 1, 85 ± 2 and 76 ± 4, respectively. The time of CR to death was 30 ± 6% at 5 years, with the median at 3.2 years. In the multivariate only Ki 67 (HR 1.04; 95% CI 1.005-1.08, p = 0.02) had an independent influence.
Conclusions:
In BCR patients treated with ADT, the median to CR was 14 years. PSA-DT <6 months, PSA velocity (ng/mL/year) and seminal vesicle involvement were influential variables. From the CR, the median time to death was 3.2 years. Ki-67 marker was an independent influence.
... Undergrading and upgrading associated with PB are well known. Changes in the latter are affected by technical factors (location and number of biopsies, the tumor volume in the sample, previous hormonal therapy), and the alterations of pathological approach and practice (nowadays, there is a tendency for general upgrading compared to a decade ago) [21,22]. Burchard has demonstrated that it is not the previous experience, but regular daily practice is the most important in regard to the correct histopathological diagnosis of PCa (19). ...
The main objective of this retrospective study was to evaluate the influence of pathological experience in histological examination of prostate cancer (PCa) on preoperative understaging (UNS), undergrading (UNG), and upgrading (UPG).
Histopathological data of prostate biopsy (PB) and radical prostatectomy (RP) specimens of patients undergoing subsequent radical prostatectomy (n = 430) in our center were compared. Histological diagnoses of PB were provided either by corresponding academic pathology institute (Group 1: 322 patients) or by external (nonacademic) departments which had a lower number (≤100/year) of PCa histopathological evaluations (Group 2 108 patients). The rate of UNG, UPG, and UNS in both groups and also the effects of institutional learning curve were analyzed in terms of grading and staging.
Significant difference was detected between Group 1 and Group 2 in average preoperative Gleason score (GS) values and in the rate of well, moderately, and poorly differentiated cancers as well. There was also a significant difference in the rate of UNG (29.1 vs. 56.5 %, p < 0.0001). The mean preoperative and postoperative GS in Group 1 was significantly lower in the first 50 than in the last 50 patients, but the rates of UNG, UPG, and UNS did not differ significantly between the groups.
The experience of pathologists has direct influence on grading concordance and on UNG and UPG, between PB and RP specimen; however, it has no significant effect on complete preoperative understaging. The bigger pathological experience improves the sensitivity of the histological diagnostic process.
... Although it is difficult to compare studies of inter-observer variability because of the differences in the study sample, pathological specimen and the experience of the pathologists involved, it has been shown that the concordance rate in achieving exact Gleason score varies between 36% and 94% [25,26]. Smith et al. [27] looked at the effect of passage of time (9 years) on reporting of grade amongst the same 2 pathologists and showed that amongst biopsies 44% of reports were changed compared to 13% of RRP specimens. In the UK, it is standard practice to review all the CaP diagnoses in a multi-disciplinary meeting by an uro-pathologist. ...
Background
Upgrading of Gleason score at radical retropubic prostatectomy (RRP) is a recognised event; however there are few large, national, multicentre studies of upgrading. With the increasing utilisation of active surveillance as an option in the treatment of prostate cancer upgrading is an increasing concern to urologists.
Objective
To analyse the discordance between the biopsy Gleason score and the RRP Gleason score using the BAUS database from a non-screened UK population.
Methods and subjects
Data were obtained from the BAUS cancer registry which holds data on national complex operations. All patients who underwent RRP with pre and post-operative Gleason score were included in the study.
Results
1420 men were included in the study, mean age 62. Comparing Gleason score between the biopsy and the RRP specimen, 30% men were found to upgraded and 9% downgraded. Clinically significant upgrading was seen in 28%. Age and PSA were found to be higher in the upgraded cohort (p < 0.02). Positive margins and seminal vesicle invasion were significantly higher in the upgraded group (p < 0.02). Univariate analysis revealed PSA and age as significant predictors of upgrading at RRP (p < 0.05).
Conclusions
This large study provides novel data from a non-screened UK population, nearly one-third of whom had clinically significant upgrading. We have also shown that adverse pathological events, positive margin and seminal vesicle invasion, are more common in the upgraded cohort. This evidence needs to be considered when managing men with localised prostate cancer especially when considering active surveillance.
... In addition, differences in PSA production in prostate tumors of different grades may have resulted in a preferential improvement in the detection of moderately differentiated tumors. Moreover, although few data have evaluated the temporal reproducibility of the GS, there is some evidence that pathologists' interpretations of prostate specimens may have shifted over time to higher scores [21]. In the present study, the frequency of patients with GSs of 8 or more dropped over the 12-year period, whereas the frequency of patients with a GS of 6 or less increased. ...
To investigate whether tumor aggressiveness in patients with prostate cancer has changed in Korea since the introduction of prostate-specific antigen (PSA) testing.
The data from 2,508 patients with pathologically confirmed prostate cancer who underwent radical prostatectomy at Asan Medical Center between 2000 and 2011 were reviewed. The patients were divided into four 3-year time series, and the changes between the groups in terms of serum PSA levels, pathological Gleason score (GS), and pathological stage were assessed. The change in GS over time in organ-confined disease and in patients whose PSA was below 10 ng/ml was also analyzed.
The mean PSA levels dropped significantly over the 12-year period (p<0.001). The frequency of organ-confined disease increased (55.7% vs. 64.7% vs. 62.9% vs. 63.5%, p=0.043). The frequency of patients with a GS of 8 or more decreased (38.9% vs. 25.7% vs. 18.2% vs. 19.7%) and the frequency of patients with a GS of 6 or less increased (15.0% vs. 18.9% vs. 26.7% vs. 18.2%, p=0.003). However, the vast majority (more than 70%) of all cases had a high GS (7 or greater) at all time points. The GS distribution did not change over time in patients whose PSA levels were below 10 ng/ml or in those who had organ-confined disease.
In 2000 to 2011, the preoperative PSA, pathological stage, and pathological GS dropped. However, the majority of the prostate cancers in Korean men were poorly differentiated, even when the patients had organ-confined disease or their PSA levels were less than 10 ng/ml.
... The shift away from reporting of Gleason scores 2-4 has been identified in other studies also and seems to be related to changes in interpretation over time. [4,16] Gleason score 7 is identified as area of difficulty in both this study and elsewhere. [4,17] Fourteen out of 63 readings of slides(22%) [ Table 2] with a consensus score of 7 were underscored in the present study which is more than the study of Melia et al. [4] in which underscoring of consensus score 7 were seen in 13%. ...
Gleason grade is the most widely used grading system for prostatic carcinoma and is recommended by World Health Organization. It is essential that there should be good interobserver reproducibility of this grading system as it has important implications in patient management.
To assess interobserver reproducibility of Gleason grading of prostatic adenocarcinoma.
A total of 20 cases of prostatic adenocarcinoma were scored using Gleason grade by 21 general pathologists. The scores were then compared using κ-coefficient and consensus score.
For Gleason score groups (2-4, 5-6, 7 and 8-10) overall agreement with consensus score was 68%. Exact agreement for Gleason scores with consensus score was 43.3% and 92.3% within ±1 of the consensus score. κ coefficient for primary grade ranged from -0.32 to 0.92 with 60% of the readings in fair to moderate agreement range; and for secondary grade κ ranged from -0.30 to 0.62 with 78% of the readings in slight to fair agreement range. Kappa for Gleason scores ranged from -0.13 to 0.55 with 80% of the readings in slight to fair agreement range; and for Gleason score groups κ ranged from -0.11 to 0.82 with 68.5% of the readings in fair to moderate agreement range.
In our study interobserver reproducibility of Gleason scores among general pathologists was at lower level and it highlights the need to improve the observer reproducibility by continuous educational sessions and taking second opinion in cases where grade could significantly influence management.
... An important consideration in evaluating the prognostic value of Gleason has been the noted shift in Gleason grading over time, which has resulted in a general increase in scores with more contemporary reads and almost no men diagnosed with Gleason <6 tumors 21,24 . Moreover, there is considerable inter-rater variability in assigning Gleason grades across institutions. ...
Clinical outcomes in prostate cancer are heterogeneous, and given the high prevalence of the disease, there is a pressing need to identify clinically useful markers of prognosis. Many clinical, pathological, molecular, and genetic factors have been investigated in this capacity, although relatively few are routinely used. With a growing understanding of the molecular pathogenesis of prostate cancer, there is the potential that the next generation of makers will prove sufficiently robust to guide the optimal management of men with prostate cancer. Here, we review the various clinical and molecular prognostic determinants in prostate cancer.
