Long-term oncological outcomes of men undergoing radical prostatectomy with preoperative prostate-specific antigen <2.5 ng/ml and 2.5–4 ng/ml

ObjectivesProstate-specific antigen (PSA) screening has increased the detection of small, organ-confined tumors, and studies suggest that these patients may have favorable outcomes following radical prostatectomy (RP). To date, there are limited data available on the outcomes of patients diagnosed with low PSA (≤4 ng/ml) who underwent RP. This study aimed to evaluate long-term oncological outcomes of patients undergoing RP with preoperative PSA <2.5 and 2.5–4 ng/ml compared with PSA 4.1–10 ng/ml.Materials and methodsData were analyzed from 3,621 men who underwent RP between 1988 and 2010 at our institution. Patients were stratified into 3 PSA groups: <2.5 ng/ml (n = 280), 2.5–4 ng/ml (n = 563), and 4.1–10 ng/ml (n = 2,778). Patient and disease characteristics were compared. Overall, biochemical disease-free (bDFS), and PCa-specific survivals were analyzed and compared between the groups. Multivariable analyses were conducted using proportional hazards model.ResultsCompared with the 4.1–10 ng/ml PSA group, Gleason score >7, extracapsular extension, and non-organ-confined disease were less common in patients with PSA ≤4 ng/ml (all P < 0.001). The incidence of organ-confined disease was similar between the PSA < 2.5 and 2.5–4 ng/ml groups while perineural invasion (P = 0.050) and Gleason score ≥7 (P = 0.026) were more common in the 2.5–4 ng/ml PSA group. Estimated 10-year overall and PCa-specific survivals were comparable across all PSA groups, whereas bDFS was significantly lower in PSA 4.1–10 group (P < 0.001). bDFS was not statistically different between PSA <2.5 and 2.5–4 groups (P = 0.300). 10-year bDFS were 59.0%, 70.1%, and 76.4% in PSA 4.1–10, 2.5–4, and <2.5, respectively. For the PSA ≤ 4 ng/ml groups, age, race, margin status, pathologic stage, but not PSA were independent predictors of bDFS, whereas age, pathologic Gleason, and biochemical recurrence were associated with overall survival.ConclusionsLong-term oncological outcomes (overall, bDFS, PCa-specific survivals) of patients presenting with low PSA (≤4 ng/ml) were excellent in this study. Compared with PSA 4.1–10 ng/ml, patients presenting with PSA ≤4 ng/ml had better bDFS outcomes. However, there was no difference in long-term outcomes between PSA <2.5 and 2.5–4 ng/ml.     

What is the optimal definition of misclassification in patients with very low-risk prostate cancer eligible for active surveillance? Results from a multi-institutional series

BackgroundThe risk of unfavorable prostate cancer in active surveillance (AS) candidates is nonnegligible. However, what represents an adverse pathologic outcome in this setting is unknown. We aimed at assessing the optimal definition of misclassification and its effect on recurrence in AS candidates treated with radical prostatectomy (RP).Materials and methodsOverall, 1,710 patients eligible for AS according to Prostate Cancer Research International: Active Surveillance criteria treated with RP between 2000 and 2013 at 3 centers were evaluated. Patients were stratified according to pathology results at RP: organ-confined disease and pathologic Gleason score ≤6 (group 1); organ-confined disease and Gleason score 3+4 (group 2); and non–organ-confined disease, Gleason score ≥4+3, and nodal invasion (group 3). Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen (PSA)≥0.2 ng/ml. Kaplan-Meier curves assessed time to BCR. Multivariable Cox regression analyses tested the association between pathologic features and BCR. Multivariable logistic regression analyses identified the predictors of adverse pathologic characteristics.ResultsOverall, 926 (54.2%), 653 (33.0%), and 220 (12.9%) patients were categorized in groups 1, 2, and 3, respectively. Median follow-up was 32.2 months. The 5-year BCR-free survival rate was 94.2%. Patients in group 3 had lower BCR-free survival rates compared with those in group 1 (79.1% vs. 97.0%, P<0.001). No differences were observed between patients included in group 1 vs. group 2 (97.0% vs. 94.7%, P = 0.1). These results were confirmed at multivariable analyses and after stratification according to margin status. Older age and PSA density≥10 ng/ml/ml were associated with higher risk of unfavorable pathologic characteristics (i.e., inclusion in group 3; all P<0.001).ConclusionsAmong patients eligible for AS treated with RP, only men with Gleason score≥4+3 or non–organ-confined disease at final pathology were at increased risk of BCR. These individuals represent the real misclassified AS patients, who can be predicted based on older age and higher PSA density.     

