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Purpose: Our goal was to evaluate the long-term prognostic value of magnetic resonance imaging of the prostatectomy bed in patients with biochemical recurrence after radical prostatectomy for prostate cancer., Materials and Methods: Men with biochemical recurrence after radical prostatectomy who were studied by prostatectomy bed magnetic resonance imaging for suspected local recurrence were retrospectively evaluated. Locally recurrent tumors were noted and measured from imaging reports. Patients with nodal/bone lesions at the time of imaging were excluded. Kaplan-Meier and Cox regression analyses were used to assess systemic progression-free and prostate cancer-specific survival., Results: A total of 896 men were enrolled and the imaging positive and negative groups for local recurrent tumor consisted of 441 and 455 men, respectively. On univariate analysis, preoperative prostate specific antigen (p=0.02), clinical tumor stage (p=0.006), pathological Gleason score from prostatectomy (p=0.02), subsequent salvage radiotherapy (p <0.001), biochemical recurrence to magnetic resonance imaging time interval (p <0.001), age at magnetic resonance imaging (p=0.047) and prostate specific antigen at magnetic resonance imaging (p <0.001) were significantly different between magnetic resonance imaging positive and negative groups. Patients with negative magnetic resonance imaging results had worse systemic progression-free survival rates (p=0.025) and better prostate cancer-specific survival (p=0.016) than those with recurrence. Larger lesion size significantly increased risk of prostate cancer death (hazard ratio: 1.07; p <0.001). On multivariable analysis, pathological Gleason scores ≥7 were independent prognostic factors of systemic progression (p <0.05)., Conclusions: Prostatectomy bed magnetic resonance imaging provides long-term prognostic information for the evaluation of patients with biochemical recurrence after prostatectomy. Post-prostatectomy patients with recurrent lesions on imaging had longer progression-free survival but shorter prostate cancer-specific survival compared to those without lesions. Additionally, those with larger lesions were associated with poorer cancer-specific survival.

Background: Metabolic syndrome (MetS) has a negative impact on functional recovery and complications after many surgical procedures., Aim: To assess the role of Mets on functional outcomes and complications after radical prostatectomy (RP) for prostate cancer., Patients and Methods: Complete data were collected from 5758 patients, undergoing RP at a single referral centers in a 10-year period and the presence of MetS before surgery was ascertained in 17.7% of them using a modified version of the IDF-AHA/NHLBI criteria. Outcomes included 1-year continence and potency rates, early (≤90 days) and late (>90 days) complications., Results: Postoperative continence (no pads) was significantly less likely in MetS patients (75.4% vs 82.6%, P < .01), despite no difference in preoperative continence. Erections with or without therapy were reached in 55.8% of non-MetS and 41.8% of MetS patients (P < .01), in this case a significant difference in preoperative function was seen. No differences in early and late complications, except for wound infections (5.8% vs 3.9%, P < .01) were observed., Conclusions: In the present study RP was safe from the complications standpoint in MetS patients, but the presence of the syndrome was a significant risk factor for post-RP incontinence and impotence., (© 2019 Wiley Periodicals, Inc.)

Background: Metabolic syndrome (MetS) is considered a potential risk factor for adverse outcomes after radical prostatectomy (RP). Furthermore, studies about the effect of MetS on low-risk prostate cancer (PCa) and its implications in active surveillance (AS) are limited., Objective: To investigate the role of MetS (using International Diabetes Federation-American Heart Association/National Heart, Lung, and Blood Institute criteria) on perioperative and oncological outcomes after RP in low-risk PCa and in a subgroup potentially eligible for AS., Design, Setting, and Participants: A total of 3662 patients treated with RP for low-risk PCa and further stratified as very low risk (VLR) PCa-prostate-specific antigen density of ≤0.15ng/ml/cm 3 , ≤2 cores involved, and no core with >50% cancer involvement-at a tertiary referral hospital were identified., Outcome Measurements and Statistical Analysis: Outcomes analyzed were pathological outcomes, perioperative complications, biochemical failure (BCF), and overall survival. Pathological outcomes and complications were analyzed with logistic regression models. Kaplan-Meier curves and Cox proportional hazards models were used to analyze survival outcomes., Results and Limitations: In univariate/multivariate analyses, MetS was associated with upgrading and positive surgical margins in the entire cohort, upgrading only in the VLR group. In Kaplan-Meier analysis, MetS patients had a higher rate of overall death (p<0.0001) and BCF (p=0.03) for MetS patients. In the VLR group, no differences were found for BCF (p=0.064). Further, in Cox proportional hazards models, MetS was not associated with BCF (hazard ratio=1.23; 95% confidence interval [CI]=0.95-1.60, p=0.12). MetS patients had a higher rate of complications compared with non-MetS patients (23.7% vs 19.7%; p=0.01). In multivariate analysis, MetS was associated with a higher rate of complications (odds ratio=1.24, 95% CI=1.04-1.49, p=0.018) but did not impact the rate of major ones. This study is limited by its retrospective design., Conclusions: In low-risk PCa treated with RP but potentially eligible for AS, MetS impacted perioperative and pathological outcomes, suggesting further study of MetS in patients undergoing AS., Patient Summary: Metabolic syndrome negatively impacts perioperative and pathological outcomes in low-risk prostate cancer patients treated with radical prostatectomy but potentially eligible for active surveillance, in a large American single-center cohort. These findings suggest the need for a more cautious approach to low-risk prostate cancer in patients with metabolic syndrome., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To test the hypothesis that chromosomal rearrangements (CRs) can distinguish low risk of progression (LRP) from intermediate and high risk of progression (IHRP) to prostate cancer (PCa) and if these CRs have the potential to identify men with LRP on needle biopsy that harbor IHRP PCa in the prostate gland., Patients and Methods: Mate pair sequencing of amplified DNA from pure populations of Gleason patterns in 154 frozen specimens from 126 patients obtained between August 14, 2001, and July 15, 2011, was used to detect CRs including abnormal junctions and copy number variations. Potential CR biomarkers with higher incidence in IHRP than in LRP to cancer and having significance in PCa biology were identified. Independent validation was performed by fluorescence in situ hybridization in 152 specimens from 124 patients obtained between February 12, 2002, and July 12, 2008., Results: The number of abnormal junctions did not distinguish LRP from IHRP. Loci corresponding to genes implicated in PCa were more frequently altered in IHRP. Integrated analysis of copy number variations and microarray data yielded 6 potential markers that were more frequently detected in Gleason pattern 3 of a Gleason score 7 of PCa than in Gleason pattern 3 of a Gleason score 6 PCa. Five of those were cross-validated in an independent sample set with statistically significant areas under the receiver operating characteristic curves (AUCs) (P≤.01). Probes detecting deletions in PTEN and CHD1 had AUCs of 0.87 (95% CI, 0.77-0.97) and 0.73 (95% CI, 0.60-0.86), respectively, and probes detecting gains in ASAP1, MYC, and HDAC9 had AUCs of 0.71 (95% CI, 0.59-0.84), 0.82 (95% CI, 0.71-0.93), and 0.77 (95% CI, 0.66-0.89), respectively (for expansion of gene symbols, use search tool at www.genenames.org)., Conclusion: Copy number variations in regions encompassing important PCa genes were predictive of cancer significance and have the potential to identify men with LRP PCa by needle biopsy who have IHRP PCa in their prostate gland., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: The associations between metabolic syndrome (MetS) and prostate cancer (CaP) outcomes following radical prostatectomy (RP) are not clear. This study aims to understand the role of MetS in influencing oncological outcomes at RP., Materials and Methods: Patients who underwent RP for CaP at our institution from 2000 to 2010 were identified; MetS prior to RP was ascertained with a modified version of the IDF-AHA/NHLBI using ICD-9 codes. Histopathological outcomes included surgical margins, pathological stage, and Gleason score (GS) upgrading. Long-term outcomes included biochemical recurrence (BCR), local recurrence, systemic progression, and CaP-specific mortality. Multivariable adjusted logistic regression and Cox proportional hazards regression assessed the association between MetS status and histopathological and long-term outcomes, respectively., Results: Of 8,504 RP patients, 1,054 (12.4%) had MetS at the time of RP. MetS patients were older, had higher biopsy GS, but lower pre-op prostatic specific antigen (PSA), higher pathological GS, and larger prostate volume. Adjusted logistic regression suggested an association between MetS and positive margins (odds ratio [OR] = 1.22, P = 0.025) and GS upgrading (OR = 1.28, P = 0.002). There was evidence of an increased risk of local recurrence (hazard ratio [HR] = 1.33, P = 0.037) and CaP-specific mortality (HR = 1.58, P < 0.001) for MetS patients. There was no evidence to suggest an association with BCR or systemic progression., Conclusion: Men with MetS are at higher risk of GS upgrade and positive surgical margins at surgery, local recurrence, and CaP-specific mortality. Pathological stage, BCR, and systemic progression were not associated with MetS. Our data may be useful in patients' counseling, especially when active surveillance is an option., (Copyright © 2018. Published by Elsevier Inc.)