Background:
Active surveillance (AS) mitigates harms from overtreatment of low-risk prostate lesions. Recalibration of diagnostic thresholds to redefine which prostate lesions are considered "cancer" and/or adopting alternative diagnostic labels could increase AS uptake and continuation.
Methods:
We searched PubMed and EMBASE to October 2021 for evidence on: (1) clinical outcomes of AS, (2) subclinical prostate cancer at autopsy, (3) reproducibility of histopathological diagnosis, and (4) diagnostic drift. Evidence is presented via narrative synthesis.
Results:
AS: one systematic review (13 studies) of men undergoing AS found that prostate cancer-specific mortality was 0%-6% at 15 years. There was eventual termination of AS and conversion to treatment in 45%-66% of men. Four additional cohort studies reported very low rates of metastasis (0%-2.1%) and prostate cancer-specific mortality (0%-0.1%) over follow-up to 15 years. Overall, AS was terminated without medical indication in 1%-9% of men. Subclinical reservoir: 1 systematic review (29 studies) estimated that the subclinical cancer prevalence was 5% at <30 years, and increased nonlinearly to 59% by >79 years. Four additional autopsy studies (mean age: 54-72 years) reported prevalences of 12%-43%. Reproducibility: 1 recent well-conducted study found high reproducibility for low-risk prostate cancer diagnosis, but this was more variable in 7 other studies. Diagnostic drift: 4 studies provided consistent evidence of diagnostic drift, with the most recent (published 2020) reporting that 66% of cases were upgraded and 3% were downgraded when using contemporary diagnostic criteria compared to original diagnoses (1985-1995).
Conclusions:
Evidence collated may inform discussion of diagnostic changes for low-risk prostate lesions.
Objective:
Active surveillance (AS) has emerged as a management strategy for preventing overtreatment of indolent prostate cancer. Selection of patients for AS has traditionally proved challenging and resulted in 20-30% misclassification rates. MRI has potential to help overcome this limitation, broaden selection criteria to increase recruitment, and minimize the invasive nature of AS follow-up.
Conclusion:
The main issues surrounding MRI and AS are the heterogeneity of inclusion criteria, the definition of significant disease, and agreement about what constitutes radiologic progression. Prospective cohorts with MRI at enrollment and long-term follow-up are required to further address these issues.
There has been significant stage migration of prostate cancer patients in the prostate-specific antigen era. Incorporating biopsy information into nomograms and risk assessment equations improves upon clinical staging and risk assessment. New imaging techniques, molecular markers and gene chip arrays hold promise for future risk assessment.
Zinc is a vital element in the nutrition of human beings, animals and plants. Although most experimental data have demonstrated the adverse effects of Zn deficiency on human and animal health, there is still evidence to support the hypothesis that Zn toxicity can also result in deleterious health effects. Conflicting views have been expressed regarding the role of Zn in carcinogenesis. Some studies emphasize the fact that Zn deficiency causes cancers, while others highlight that Zn is involved in tumour growth and development of neoplastic transformation. These conflicting observations suggest that the role of Zn in different organs may be different. Based on the results of a micro-beam synchrotron X-ray fluorescence technique (micro-SRIXE) applied to the quantitative analysis of Zn, we correlated Zn concentration levels with the clinical stage of prostate cancer at the time of operation (described by the Gleason grade system). Serial sections of prostate tissues were collected from patients undergoing radical prostatectomy. Our results seem to be valuable in light of determination of the potential changes in Zn concentration as a diagnostic marker and its etiological involvement in the different stages of prostate diseases.
A patient newly diagnosed with prostate cancer in 2011 faces a potentially bewildering menu of treatment options. Alternatives endorsed by the American Urological Association (AUA)'s 2007 practice guideline for localized prostate cancer [1], for example, include active surveillance, radical prostatectomy, interstitial radiation (brachytherapy), or external beam radiation therapy (EBRT). However, the detailed list of options becomes longer, including among surgical options open radical retropubic prostatectomy (ORRP), radical perineal prostatectomy (RPP), straight laparoscopic radical prostatectomy (LRP), and robot-assisted radical prostatectomy (RARP), within brachytherapy, permanent (low-dose rate) seed implantation or temporary (high-dose rate [HDR]) via catheters, and within EBRT, conventional 3-D conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), or proton beam therapy, possibly combined with brachytherapy and/or with androgen deprivation therapy (ADT). Other options not necessarily endorsed by the guideline but frequently used in practice include primary ADT (PADT) monotherapy and cryotherapy; those traveling outside the United States also have the option of high-intensity focused ultrasound (HIFU).
The life expectancy of prostate patients is long and patients will spend many years carrying the burdens & benefits of the treatment decisions they have made, therefore, it is vital that decisions on treatments are shared between patient and physician. The objective was to determine if consultation audio-recording improves quality of life, reduces regret or improves patient satisfaction in comparison to standard counselling.
In 2012 we initiated consultation audio-recordings, where patients are given a CD of their consultation to keep and replay at home. We conducted a prospective non-randomised study of patient satisfaction, quality of life (QOL) and decision regret at 12 months follow-up using posted validated questionnaires for the audio-recording (AR) patients and a control cohort. Qualitative and thematic analyses were used.
Forty of 59 patients in the AR group, and 27 of 45 patients in the control group returned the questionnaires. Patient demographics were similar in both groups with no statistically significant differences between the two groups. Decision regret was lower in the audio-recording group (11/100) vs control group (19/100) (p = 0.04). The risk ratio for not having any long-term decision regret was 5.539 (CI 1.643-18.674), with NNT to prevent regret being 4. Regression analysis showed that receiving audio-recording was strongest predictor for absence of regret even greater than potency and incontinence.
The study has shown that audio-recording clinic consultation reduces long-term decision regret, increases patient information recall, understanding and confidence in their decision. There is great potential for further expansion of this low-cost intervention.
Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.
Objective:
To study the influence, in terms of prognosis, of the finding of seminal vesicle involvement in patients with prostate adenocarcinoma treated with radical prostatectomy.
Material and method:
We reviewed a series of patients with seminal vesicle involvement with clinically localized prostate adenocarcinoma who underwent radical prostatectomy between 1989 and 2009, focusing on their clinical-pathological characteristics, biochemical progression-free survival (BPFS) and specific survival (SS). We assessed the variables that influenced BPFS and designed a risk model.
Results:
A total of 127 out of 1,132 patients who underwent surgery (11%) presented seminal vesicle invasion (i.e., pT3b). In the multivariate study of the entire series (Cox model), pT3b affects the BPFS (HR: 2; 95% CI: 1.4-3.3; P=.001). Other influential factors were the affected borders, initial prostate-specific antigen levels, pathological Gleason score and the presence of palpated tumor. The pT3b tumors have poorer clinical-pathological variables when compared with pT2 and pT3a tumors. Sixty-five percent of the patients evidenced biochemical progression. The BPFS was significantly poorer for pT3b (40 ± 4% and 28 ± 4% at 5 and 10 years, respectively) than for pT2 and pT3a (P<.0001). The SS was also poorer in patients with pT3b tumors (91 ± 2% and 76 ± 4% at 5 and 10 years, respectively) (P<.0001). The predictors within the pT3b patient group were: PSA levels >10 ng/mL (HR: 1.9; 95% CI: 1.04-3.6; P=.04) and pathological Gleason score 8-10 (HR: 2.1; 95% CI: 1.2-3.5; P=.03). We designed a risk model that accounts for the variables involved, which entails 2 groups with different BPFS (P=.004): Group 1 (0-1 variable), with a BPFS of 46 ± 7% and 27 ± 8% at 5 and 10 years, respectively; and Group 2 (2 variables), with a BPFS of 14 ± 7% and 5 ± 5% at 5 and 10 years, respectively.
Conclusion:
Seminal vesicle involvement severely and negatively affects the BPFS and SS. We designed a risk model with the independent influential variables in BPFS (pathological Gleason score 8-10 and PSA levels >10 ng/mL). This model confirms that pT3b tumors are a heterogeneous group, which includes an important group with better prognosis when surgical treatment is performed.
Objective
To study the influence, in terms of prognosis, of the finding of seminal vesicle involvement in patients with prostate adenocarcinoma treated with radical prostatectomy.
Material and method
We reviewed a series of patients with seminal vesicle involvement with clinically localized prostate adenocarcinoma who underwent radical prostatectomy between 1989 and 2009, focusing on their clinical-pathological characteristics, biochemical progression-free survival (BPFS) and specific survival (SS). We assessed the variables that influenced BPFS and designed a risk model.