Smaller prostate gland size and older age predict Gleason score upgrading

ObjectivesGleason score is important for prostate cancer (CaP) risk stratification and prognostication but has a significant rate of upgrading. We examined the effect of prostate size and age on upgrading of Gleason 6 CaP.Materials and methodsA retrospective review was performed of patients with Gleason 6 CaP who underwent radical prostatectomy from 2001 through 2010. Preoperative clinical and pathologic variables were assessed to determine association with risk of upgrading at prostatectomy.ResultsA total of 1,836 patients were identified with Gleason 6 on prostate biopsy. Upgrading was observed in 543 (29.6%) patients with a final Gleason score of 3+4 in 463 (25.2%), 4+3 in 49 (2.7%), and 8–10 in 31 (1.7%). On univariate logistic regression, age, prostate weight, and PSA were significant predictors of Gleason score upgrading and remained significant on multiple logistic regression. Prostate weight was inversely related to risk of upgrading. To further explore this effect, we performed multiple logistic regression to examine risk of Gleason 6, 7, or 8–10 disease in 2,493 patients with Gleason 6–10 at prostatectomy. After controlling for age and PSA, there was a progressively increased risk of Gleason 6, 7, and 8–10 disease with decreasing prostate weight.ConclusionsOlder age, higher PSA, and smaller prostate gland size are associated with increased risk of Gleason score upgrading. The inverse relationship of prostate weight to risk of Gleason upgrading may be related to increased high-grade disease in smaller glands.     

Multiple Tissue Biomarkers Independently and Additively Predict Prostate Cancer Pathology Outcomes

BackgroundDistinguishing indolent from aggressive prostate cancer remains a key challenge for decision making regarding prostate cancer management. A growing number of biomarkers are now available to help address this need, but these have rarely been examined together in the same patients to determine their potentially additive value.ObjectiveTo determine whether two previously validated plasma markers (transforming growth factor β1 [TGFβ1] and interleukin-6 soluble receptor [IL6-SR]) and two validated tissue scores (the Genomic Evaluators of Metastatic Prostate Cancer [GEMCaP] and cell cycle progression [CCP] scores) can improve on clinical parameters in predicting adverse pathology after prostatectomy, and how much they vary within tumors with heterogeneous Gleason grade.Design, setting, and participantsA case-control study was conducted among men with low-risk cancers defined by biopsy grade group (GG) 1, prostate-specific antigen (PSA) ≤10 ng/mL, and clinical stage ≤ T2 who underwent immediate prostatectomy. We collected paraffin-fixed prostatectomy tissue and presurgical plasma samples from 381 cases from the University of California, San Francisco, and 260 cases from the University of Washington.Outcome measurements and statistical analysisPathologic outcomes were minor upgrading/upstaging (GG 2 or pT3a) or major upgrading/upstaging (GG ≥ 3 or ≥ pT3b), and multinomial regression was performed to determine putative markers’ ability to predict these outcomes, controlling for PSA, percent of positive biopsy cores, age, and clinical site. For upgraded tumors, a secondary analysis of the GEMCaP and CCP scores from the higher-grade tumor was also performed to evaluate for heterogeneity.Results and limitationsOverall, 357 men had no upgrading/upstaging event at prostatectomy, 236 had a minor event, and 67 had a major event. Neither TGFβ1 nor IL6-SR was statistically significantly associated with any upgrading/upstaging. On the contrary, both the CCP and the GEMCaP score obtained from Gleason pattern 3 tissue were directly associated with minor and major upgrading/upstaging on univariate analysis. The two scores correlated with each other, but weakly. On multinomial analysis including both scores in the model, the CCP score predicted minor upgrading/upstaging (odds ratio [OR] 1.62, 95% confidence interval [CI] 1.05–2.49) and major upgrading/upstaging (OR 2.26, 95% CI 1.05–4.90), p = 0.04), and the GEMCaP score also predicted minor upgrading/upstaging (OR 1.05, 95% CI 1.03–1.08) and major upgrading/upstaging (OR 1.07, 95% CI 1.04–1.11), p < 0.01). The other clinical parameters were not significant in this model. Among upgraded tumors including both Gleason patterns 3 and 4, both the GEMCaP and the CCP score tended to be higher from the higher-grade tumor. The main limitation was the use of virtual biopsies from prostatectomy tissue as surrogates for prostate biopsies.ConclusionsBiomarker signatures based on analyses of both DNA and RNA significantly and independently predict adverse pathology among men with clinically low-risk prostate cancer undergoing prostatectomy.Patient summaryValidated biomarker scores derived from both prostate cancer DNA and prostate cancer RNA can add independent information to help predict outcomes after prostatectomy.     