Purpose: We sought to determine clinicopathological factors associated with early progression in men on androgen deprivation therapy as well as cancer specific and overall survival. We also assessed whether certain prostate specific antigen thresholds at androgen deprivation therapy initiation are associated with poorer outcomes., Materials and Methods: We identified 2,418 men with rising prostate specific antigen after undergoing radical prostatectomy at a single institution between 1987 and 2007 in a prospectively maintained registry. Early progression was defined as clinical progression within 2 years of initiating androgen deprivation therapy. The primary study outcome was cancer specific and overall survival., Results: The risk of early progression while on androgen deprivation therapy was lower for prostate specific antigen doubling time 3 to less than 9 months (OR 0.19) and less than 9 months or longer (OR 0.10, each p <0.001) prior to androgen deprivation therapy. Independent predictors of cancer specific survival were metastatic disease at androgen deprivation therapy initiation (HR 2.60), prostate specific antigen 5 to 50 ng/ml (HR 2.68) and 50 ng/ml or greater (HR 4.33), and doubling time 3 to less than 9 months (HR 0.54) and 9 months or longer (HR 0.45, all p <0.001). Independent predictors of overall survival were prostate specific antigen 5 to 50 ng/ml (HR 3.10) and 50 ng/ml or greater (HR 5.20, each p <0.001)., Conclusions: In men in whom androgen deprivation therapy was initiated for relapse after radical prostatectomy prostate specific antigen doubling time less than 3 months and prostate specific antigen 5 ng/ml or greater were adverse prognostic factors for early progression and cancer specific survival. Prostate specific antigen 5 ng/ml or greater also predicted shorter overall survival. Longer doubling time and prostate specific antigen less than 5 ng/ml were associated with lower risk and these men may not require immediate androgen deprivation therapy., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Recent NCCN ® (National Comprehensive Cancer Network®) Guidelines® show that patients with biopsy Gleason score 3 + 4/Grade Group 2 but otherwise favorable features are active surveillance candidates. However, little is known about the long-term outcomes compared to that in men in the low risk Gleason score 6/Grade Group 1 group. We sought to clarify the risk of adverse features and oncologic outcomes in surgically treated, favorable Grade Group 2 vs 1 cases., Materials and Methods: We queried our prospectively maintained radical prostatectomy database for all 8,095 patients with biopsy Grade Group 1 or 2 prostate cancer who otherwise fulfilled the NCCN low risk definition of prostate specific antigen less than 10 ng/ml and cT2a or less, and who underwent radical prostatectomy from 1987 to 2014. Multivariable logistic regression and Kaplan-Meier methods were used to compare pathological and oncologic outcomes., Results: Organ confined disease was present in 93.9% and 82.6% of Grade Group 1 and favorable intermediate risk Grade Group 2 cases while seminal vesicle invasion was noted in 1.7% and 4.7%, and nodal disease was noted in 0.3% and 1.8%, respectively (all p <0.0001). On multivariable logistic regression biopsy proven Grade Group 2 disease was associated with a threefold greater risk of nonorgan confined disease (OR 3.1, 95% CI 1.7-5.7, p <0.001). The incidence of late treatment (more than 90 days from surgery) in Grade Group 1 vs 2 was 3.1% vs 8.5% for hormonal therapy and 6.0% vs 12.2% for radiation (p <0.001). In the Grade Group 1 vs 2 cohorts the 10-year biochemical recurrence-free survival rate was 88.9% vs 81.2% and the 10-year systemic progression-free survival rate was 99% vs 96.5% (each p <0.001)., Conclusions: Men at favorable risk with Grade Group 2 disease who are considering active surveillance should be informed of the risks of harboring adverse pathological features which impact secondary therapies and an increased risk of cancer progression., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We sought to independently validate the AJCC (American Joint Committee on Cancer) 8th edition prostate cancer staging classification, which includes the elimination of pT2 subcategories and the reclassification of patients with prostate specific antigen 20 ng/ml or greater and Gleason Grade Group 5 as stage groups III-A and III-C, respectively., Materials and Methods: We identified 13,839 men who underwent radical prostatectomy at Mayo Clinic between 1987 and 2011 from our institutional registry. Outcomes included biochemical recurrence-free, metastasis-free and cancer specific survival. Kaplan-Meier analyses and Cox regression models with the c-index were used., Results: Median followup was 10.5 years (IQR 7.1-15.3). Among patients with pT2 prostate cancer the subclassification demonstrated limited discrimination for biochemical recurrence-free, metastasis-free and cancer specific survival (c-index 0.531, 0.545 and 0.525, respectively). At the same time patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly worse 15-year biochemical recurrence-free survival (42.2% vs 58.8%), metastasis-free survival (78.2% vs 88.8%) and cancer specific survival (88.0% vs 94.4%, all p <0.001) than patients with 7th edition stage group II prostate cancer and prostate specific antigen less than 20 ng/ml. However, patients with 7th edition stage group II prostate cancer and prostate specific antigen 20 ng/ml or greater had significantly better 15-year biochemical recurrence-free survival (42.2% vs 31.3%, p = 0.007), metastasis-free survival (78.2% vs 68.0%, p <0.001) and cancer specific survival (88.0% vs 83.4%, p = 0.01) than patients with 7th edition stage group III. Also, patients with 7th edition stage group II prostate cancer and Gleason Grade Group 5 had significantly worse 15-year biochemical recurrence-free survival (37.1% vs 57.9%, p <0.001), metastasis-free survival (63.8% vs 88.5%, p <0.001) and cancer specific survival (73.0% vs 94.3%, p <0.001) than patients with 7th edition stage group II prostate cancer and Gleason Grade Group 1-4 as well as worse 15-year cancer specific survival (73.0% vs 83.4%, p = 0.005) than patients with 7th edition stage group III prostate cancer., Conclusions: Our data support the changes in the new AJCC classification., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

TMPRSS2-ERG gene fusions occur in over 50% of prostate cancers, but their impact on clinical outcomes is not well understood. Retention of interstitial genes between TMPRSS2 and ERG has been reported to influence tumor progression in an animal model. In this study, we analyzed the status of TMPRSS2-ERG fusion genes and interstitial genes in tumors from a large cohort of men treated surgically for prostate cancer, associating alterations with biochemical progression. Through whole-genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate-, and high-risk prostate cancer from radical prostatectomy specimens. TMPRSS2-ERG gene fusions were observed in 44% of cases, and over 90% of these fusions occurred in ERG exons 3 or 4. ERG fusions retaining interstitial sequences occurred more frequently in very low-risk tumors. These tumors also frequently displayed ERG gene fusions involving alternative 5'-partners to TMPRSS2 , specifically SLC45A3 and NDRG1 and other ETS family genes, which retained interstitial TMPRSS2/ERG sequences. Lastly, tumors displaying TMPRSS2-ERG fusions that retained interstitial genes were less likely to be associated with biochemical recurrence ( P = 0.028). Our results point to more favorable clinical outcomes in patients with ETS family fusion-positive prostate cancers, which retain potential tumor-suppressor genes in the interstitial regions between TMPRSS2 and ERG Identifying these patients at biopsy might improve patient management, particularly with regard to active surveillance. Cancer Res; 77(22); 6157-67. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Background: According to a recent National Comprehensive Cancer Network (NCCN) guidelines update, patients with Gleason score (GS) 3 + 4 prostate cancer (PCa) and "favorable intermediate-risk" (FIR) characteristics might be offered active surveillance (AS). However, the risk of unfavorable disease features and its prediction in this subset of patients is not completely understood., Objective: To identify the risk of unfavorable disease and potential predictors of adverse outcomes among GS 3 + 4 FIR PCa patients., Design, Setting, and Participants: The study included patients with biopsy GS 3 + 4 and otherwise fulfilling the NCCN low-risk definition (prostate-specific antigen [PSA] <10 ng/ml, cT2a or lower) undergoing radical prostatectomy (RP) from 2006 to 2014 at a single institution., Outcome Measurements and Statistical Analysis: Complete information on PSA, PSA density (PSAD), clinical stage, percentage of positive cores, percentage of maximum surface specimen involvement, and RP pathology were available. GS upgrade and downgrade, non-organ-confined and non-specimen-confined disease, unfavorable disease (pT3-T4 and/or pN1 and/or a pGS ≥4 + 3) were the outcomes. Statistical analysis included descriptive statistics and multivariable logistic regression., Results and Limitations: A total of 156 patients (13.1%) experienced GS upgrade; 201 (16.9%) were downgraded. Overall, 205 men (17.2%) harbored non-organ-confined disease, and 295 (24.8%) had unfavorable disease. Age (odds ratio [OR]: 1.06), percentage surface involvement (OR: 1.01), and PSAD (OR: 1.83) were the only significant predictors of upgrade. Age (OR: 1.05), clinical stage (OR: 1.74), percentage of positive cores >50% (OR 1.57), percentage of surface area (OR: 1.02), and perineural invasion (OR: 1.89) were significant predictors of unfavorable disease at RP. The retrospective design is a limitation., Conclusions: AS is a possible option for a subset of men with FIR GS 3 + 4. However, clinical models alone have a limited role in GS upgrade prediction, and alternative tools warrant further investigation., Patient Summary: Patients with Gleason score 3 + 4 at biopsy, low prostate-specific antigen, and low stage might consider the option of active surveillance, but the use of clinical information alone might be not adequate for thorough risk-adapted counseling., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Long-term data supporting the role of primary tumor resection in node positive prostate cancer are lacking. We evaluated the impact of adding radical retropubic prostatectomy to surgical castration on long-term oncologic outcomes in pathological node positive prostate cancer., Materials and Methods: We identified men who underwent pelvic lymphadenectomy and orchiectomy within 90 days for pathological node positive prostate cancer from 1966 to 1995. Men treated with radical retropubic prostatectomy in addition to orchiectomy were matched 1:1 to men who underwent orchiectomy alone based on age, year of surgery, clinical grade, clinical T stage, number of positive nodes and preoperative serum prostate specific antigen, the latter from 1987 and thereafter. Kaplan-Meier and Cox regression analyses were done to compare cancer specific and overall survival., Results: The matched cohort included 158 men with 79 in each group. Of men who underwent orchiectomy alone 76 died, including 60 of prostate cancer. Of patients treated with radical retropubic prostatectomy plus orchiectomy 70 died, including 28 of prostate cancer. On Kaplan-Meier analyses prostatectomy plus orchiectomy vs orchiectomy alone was associated with prolonged cancer specific survival (at 20 years 59% vs 18%, log rank p <0.001) and overall survival (at 20 years 22% vs 9%, log rank p <0.001). In Cox models prostatectomy plus orchiectomy vs orchiectomy alone was associated with improved cancer specific survival (HR 0.28, 95% CI 0.17-0.46, p <0.001) and overall survival (HR 0.48, 95% CI 0.34-0.66, p <0.001). Findings were similar in the subset with available preoperative prostate specific antigen values., Conclusions: With lifelong followup in nearly the entire cohort, this study demonstrates that adding radical retropubic prostatectomy to surgical castration for pathological node positive prostate cancer is associated with improved cancer specific and overall survival. When technically feasible in well selected patients, aggressive locoregional resection should be considered for node positive prostate cancer as part of a multimodal approach., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