Results
A total of 127 out of 1,132 patients who underwent surgery (11%) presented seminal vesicle invasion (i.e., pT3b). In the multivariate study of the entire series (Cox model), pT3b affects the BPFS (HR: 2; 95% CI: 1.4-3.3; P = .001). Other influential factors were the affected borders, initial prostate-specific antigen levels, pathological Gleason score and the presence of palpated tumor. The pT3b tumors have poorer clinical-pathological variables when compared with pT2 and pT3a tumors. Sixty-five percent of the patients evidenced biochemical progression. The BPFS was significantly poorer for pT3b (40 ± 4% and 28 ± 4% at 5 and 10 years, respectively) than for pT2 and pT3a (P < .0001). The SS was also poorer in patients with pT3b tumors (91 ± 2% and 76 ± 4% at 5 and 10 years, respectively) (P <. 0001). The predictors within the pT3b patient group were: PSA levels > 10 ng/mL (HR: 1.9; 95% CI: 1.04–3.6; P = .04) and pathological Gleason score 8-10 (HR: 2.1; 95% CI: 1.2-3.5; P = .03). We designed a risk model that accounts for the variables involved, which entails 2 groups with different BPFS (P = .004): Group 1 (0-1 variable), with a BPFS of 46 ± 7% and 27 ± 8% at 5 and 10 years, respectively; and Group 2 (2 variables), with a BPFS of 14 ± 7% and 5 ± 5% at 5 and 10 years, respectively.
Conclusion
Seminal vesicle involvement severely and negatively affects the BPFS and SS. We designed a risk model with the independent influential variables in BPFS (pathological Gleason score 8-10 and PSA levels >10 ng/mL). This model confirms that pT3b tumors are a heterogeneous group, which includes an important group with better prognosis when surgical treatment is performed.
Purpose
More than 50,000 Americans were diagnosed with kidney and renal pelvis cancer in 2010. The National Program of Cancer Registries and SEER (Surveillance, Epidemiology and End Results) combined data include cancer incidences from the entire United States. Our study presents updated incidence data, evaluates trends and adds geographic distribution to the literature.
Materials and Methods
We examined invasive, microscopically confirmed kidney and renal pelvis cancers diagnosed from 2001 to 2010 that met United States Cancer Statistics reporting criteria for each year, excluding cases diagnosed by autopsy or death certificate. Histology codes classified cases as renal cell carcinoma. Rates and trends were estimated using SEER∗Stat.
Results
A total of 342,501 renal cell carcinoma cases were diagnosed. The renal cell carcinoma incidence rate increased from 10.6/100,000 individuals in 2001 to 12.4/100,000 in 2010 and increased with age until ages 70 to 74 years. The incidence rate in men was almost double that in women. The annual percent change was higher in women than in men, in those 20 to 24 years old and in grade III tumors.
Conclusions
The annual percent change incidence increased from 2001 to 2010. Asian/Pacific Islanders and 20 to 24-year-old individuals had the highest annual percent change. While some increase resulted from localized disease, the highest annual percent change was in grade III tumors, indicating more aggressive disease. Continued monitoring of trends and epidemiological study are warranted to determine risk factors.
To analyze the influential factors in the response in prostatectomized patients with subsequent biochemical relapse (BCR) and treated with salvage radiotherapy (RTP).
We analyzed 313 patients with pT2/pT3 prostate cancer who were receiving salvage therapy due to biochemical relapse (from a series of 1,310 radical prostatectomies between 1989-2012). Of the 313 patients; 159 (50.8%) only received androgen deprivation (AD), 63 (20.1%) Radiotherapy (RTP) plus concomitant AD and 91 (29.1%) only RTP. Of these, 57 (62.6%) have maintained complete response and 34 (37.4%) had failure response with post-RTP BCR.
Study of the group treated exclusively with salvage RTP. Ninety-one patients were treated with salvage RTP. Median follow-up was 6.4 years and median to recurrence 11 months. Post-RTP biochemical relapse-free survival (PRBRFS) was 68±7% and 30±10% in 5 to 10 years. Median PRBRFS was 7.3 years (6.3-8.3). Initial PSA (HR: 1.08; 95% CI: 1.01-1.1 P=.02) with best PSA cut-off point PSA>20ng/ml (HR: 13.6; 95% CI: 2.1-86 P=.005) and PSA pre-RTP (HR: 1.9; 95% CI: 1.2-3.3; P=.009), best PSA cut-off point PSA preRTP 0.92 ng/ml (HR: 4.5; 95% CI: 1.3-15.6; P=.01) showed independent influence in the response in the multivariate study. PRBRFS at 5 years, 81±9% versus 58±9% with initial PSA <20 or >20 ng/ml (P=.03). PRBRFS at 5 years, 93±5% versus 53±10% according to PSA pre-RTP <0.9 or >0.9 ng/ml (P=.02).
In patients treated with salvage RTP after radical prostatectomy, the preoperative PSA>20ng/ml and PSA preRTP>0.92 ng/ml shows an independent influence on the response.
Objective
To analyze the influential factors in the response in prostatectomized patients with subsequent biochemical relapse (BCR) and treated with salvage radiotherapy (RTP).
Material and methods
We analyzed 313 patients with pT2/pT3 prostate cancer who were receiving salvage therapy due to biochemical relapse (from a series of 1,310 radical prostatectomies between 1989-2012). Of the 313 patients; 159 (50.8%) only received androgen deprivation (AD), 63 (20.1%) Radiotherapy (RTP) plus concomitant AD and 91 (29.1%) only RTP. Of these, 57 (62.6%) have maintained complete response and 34 (37.4%) had failure response with post-RTP BCR.
Results
Study of the group treated exclusively with salvage RTP. Ninety-one patients were treated with salvage RTP. Median follow-up was 6.4 years and median to recurrence 11 months. Post-RTP biochemical relapse-free survival (PRBRFS) was 68 ± 7% and 30 ± 10% in 5 to 10 years. Median PRBRFS was 7.3 years (6.3-8.3). Initial PSA (HR: 1.08; 95% CI: 1.01-1.1 P = .02) with best PSA cut-off point PSA > 20 ng/ml (HR: 13.6; 95% CI: 2.1-86 P = .005) and PSA pre-RTP (HR: 1.9; 95% CI: 1.2-3.3; P = .009), best PSA cut-off point PSA preRTP 0.92 ng/ml (HR: 4.5; 95% CI: 1.3-15.6; P = .01) showed independent influence in the response in the multivariate study. PRBRFS at 5 years, 81 ± 9% versus 58 ± 9% with initial PSA < 20 or > 20 ng/ml (P = .03). PRBRFS at 5 years, 93 ± 5% versus 53 ± 10% according to PSA pre-RTP < 0.9 or > 0.9 ng/ml (P = .02).
Conclusions
In patients treated with salvage RTP after radical prostatectomy, the preoperative PSA > 20 ng/ml and PSA preRTP > 0.92 ng/ml shows an independent influence on the response.
Objective
To know the changes that there has experienced the profile of patient candidate to prostatectomía radically throughout last 2 decades in our institution.Material and methodsWe analyze retrospectively a series of 1.132 patients with prostate cancer stadium T1-T2, submitted to radical prostatectomy during the period 1989-2009. The series divides in five homogeneous groups as for the number of patients and arranged chronologically. There uses the free survival of biochemical progression (SLPB) as criterion principal forecast.ResultsIn spite of the changes in the diagnosis and treatment of the disease, from the point of view of the forecast (SLPB) we estimate two groups different from patients: the first 250 controlled ones and the rest. The point of chronological cut places in this series in 1.999. We find significant differences in the majority of the clinical - pathological variables as PSA's level to the diagnosis (P <0,001), percentage of palpable tumors (P <0,001), clinical stadium (P <0,001), Gleason in the prostate biopsy (P =0,004), groups at risk of D’Amico (P <0,001), pathological stadium (P <0,001) and percentage of patients mincingly ganglionar (P <0,001). Nevertheless, there are not detected differences of statistical significance in the Gleason of the specimen of prostatectomy (P =0,06) and in the percentage of surgical margins (P =0,6).Conclusions
This study analyzes a patients’ wide proceeding sample from the whole Spanish geography and presents some important information that reflect the evolution that has suffered the cancer of prostate located, so much regarding the diagnosis as to the forecast, in our country in the last 20 years.