Role of radical prostatectomy in patients with prostate cancer of high Gleason score

BACKGROUND: The routine use of serum prostate-specific antigen (PSA) testing combined with digital rectal examination has lowered tumor volume and clinical-pathological stage of men undergoing radical prostatectomy. Therefore, we may identify more men with poorly differentiated tumors of early clinical stage. In order to identify those who may benefit from radical prostatectomy, we evaluated known prognostic variables in patients with prostate cancer of high Gleason score (8-10). METHODS: Of 652 patients who underwent a radical prostatectomy as monotherapy for clinically localized prostate cancer between March 1991-December 1995, 84 patients with prostatectomy specimen Gleason score 8-10 tumors were identified. Clinical-pathological data were obtained from our prostate cancer database. Gleason score, PSA level, margin status, pathologic stage, and tumor volume were analyzed as general prognostic variables for disease-free survival (DFS). Follow-up ranged from 13-84 months (median, 36.2). Biochemical recurrence was defined as a postoperative PSA elevation greater than 0.4 ng/ml. RESULTS: The DFS for patients with Gleason score 8-10 and pathologically organ-confined disease was 62.5%. DFS was 56.2% for patients with PSA < or =10 ng/ml, compared to 19.2% for patients with serum PSA >10 ng/ml (P = 0.009). Patients with nonspecimen-confined disease (positive margins) had a DFS rate of 26.6% vs. 55% for patients with specimen-confined disease (negative margins) (P = 0.009). On multivariable analysis, only preoperative PSA < or =10 ng/ml (P = 0.02) and surgical margin status (P = 0.04) were significant predictors of DFS. CONCLUSIONS: Surgical margin status and preoperative serum PSA level are independent predictors of DFS for patients with high Gleason score prostate cancer treated by radical prostatectomy as monotherapy. Patients with poorly differentiated prostate cancer treated surgically at an early stage can have a favorable prognosis, especially if negative surgical margins are obtained. A preoperative serum PSA level < or =10 ng/ml carries the greatest likelihood of achieving prolonged DFS in this group of patients.     

Prediction of Gleason score upgrading in low-risk prostate cancers diagnosed via multi (≥12)-core prostate biopsy

Objectives  A paucity of data exists on actual pathology of the contemporary patients strictly categorized as having low-risk prostate cancer. We tried to identify useful preoperative predictors of Gleason score upgrading in patients who underwent radical retropubic prostatectomy (RRP) for low-risk prostate cancer diagnosed via multi-core prostate biopsy. Methods  A total of 203 patients who underwent radical RRP for low-risk prostate cancer, as defined by D’Amico et al.'s classification (clinical stage ≤T2a, biopsy Gleason sum ≤6, and PSA ≤10 ng/ml), detected via multi (≥12)-core prostate biopsy were enrolled. We reviewed patients preoperative and pathological data. Results  Among all subjects, 81 (39.9%) were upgraded to Gleason score ≥7 after RRP, whereas no downgrading was observed. In multivariate analysis, only preoperative PSA level (P = 0.024) and number of positive cores (P = 0.027) were observed to be independent predictors of Gleason score upgrading following RRP. Also, Gleason core upgrading was observed to be significantly associated with extraprostatic extension of tumor (P < 0.001) and positive surgical margin (P = 0.002). Conclusions  A significant proportion of patients with low-risk prostate cancer as defined by D’Amico et al.’s classification diagnosed via multi-core prostate biopsy in contemporary period may have Gleason score upgrading following RRP. For patients with low-risk prostate cancer, preoperative PSA level and number of positive cores may be useful predictors of Gleason score upgrading, which was observed to significantly associated with other adverse pathologic features.     

Can we expand active surveillance criteria to include biopsy Gleason 3+4 prostate cancer? A multi-institutional study of 2,323 patients

ObjectiveTo test the expandability of active surveillance (AS) to Gleason score 3+4 cancers by assessing the unfavorable disease risk in a large multi-institutional cohort.Materials and methodsWe performed a retrospective analysis including 2,323 patients with localized Gleason score 3+4 prostate cancer who underwent a radical prostatectomy between 2005 and 2013 from 6 academic centers. We analyzed the rates of biopsy downgrading/upgrading and advanced stage in the overall cohort by employing standardized AS criteria (using biopsy Gleason score 3+4).ResultsThe final pathologic Gleason score was 3+3 = 6 in 8%, 3+4 = 7 in 67%, 4+3 = 7 in 20%, and 8 to 10 in 5% cases. The overall rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In multivariable analysis, prostate-specific antigen (PSA) level>10 ng/ml, PSA density (PSAD) >0.15 ng/ml/g, clinical stage >T1, and>2 positive cores were predictors of unfavorable disease. According to the AS criteria used, the risk of unfavorable disease ranged from 30% to 42%. In patients without any risk factor (PSA level≤10 ng/ml, PSAD ≤0.15 ng/ml/g, T1c, and≤2 positive cores), the unfavorable disease rate was 19%. The main limitations of this study are the retrospective design and nonstandardization of pathologic assessment between centers.ConclusionsApproximately half of patients with biopsy Gleason score 3+4 cancer have unfavorable disease at final pathology. Nevertheless, expanding AS eligibility to these patients may be acceptable provided adherence to strict selection criteria leading to a<20% risk of unfavorable disease. Future tools for selection such as magnetic resonance imaging, early rebiopsy, and serum markers may be especially beneficial in this group of patients.     