In the present report we aimed to analyze the incremental value of preoperative magnetic resonance imaging (MRI), in addition to clinical variables and clinically-derived nomograms, in predicting outcomes radical prostatectomy (RP). All Mayo Clinic RP patients who underwent preoperative 1.5-Tesla MRI with endo-rectal coil from 2003 to 2013 were identified. Clinical and histopathological variables were used to calculate Partin estimates and Cancer of the Prostate Risk Assessment (CAPRA) score. MRI results in terms of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph-node invasion (N+) were recorded. Using RP pathology as gold standard, we developed multivariate logistic regression models based on clinical variables, Partin Tables, and CAPRA score, and assessed their predictive accuracy before and after the addition of MRI results. Five hundred and one patients were included. MRI + clinical models outperformed clinical-based models alone for all outcomes. Comparing Partin and Partin + MRI predictive models, the areas under the curve were 0.61 versus 0.73 for ECE, 0.75 versus 0.82 for SVI, and 0.82 versus 0.85 for N+. Comparing CAPRA and CAPRA + MRI models, the areas under the curve were 0.69 versus 0.77 for ECE, 0.75 versus 0.83 for SVI, and 0.82 versus 0.85 for N+. Our data show that MRI can improve clinical-based models in prediction of nonorgan confined disease, particularly for ECE and SVI., Patient Summary: Magnetic resonance imaging, together with clinical information, can be useful in preoperative assessment before radical prostatectomy., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the incidence, predictors and oncological outcomes of pT0 prostate cancer (PCa)., Methods: We conducted a retrospective analysis of 20 222 patients undergoing radical prostatectomy (RP) for PCa at the Mayo Clinic between 1987 and 2012. Disease recurrence was defined as follow-up PSA >0.4 ng/mL or biopsy-proven local recurrence. Systemic progression was defined as development of metastatic disease on imaging. Comparisons of baseline characteristics between pT0 and non-pT0 groups were carried out using chi-squared tests. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log-rank test., Results: A total of 62 patients (0.3%) had pT0 disease according to the RP specimen. In univariable analysis, pT0 disease was significantly associated with older age (P = 0.045), lower prostate-specific antigen (PSA; P = 0.002), lower clinical stage (P < 0.001), lower biopsy Gleason score (P = 0.042), and receipt of preoperative transurethral resection, hormonal and radiation therapies (all P < 0.001). In multivariable analysis, lower PSA levels, lower Gleason score, and receipt of preoperative treatment were independently associated with pT0 (all P < 0.05). Seven patients (11%) with pT0 PCa developed disease recurrence over a median follow-up of 10.9 years. All seven patients had preoperative treatment(s) and three had recurrence with a PSA doubling time of <9 months. Compared with non-pT0 disease, pT0 disease was associated with longer recurrence-free survival (P < 0.05). Only one (1.6%) patient with pT0 disease developed systemic progression., Conclusions: pT0 stage PCa is a rare phenomenon and is associated with receipt of preoperative treatment and features of low-risk PCa. Although pT0 has a very favourable prognosis, some men, especially those who received preoperative treatment, experience a small but non-negligible risk of disease recurrence and systemic progression., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Multiple definitions of biochemical recurrence for prostate cancer exist after radical prostatectomy, and variation continues in prostate cancer outcome reporting and secondary treatment initiation. We reviewed long-term prostatectomy outcomes to assess the most appropriate prostate specific antigen cut point that predicts future disease progression., Materials and Methods: We identified 13,512 patients with cT1-2N0M0 prostate cancer who underwent radical prostatectomy between 1987 and 2010. Single prostate specific antigen cut points of 0.2, 0.3, 0.4 and 0.5 ng/ml or greater, as well as confirmatory prostate specific antigen value definitions of 0.2 ng/ml or greater followed by prostate specific antigen greater than 0.2 ng/ml and 0.4 ng/ml or greater followed by prostate specific antigen greater than 0.4 ng/ml were tested. Continued prostate specific antigen increase after a designated cut point definition was estimated using cumulative incidence. The strength of association between biochemical recurrence definitions and subsequent systemic progression were analyzed using Cox proportional hazard models and the O'Quigley event based R(2) test., Results: At a median postoperative followup of 9.1 years (IQR 4.9-14.3) a detectable prostate specific antigen developed in 5,041 patients and systemic progression developed in 512. After reaching the prostate specific antigen cut point of 0.2, 0.3 and 0.4 ng/ml, the percentage of patients experiencing a continued prostate specific antigen increase over 5 years was 61%, 67% and 74%, respectively, plateauing at 0.4 ng/ml. The strongest association between biochemical recurrence and systemic progression occurred using a single prostate specific antigen cut point of 0.4 ng/ml or greater (HR 36, R(2) 0.92)., Conclusions: A prostate specific antigen cut point of 0.4 ng/ml or greater reflects the threshold at which a prostate specific antigen increase becomes durable and shows the strongest correlation with subsequent systemic progression. Consideration should be given to using a prostate specific antigen of 0.4 ng/ml or greater as the standard biochemical recurrence definition after radical prostatectomy., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Patients with clinically insignificant prostate cancer remain a major over-treated population. PTEN loss is one of the most recurrent alterations in prostate cancer associated with an aggressive phenotype, however, the occurrence of PTEN loss in insignificant prostate cancer has not been reported and its role in the separation of insignificant from significant prostate cancer is unclear. An integrated analysis of PTEN loss was, therefore, performed for structural variations, point mutations and protein expression in clinically insignificant (48 cases) and significant (76 cases) prostate cancers treated by radical prostatectomy. Whole-genome mate pair sequencing was performed on tumor cells isolated by laser capture microdissection to characterize PTEN structural alterations. Fluorescence in situ hybridization probes were constructed from the sequencing data to detect the spectrum of these PTEN alterations. PTEN loss by mate pair sequencing and fluorescence in situ hybridization occurred in 2% of insignificant, 13% of large volume Gleason score 6, and 46% of Gleason score 7 and higher cancers. In Gleason score 7 cancers with PTEN loss, PTEN alterations were detected in both Gleason pattern 3 and 4 in 57% of cases by mate pair sequencing, 75% by in situ hybridization and 86% by immunohistochemistry. PTEN loss by sequencing was strongly associated with TMPRSS2-ERG fusion, biochemical recurrence, PTEN loss by in situ hybridization and protein loss by immunohistochemistry. The complex nature of PTEN rearrangements was unveiled by sequencing, detailing the heterogeneous events leading to homozygous loss of PTEN. PTEN point mutation was present in 5% of clinically significant tumors and not in insignificant cancer or high-grade prostatic intraepithelial neoplasia. PTEN loss is infrequent in clinically insignificant prostate cancer, and is associated with higher grade tumors. Detection of PTEN loss in Gleason score 6 cancer in a needle biopsy specimen indicates a higher likelihood of clinically significant prostate cancer.