Background: The Gleason histological score is an independent prognostic factor in prostate cancer that helps in therapeutic decisions. Aim: To analyze the concordance between the Gleason score of needle prostatic biopsy and the score from the study of the surgical piece obtained during radical prostatectomy. Material and methods: Retrospective analysis of 212 cases of prostate cancer, diagnosed between February 1993 and March 2003. All had the Gleason histological scores from needle prostatic biopsies and in the surgical piece obtained during radical prostatectomy. All pathological studies were done by the same observer. Results: There was an exact concordance of Gleason scores between needle biopsy and the surgical piece in 49% of cases and a concordance of ± 1 unit in 89%. The concordance improved in the second half of the study period. No cases with a Gleason score of less than 5 were detected since 1999 in the surgical piece. Conclusions: The concordance of Gleason score of needle prostatic biopsies and surgical pieces is good. This concordance increases with the experience of the pathologist (Rev Méd Chile 2004; 132: 971-8)
Introduction: we aimed to analyse the effects of radiotherapy dose and the use of neoadjuvant hormone therapy on survival without biochemical relapse, on specific cause mortality and on overall mortality, in patients with prostate cancer. Methods: we analysed 910 consecutive patients treated with radical tridimensional conformal radiotherapy between 1993 and 2005. Results: actuarial biochemical control at 10 years for the subset of patients who received a median dose of 74 Gy was 78%, 60% and 40% for the low, medium and high-risk groups, respectively. Biochemical control of patients receiving a median dose of 78 Gy was 96%, 81% and 40% for the same risk-groups. The difference between low and medium risk groups was p=0,029 y 0,008, respectively. Mulitvariate analysis confirmed that dose escalation significantly correlated with biochemical control and cause-specific survival. Likewise, hormone therapy was a significant factor for biochemical control and cause-specific survival. The 10-year actuarial rate of Grade 2 and Grade 3 late complications (there were no Grade 4 or 5 complications) presented non-significant differences between four subsets of patients treated with doses from 64 to 80 Gy. 4.8% of patients treated with doses between 78 and 80 Gy presented late urinary complications, and 5.3% of them showed late rectal complications. In hormone therapy naïve patients a
Objective:
To know the changes experienced by the patient profile candidate for radical prostatectomy over the last 2 decades in our institution..
Material and methods:
We analyze retrospectively a series of 1.132 patients with prostate cancer stadium T1-T2, submitted to radical prostatectomy during the period 1989-2009. The series divides in five homogeneous groups as for the number of patients and arranged chronologically. There uses the free survival of biochemical progression (SLPB) as criterion principal forecast.
Results:
In spite of the changes in the diagnosis and treatment of the disease, from the point of view of the forecast (SLPB) we estimate two groups different from patients: the first 250 controlled ones and the rest. The point of chronological cut places in this series in 1.999. We find significant differences in the majority of the clinical-pathological variables as PSA's level to the diagnosis (P <0,001), percentage of palpable tumors (P <0,001), clinical stadium (P <0,001), Gleason in the prostate biopsy (P =0,004), groups at risk of D'Amico (P <0,001), pathological stage (P <0,001), and percentage of patients with lymph node (P <0,001). Nevertheless, there are not detected differences of statistical significance in the Gleason of the specimen of prostatectomy (P =0,06) and in the percentage of surgical margins (P =0,6).
Conclusions:
This study analyzes a patients' wide proceeding sample from the whole Spanish geography and presents some important information that reflect the evolution that has suffered the cancer of prostate located, so much regarding the diagnosis as to the forecast, in our country in the last 20 years.
Accumulating evidence points to a role of chronic inflammation in the pathogenesis and progression of cancers, including prostate. Infections are important agents in the genesis of inflammation. For prostate cancer, several lines of evidence point to a role of infections as important agents, although no specific infection has consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T vaginalis, the most common non-viral sexually transmitted infection, and the recently identified retrovirus XMRV. The aims of this study are 1-) To assess the role of the newly identified XMRV virus in prostate carcinogenesis and progression; 2-) To characterize the role of the infectious protozoa T. vaginalis in prostate carcinogenesis and progression. The current study is nested within the Swedish Watchful Waiting Cohort, a population-based cohort of 1,256 Swedish men diagnosed with localized prostate cancer. During 28 years of follow-up, 320 men have died of cancer, and thus this is a powerful population in which to examine determinants of prostate cancer progression. A tumor repository from archival tissue specimens have been collected from all men in the cohort and will be used to assay for presence of the infections.
Background:
Consensus on prostate cancer (PCA) treatment in older men is currently lacking. We evaluated clinicopathological and oncological outcomes in patients >70-year-old treated with radical prostatectomy (RP).
Methods:
Clinicopathological and follow-up (FU) data for >70-year-old RP men (2000-2011) were recorded. Association between preoperative features, extraprostatic extension (EPE) and biochemical failure (bF), and postoperative features and bF, was explored. Patients >70-year-old were matched with younger (50- to 70-year-old) men with similar RP features to analyze the effect of age on bF.
Results:
Two hundred eighteen RP patients were >70-year-old. Clinical stage (cT) was T1 in 74.1%. Biopsy (Bx) Gleason score (GS) was 6 (35.8%), 7 (45.9%), and ≥8 (18.3%); RP GS was 6 (10.1%), 7 (63.3%), and ≥8 (26.6%). Median PSAD was 0.14 (range: 0.01-1.12). Pathologic stage (pT) was pT3 in 45.9%. bF occurred in 14.0%. Best preoperative predictive model for pT3 disease included D'Amico risk, number of Bx positive cores, PSAD, maximum % of PCA per core (P < 0.0001); cT, PSAD and primary Bx Gleason pattern best predicted bF preoperatively (P = 0.0031). Among postoperative features, high RP GS, positive margins, and pT3 were significantly associated with bF. Margin status and pT best predicted bF. Patients >70-year-old had 85% higher odds of bF compared to younger men (P = 0.036).
Conclusions:
PCA detected in >70-year-old men shows adverse pathologic features. Failure rate is significantly higher in older than in matched younger patients.
The technique for taking prostatic biopsies has received a major evaluation from many departments around the world in terms of the number of cores, site of biopsy, complications, need for local anaesthesia or sedation, etc., and the authors from Charlottesville review their technique. They present data confirming the impression that increasing the number of cores increases diagnostic sensitivity.Authors from Chapel Hill have performed a pilot study into the concept that cyclooxygenase (COX)-2 inhibitors inhibit tumour growth in prostate cancer, both in vivo and in vitro. In a few patients they found evidence to suggest that COX-2 inhibitors may be of value in patients with prostate cancer, concluding that a large trial is indicated.Vascular endothelial growth factor (VEGF) is known to be an important angiogenic factor. The authors from Sweden assessed its value as a marker in renal cancer cells. They found it to be present in most such cells, and found that the correlation between VEGF expression and tumour stage and prognosis was valuable in terms of progression of renal cancer.OBJECTIVE
To determine if increasing the number of cores at biopsy improves the predictive accuracy of the Gleason score or aids in anticipating the location and volume of prostate tumour.PATIENTS AND METHODS
The charts of 75 consecutive patients who underwent radical retropubic prostatectomy for clinical T1–2 adenocarcinoma of the prostate were reviewed retrospectively; 31 patients had a sextant biopsy (group 1) and 44 had ≥ 8 cores taken (group 2). The concordance between biopsy data and final prostatectomy Gleason score, tumour location and volume was determined for each group.RESULTSThere were no differences in mean age, prostate-specific antigen level before biopsy or biopsy Gleason score for the two groups; 58% of group 1 had their final pathological grade changed after prostatectomy, vs 29% of group 2 (P < 0.05). In neither group was there a significant correlation between the percentage of cores positive for tumour and the percentage volume of prostate involved with cancer, or the ability of the biopsy to predict tumour location.CONCLUSION
Taking ≥ 8 biopsy cores improved the pathological grading accuracy, which may be valuable in choosing a treatment for the patient with newly diagnosed prostate cancer.
The Will Rogers phenomenon is a possible cause of systematic distortions in the results of clinical studies, which can be produced if stage migration occurs during a disease. The term refers to the apparent paradox which is observed when an element is changed from one set to another and the average values of both sets are altered in the same way. The effect is due to the prerequisite that the numerical value of the element being moved is placed between the mean values of both groups. In medicine, this phenomenon is a consequence of the evolution of staging procedures and may be source of misleading statistics for survival in cancer. Both advanced pathological assessment and modern imaging techniques may be involved. The wrong conclusions are induced by comparing the effects of treatment in contemporary patient groups, which profit from extensive diagnostic procedures, to those of historical controls. Treatise informs about the history of the term and illustrates its effects by numerical examples and clinical data. Finally, a model computation based on current PET/CT figures is offered.