Oncologic outcomes after minimally invasive radical prostatectomy in patients with seminal vesicle invasion (pT3b) without adjuvant therapy

Purpose

To evaluate the long-term outcomes of patients with prostate cancer who have pathological pT3b N0–Nx, with postoperative PSA < 0.1 ng/ml and no systematic adjuvant treatment.

Materials and methods

Using a monocentric prospectively maintained database, we identified among 2,142 men who underwent minimally invasive radical prostatectomy, 104 pT3b N0–Nx patients, with postoperative PSA < 0.1 ng/ml and at least 5 years of follow-up. Patients were considered for salvage treatment at biochemical recurrence (PSA ≥ 0.2 ng/ml).

Results

The median time of follow-up was 83.5 months (interquartile range [IQR]: 69–99). Overall, 102 patients (98 %) had T2 clinical stage or less. Specimen Gleason score was 7 in 71 patients (68 %) and <7 in 15 (14 %). Thirty-eight patients (37 %) were upgraded for Gleason score after radical prostatectomy. The overall 5-year probability of freedom from biochemical recurrence for the entire cohort was 55.8 % (95 % CI 45.8–65.8) and 73.3 % for patients who had specimen Gleason score <7 (p = 0.005). In univariate analysis, specimen Gleason score and surgical margin status were significant predictors for biochemical failure after radical prostatectomy (p = 0.05 and 0.007, respectively). In multivariate analysis, only specimen Gleason score >7 was significantly associated with biochemical failure (p = 0.009).

Conclusion

SVI is an adverse prognostic factor, but it is not associated with a uniformly poor prognosis. Specimen Gleason score and surgical margin status are significant predictors of recurrence after radical prostatectomy in patients with prostate cancer and SVI.     

Endorectal T2-weighted MRI does not differentiate between favorable and adverse pathologic features in men with prostate cancer who would qualify for active surveillance

ObjectiveWith the increased diagnosis of low grade, low volume, potentially non-lethal disease, active surveillance (AS) has become an increasingly popular alternative for select men with low-risk prostate cancer. The absence of precise clinical staging modalities currently makes it difficult to predict which patients are most appropriate for AS. The goal of our study was to evaluate the ability of endorectal MRI (eMRI) to predict adverse pathologic features in patients who would otherwise qualify for an AS program.Materials and methodsWe retrospectively reviewed our institution's radical prostatectomy (RP) database from 1991 to 2007 and identified 172 patients who would have qualified for AS and underwent preoperative staging eMRI with T2-weighted (T2W) sequences. MRI findings were correlated to final pathology in order to assess the ability of staging eMRI to predict adverse pathologic features in patients suitable for AS.ResultsThe mean age of our cohort was 59.8 ± 6.2 years. The mean PSA at the time of diagnosis was 5.2 ± 2.2 ng/ml. In 51% of patients, no discrete tumor was visualized on eMRI and in 49% of patients a discrete tumor was detected. At the time of RP, Gleason score upgrading, extracapsular extension, and a positive surgical margin occurred in 17%, 6%, and 5% of cases, respectively. Patients with documented tumor on eMRI did not have an increased incidence of adverse pathologic findings with regard to tumor volume (P = 0.31), extra-capsular extension (P = 0.82), Gleason upgrading (P = 0.92), seminal vesicle invasion (P = 0.97), or positive surgical margin rate (P = 0.95) compared with those in whom no tumor was seen.ConclusionDiscrete tumor identification on eMRI is not predictive of adverse pathologic features in patients who would otherwise qualify for AS. eMRI likely does not provide additional information when prospectively evaluating patients for AS protocols.     

Oncologic control obtained after radical prostatectomy in men with a pathological Gleason score ≥ 8: A single-center experience