Background: The presence of a positive surgical margin (PSM) at radical prostatectomy (RP) has been linked to an increased risk of biochemical recurrence and receipt of secondary therapy; however, its association with other oncologic end points remains controversial., Objective: To evaluate the association of primary Gleason grade (GG) at the site of PSM with subsequent clinical progression and mortality among patients with Gleason score (GS) 7 prostate cancer (PCa)., Design, Setting, and Participants: We identified 1036 patients who underwent RP between 1996 and 2002. A single uropathologist re-reviewed all specimens noted to have a PSM to record GG at the margin., Outcome Measurements and Statistical Analysis: Survival was estimated using the Kaplan-Meier method. Cox models were used to analyze the association of margin primary GG with outcome., Results and Limitations: Overall, 338 men (33%) had a PSM; of those, 242 had PSM GG3 and 96 had PSM GG4. Median postoperative follow-up was 13 yr. Compared with men with PSM GG3 or a negative SM, we noted that men with PSM GG4 had significantly worse 15-yr systemic progression-free survival (74% vs. 90% vs. 93%, respectively; p<0.001) and cancer-specific survival (86% vs. 96% vs. 97%, respectively; p=0.002). On multivariable analysis, the presence of PSM GG4 was associated with increased risks of systemic progression (hazard ratio [HR]: 2.77; p=0.003) and death from PCa (HR: 3.93; p=0.02) among men with a PSM. Limitations include the relatively small rate of disease recurrence., Conclusions: PSM primary GG4 was independently associated with adverse oncologic outcomes among men with GS7 PCa. Pending external validation, GG at the PSM may be considered for inclusion in pathologic reports and risk stratification following RP., Patient Summary: Among patients with Gleason grade 7 prostate cancer and a positive surgical margin at the time of prostatectomy, we found that higher Gleason grade at the margin was associated with worse oncologic outcomes., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: Our objective is to assess the outcomes of patients with prostate cancer (PCa) diagnoses undergoing holmium laser enucleation of the prostate (HoLEP)., Methods: From 2009 to 2012, 450 patients underwent HoLEP at our institution. We performed a retrospective review of these patients to identify those with PCa., Results: PCa was diagnosed in 57 (12.7%) HoLEP patients: 11 (19.2%) preoperatively, 43 (75.4%) in the operative specimen, and 3 (5.4%) during follow-up. Mean time to PCa development in the postoperative group was 16 months (9-23). There was no difference in patient characteristics for those diagnosed with PCa at the time of HoLEP or in the postoperative period. There were 5 patients with a Gleason score (GS)>8 and 52 with GS<8 PCa. In the operative group, 39 (91%) elected for active surveillance and 4 (9%) elected to have cancer treatment. In subgroup analysis, men diagnosed with GS>8 intraoperatively or postoperatively had significantly elevated preoperative, postoperative, and percent change prostate-specific antigen (PSA) levels when compared to patients diagnosed GS ≤ 7 (P=0.01, 0.02, and 0.01, respectively). There were no complications, all voided spontaneously, and one patient had persistent incontinence., Conclusion: HoLEP for the treatment of lower urinary tract symptoms (LUTS) in selectively chosen men with known PCa can safely improve urination. Furthermore, PCa is diagnosed at the time of or post HoLEP in nearly 12% of patients. Those patients with persistently elevated post HoLEP PSA levels or low percent change PSA levels should raise suspicion for high GS PCa. Finally, HoLEP does not preclude active surveillance or treatment for PCa when appropriate.

Introduction: To evaluate the ability of endorectal coil (e-coil) magnetic resonance imaging (MRI) to identify early prostatic fossa recurrence after radical prostatectomy., Materials and Methods: We identified 187 patients from 2005-2011 who underwent e-coil MRI with dynamic gadolinium-contrast enhancement followed by transrectal ultrasound (TRUS) guided prostatic fossa biopsy for possible local prostate cancer recurrence. For analysis, local recurrence was defined as a negative evaluation for distant metastatic disease with a positive prostatic fossa biopsy, decreased prostate-specific antigen (PSA) following salvage radiation therapy, or increased lesion size on serial imaging., Results: Local recurrence was identified in 132 patients, with 124 (94%) detected on e-coil MRI. The median PSA was 0.59 ng/mL (range < 0.1-13.1), and median lesion size on MRI was 1 cm. The sensitivity of MRI was 91%, with a specificity of 45%. The positive predictive value was 85%, with a negative predictive value of 60%. For patients with a PSA < 0.4 ng/mL the sensitivity of e-coil MRI was 86%. When a lesion was identified on MRI, the positive biopsy rate was 65% and lesion size was a significant predictor of positive biopsies. The positive biopsy rates were 51%, 74%, and 88% when the lesion was < 1 cm, 1 cm-2 cm, or > 2 cm, respectively (p = 0.0006)., Conclusions: E-coil MRI has a high level of sensitivity in identifying local recurrence of prostate cancer following radical prostatectomy, even at low PSA levels. E-coil MRI should be considered as the first imaging evaluation for biochemical recurrence for identifying patients suitable for localized salvage therapy.

Objective: To determine the role of cellular proliferation and other biopsy-based features in the prediction of prostate cancer mortality., Patients and Methods: Between 1993 and 2012, our institution has performed quantitation of prostate cancer DNA ploidy and Ki-67 (MIB-1) on most prostate cancer needle biopsy specimens. The outcomes of 451 consecutive patients with biopsy-proven cancer treated by radical prostatectomy between January 24, 1995, and December 29, 1998, without neoadjuvant hormonal therapy were assessed. Clinical and biopsy information obtained before radical prostatectomy was placed in multivariate Cox proportional hazards regression models to predict local or systemic progression and cancer-specific death. Predictive ability was evaluated using a concordance index., Results: With a median follow-up of 12.9 years, 46 patients experienced local or systemic progression, and 18 patients died of prostate cancer. On multivariate analysis, the biopsy features of Ki-67 expression, perineural invasion, and Gleason score were associated with local or systemic progression. Ki-67 expression, perineural invasion, and Gleason score were associated with cancer-specific death with a concordance index of 0.892. After adjusting for perineural invasion and Gleason score, each 1% increase in Ki-67 expression was associated with a 12% increased risk of cancer-specific death (P<.001). Ki-67 expression alone was a strong predictor of cancer-specific outcomes and improved the predictive ability of currently used algorithms., Conclusion: This study documents that long-term prostate cancer outcomes are best estimated with a combination of Gleason score, perineural invasion, and Ki-67 expression. Given its low cost, rapid assessment, and strong predictive power, we believe that adding Ki-67 expression to perineural invasion and Gleason score at biopsy should be considered a standard by which all new biomarkers are compared before introducing them into clinical practice., (Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: Recent studies have shown a relative risk reduction in the incidence of prostate cancer in patients taking metformin. However, there are conflicting findings on the effect of metformin on established cases of prostate cancer. In this study we evaluated the effect of metformin on survival and pathologic outcomes in established prostate cancer., Materials and Methods: We retrospectively identified 12,052 patients who underwent radical prostatectomy between 1997 and 2010 at Mayo Clinic. Among these, 885 (7.3%) were diabetics, including 323 taking and 562 not taking metformin. Kaplan-Meier method was utilized to calculate rates of biochemical recurrence (BCR), systemic progression (SP), and all-cause mortality (ACM). Cox models were used to estimate the metformin hazard ratio (HR) adjusted for clinical and pathologic variables., Results and Conclusions: Median follow-up was 5.1 years. In univariate analysis, metformin HR (95% confidence intervals) was not significant for BCR (1.13 [0.84, 1.52]; P = 0.40), SP (1.37 [0.69, 2.72]; P = 0.37), and ACM (1.32 [0.84, 2.05]; P = 0.23). After adjusting for covariates of interest, the HRs for metformin among diabetics remained nonsignificant for BCR (0.91 [0.67, 1.24]; P = 0.55), SP (0.83 [0.39, 1.74]; P = 0.62); and ACM (1.16 [0.73, 1.86]; P = 0.53). No significant difference was seen between metformin users and nonusers in the final pathologic Gleason score (P = 0.33), stage (P = 0.1), rate of positive surgical margins (P = 0.29), or tumor volume (P = 0.76). Metformin use was not associated with a risk reduction in BCR, SP, or ACM. Besides presenting survival data, our results describing metformin's effect on final pathology are unique., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: Determining clinicopathologic features that stratify the risk of disease progression in patients with seminal vesicle invasion at radical prostatectomy remains critical for patient counseling, clinical trial enrollment, and the judicious application of secondary therapies. Then, we evaluated the prognostic significance of concomitant extracapsular extension (ECE) in patients with seminal vesicle invasion and negative lymph nodes at radical prostatectomy., Methods: We identified 1,132 patients who underwent prostatectomy between 1987 and 2009 and were found to have pT3bN0 disease. Median postoperative follow-up was 10.6 years (interquartile range, 5.9-15.3). Survival was estimated using the Kaplan-Meier method and compared for patients with and without ECE with the log-rank test. The association of ECE with outcome was evaluated using Cox proportional hazards regression models., Results: A total of 693 (61%) patients were noted to have ECE. Compared with pT3bN0 patients without ECE, patients with pT3bN0 tumors and ECE had a significantly worse 15-year biochemical recurrence-free survival (29% vs. 39%; P<0.001), systemic progression-free survival (71% vs. 81%; P<0.001), cancer-specific survival (80% vs. 89%; P<0.001), and overall survival (50% vs. 63%; P<0.001). On multivariate analysis, the presence of ECE was associated with significantly increased risks of systemic progression (hazard ratio [HR], 1.56; P=0.006), death from prostate cancer (HR, 1.71; P=0.01), and all-cause mortality (HR, 1.35; P=0.007). Meanwhile, adjuvant hormonal therapy, which was received by 334 patients (29.5%), was associated with significantly decreased risks of systemic progression (HR, 0.50; P=0.0004) and cancer death (HR, 0.57; P=0.03), but not all-cause mortality (HR, 0.81; P=0.09). Limitations included retrospective design and nonstandardized application of secondary treatments., Conclusions: The presence of ECE in patients with pT3bN0 prostate cancer is associated with increased risks of systemic progression and cancer death. Pending validation, ECE may be incorporated into risk stratification or staging classification or both. Meanwhile, these patients continue to represent ideal candidates for adjuvant therapy trials., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Assessment of overall health is a critical component in the evaluation of patients presenting with clinically localized prostate cancer. Estimated glomerular filtration rate (eGFR) has been associated with increased risk of cardiovascular and overall mortality. Therefore, the objective of our study was to evaluate the impact of baseline renal function on oncologic outcomes and overall survival following radical prostatectomy., Materials and Methods: We identified 10,099 patients who underwent radical prostatectomy at our institution from 1990 to 2004 with a preoperative serum creatinine available for analysis. eGFR was calculated by the chronic kidney disease-epidemiology formula (CKD-EPI) and reported as ml/min per 1.73 m(2). Patients were then classified according to their eGFR: <30, 30-59, 60-89, 90-119, and 120-150 ml/min/1.73 m(2). Multivariate Cox proportional hazard regression models were used to analyze the impact of eGFR on postoperative outcomes., Results: At the time of surgery, 25 patients (0.1%) had an eGFR <30 ml/min/1.73 m(2), 2,398 (23.7%) between 30 and 60, 7,097 (70.3%) between 60 and 90, and 605 (6.0%) patients had an eGFR >90. eGFR was not associated with oncologic outcomes, including biochemical recurrence, systemic progression or cancer-specific survival (P > 0.05 for all). However, eGFR was strongly associated with all-cause mortality and non-prostate cancer death. On multivariate analysis, after controlling for age, BMI, prostate-specific antigen doubling time (PSA), Gleason score, and clinical stage, eGFR remains a statistically significant predictor of all-cause mortality., Conclusions: Assessment of eGFR is an important metric in the overall evaluation of patient health and should be considered in combination with patient age and other medical comorbidities when selecting the initial treatment of prostate cancer. While prostate cancer-specific outcomes do not appear to be impacted by renal function, overall survival is decreased in those with lower and higher than normal eGFR., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To examine the ability of standard and saturation transrectal prostate biopsy techniques to predict appropriate candidates for active surveillance., Methods: Between 2005 and 2007, 500 consecutive patients underwent transrectal ultrasound-guided biopsy by a standard template (12 cores) or saturation template (≥18 cores, median 27 cores), with subsequent radical prostatectomy. Using the criteria of Gleason score ≤6, clinical stage T1 or T2a, prostate-specific antigen <10 and ≤33% of cores involved, 218 patients were potential candidates for active surveillance. Pathology results from the prostatectomy specimens were used to determine the accuracy of each biopsy technique. Biochemical failure after prostatectomy was evaluated using logistic and Cox proportional hazards regression., Results: A standard biopsy was carried out for 124 patients and saturation biopsy for 94 patients. There was no statistically significant difference between the groups in terms of median age (P = 0.14), preoperative prostate-specific antigen (P = 0.52) and clinical stage (P = 0.23). Similar rates of Gleason score ≥7 at the time of radical prostatectomy were found, with 14% for standard biopsy and 15% for saturation biopsy (P = 0.70). Upstaging was shown in two standard biopsy patients (1.6%) and no saturation biopsy patients (P = 0.62). A multivariate analysis adjusting for prior prostate biopsy, preoperative prostate-specific antigen and clinical stage showed no difference in the rate of upgrading based on biopsy technique (P = 0.26). During follow up, 5-year biochemical failure-free survival estimates were not significantly different (P = 0.11)., Conclusions: In men with prostate cancer, standard and saturation transrectal prostate biopsies techniques are equally predictive of candidates for active surveillance., (© 2012 The Japanese Urological Association.)