The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) is a national disease registry of more than 10,000 patients with prostate cancer treated at 31 primarily community-based sites across the country. The database tracks oncologic and health-related quality-of-life outcomes. Because the urologists participating in the project treat according to their usual practices, CaPSURE facilitates the study of trends in disease-management strategies, offering a reflection of "real world" practice patterns. This review highlights key studies during the past several years that document downward risk migration, validates widely used prognostic nomograms, establishes prostate-specific antigen doubling time as a surrogate endpoint for disease-specific mortality, assesses the impact of treatment on patient-reported quality of life, and presents national trends in imaging test use and primary treatment strategies for localized disease.
To identify predictors of metastatic disease after brachytherapy treatment for prostate cancer.
All patients who received either brachytherapy alone (implant) or brachytherapy in combination with external beam radiation therapy for treatment of localized prostate cancer at The Mount Sinai Hospital between June 1990 and March 2007 with a minimum follow-up of 2 years were included. Univariate and multivariable analyses were performed on the following variables: risk group, Gleason score (GS), clinical T stage, pretreatment prostate-specific antigen level, post-treatment prostate-specific antigen doubling time (PSA-DT), treatment type (implant vs. implant plus external beam radiation therapy), treatment era, total biological effective dose, use of androgen deprivation therapy, age at diagnosis, and race. PSA-DT was analyzed in the following ordinate groups: 0 to 90 days, 91 to 180 days, 180 to 360 days, and greater than 360 days.
We included 1,887 patients in this study. Metastases developed in 47 of these patients. The 10-year freedom from distant metastasis (FFDM) rate for the entire population was 95.1%. Median follow-up was 6 years (range, 2-15 years). The only two significant predictors of metastatic disease by multivariable analyses were GS and PSA-DT (p < 0.001 for both variables). Estimated 10-year FFDM rates for GS of 6 or less, GS of 7, and GS of 8 or greater were 97.9%, 94.3%, and 76.1%, respectively (p < 0.001). Estimated FFDM rates for PSA-DT of 0 to 90 days, 91 to 180 days, 181 to 360 days, and greater than 360 days were 17.5%, 67.9%, 74%, and 94.8%, respectively (p < 0.001). Estimated 10-year FFDM rates for the low-, intermediate-, and high-risk groups were 98.6%, 96.2%, and 86.7%, respectively. A demographic shift to patients presenting with higher-grade disease in more recent years was observed.
GS and post-treatment PSA-DT are both statistically significant independent predictors of metastatic disease. Patients with a high GS and/or short PSA-DT have a higher likelihood of developing metastatic disease and should be considered for systemic therapy.
Widespread prostate-specific antigen (PSA) -based screening and aggressive treatment of prostate cancer have reduced mortality rates substantially, but both remain controversial in large part because of high rates of overdiagnosis and overtreatment of otherwise indolent tumors. Active surveillance--or close monitoring of PSA levels combined with periodic imaging and repeat biopsies--is gaining acceptance as an alternative initial management strategy for men with low-risk prostate cancer. In reported series, rates of progression to active treatment with intermediate-term follow-up have ranged from 14% to 41%, and likelihood of subsequent cure with surgery or radiation does not seem to be compromised by an initial trial of surveillance. Two related challenges to broader acceptance of surveillance are better characterization at time of diagnosis of the risk of progression (including likelihood that given tumor may have been undersampled by diagnostic biopsy) and validation of optimal end points once surveillance begins. Both are subjects of intense ongoing investigation, with emerging biomarkers and novel imaging tests expected to facilitate decision making substantially. Recent reports have suggested active surveillance can be a cost-effective approach and preserve quality of life, but these questions must be assessed more definitively in prospective cohorts. Ultimately, by minimizing the harms of overtreating low-risk prostate cancer, active surveillance may help settle the controversy surrounding prostate cancer screening and management.
Men with high-risk features (extraprostatic extension or high Gleason grade) face a high risk of prostate cancer recurrence after radical prostatectomy. Clinical trials of adjuvant systemic therapy for such patients have been limited.
The SWOG (Southwest Oncology Group) S9921 study randomly assigned 983 men with high-risk features at prostatectomy to receive adjuvant therapy with androgen deprivation (ADT) alone or in combination with mitoxantrone chemotherapy. ADT consisted of goserelin and bicalutamide for 2 years.
Although the final primary treatment comparison results are not ready for publication, this article reports results in the ADT-alone control arm with a median follow-up of 4.4 years. For these 481 men, the estimated 5-year biochemical failure-free survival is 92.5% (95% CI, 90 to 95), and 5-year overall survival is 95.9% (95% CI, 93.9 to 97.9).
The results of this trial, taken in context, make a compelling argument for counseling all high-risk patients with prostate cancer about adjuvant ADT. This article discusses the challenges in the design and implementation of clinical trials to take the next step forward in adjuvant therapy for prostate cancer because of the excellent survival achieved with currently available therapies and highlights the need for better molecular markers to personalize care.
We investigated the clinical significance of large difference (≥ 2 points) between biopsy-derived (bGS) and post-prostatectomy Gleason scores (pGS). At 14 medical centers in Korea, 1,582 men who underwent radical prostatectomy for prostate cancer were included. According to the difference between bGS and pGS, the patients were divided into three groups: A (decreased in pGS ≥ 2, n = 30), B (changed in pGS ≤ 1, n = 1,361; control group), and C (increased in pGS ≥ 2, n = 55). We evaluated various clinicopathological factors of prostate cancer and hazards for biochemical failure. Group A showed significantly higher mean maximal percentage of cancer in the positive cores (max%) and pathological T stage than control. In group C, the number of biopsy core was significantly smaller, however, tumor volume and max% were significantly higher and more positive biopsy cores were presented than control. Worse pathological stage and more margin-positive were observed in group A and C than in control. Hazard ratio for biochemical failure was also higher in group A and C (P = 0.001). However, the groups were not independent factors in multivariate analysis. In conclusion, large difference between bGS and pGS shows poor prognosis even in the decreased group. However it is not an independent prognostic factor for biochemical failure.
Despite earlier detection and stage migration, seminal vesicle invasion is still reported in the prostate specific antigen era and remains a poor prognostic indicator. We investigated outcomes in men with pT3b disease in the contemporary era.
The institutional radical prostatectomy database (1982 to 2010) of 18,505 men was queried and 989 with pT3b tumors were identified. The cohort was split into pre-prostate specific antigen (1982 to 1992), and early (1993 to 2000) and contemporary (2001 to present) prostate specific antigen eras. Of the 732 men identified in the prostate specific antigen era 140 had lymph node involvement and were excluded from study. The Kaplan-Meier method was used to determine biochemical recurrence-free, metastasis-free and prostate cancer specific survival. Proportional hazard models were used to determine predictors of biochemical recurrence-free, metastasis-free and cancer specific survival.
In the pre-prostate specific antigen, and early and contemporary prostate specific antigen eras, 7.7%, 4.3% and 3.3% of patients, respectively, had pT3bN0 disease (p >0.001). In pT3bN0 cases, the 10-year biochemical recurrence-free survival rate was 25.8%, 28.6% and 19.6% (p = 0.8), and the cancer specific survival rate was 79.9%, 79.6% and 83.8% (p = 0.6) among the eras, respectively. In pT3bN0 cases in the prostate specific antigen era, prostate specific antigen, clinical stage T2b or greater, pathological Gleason sum 7 and 8-10, and positive surgical margins were significant predictors of biochemical recurrence-free survival on multivariate analysis while clinical stage T2c or greater and Gleason 8-10 were predictors of metastasis-free and cancer specific survival.
Despite a decreased frequency of pT3b disease, and lower rates of positive surgical margins and lymph nodes, patients with seminal vesicle invasion continue to have low biochemical recurrence-free survival. Advanced clinical stage, intermediate or high risk Gleason sum at pathological evaluation and positive surgical margins predict biochemical recurrence. High risk clinical stage and Gleason sum predict metastasis-free and cancer specific survival.
Prostate-specific antigen (PSA) testing has been associated with a sharp increase in prostate cancer (PCA) detection after its introduction in the late 1980s. Since its launch and its implementation as diagnostic test in 1994, temporal patterns in patients' age and serum PSA level at presentation have changed, with younger patients being diagnosed at lower PSA cutoff levels. Many studies suggest that PSA screening has resulted in a profound downward migration in clinical and pathologic stage of newly diagnosed PCA, although the effect has slowed in the most recent years. The impact on tumor grading is less clear. Histologic grading of PCA, based on the Gleason system, is predictive of the biological behavior and prognosis of the tumor. If tumor progresses from low grade to high grade, the early detection would lead to a higher percentage of low-grade disease diagnosed over time. However, published data suggest that tumor grade shifts have occurred over time and are unlikely to be attributable to changes in tumor biology, but rather to changes in practice with respect to Gleason grading. This review will address PCA staging and grading trends from the pre-PSA era to the present time with emphasis on the potential role played by changes in clinical and pathologic practice.