ObjectiveTo assess the oncologic control afforded by radical prostatectomy (RP) in high-risk prostate cancers with a Gleason score ≥ 8.Materials and methodsWe performed a retrospective review of prostate cancer patients who underwent RP between 1995 and 2005 for prostate cancer and who had a pathologic Gleason score ≥ 8. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery.ResultsOverall, 64 patients were included and followed for a median time of 84.3 months. The mean age was 63 ± 5.2 years. The mean preoperative PSA was 11.9 ± 7.3 ng/ml (1.9–31), and 29 patients (46%) had a PSA > 10 ng/ml. The biopsy Gleason score was ≤7 for 49 patients (76.6%). After pathologic analysis, there were 25 (39%) stage pT2, 37 (58%) stage pT3, and 2 (3%) stage pT4 patients. Nine patients had lymph node involvement (14%). The surgical margins were positive in 25 patients (39%). In 51 patients, (80%) the Gleason score was underestimated by biopsies: 40 patients with a definitive score of Gleason 8 had a Gleason score of 6 or 7 on biopsies, while 11 patients with a Gleason score of 9 initially, had a Gleason score of 7 or 8. Twenty-seven patients underwent adjuvant treatment: external radiation therapy (n = 19), HRT (n = 3), or both (n = 5). During follow-up, 41 patients (64%) presented with a biochemical recurrence, and 11 (17%) died. The PSA-free survival rate at five year was 44%.ConclusionRP remains a possible therapeutic option in certain cases of the high-risk cohort of patients with a Gleason score ≥ 8. However, patients should be warned that surgery might only be the first step of a multi-modal treatment approach. The modalities of adjuvant treatments and the right schedule to deliver it following RP still need to be defined.     

Predicting recurrence after radical prostatectomy for patients with high risk prostate cancer

PURPOSE: Previous studies have shown that patients with clinical stage T2c-T3 prostate cancer, serum prostate specific antigen (PSA) at diagnosis greater than 20 ng./ml. or a biopsy Gleason score of 8 to 10 are at high risk for disease recurrence after radical prostatectomy. We determined the most important pretreatment predictors of disease recurrence in this high risk population. MATERIALS AND METHODS: We identified 547 patients with high risk prostate cancer who underwent radical prostatectomy at University of California, San Francisco or as part of the Cancer of the Prostate Strategic Urological Research Endeavor data base, a longitudinal disease registry of patients with prostate cancer. High risk disease was defined as 1992 American Joint Committee on Cancer clinical stage T2c-T3 disease in 411 patients, serum PSA at diagnosis greater than 20 ng./ml. in 124 and/or biopsy Gleason score 8 to 10 in 114. Disease recurrence was defined as PSA 0.2 ng./ml. or greater on 2 consecutive occasions after radical prostatectomy or second cancer treatment more than 6 months after surgery. The Cox proportional hazards analysis was performed to determine significant independent predictors of disease recurrence. The likelihood of disease recurrence for clinically relevant patient groups was determined using the Kaplan-Meier method and compared using the log rank test. RESULTS: Median followup after surgery was 3.1 years. Disease recurred in 177 patients (32%). Multivariate analysis demonstrated that serum PSA at diagnosis, biopsy Gleason score, ethnicity and the percent of positive prostate biopsies were significant independent predictors of disease recurrence, while patient age and clinical tumor stage were not. Patients with a Gleason score 8 to 10 tumor and a serum PSA of 10 ng./ml. or less had a significantly higher likelihood of remaining disease-free 5 years after surgery than those with PSA greater than 10 ng./ml. (47% versus 19%, p <0.05). Patients with a serum PSA at diagnosis of greater than 20 ng./ml. and a Gleason score of less than 8 had a significantly higher likelihood of remaining disease-free 5 years after surgery than similar patients with a Gleason score of 8 or greater (45% versus 0%, p <0.05). CONCLUSIONS: PSA, Gleason score, ethnicity and the percent of positive prostate biopsies appear to be the most important pretreatment predictors of disease recurrence in men with high risk prostate cancer. Patients with high grade disease may continue to be appropriate candidates for local therapy if PSA is less than 10 ng./ml. at diagnosis or there are fewer than 66% positive prostate biopsies.     

Analysis of expanded criteria to select candidates for active surveillance of low-risk prostate cancer

We aimed to analyze the value of each criterion for clinically insignificant prostate cancer (PCa) in the selection of men for active surveillance (AS) of low-risk PCa. We identified 532 men who were treated with radical prostatectomy from 2006 to 2013 who met 4 or all 5 of the criteria for clinically insignificant PCa (clinical stage ≤ T1, prostate specific antigen [PSA] density ≤ 0.15, biopsy Gleason score ≤ 6, number of positive biopsy cores ≤ 2, and no core with > 50% involvement) and analyzed their pathologic and biochemical outcomes. Patients who met all 5 criteria for clinically insignificant PCa were designated as group A (n = 172), and those who met 4 of 5 criteria were designated as group B (n = 360). The association of each criterion with adverse pathologic features was assessed via logistic regression analyses. Comparison of group A and B and also logistic regression analyses showed that PSA density > 0.15 ng ml⁻¹ and high (≥7) biopsy Gleason score were associated with adverse pathologic features. Higher (> T1c) clinical stage was not associated with any adverse pathologic features. Although ≤ 3 positive cores were not associated with any adverse pathology, ≥4 positive cores were associated with higher risk of extracapsular extension. Among potential candidates for AS, PSA density > 0.15 ng ml⁻¹ and biopsy Gleason score > 6 pose significantly higher risks of harboring more aggressive disease. The eligibility criteria for AS may be expanded to include men with clinical stage T2 tumor and 3 positive cores.     