Background: To evaluate the impact of adjuvant hormonal therapy after radical prostatectomy on overall survival in high-risk prostate cancer patients, stratified by comorbidity status., Methods: We identified 1247 patients who underwent radical prostatectomy from 1988 to 2004 for high-risk prostate cancer, as defined by National Comprehensive Cancer Network classification. Comorbidity status was stratified by Charlson Comorbidity Index as 0, 1 or >2, as well as by the presence or absence of cardiovascular disease. Overall survival was estimated by the Kaplan-Meier method, and compared within each comorbidity category/adjuvant hormonal therapy strata with the log-rank test., Results: Median patient age was 65 years, and the median postoperative follow up was 11.2 years. In total, 419 patients (34%) received adjuvant hormonal therapy. The distribution of Charlson Comorbidity Index was 0, 1 and ≥ 2 in 861 (69%), 244 (20%) and 142 (11%) patients, respectively. The 10-year overall survival for patients who received adjuvant hormonal therapy versus those who did not was 75% versus 82% (P=0.54) for patients with Charlson Comorbidity Index=0, 72% versus 76% (P=0.83) with Charlson Comorbidity Index=1, and 70% versus 68% (P=0.33) with Charlson Comorbidity Index ≥ 2. Meanwhile, 155 (12%) patients had cardiovascular disease, and the 10-year overall survival for patients with cardiovascular disease who received adjuvant hormonal therapy was 72%, compared with 76% without adjuvant hormonal therapy (P=0.97). On multivariate analysis, receipt of adjuvant hormonal therapy was not associated with non-prostate cancer mortality (P=0.24)., Conclusions: Adjuvant hormonal therapy after radical prostatectomy for high-risk prostate cancer does not increase non-prostate cancer mortality, even among patients with multiple comorbidities. Additional studies are warranted to determine optimal multimodal treatment approach for high-risk patients., (© 2012 The Japanese Urological Association.)

Purpose: Clinical stage has been incorporated into multiple risk stratification models for patients with newly diagnosed prostate cancer. However, the independent prognostic value of this variable remains open to debate. In this study we evaluated the association of clinical stage with death from prostate cancer in men who underwent radical prostatectomy and assessed for changes in its prognostic value over time., Materials and Methods: We reviewed the records of 14,842 consecutive patients who underwent radical prostatectomy at our institution between 1970 and 2008 without having received preoperative hormone or radiation therapy. Postoperative disease recurrence was estimated using the Kaplan-Meier method and compared using the log rank test. Multivariate Cox proportional hazard regression models were used to analyze the association of clinical stage with outcome., Results: A total of 5,725 (38.6%) men were classified as having cT1 tumors, 8,160 (55.0%) cT2 tumors and 957 (6.4%) cT3 disease. On univariate analysis clinical stage was significantly associated with postoperative biochemical recurrence, systemic progression and death from prostate cancer (p <0.001 for each). Moreover on multivariate analysis clinical stage was significantly associated with death from cancer for patients treated before (1.45, p = 0.006) and those treated during (1.96, p <0.001) the prostate specific antigen era. Furthermore, the incorporation of clinical stage into contemporary risk stratification improved the prediction of cancer specific survival (c statistic 0.782 without and 0.802 with clinical stage)., Conclusions: Clinical stage is significantly associated with systemic progression and death from prostate cancer. Inclusion of this variable in multivariate prediction models improves the prediction of systemic progression and cancer specific survival., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We examined the performance of (11)C-choline positron emission tomography/computerized tomography for its ability to delineate prostate cancer distribution and extent after initial therapy., Materials and Methods: A consecutive series retrospective review was performed of all patients with prostate cancer who were evaluated using (11)C-choline positron emission tomography/computerized tomography from September 2007 to November 2010 at the Mayo Clinic. Statistical analysis was performed to determine the sensitivity, specificity, positive predictive value, negative predictive value and prostate specific antigen threshold for the detection of recurrent lesions., Results: In the study period 176 patients with biochemical recurrence after primary treatment failure underwent (11)C-choline positron emission tomography/computerized tomography. Using patient based analysis (11)C-choline positron emission tomography yielded a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 76%, 91% and 81%, respectively. Of the 176 positron emission tomography/computerized tomography scans performed 56 (32%) were deemed clinically useful as defined by the ability to identify lesions not delineated using conventional imaging, thereby prompting changes in clinical management. The optimal prostate specific antigen for lesion detection was 2.0 ng/ml. On multivariate analysis prostate specific antigen at positron emission tomography (HR 1.37, p = 0.04) and clinical stage at initial diagnosis of prostate cancer (HR 5.19, p = 0.0035) were significant predictors of positive (11)C-choline positron emission tomography/computerized tomography., Conclusions: (11)C-choline positron emission tomography/computerized tomography performs well in men with biochemical recurrence after primary treatment failure. The optimal prostate specific antigen value for lesion detection is approximately 2.0 ng/ml. We found that (11)C-choline positron emission tomography/computerized tomography substantially enhances the rate of prostate cancer lesion detection by approximately 32% beyond what can be garnered using conventional imaging techniques and at a lower prostate specific antigen value., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Despite a lack of randomised controlled trials, most men with locally advanced prostate cancer are recommended to undergo external beam radiotherapy (EBRT), often combined with long-term androgen-deprivation therapy (ADT). Many of these men are not offered radical prostatectomy (RP) by their treating urologist. Additionally, it is know that EBRT with long-term ADT does provide good cancer control (88% at 10 years). We have previously published intermediate-term follow-up of a large series of men treatment with RP for cT3 prostate cancer. We report long-term follow-up of a large series of men treated with RP as primary treatment for cT3 prostate cancer. Our study shows that with long-term follow-up RP provides excellent oncological outcomes even at 20 years. While most men do require a multimodal treatment approach, many men can be managed successfully with RP alone., Objective: • To present long-term survival outcomes after radical prostatectomy (RP) for patients with cT3 prostate cancer, as the optimal treatment for patients with clinical T3 prostate cancer is debated., Patients and Methods: • We identified 843 men who underwent RP for cT3 tumours between 1987 and 1997. • Survival was estimated using the Kaplan-Meier method. • Cox proportional hazards regression models were used to evaluate the association of clinicopathological features with outcome, Results: • The median (range) postoperative follow-up was 14.3 (0.1-23.5) years. • Down-staging to pT2 disease occurred in 26% (223/843) at surgery. • Local recurrence-free, systemic progression-free and cancer-specific survival for men with cT3 prostate cancer after RP was 76%, 72%, and 81%, respectively, at 20 years. • On multivariate analysis, increasing RP Gleason score (hazard ratio [HR] 1.8; P = 0.01), non-diploid chromatin content (HR 1.8; P = 0.01), positive surgical margins (HR 2.1; P = 0.007), and seminal vesicle invasion (HR 2.1; P = 0.005) were associated with a significant risk of prostate cancer death, while a more recent year of surgery was associated with a decreased risk of cancer-specific mortality (HR 0.88; P = 0.01), Conclusions: • RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow-up presented here. • RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumours., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Purpose: We evaluated the long-term outcome of patients with biochemical recurrence following radical prostatectomy with adjuvant radiation therapy and determined predictors of systemic progression in these men., Materials and Methods: We identified 134 men with biochemical recurrence following radical prostatectomy plus adjuvant radiation therapy for pT(any)N0M0 disease. Median followup was 13.1 years. Survival after biochemical recurrence was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze clinicopathological variables associated with systemic progression after biochemical recurrence., Results: Overall, 41 patients (31.5%) with biochemical recurrence experienced systemic progression and 57 (42.5%) died, including 19 (14.2%) of prostate cancer. Median systemic progression-free and cancer specific survival were not attained at 15 years of followup after biochemical recurrence. Median time from prostatectomy to recurrence was 3.3 years. Ten-year cancer specific survival was not significantly different for patients who experienced biochemical recurrence less and greater than 3.3 years after radical prostatectomy (83% and 83%, respectively, p = 0.39). Moreover, on multivariate analysis increased pathological Gleason score (HR 1.78, p = 0.02) and rapid prostate specific antigen doubling time (less than 6-month doubling time HR 11.39, p <0.0001) were significantly associated with the risk of systemic progression., Conclusions: The natural history of biochemical recurrence after radical prostatectomy plus adjuvant radiation therapy is heterogeneous with only a minority of these men experiencing systemic progression and death from prostate cancer. The decision to begin additional therapies in such patients must balance the risk of disease progression, based on pathological Gleason score and postoperative prostate specific antigen doubling time, against the cost and morbidity of treatment., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of the body mass index (BMI) as it relates to the predictive value of the preoperative prostate-specific antigen (PSA) level regarding the tumor volume at radical prostatectomy. Stage migration with the widespread use of PSA screening is well documented; however, the association between the PSA level and tumor volume is less defined. Additionally, the effect of obesity on the serum PSA level might cause relative hemodilution and account for the decreased predictive ability of the PSA level to determine the tumor volume in the modern era., Methods: We identified 14 293 patients who had undergone radical prostatectomy for prostate cancer from 1987 to 2007 and had a documented BMI. Using the clinicopathologic variables, we examined the relationship among the BMI, preoperative PSA level, and tumor volume at radical prostatectomy using multiple linear regression analysis., Results: An elevated BMI was associated with an increased pathologic Gleason score (P < .0001), increased tumor volume (P < .0001), and increased prostate size (P < .0001). The preoperative PSA level correlated significantly with the tumor volume (P < .0001). No significant correlation was found between the BMI and preoperative PSA level (P = .39). On multivariate analysis, controlling for the BMI, the preoperative PSA level remained a significant predictor of the tumor volume (P < .0001). The interaction between the preoperative PSA level and BMI in the prediction of the tumor volume was not statistically significant (P = .56), suggesting that the BMI does not affect the association between the PSA level and tumor volume., Conclusion: Our results have shown that the predictive ability of the PSA level for tumor volume is not affected by the BMI. There does not appear to be a need to correct the serum PSA level in relation to the BMI when used in preoperative prediction models of the tumor volume., (Published by Elsevier Inc.)