The Roach formula [2/3 × prostate-specific antigen + (Gleason score--6) × 10], derived in 1993 during the early prostate specific antigen (PSA) screening era, has been used to predict the risk of pelvic lymph node involvement in patients with prostate cancer. In the current era of widespread PSA screening with a shift to earlier disease stages, there is evidence to suggest that the Roach score overestimates risk of nodal metastasis. This study retrospectively reviews the validity of this formula as a prediction tool.
We conducted a retrospective institutional review including men with clinical T1c-T3 prostate cancer, with baseline PSA levels and biopsy-obtained Gleason scores who underwent radical prostatectomy with pelvic node dissection from 2001 through 2009 (N = 1,022). The predicted risk of nodal involvement was calculated for each patient using the Roach formula and then compared with actual rates following surgery.
The study included 1,022 patients; 99.6% had clinical T1c/T2 disease, with a mean of 10.3 lymph nodes surgically evaluated. Overall, 42 patients (4.1%) had nodal metastasis. For every range of scores, the Roach formula overestimates the risk of nodal involvement. Observed nodal positivity was 1%, 6.3%, 10%, 15.2%, and 16.7% for Roach scores ≤ 10%, >10%-20%, >20%-30%, >30%-40%, and >40%, respectively. The Roach score overestimates the risk by approximately 4.5-fold in patients with scores ≤ 10%, by 2.5-fold for all scores between 10% and 40%, and by 4-fold for scores >40%.
The Roach formula overpredicts the risk of pelvic nodal involvement in current-era prostate cancer patients undergoing regular PSA screening and with mainly T1c/T2 disease. Contemporary patients are much less likely to have nodal involvement for a given PSA and Gleason score.
Active surveillance (AS) is an option for the initial management of early-stage prostate cancer. Current risk stratification schema identify patients with low-risk disease who are presumed to be most suitable for AS. However, some men with higher risk disease also elect AS; outcomes for such men have not been widely reported.
Men managed with AS at University of California, San Francisco, were classified as low- or intermediate-risk based on serum prostate-specific antigen (PSA), Gleason grade, extent of biopsy involvement, and T stage. Clinical and demographic characteristics, and progression in terms of Gleason score, PSA kinetics, and active treatment were compared between men with low- and intermediate-risk tumors.
Compared to men with low-risk tumors, those with intermediate-risk tumors were older (mean, 64.9 v 62.3 years) with higher mean PSA values (10.9 v 5.1 ng/mL), and more tumor involvement (mean, 20.4% v 15.3% positive biopsy cores; all P < .01). Within 4 years of the first positive biopsy, the clinical risk group did not differ in terms of the proportions experiencing progression-free survival, (low [54%] v intermediate [61%]; log-rank P = .22) or the proportions who underwent active treatment (low [30%] v intermediate [35%]; log-rank P = .88). Among men undergoing surgery, none were node positive and none had biochemical recurrence within 3 years.
Selected men with intermediate-risk features be appropriate candidates for AS, and are not necessarily more likely to progress. AS for these men may provide an opportunity to further reduce overtreatment of disease that is unlikely to progress to advanced cancer.
The EORTC 22911 and the SWOG 8794 studies, presented in 2004 and 2005, showed that adjuvant radiation therapy after prostatectomy improved biochemical disease-free survival in men with adverse pathological features. In this study we evaluated the use of post-prostatectomy radiation therapy following the presentation of these results, and the impact of margin involvement, pathological tumor stage, Gleason score and sociodemographic factors on post-prostatectomy radiation therapy recommendations.
The SEER cancer registry was used to identify 21,917 men who underwent radical prostatectomy for N0M0 prostate cancer with adverse pathological features (pT3 or margin positive pT2 disease) from 2000 through 2007.
After adjusting for age, diagnosis year, race, SEER region and county education level in a multivariable regression model, decreasing age, margin involvement and Gleason 8 to 10 cancer were associated with receiving post-prostatectomy radiation therapy (all p < 0.001). Men with pT3a (AOR 2.95, CI 2.64-3.29) and pT3b disease (AOR 6.77, CI 5.75-7.97) were more likely to receive post-prostatectomy radiation therapy than those with pT2 disease. The use of post-prostatectomy radiation therapy did not increase after the presentation of study results (p = 0.166).
While men with involved margins and more aggressive pathological disease features were more likely to receive post-prostatectomy radiation therapy, recommendations for post-prostatectomy radiation did not increase after the initial reports from the randomized trials, perhaps because these studies initially reported improved biochemical disease-free survival but not overall survival. Whether the recent report of a survival benefit from adjuvant radiation therapy in the SWOG trial will impact patterns of care requires further followup.
To report 15-year biochemical relapse-free survival (BRFS), cause-specific survival (CSS), and overall survival (OS) outcomes of patients treated with I(125) brachytherapy monotherapy for clinically localized prostate cancer early in the Seattle experience.
Two hundred fifteen patients with clinically localized prostate cancer were consecutively treated from 1988 to 1992 with I(125) monotherapy. They were prospectively followed as a tight cohort. They were evaluated for BRFS, CSS, and OS. Multivariate analysis was used to evaluate outcomes by pretreatment clinical prognostic factors. BRFS was analyzed by the Phoenix (nadir + 2 ng/mL) definition. CSS and OS were evaluated by chart review, death certificates, and referring physician follow-up notes. Gleason scoring was performed by general pathologists at a community hospital in Seattle. Time to biochemical failure (BF) was calculated and compared by Kaplan-Meier plots.
Fifteen-year BRFS for the entire cohort was 80.4%. BRFS by D'Amico risk group classification cohort analysis was 85.9%, 79.9%, and 62.2% for low, intermediate, and high-risk patients, respectively. Follow-up ranged from 3.6 to 18.4 years; median follow-up was 15.4 years for biochemically free of disease patients. Overall median follow-up was 11.7 years. The median time to BF in those who failed was 5.1 years. CSS was 84%. OS was 37.1%. Average age at time of treatment was 70 years. There was no significant difference in BRFS between low and intermediate risk groups.
I(125) monotherapy results in excellent 15-year BRFS and CSS, especially when taking into account the era of treatment effect.
The causes of prostate cancer are still obscure but some evidence indicates that there is a close connection between several trace elements and processes which may lead to malignant cells. In our study the microbeam synchrotron radiation X-ray fluorescence emission (micro-SRIXE) technique was applied for quantitative analysis of selected elements. For the first time, we correlate the concentrations of Mn, Fe, Cu, and Zn with the clinical stage of the prostate cancer at the time of operation (described by Gleason grade). Serial sections of prostate tissues were collected from patients undergoing radical prostatectomy. One section, stained with hematoxylin and eosin, was prepared for histopathological analysis; a second, adjacent unstained section was used in micro-SRIXE experiments. All experiments were performed at beamline L at HASYLAB, DESY, Germany. Our results seem to be valuable in light of the determination of the changes in the concentrations of trace elements as a potential diagnostic marker and their etiological involvement in the different stages of prostate diseases.
to assess the patterns of care for low-risk localized prostate cancer. Management of this condition is highly controversial, with a range of treatment options, but there are no published UK data.
data from the British Association of Urological Surgeons (BAUS) Cancer Registry were linked to the UK Association of Cancer registries postcode directory. The demographic and clinical characteristics, and the initial management of men diagnosed with low-risk localized prostate cancer in the UK between 2000 and 2006 were analysed.
In all, 43,322 cases of localized prostate cancer were recorded in the BAUS Registry between 2000 and 2006, of which 8861 (20%) met the criteria for low-risk disease. The proportion classified as low risk ranged from 16% in 2000 to 21% in 2006. The proportion of men with low-risk disease opting for 'watchful waiting' increased from 0% to 39% over the same period. Treatment choice was associated with socio-economic status. For example, radical prostatectomy was chosen by 34% of patients in the most affluent quintile, compared with 19% in the most deprived quintile (P= 0.01).
the management of low-risk localized prostate cancer in the UK has changed markedly in recent years, and contrasts with that in the USA. The association observed between socio-economic status and choice of treatment deserves further study.