Pathologic outcomes for low-risk prostate cancer after delayed radical prostatectomy in the United States

ObjectivesTo measure adverse pathologic outcomes following radical prostatectomy (RP) for men with low-risk prostate cancer in the United States based on time from diagnosis to surgery.MethodsWe extracted data from the National Cancer Database in 2010 and 2011 on 17,943 low-risk patients (Gleason score = 3+3, prostate-specific antigen <10 ng/ml, and cT1–T2) who underwent RP. We identified men who delayed RP by>6 months after diagnosis and measured the effect of delayed RP on pathologic upgrading, upstaging, nodal metastases, and positive surgical margins.ResultsOverall, 16,818 underwent RP≤6 months, 894 at 6 to 9 months, 169 at 9 to 12 months, and 62 at>12 months from diagnostic biopsy. Furthermore, upgrading occurred in 43%, upstaging in 9%, positive surgical margins in 16%, and nodal metastases in 0.3% of men. Upgrading, upstaging, or nodal metastases occurred in 45% of men. On multivariable analysis, higher prostate-specific antigen (4.1–9.9 ng/ml vs. 0.1–2.4 ng/ml; odds ratio [OR] = 1.87, 95% CI: 1.66–2.10),>2 positive biopsy cores (OR = 1.68, 95% CI: 1.57–1.81),≥34% positive biopsy cores (OR = 1.28, 95% CI: 1.18–1.39), black race (OR = 1.16, 95% CI: 1.05–1.28), and time from biopsy to RP>12 months (vs.≤6 mo: OR = 1.70, 95% CI: 1.01–2.84) each independently increased the composite risk of adverse pathology (all P< 0.05).ConclusionIn the United States, nearly half of men with low-risk prostate cancer experience at least one adverse pathologic outcome at RP. Delaying RP up to 12 months did not change the risk of adverse pathology. Men may safely use the time following their initial biopsy to consider management options and obtain a restaging biopsy, if recommended.     

Screening with low PSA cutoff values results in low rates of positive surgical margins in radical prostatectomy specimens

BACKGROUND: In the literature, positive margins in radical prostatectomy specimens, the rate of which ranges between 7% and 46%, are associated with adverse patient survival. The aim of the present study was to determine the predictive value of preoperative serum prostate specific antigen (PSA) values for the rate of positive margins in radical retropubic prostatectomy. METHODS: The study included a cohort of 845 patients who underwent radical retropubic prostatectomy between October of 1993 and December of 1999. All patients were stratified in groups on the basis of their preoperative PSA values: PSA group I, 0-1.99 ng/ml; PSA group II, 2-3.99 ng/ml; PSA group III, 4-5.99 ng/ml; PSA group IV, 6-7.99 ng/ml; PSA group V, 8-9.99 ng/ml; and PSA group VI, >10 ng/ml. For each group, the pathologic stage, Gleason score, and the incidence of positive margins were analyzed. For statistical analysis, the Mann Whitney U-test was used. RESULTS: Our data show a significantly higher rate of organ-confined prostate cancers and a significantly lower rate of positive surgical margins in patients with preoperative total PSA values of less than 4 ng/ml compared with patients with higher preoperative total PSA levels. CONCLUSION: As tumor stage and surgical margin status after radical prostatectomy are important predictors of the likelihood of PSA recurrence, which necessitates additional therapy, these findings support the concept of PSA screening by using low PSA cutoff levels.     

PSA in the new millennium: a powerful predictor of prostate cancer prognosis and radical prostatectomy outcomes--results from the SEARCH database

OBJECTIVES: As a result of prostate-specific antigen (PSA) screening, most men today with prostate cancer present with localized disease and serum PSA values < 10 ng/ml. Within this context, it is debated whether PSA remains an important prognostic variable in more recently treated patients. We examined the prognostic significance of preoperative PSA to predict pathologic stage and biochemical progression among men undergoing radical prostatectomy in the new millennium (2000-2006). METHODS: We performed a review of 925 men with prostate cancer treated by radical prostatectomy since 2000 within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We examined the association between preoperative PSA and risk of adverse pathologic features and biochemical progression using logistic regression and Cox proportional hazards analysis. RESULTS: After adjusting for multiple clinical preoperative characteristics, higher preoperative PSA values were associated with increased odds of extracapsular extension (p<0.001), positive surgical margins (p<0.001), and seminal vesicle invasion (p<0.001) and increased risk of biochemical progression (p=0.009). When the analyses were limited to the 690 men with a preoperative PSA<10 ng/ml and after adjusting for multiple clinical characteristics, higher preoperative PSA values remained associated with increased risk of biochemical progression (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.06-1.28, p=0.002). Even among the 448 men with a PSA<10 ng/ml and clinical stage T1c disease, preoperative PSA was associated with increased risk of biochemical progression (HR 1.14, 95%CI 1.00-1.31, p=0.047). CONCLUSIONS: PSA remains an important prognostic marker among men diagnosed with prostate cancer in the new millennium treated with radical prostatectomy and remains an important predictor of outcome even among men with preoperative PSA level < 10 ng/ml.     