Background: The long-term survival of patients with high-risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen-deprivation therapy (ADT)., Methods: In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate-specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow-up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer-specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk-regression model., Results: The 10-year cancer-specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51-1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68-1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all-cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25-2.05; P = .0002)., Conclusions: RRP alone and EBRT plus ADT provided similar long-term cancer control for patients with high-risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality-of-life and noncancer mortality will be necessary to determine the optimal management approach for these patients., (Copyright © 2011 American Cancer Society.)

Background: The natural history of biochemical recurrence (BCR) after radical retropubic prostatectomy (RRP) is variable and does not always translate into systemic progression or prostate cancer (PCa) death., Objective: To evaluate long-term clinical outcomes of patients with BCR and to determine predictors of disease progression and mortality in these men., Design, Setting, and Participants: We reviewed our institutional registry of 14 632 patients who underwent RRP between 1990 and 2006 to identify 2426 men with BCR (prostate-specific antigen [PSA] levels ≥ 0.4 ng/ml) who did not receive neoadjuvant or adjuvant therapy. Median follow-up was 11.5 yr after RRP and 6.6 yr after BCR., Intervention: RRP., Measurements: Patients were grouped into quartiles according to time from RRP to BCR. Survival after BCR was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression models were used to analyze clinicopathologic variables associated with systemic progression and death from PCa., Results and Limitations: Median systemic progression-free survival (PFS) and cancer-specific survival (CSS) had not been reached after 15 yr of follow-up after BCR. Cancer-specific mortality 10 yr after BCR was 9.9%, 9.3%, 7.8%, and 4.7% for patients who experienced BCR <1.2 yr, 1.2-3.1 yr, 3.1-5.9 yr, and >5.9 yr after RRP, respectively (p=0.10). On multivariate analysis, time from RRP to BCR was not significantly associated with the risk of systemic progression (p=0.50) or cancer-specific mortality (p=0.81). Older patient age, increased pathologic Gleason score, advanced tumor stage, and rapid PSA doubling time (DT) predicted systemic progression and death from PCa. Limitations included retrospective design, varied utilization of salvage therapies, and the inclusion of few patients with positive lymph nodes., Conclusions: Only a minority of men experience systemic progression and death from PCa following BCR. The decision to institute secondary therapies must balance the risk of disease progression with the cost and morbidity of treatment, independent of time from RRP to BCR., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate the effect of preoperative total serum calcium on disease progression after radical prostatectomy (RP). Elevated total serum calcium has been linked to death from prostate cancer in the National Health and Nutrition Examination Surveys I and II. However, these findings have not been studied in a large cohort of patients with prostate cancer., Methods: We identified 10,532 consecutive patients who had undergone RP from 1990 to 2004 for prostate cancer. Total serum calcium levels were available for 7648 (72.6%) of these patients within 90 days before RP. Postoperative survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression models were used to analyze the ability of serum calcium to predict biochemical recurrence, systemic progression, and cancer-specific survival., Results: The median patient age at surgery was 64 years. The median total serum calcium level was 9.4 mg/dL (range 6.8-11.2). On univariate analysis, the total serum calcium level was not significantly associated with any clinical or pathologic variables, including tumor stage, preoperative prostate-specific antigen, Gleason score, tumor volume, surgical margins, or lymph node status. Furthermore, the serum calcium level was not significantly associated with biochemical failure, systemic progression, or prostate cancer death on univariate or multivariate analysis., Conclusions: The total serum calcium level was not predictive of cancer outcomes in patients who had undergone RP. Additional investigations of the preoperative disease predictors after RP for patients with nonmetastatic disease might be better directed toward other markers., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To determine the impact of adjuvant androgen deprivation therapy (ADT) on survival in patients with seminal vesicle invasion (pT3b) at radical prostatectomy., Patients and Methods: We reviewed 12,115 patients who underwent radical prostatectomy between 1987 and 2002 to identify patients with pT3bN0 prostate cancer who received adjuvant ADT (n= 191). These patients were matched by clinical and pathological variables to a group of patients with pT3b prostate cancer who did not receive adjuvant ADT. Median postoperative follow-up was 10 years. Clinical endpoints included biochemical progression-free survival (BPFS), local recurrence-free survival (LRFS), systemic progression-free survival (SPFS), cancer-specific survival (CSS) and overall survival., Results: Patients who underwent adjuvant ADT experienced improved 10-year BPFS (60% vs 16%, P < 0.001), LRFS (87% vs 76%, P= 0.002), SPFS (91% vs 78%, P= 0.004) and CSS (94% vs 87%, P= 0.037). Overall survival was not significantly different between groups (75% vs 69%, P= 0.12). Both luteinizing hormone-releasing hormone agonists (hazard ratio, 0.26; 95% CI, 0.15-0.46; P < 0.001) and bilateral orchiectomy (hazard ratio, 0.13; 95% CI, 0.06-0.31; P < 0.001) improved BPFS. When stratified by type of ADT (hormonal therapy vs orchiectomy), there was no difference in survival outcomes., Conclusions: Adjuvant ADT improves local, and systemic control after radical prostatectomy for pT3b prostate cancer. There is no difference in survival between patients receiving medical hormonal therapy vs patients undergoing orchiectomy. Given the lack of improvement in overall survival, continued investigation is needed to identify the cohort of pT3b patients at highest risk for cancer progression and therefore most likely to benefit from a multimodal treatment approach., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Purpose: Many patients undergoing radical prostatectomy in the prostate specific antigen era have a low risk of recurrence. Aggressive postoperative prostate specific antigen surveillance is costly and anxiety provoking. In this study we investigate the need for yearly prostate specific antigen measurements in patients with surgically treated low risk prostate cancer., Materials and Methods: We identified 2,219 patients who underwent radical prostatectomy between 1994 and 2004 for low risk localized prostate cancer. Low risk was defined as prostate specific antigen less than 10 ng/ml, pathological stage pT2c or less, Gleason score 6 or less, negative lymph nodes and negative surgical margins. Patients who underwent neoadjuvant or adjuvant therapy were excluded from analysis. Biochemical failure was defined as a prostate specific antigen greater than 0.4 ng/ml and prostate specific antigen values less than 0.15 ng/ml were considered undetectable. Biochemical failure rates were calculated according to the duration of the prostate specific antigen-free period after radical prostatectomy., Results: A total of 142 (6.4%) patients experienced biochemical failure during the course of the study. The risk of biochemical failure decreased with increasing duration of the prostate specific antigen-free interval. For example 1, 3 and 5-year biochemical failure rates calculated at surgery were 1.8%, 4.2% and 6.3%, respectively. For patients with undetectable prostate specific antigen measurements 5 years after surgery the 1, 3 and 5-year biochemical failure rates were 0.0%, 0.7% and 1.3%, respectively. In addition, 1-year biochemical failure rates were 0.2%, 0.4%, 0.0% and 0.0% after a prostate specific antigen-free period of 1, 3, 5 and 10 years, respectively., Conclusions: The risk of biochemical failure is inversely proportional to the duration of the prostate specific antigen-free interval after radical prostatectomy in low risk patients. Biochemical failure 1 year after an undetectable prostate specific antigen is uncommon, especially after a prostate specific antigen-free period of 3 years. These data suggest that annual prostate specific antigen measurements are unnecessary, especially after a prostate specific antigen-free interval of 3 years. Prostate specific antigen measurements every 2 years should capture the majority of low risk patients who experience progression., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the influence of the pathological Gleason score on the predictive value of the prostate-specific antigen (PSA) doubling time (DT), as this variable predicts a patient's risk of disease progression both before and after definitive therapy for prostate cancer, and there is an inverse correlation between the Gleason score and PSA production., Patients and Methods: We evaluated all men treated with radical prostatectomy (RP) between 1990 and 1999 who did not receive neoadjuvant or adjuvant therapy. We identified 2296 patients who had multiple PSA values available before RP, and 1323 who had biochemical recurrence after RP and had at least two PSA values available before starting secondary therapy. Systemic progression and cancer-specific survival (CSS) rates were estimated using the Kaplan-Meier method and Cox proportional hazard regression models., Results: A PSA DT of <18 vs >18 months predicted a lower 10-year systemic progression-free survival for patients with tumours having a pathological Gleason score of <7 (98% vs 99%, P = 0.005), 7 (82% vs 91%, P = 0.003) and 8-10 (57% vs 73%, P = 0.042). A PSA DT after RP of <12 months was significantly associated with a lower 10-year systemic progression-free survival for patients with tumours having a Gleason score of <7 (77% vs 94%, P < 0.001) and 7 (61% vs 86%, P < 0.001), but not 8-10 (61% vs 75%, P = 0.11). The ability of PSA DT before and after RP to predict systemic progression and CSS decreased with increasing Gleason score., Conclusions: The PSA DT remains associated with outcome both before and after RP across increasing pathological Gleason scores, although the predictive ability of PSA DT is diminished in Gleason 8-10 cancers.