Since at least the early 1990s, stage and risk migration have been seen in patients with prostate cancer, likely corresponding to the institution of prostate specific antigen (PSA) screening in health systems. Preoperative risk factors, including PSA level and clinical stage, have decreased significantly. These improved prognostic variables have led to a larger portion of men being stratified with low-risk disease, as per the classification of D'Amico and associates. This, in turn, has corresponded with more favorable postoperative variables, including decreased extraprostatic tumor extension and prolonged biochemical-free recurrence rates. The advent of focal therapy is bolstered by findings of increased unilateral disease with decreased tumor volume. Increasingly, targeted or delayed therapies may be possible within the current era of lower risk disease.
Men diagnosed with prostate cancer receive therapy based on various clinical characteristics, including the Gleason score, a measurement (range, 2-10) describing a tumor's histological appearance. An upward shift has occurred in the distribution of Gleason scores during the past decade; this change was influenced by reports suggesting that lower scores (range, 2-4) should not be assigned to biopsy specimens.
We (1) compared Gleason scores from 1994-1995 and 2004-2005 at the same institution, (2) reviewed representative articles examining changes in Gleason scores during the last 2 decades, and (3) assessed the implications of a change in histological measurements.
Among men diagnosed with prostate cancer at VA Connecticut, Gleason scores 2 to 4 were reported for 11.4% (19/167) of specimens in 1994-1995 but only 0.4% (1/260) of specimens in 2004-2005; this difference persisted after adjusting for age, clinical stage, and prostate-specific antigen (P < 0.001). Similar results were evident in previous publications on this topic. A change in criteria for a clinical measurement may have unintended consequences, including problems of inconsistency across "time" and "place."
Recent shifts in Gleason scores have led to fewer patients being diagnosed with low-grade prostate cancer; this change can have adverse impacts in clinical care and research.
Evaluation der präoperativen Diagnostik (klinisches Staging - digitale rektale Untersuchung, transrektaler Ultraschall -, Prostatastanzbiopsie, Gleason Score, PSA) des Prostatakarzinoms bezüglich der Tumorausbreitung und des Malignitätsgrades. Hierzu wurden unter anderem die Partin Tables als international anerkanntes und reevaluiertes statistisches Nomogramm eingesetzt. ---
Objective.
—To determine whether prostate-specific antigen (PSA)—based screening alters the proportion of organ-confined prostate cancers detected.Design.
—A prospective, nonrandomized, serial PSA-based screening trial (follow-up from 6 to 37 months), and a concurrent comparison group.Setting.
—Genera community outpatient screening program based at a university center.Patients.
—The study group consisted of 10251 men aged 50 years and older (mean and median age, 63 years; mean and median age of patients who underwent biopsies, 66 years) who presented to a prostate cancer screening program and consented to phlebotomy. The comparison group consisted of 266 concurrently studied private patients in the same age range (mean and median age, 68 years) who were referred for prostatic ultrasonography and biopsy because of an abnormal digital rectal examination (DRE).Main Outcome Measure.
—Proportion detected with clinically or pathologically advanced prostate cancer.Results.
—The men were divided into three groups: the comparison group, the initial PSA-based screening group, and the serial PSA-based screening group. The proportions of prostate cancers detected that were clinically or pathologically advanced were as follows: comparison group, 57% (27/47); initial PSA-based screening group, 37% (91/244); and serial PSA-based screening group, 29% (37/ 129). Screened patients had a lower proportion of advanced cancers than the comparison group (χ2 [2]=12.3; P=.002); this advantage was observed principally in patients younger than 70 years. Surgical staging revealed that the cancer was microscopically focal and well differentiated (possibly latent cancer) in 2.5% (1/40) of the nonscreened group, 2.9% (7/244) of the initially screened group, and 7.8% (10/129) of the serially screened group (generalized Fisher's Exact Test, P=.08).Conclusion.
—Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal DRE alone.(JAMA. 1993;270:948-954)
The wide-ranging biologic malignancy of prostate cancer is strongly correlated with its extensive and diverse morphologic appearances. Histologic grading is a valuable research tool that could and should be used more extensively and systematically in patient care. It can improve clinical staging, as outlined by Oesterling et al (J Urol 138: 92-98, 1987), during selection of patients for possible prostatectomy by helping to identify the optimal treatment. Some of the recurrent practical problems with grading (reproducibility, "undergrading" of biopsies, and "lumping" of grades) are discussed and recommendations are made. The newer technologically sophisticated but single-parameter tumor measurements are compared with one important advantage of histologic grading: the ability to encompass the entire low to high range of malignancy. The predictive success of grading suggests that prostate cancers have more or less fixed degrees of malignancy and growth rates (a hypothesis of "biologic determinism") rather than a steady increase in malignancy with time. Most of the observed facts can be interpreted on that basis, including the interrelations of tumor size, grade, and malignancy. The increasing age-adjusted incidence of diagnosed prostate cancer is attributed to new diagnostic tools and increased diagnostic zeal.
Intraobserver variation of three grading systems--Mostofi, Gleason and Böcking--is examined. No significant difference was noted between the histological grades found in the two examinations by any of the three methods used. Neither the type of surgical procedure nor the number of slices with tumour influenced the reproducibility of histological grading within each system studied. In the Gleason system the intraobserver highest disagreement would not have resulted in change of therapy choice, but in 2% of tumours graded according to the Mostofi system this would have occurred if the choice of therapy would depend on the grading results.
The Gleason histologic score of prostatic adenocarcinoma in biopsy specimens (needle cores or transurethral chips) was compared with the Gleason score of corresponding radical prostatectomy specimens from 53 patients with localized prostatic carcinoma. The Gleason score assigned to the biopsy specimen was identical to that of the prostatectomy specimen in 51% of cases, was greater than that of the prostatectomy specimen in 4%, and was less than that of the prostatectomy specimen in 45%. The magnitude of discrepancy between the scores of the biopsy specimen and the prostatectomy specimen was directly related to the quantity of neoplastic tissue in the biopsy specimen. Discrepancies between the Gleason score of biopsy material and prostatectomy specimens were greater among biopsy specimens with low Gleason scores as compared with biopsy specimens with high Gleason scores. Given the small number of cases, these differences were not statistically significant. Clinical understaging of the primary tumor did not correlate with histologic undergrading of the prostatectomy specimen. It was concluded that prostatic biopsy should be repeated when the initial diagnosis of adenocarcinoma is based on only limited quantities of neoplastic tissue with a low Gleason score and management decisions may be influenced by the true Gleason score of the tumor.
To determine whether prostate-specific antigen (PSA)-based screening alters the proportion of organ-confined prostate cancers detected.
A prospective, nonrandomized, serial PSA-based screening trial (follow-up from 6 to 37 months), and a concurrent comparison group.
General community outpatient screening program based at a university center.
The study group consisted of 10,251 men aged 50 years and older (mean and median age, 63 years; mean and median age of patients who underwent biopsies, 66 years) who presented to a prostate cancer screening program and consented to phlebotomy. The comparison group consisted of 266 concurrently studied private patients in the same age range (mean and median age, 68 years) who were referred for prostatic ultrasonography and biopsy because of an abnormal digital rectal examination (DRE).
Proportion detected with clinically or pathologically advanced prostate cancer.
The men were divided into three groups: the comparison group, the initial PSA-based screening group, and the serial PSA-based screening group. The proportions of prostate cancers detected that were clinically or pathologically advanced were as follows: comparison group, 57% (27/47); initial PSA-based screening group, 37% (91/244); and serial PSA-based screening group, 29% (37/129). Screened patients had a lower proportion of advanced cancers than the comparison group (chi 2 [2] = 12.3; P = .002); this advantage was observed principally in patients younger than 70 years. Surgical staging revealed that the cancer was microscopically focal and well differentiated (possibly latent cancer) in 2.5% (1/40) of the nonscreened group, 2.9% (7/244) of the initially screened group, and 7.8% (10/129) of the serially screened group (generalized Fisher's Exact Test, P = .08).
Screening based on PSA identifies some men with prostate cancer who have a significantly increased proportion of organ-confined tumors compared with those detected through evaluation for an abnormal DRE alone.
In this study a total of 96 patients with prostatic carcinoma were evaluated retrospectively. Sections prepared from paraffin blocks were examined and all cases were scored according to the World Health Organization (WHO) and Gleason grading systems. We investigated intraobserver and interobserver reproducibility of two grading systems in prostatic adenocarcinomas. In our study the intraobserver reproducibilities of the WHO and Gleason systems were 75.0% and 78.1%, respectively. The interobserver reproducibilities of the WHO and Gleason grading systems were 60.4% and 70.8%, respectively. While there was no difference between intraobserver and interobserver variations in the Gleason system (p > 0.05), there was significant difference between intraobserver and interobserver variations in the WHO system (p < 0.05).