Association of MyProstateScore (MPS) with prostate cancer grade in the radical prostatectomy specimen

BackgroundTo evaluate the association between urinary MyProstateScore (MPS) and pathologic grade group (GG) at surgery in men diagnosed with GG1 prostate cancer (PCa) on biopsy.MethodsUsing an institutional biospecimen protocol, we identified men with GG1 PCa on biopsy and PSA ≤10 ng/ml who underwent radical prostatectomy (RP) at the University of Michigan. MPS was retrospectively calculated using prospectively collected, post-DRE urine samples. The primary outcome was upgrading on RP pathology, defined as GG ≥ 2. The associations of MPS, PSA, and PSA density (PSAD) with upgrading were assessed on univariable logistic regression, and the predictive accuracy of each marker was estimated by the area under the receiver operating characteristic curve (AUC).ResultsThere were 52 men with urinary specimens available that met study criteria, based on biopsy Gleason Grade and specimen collection. At RP, 17 men (33%) had GG1 cancer and 35 (67%) had GG ≥ 2 cancer. Preoperative MPS was significantly higher in patients with GG ≥ 2 cancer at surgery (median 37.8 [IQR, 22.2–52.4]) as compared to GG1 (19.3 [IQR, 9.2–29.4]; P = 0.001). On univariable logistic regression, increasing MPS values were significantly associated with upgrading (odds ratio 1.07 per one-unit MPS increase, 95% confidence interval 1.02–1.12, P = 0.004), while PSA and PSAD were not significantly associated with upgrading. Similarly, the discriminative ability of the MPS model (AUC 0.78) for upgrading at RP was higher compared to models based on PSA (AUC 0.52) and PSAD (AUC 0.62).ConclusionsIn men diagnosed with GG1 PCa who underwent surgery, MPS was significantly associated with RP cancer grade. In this limited cohort of men, these findings suggest that MPS could help identify patients with undetected high-grade cancer. Additional studies are needed to better characterize this association.     

Intermittent androgen suppression in patients with prostate cancer: De La Taille A,Zerbib M,Conquy S,Amsellem-Ouazana D,Thiounn N,Flam TA,Debre B,Department of Urology,CHU Cochin,Paris, France. BJU Int 2003;91:18–22

ObjectivesTo evaluate intermittent androgen suppression (IAS) in patients with prostate cancer and to try to define predictive factors for biochemical progression.Patients and methodsFrom 1989 to 2001, 146 patients received IAS as a primary treatment for localized, advanced or metastatic prostate cancer (72 men) or as a treatment for prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP) and/or radiation therapy (74 men). Androgen-deprivation treatment (ADT) was continued up to 6 months after PSA became undetectable or a nadir PSA level was reached. ADT was then re-instituted when the PSA level was >4 ng/mL for patients who had RP or >10 ng/mL for the others.ResultsAfter a mean (range) follow-up of 45.6 (12–196.9) months, 24 patients had biochemical progression. These patients were younger than those with no biochemical progression (67 vs 72 years, P = .004) and had a statistically higher Gleason score (7.21 vs. 6.52, P = .01) and PSA level (111.1 vs. 32.1 ng/mL, P = .05), and a shorter first phase without treatment (7.6 vs. 11.2 months, P = .05). Overall 5-year metastatic disease free survival of 91.3%. The overall 5-year biochemical recurrence-free survival was 68%. Using multivariate analysis, a Gleason score of more than or equal to 8 (P = .021), first-phase duration with no treatment of <1 year (P = .044), positive lymph nodes or metastatic disease at the time of starting IAS (P = .023) and age <70 years (P = .037) were the strongest predictors of biochemical progression.ConclusionIAS appeared to be a feasible treatment; the best candidates being those aged >70 years with localized prostate cancer and a Gleason score of less than or equal to 7.     