Purpose: The presence of a positive surgical margin at radical prostatectomy has been linked to an increased risk of postoperative biochemical recurrence. We evaluated the impact of margin status on subsequent clinical progression and mortality., Materials and Methods: We reviewed the records of 11,729 patients who underwent prostatectomy between 1990 and 2006. Survival was estimated for patients with vs without a positive margin and compared using the log rank test. Cox proportional hazards regression models were used to analyze the impact of margin status on survival., Results: Overall 3,651 (31.1%) men were identified with a positive margin. Median postoperative followup was 8.2 years (IQR 4.4, 12.1). The 10-year biochemical recurrence-free rate for patients with and without a positive margin was 56% and 77%, respectively (p <0.001), while 10-year local recurrence-free survival was 89% vs 95% (p <0.001). Margin status also stratified systemic progression-free survival (93% vs 97%, p <0.001), cancer specific survival (96% vs 99%, p <0.001) and overall survival (83% vs 88%, p <0.001). On multivariate analysis the presence of a positive margin was associated with increased risk of biochemical recurrence (HR 1.63, 95% CI 1.47-1.80, p <0.0001), local recurrence (HR 1.78, 95% CI 1.45-2.19, p <0.0001) and receipt of salvage therapy (HR 1.79, 95% CI 1.58-2.02, p <0.0001) but was not a significant predictor of systemic progression (p = 0.95), cancer specific death (p = 0.15) or overall mortality (p = 0.16)., Conclusions: The presence of a positive margin increased the risk of biochemical recurrence, local recurrence and the need for salvage treatment but was not independently associated with systemic progression, cancer specific death or overall mortality. These results should be considered when evaluating patients for adjuvant therapy., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Although secondary radiation therapy decreases the risk of biochemical progression after radical prostatectomy, its impact on metastasis and survival is less well established. We evaluated the impact of adjuvant and salvage radiotherapy on clinical progression and mortality., Materials and Methods: A total of 361 patients who received adjuvant radiation were matched based on clinicopathological features to patients who did not receive adjuvant radiation in a 2:1 case-control ratio. Postoperative survival was estimated using the Kaplan-Meier method and compared using the log rank test. A second cohort of 2,657 men who experienced biochemical recurrence after prostatectomy was separately evaluated. Cox proportional hazard regression models were used to analyze the impact of salvage radiotherapy on disease progression and survival., Results: Adjuvant radiotherapy was associated with significantly improved 10-year biochemical recurrence-free survival (63% vs 45%, p <0.001), local recurrence-free survival (97% vs 82%, p <0.001) and a decreased need for late hormone therapy (17% vs 28%, p = 0.002) but did not impact systemic progression and overall survival (p = 0.94 and 0.27, respectively). Of the 2,657 patients who experienced biochemical recurrence after surgery 856 (32.3%) received salvage radiation. On multivariate analysis salvage radiotherapy decreased the risk of local recurrence (HR 0.13, 95% CI 0.06-0.28, p <0.0001) and delayed hormonal therapy (HR 0.81, 95% CI 0.71-0.93, p = 0.003) and systemic progression (HR 0.24, 95% CI 0.13-0.45, p <0.0001) but did not significantly impact mortality (p = 0.48)., Conclusions: Adjuvant and salvage radiation provide long-term local control and decrease the need for delayed hormonal therapy but neither improves survival. These results must be weighed against the potential morbidity of postoperative radiation when counseling patients.

Objective: To assess the perioperative complications and early oncological results in a comparative study matching open radical retropubic (RRP) and robot-assisted radical prostatectomy (RARP) groups., Patients and Methods: From August 2002 to December 2005 we identified 294 patients undergoing RARP for clinically localized prostate cancer. A comparison RRP group of 588 patients from the same period was matched 2:1 for surgical year, age, preoperative prostate-specific antigen level, clinical stage and biopsy Gleason grade. Perioperative complications were compared. Patients completed a standardized quality-of-life questionnaire. Pathological features were assessed and Kaplan-Meier estimates of biochemical progression-free survival (PFS) were compared., Results: There was no significant difference in overall perioperative complications between the RARP and RRP groups (8.0% vs 4.8%, P = 0.064). Wound herniation was more common after RARP (1.0% vs none, P = 0.038), and development of bladder neck contracture was more common after RRP (1.2% vs 4.6%; P < 0.018). The hospital stay was less after RARP (29.3% vs 19.4%, P = 0.004, for a stay of 1 day). At the 1-year follow-up there was no significant difference in continence (RARP 91.8%, RRP 93.7%, P = 0.344) or potency (RARP 70.0%, RRP 62.8%, P = 0.081) rates. The biochemical PFS was no different between treatments at 3 years (RARP 92.4%, RRP 92.2%; P = 0.69)., Conclusion: There was no significant difference in overall early complication, long-term continence or potency rates between the RARP and RRP techniques. Furthermore, early oncological outcomes were similar, with equivalent margin positivity and PFS between the groups.

Purpose: Although discordance in the Gleason score between biopsy and radical prostatectomy specimens has been well recognized, the prognostic importance of this discrepancy has not been definitively established. We investigated the association of Gleason score discordance with postoperative systemic progression and death from prostate cancer., Materials and Methods: We evaluated the records of 8,054 consecutive patients who underwent radical prostatectomy between 1987 and 2003. Gleason score at biopsy and prostatectomy was categorized as 6 or less, 3 + 4, 4 + 3 and 8 to 10. Cox proportional hazard regression models were used to analyze the impact of biopsy Gleason score on postoperative survival in patients in each pathological Gleason score stratum., Results: Discordance in Gleason score was associated with adverse pathological features, including advanced tumor stage, lymph node metastasis and positive surgical margins (each p <0.001). On multivariate analysis increasing biopsy Gleason score was significantly associated with systemic progression in patients with pathological 3 + 4 and 8 to 10 cancer (HR 1.44, 95% CI 1.17-1.76, p <0.001 and HR 1.24, 95% CI 1.03-1.48, p = 0.023, respectively). It was also an independent predictor of death from prostate cancer in patients with pathological Gleason 3 + 4 tumors (HR 1.62, 95% CI 1.23-2.15, p <0.001). However, adding biopsy Gleason score to our institutional Gleason score, prostate specific antigen, and seminal vesicle and margin status scoring algorithm minimally increased the concordance statistic for the association of that algorithm with cancer specific mortality from 0.827 to 0.842., Conclusions: Biopsy Gleason score predicts systemic progression and cancer death in patients with pathological Gleason 3 + 4 tumors. Nevertheless, adding biopsy Gleason score to Gleason score, prostate specific antigen, and seminal vesicle and margin status did little to increase the predictive value of the model, which emphasizes the relative importance of pathological criteria for risk stratification.