Background:
The rapid escalation in the incidence of prostate carcinoma between the years 1988 and 1992 has been attributed to prostate specific antigen screening. There have been concerns regarding the possible diagnosis and treatment of insignificant tumors in the absence of randomized, controlled trial evidence of a decrease in mortality. Descriptive studies suggest that serial screening decreases the detection of advanced disease. In November 1996, the National Center for Health Statistics recorded a decrease in prostate carcinoma mortality.
Methods:
The basis of this analysis is 208,234 prostate carcinoma cases diagnosed between 1973 and 1993 in population-based Surveillance, Epidemiology, and End Results registries. The general staging system was used rather than that of the American Joint Committee on Cancer to permit observation of long term trends. Grade incorporating Gleason scores was used as an indication of the significance of the prostate carcinoma. Age-adjusted survival rates were used to separate prostate carcinoma deaths from deaths due to other causes.
Results:
The increase in the incidence of prostate carcinoma has been greater than for any other malignancy. The increase was largely in Grade 2 significant tumors and not in Grade 1 (15%) insignificant tumors. There was a decrease in the detection of advanced disease. After the peak incidence in 1992, a progressive decrease to near baseline levels occurred. Approximately 38% of all deaths were from prostate carcinoma. Deaths from other causes increased with age. When corrected for death from other causes, men age > 69 years had a greater rate of death from prostate carcinoma than men age 50-69 years. Approximately 61% of all deaths from prostate carcinoma occurred within 5 years of diagnosis and 88% within 10 years. The 10-year survival rate for patients treated by radical prostatectomy was 100%, 78% for patients treated by radiation, and 33% for patients treated with other (noncomparable modalities).
Conclusions:
The indirect evidence suggested that prostate carcinoma screening of men ages >50 years decreased the incidence of distant disease, which influences the mortality rate.
We reviewed prostate cancer trends prior to and during the prostate-specific antigen (PSA) era using data reported from population-based tumor registries in the United States. On the basis of a summary of reports from several population-based tumor registries, prostate cancer incidence rose abruptly during the PSA era, peaked in 1992, and then fell just as abruptly. Prostate cancer incidence in the United States now appears to be approaching levels seen in the pre-PSA era. The flux in prostate cancer incidence (in both magnitude and slope) during the years 1988-1995 is without precedent in oncology. As expected, an age and stage migration toward early age and early stage has been observed. Unexpectedly, grade has shifted heavily toward moderate differentiation, whereas rates of poorly and well-differentiated disease have remained relatively stable. Local treatment rates, particularly radical prostatectomy rates, have risen substantially. Mortality rates appear to have leveled or declined slightly since 1991 after years of steady rise.
Prostate-specific antigen (PSA)-based screening is responsible for a profound clinical stage migration in newly detected prostate cancers. Extracapsular extension (ECE) is an important predictor of outcome after radical prostatectomy (RP). We examined trends in the rate of ECE for cancers detected by PSA screening in 731 RP specimens between 1987 and 1997, when screening became routine urologic practice in the United States.
The rates of ECE were examined in 311 prostates with nonpalpable (stage T1c) disease and 420 with palpable but clinically localized (stage T2) disease. Specimens were step-sectioned and examined by a senior pathologist. Rates of ECE were compared with respect to time, and logistic regression was used to identify predictors of ECE.
The rate of ECE decreased from 81% to 36% during the 10-year observation period. Multivariateanalysis involving clinical tumor stage, preoperative serum PSA level, and Gleason score demonstrated that year of treatment was an independent predictor of ECE, with a two-fold reduction of risk occurring during the study period (P <. 001; odds ratio, 1.96; 95% confidence interval, 1.37 to 2.78).
PSA screening has resulted in a downward trend in pathologic stage in clinically localized prostate cancer, independent of preoperative PSA level, tumor stage, and Gleason score. This time-dependent downward stage migration suggests the need for continuous updating of predictive nomograms and caution in interpreting differences in contemporarily treated patients compared with historical controls. Further study is needed to determine whether this trend will translate into improved disease-free survival.
The Surveillance Research Program of the American Cancer Society's Department of Epidemiology and Surveillance Research reports its annual compilation of estimated cancer incidence, mortality, and survival data for the United States in the year 2000. After 70 years of increases, the recorded number of total cancer deaths among men in the US declined for the first time from 1996 to 1997. This decrease in overall male mortality is the result of recent down-turns in lung and bronchus cancer deaths, prostate cancer deaths, and colon and rectum cancer deaths. Despite decreasing numbers of deaths from female breast cancer and colon and rectum cancer, mortality associated with lung and bronchus cancer among women continues to increase. Lung cancer is expected to account for 25% of all female cancer deaths in 2000. This report also includes a summary of global cancer mortality rates using data from the World Health Organization.
To determine whether migration of pathological tumor stages in patients with clinically localized prostate cancer exists and whether this is due to an increasing frequency of treating patients with clinically insignificant cancer.
1,063 radical retropubic prostatectomies were performed in patients with clinically localized prostate cancer in one institution within 7.5 years (from 1992 until June 1999). All specimens were prospectively processed according to the Stanford protocol. These were then analyzed regarding the migration of pathological tumor stages and cancer volumes.
Within the observation period, the annual rate of radical retropubic prostatectomies increased by 225% from 69 to 224 cases. The authors noted a decline of advanced tumor stages (from 65 to 40%) and an increase in pathological T2 tumors (from 30 to 55%). The rate of small cancers (<0.5 cm(3)) remained stable between 2 and 5% over the last 5 years.
The data confirm trends which were observed in large US centers with increasing detection and treatment of localized prostate cancer without unnecessary treatment of clinically insignificant cancers.
Objectives:
To report the overall survival for 126 patients more than 15 years after iodine-125 interstitial therapy; to report the biochemical progression status for those alive and clinically without evidence of disease for longer than 15 years; to document the upward migration of grade by date of grade assignment; to compare the tumor stage and grade profile of this mature series with our current experience; and to clarify the prostate-specific antigen (PSA) data when this series is used as a historical comparison.
Methods:
The records of 126 patients who underwent interstitial therapy more than 15 years previously were reviewed for assessment of the current TNM stage and Gleason grade and the current PSA level for patients clinically free of disease. The tumor grade and stage of these patients were compared with those of the first 126 patients treated by transrectal ultrasound-guided brachymonotherapy at our center between January 1995 and January 1999. The methodology of our 1993 publication was also reviewed.
Results:
Of the 16 patients clinically free of disease (13 still alive and 3 dead of other causes more than 15 years after therapy), a review of the initial diagnostic needle biopsy was unable to confirm the presence of tumor in 3 patients. Of the remaining 13, 4 had a PSA level of 0.2 ng/mL or less, 4 a PSA level between 0.21 and 0.9 ng/mL, and 5 a PSA level between 1 and 2.5 ng/mL. Re-evaluation of the histopathologic findings using current criteria increased the Gleason score and World Health Organization grade. Patients currently selected for brachytherapy have a lower Gleason grade and TNM stage than recorded for patients treated in the past. The actuarial progression probability curves using the 0.5 or less cutpoint published in 1993 represented the best possible outcome and cannot serve as a historical control for current series comparisons.
Conclusions:
For patients who were alive and clinically free of disease longer than 15 years after therapy, the biochemical PSA levels were low. This may be attributed to the therapeutic radiation effect. Whether the improved technology of current transrectal ultrasound-guided implants can extend these favorable results from a small minority to a significant majority and whether it can approach the therapeutic results of radical prostatectomy may be partially answered with a longer follow-up of the current series. The histopathologic criteria have been refined, and upgrading from the initially assigned grade is common. In some cases, a prostate cancer diagnosis could not be confirmed. These findings limit the ability to match patients across time and institution. The results of our 1993 report of biochemical chemical progression-free probability 10 years after iodine-125 implantation cannot be used as a comparator for current studies. Ultimately, a valid comparison between treatment options will only be achieved through a randomized controlled trial.
Grade Migration in Prostate Carcinoma
- Smith
Grade Migration in Prostate Carcinoma/Smith et al.
- Rt Greenlee
- T Murray
- S Bolden
- Pa Wingo
Greenlee RT, Murray T, Bolden S, Wingo PA. Cancer statistics, 2000. CA Cancer J Clin. 2000;50:7–33.
Histologic grading of prostate cancer: a perspective
- Df Gleason
Gleason DF. Histologic grading of prostate cancer: a perspective. Hum Pathol. 1992;23:273–279.
Cancer statistics, 2000
- Greenlee RT
- Murray T
- Bolden S
- Wingo PA
- Mills
- Smart
- Mettlin