Heterogeneity in D׳Amico classification–based low-risk prostate cancer: Differences in upgrading and upstaging according to active surveillance eligibility

BackgroundTo date, no study has examined clinical, pathological, and surgical characteristics of D׳Amico low-risk patients according to active surveillance (AS) eligibility.Material and methodsWe relied on patients with low-risk prostate cancer, who were classified based on the D׳Amico classification, treated with radical prostatectomy (RP) between 2008 and 2013 at the Martini-Clinic Prostate Cancer Center. We assessed differences in clinical, pathological, and surgical characteristics in D׳Amico low-risk patients according to AS eligibility (prostate-specific antigen [PSA]≤10 ng/ml, Gleason score≤3+3, ≤2 positive cores,≤50% tumor content per core, and≤cT1-2a). Multivariable logistic regression analyses targeted 2 end points: (1) presence of either intermediate- or high-risk characteristics (Gleason score≥3+4 or≥pT3 or pN1) or (2) exclusive presence of high-risk characteristics (Gleason score≥4+4 or≥pT3 or pN1) at RP.ResultsOf 1,331 patients low-risk prostate cancer classified based on the D׳Amico classification, 825 (62%) men were eligible for AS. AS candidates were less frequently either upgraded (55% vs. 78%, P<0.001) or upstaged (8% vs. 15%, P<0.001). Similarly, at final pathology, AS candidates less frequently harbored either intermediate- or high-risk (56% vs. 78%, P<0.001), or exclusive high-risk characteristics (9% vs. 16%, P<0.001). Tumor involvement per core (>50%) (most powerful), number of positive cores, PSA values, and age were independent predictors for either intermediate- or high-risk characteristics at RP. Tumor involvement per core and PSA values were independent predictors for exclusive high-risk characteristics at RP.ConclusionsD׳Amico low-risk patients did not have a homogeneous histology at RP. Especially, non-AS candidates were at a higher risk of either upgrading or upstaging at final pathology. Tumor involvement greater than 50% per core was the most powerful indicator of adverse pathology. Therefore, DʼAmico low-risk criteria are not safe enough to identify AS candidates.     

Dutasteride monotherapy in men with serologic relapse following radical therapy for adenocarcinoma of the prostate: A pilot study

ObjectiveThe objective of this study was to assess the effect of dutasteride on serum prostate specific antigen (PSA) levels in men with serologic relapse following radical prostatectomy and/or radiation therapy for clinically localized adenocarcinoma of the prostate.MethodsA prospective, single institution, IRB approved trial was conducted. Entry criteria required that all participants have serologic disease relapse only with serum PSA levels between 0.4 and 10.0 ng/ml. Enrolled participants were treated with 0.5 mg dutasteride daily. The primary endpoints were serum PSA level and clinical recurrence. The rate of durable decline in PSA was assessed according to the recommendations of the Prostate-Specific Antigen Working Group.ResultsThirty-five patients provided informed consent and participated in the present study. At a median follow-up duration of 27 months (range, 4–42 months), 46% of enrolled men had a serum PSA decrease of greater than 10%, and 25% had a serum PSA decrease of greater than 50% (P < 0.001). Pre-study PSA doubling time (PSADT) (≥12 months vs. <12 months), and Gleason score (≤6 vs. ≥7) were associated with a better response to dutasteride, but only PSADT was statistically significant (P < 0.001). Thirty percent of patients experienced PSA progression (increase in serum PSA of greater than 50%). Two (6%) patients developed bone metastasis. No patient was removed from the study for drug-related toxicity.ConclusionsIn the present pilot study, treatment with dutasteride resulted in a significant decrease in serum PSA in men with serologic relapse following radical treatment for adenocarcinoma of the prostate. These data appear to suggest that dutasteride may delay or prevent progression of prostate cancer in some men with biochemical relapse after radical therapy. These findings require confirmation in the setting of a larger, longer trial.     

Cancer detection and cancer characteristics in the European Randomized Study of Screening for Prostate Cancer (ERSPC)--Section Rotterdam. A comparison of two rounds of screening

OBJECTIVES: To evaluate the features, rates, and characteristics of prostate cancer detected during two subsequent screening rounds. METHODS: Data were retrieved from the database of European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. Men, ages 55-74 yr were screened with a 4-yr interval. Different biopsy indications were used in the first and second screens in the PSA range <4.0 ng/ml. Clinical features and a total of 1548 sextant biopsies were recorded for Gleason score and tumour extent, and 550 radical prostatectomy specimens were evaluated for Gleason score, pathologic T category, and tumour volume. RESULTS: Clinical stage, Gleason score, involvement of biopsy by tumour, and PSA levels were more favourable in patients of the second round compared with those of the first round. The number of men chosen for watchful waiting increased from 98 (10%) to 123 (22%) in the second round (p<0.0001). In patients undergoing radical prostatectomy, median tumour volume in the first and second screening round was 0.65 and 0.45 ml (p=0.001). Minimal cancer (cancer <0.5 ml, organ-confined, no Gleason pattern 4 or 5) was found in 122 (31.6%) in the first and 60 (42.6%) in the second screening round (p=0.03). The 5-yr PSA progression-free survival after radical prostatectomy was 87%. CONCLUSIONS: Despite the 4-yr interval an important shift of all prognostic factors occurred in favour of round 2. In those men who underwent radical prostatectomy, 42.6% fulfilled the criteria of minimal cancer. These data suggest that overdiagnosis increases with repeat screening.