Background: The authors evaluated the long-term outcomes of men with prostate cancer and very high (> or =50 ng/mL) preoperative serum prostate-specific antigen (PSA) values that were treated with radical prostatectomy., Methods: This study included 236 men with preoperative serum PSA values > or =50 ng/mL who underwent radical retropubic prostatectomy between 1987 and 2004. For comparison, the study cohort was divided into 2 groups: patients with PSA levels between 50 and 99 ng/mL and patients with PSA levels > or =100 ng/mL. Biochemical recurrence was defined as a single postoperative serum PSA value of 0.4 ng/mL or greater. Systemic disease progression was defined as the development of a local recurrence or systemic metastases, and any death resulting from prostate cancer or its treatment was defined as a cancer-specific mortality., Results: Biochemical recurrence-free survival rates in the groups of patients with a PSA level 50 to 99 ng/mL and > or =100 ng/mL were 43% and 36% at 10 years, respectively. Systemic progression-free survival rates in the PSA 50 to 99 ng/mL and PSA > or =100 ng/mL groups were 83% and 74% at 10 years, respectively. Estimated overall cancer-specific survival was 87% at 10 years., Conclusions: Patients with prostate cancer and a serum PSA level > or =50 ng/mL have very high-risk prostate cancer that carries a high likelihood of being pathologically advanced. Although the probability of realizing long-term survival in these high-risk patients is less than in patients with more favorable disease, 10-year survival outcomes remain excellent and argue for aggressive management of these cases.

Purpose: In men who are at high-risk of prostate cancer, progression and death from cancer after radical retropubic prostatectomy (RRP), limited prognostic information is provided by established prognostic features. The objective of this study was to develop a model predictive of outcome in this group of patients., Methods: Candidate genes were identified from microarray expression data from 102 laser capture microdissected prostate tissue samples. Candidates were overexpressed in tumor compared with normal prostate and more frequently in Gleason patterns 4 and 5 than in 3. A case control study of 157 high-risk patients, matched on Gleason score and stage with systemic progression or death of prostate cancer as the end point, was used to evaluate the expression of candidate genes and build a multivariate model. Tumor was collected from the highest Gleason score in paraffin-embedded blocks and the gene expression was quantified by real-time reverse transcription polymerase chain reaction. Validation of the final model was performed on a separate case-control study of 57 high-risk patients who underwent RRP., Results: A model incorporating gene expression of topoisomerase-2a, cadherin-10, the fusion status based on ERG, ETV1, and ETV4 expression, and the aneuploidy status resulted in a 0.81 area under the curve (AUC) in receiver operating characteristic statistical analysis for the identification of men with systemic progression and death from high grade prostate cancer. The AUC was 0.79 in the independent validation study., Conclusion: The model can identify men with high-risk prostate cancer who may benefit from more intensive postoperative follow-up and adjuvant therapies.

Purpose: The D'Amico risk group classification was originally developed to estimate the risk of biochemical recurrence following treatment for localized prostate cancer. We externally validated the ability of the risk groups to predict clinical progression, and cancer specific and overall survival following radical prostatectomy, and identify predictors of outcome in patients with high risk disease., Materials and Methods: We evaluated the records of 7,591 consecutive patients who underwent radical prostatectomy at our institution between 1987 and 2003. Postoperative survival was estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to analyze the ability of the risk groups to predict survival and to evaluate the impact of clinicopathological factors on outcome in patients at high risk., Results: Preoperative risk group stratification predicted the patient risk of biochemical and local recurrence, systemic progression, and cancer specific and overall survival (each p <0.001). The HR of death from prostate cancer after surgery in patients with high or intermediate risk disease was 11.5 (95% CI 5.9 to 22.3, p <0.0001) and 6.3 (95% CI 3.3 to 12.3, p <0.0001), respectively, compared to patients at low risk. In patients in the high risk group biopsy Gleason score (p = 0.006), pathological Gleason score (p = 0.006), pathological tumor stage (p = 0.04), positive lymph nodes (p = 0.02) and positive surgical margins (p = 0.008) predicted death from prostate cancer., Conclusions: We validated the ability of the risk group stratification to predict disease progression and patient survival following radical prostatectomy. Additional prognostic information from surgical staging may assist in individualized postoperative management, particularly for patients at high risk.

Objective: To investigate whether the clinical and pathological outcomes after radical retropubic prostatectomy (RRP) have changed since the advent of prostate-specific antigen (PSA) testing for patients with Gleason 8-10 cancers., Patients and Methods: We identified 584 men treated with RRP between 1988 and 2001 for pathological Gleason 8-10 tumours. Patients were divided for analysis by year of surgery, i.e. early (1988-93), mid (1994-97) and late PSA era (1998-2001). Survival rates after RRP were estimated using the Kaplan-Meier method, and the effect of clinicopathological factors on outcome was analysed using Cox proportional hazard regression models., Results: The median preoperative PSA level decreased from 15 ng/mL in the early to 10 ng/mL in the late PSA era (P < 0.001), while the rate of organ-confined disease increased from 22.9% to 35.1% (P = 0.007). However, the 7-year biochemical recurrence-free (37% vs 45%, P = 0.087) and cancer-specific survival (89% to 91%, P = 0.73) did not change significantly from the early to the late PSA era. Increased preoperative PSA level (P < 0.001), seminal vesicle invasion (P < 0.001) and positive lymph nodes (P = 0.02) were associated with biochemical recurrence. Seminal vesicle invasion (P = 0.005), positive nodes (P < 0.001) and positive surgical margins (P = 0.03) predicted death from cancer., Conclusion: Although the pathological features of Gleason 8-10 cancers have become more favourable over the PSA era, survival has not changed. This lack of improvement in clinical outcome probably reflects the inherent biological aggressiveness of these cancers. While RRP provides long-term cancer control in a subset of these patients, continued investigation of multi-modal treatment options is warranted.

Purpose: Our goal was to evaluate the long-term prognostic value of magnetic resonance imaging of the prostatectomy bed in patients with biochemical recurrence after radical prostatectomy for prostate cancer. Materials and Methods: Men with biochemical recurrence after radical prostatectomy who were studied by prostatectomy bed magnetic resonance imaging for suspected local recurrence were retrospectively evaluated. Locally recurrent tumors were noted and measured from imaging reports. Patients with nodal/bone lesions at the time of imaging were excluded. Kaplan-Meier and Cox regression analyses were used to assess systemic progression-free and prostate cancer-specific survival. Results: A total of 896 men were enrolled and the imaging positive and negative groups for local recurrent tumor consisted of 441 and 455 men, respectively. On univariate analysis, preoperative prostate specific antigen (p[0.02), clinical tumor stage (p[0.006), pathological Gleason score from prostatectomy (p[0.02), subsequent salvage radiotherapy (p <0.001), biochemical recurrence to magnetic resonance imaging time interval (p <0.001), age at magnetic resonance imaging (p[0.047) and prostate specific antigen at magnetic resonance imaging (p <0.001) were significantly different between magnetic resonance imaging positive and negative groups. Patients with negative magnetic resonance imaging results had worse systemic progression-free survival rates (p[0.025) and better prostate cancer-specific survival (p[0.016) than those with recurrence. Larger lesion size significantly increased risk of prostate cancer death (hazard ratio: 1.07; p <0.001). On multivariable analysis, pathological Gleason scores -7 were independent prognostic factors of systemic progression (p <0.05). Conclusions: Prostatectomy bed magnetic resonance imaging provides long-term prognostic information for the evaluation of patients with biochemical recurrence after prostatectomy. Post-prostatectomy patients with recurrent lesions on imaging had longer progression-free survival but shorter prostate cancer-specific survival compared to those without lesions. Additionally, those with larger lesions were associated with poorer cancer-specific survival. [ABSTRACT FROM AUTHOR]

Purpose: We examined the performance of 11C-choline positron emission tomography/computerized tomography for its ability to delineate prostate cancer distribution and extent after initial therapy. Materials and Methods: A consecutive series retrospective review was performed of all patients with prostate cancer who were evaluated using 11C-choline positron emission tomography/computerized tomography from September 2007 to November 2010 at the Mayo Clinic. Statistical analysis was performed to determine the sensitivity, specificity, positive predictive value, negative predictive value and prostate specific antigen threshold for the detection of recurrent lesions. Results: In the study period 176 patients with biochemical recurrence after primary treatment failure underwent 11C-choline positron emission tomography/computerized tomography. Using patient based analysis 11C-choline positron emission tomography yielded a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 76%, 91% and 81%, respectively. Of the 176 positron emission tomography/computerized tomography scans performed 56 (32%) were deemed clinically useful as defined by the ability to identify lesions not delineated using conventional imaging, thereby prompting changes in clinical management. The optimal prostate specific antigen for lesion detection was 2.0 ng/ml. On multivariate analysis prostate specific antigen at positron emission tomography (HR 1.37, p = 0.04) and clinical stage at initial diagnosis of prostate cancer (HR 5.19, p = 0.0035) were significant predictors of positive 11C-choline positron emission tomography/computerized tomography. Conclusions: 11C-choline positron emission tomography/computerized tomography performs well in men with biochemical recurrence after primary treatment failure. The optimal prostate specific antigen value for lesion detection is approximately 2.0 ng/ml. We found that 11C-choline positron emission tomography/computerized tomography substantially enhances the rate of prostate cancer lesion detection by approximately 32% beyond what can be garnered using conventional imaging techniques and at a lower prostate specific antigen value. [Copyright &y& Elsevier]