Biochemical recurrence (BCR) after primary treatment of localized prostate cancer does not necessarily lead to clinically apparent progressive disease. To aid in prognostication, the European Association of Urology prostate cancer guidelines panel undertook a systematic review and successfully developed a novel BCR risk stratification system (groups with a low risk or high risk of BCR) based on disease and prostate-specific antigen characteristics. PATIENT SUMMARY: Following treatment to cure prostate cancer, some patients can develop recurrence of disease identified via a prostate-specific antigen blood test (ie, biochemical recurrence, or BCR). However, not every man who experiences BCR develops progressive disease (symptoms or evidence of disease progression on imaging). We conducted a review of the literature and developed a classification system for predicting which patients might progress to optimize treatment decisions.

BACKGROUND: Current treatment plans for localized prostate carcinoma (PC) are based on core needle biopsies (CNB) classified using the Gleason score (GS). Recently, many institutions have started using the latest version of International Society of Urological Pathology (ISUP) guideline revision from 2014 for PC grading. Interestingly, this adoption is occurring without first understanding whether the 2005 ISUP revisions had a positive clinical impact. CNB-based GS may underestimate tumor aggressiveness and, therefore, critically impact patient eligibility for active surveillance (AS). The 2005 ISUP recommendations bore a significant impact on the grading of Gleason 6 and 7 PCs - a range that is meaningful for AS. The objective of this study was to compare the concordance between GS in CNB and radical prostatectomy (RP) before and after the 2005 ISUP guideline revisions, with an emphasis on its clinical impact on AS.
METHODS: This was a single-center, prospective observational study. CNB were performed in a standardized manner. GS of CNB and RP specimens were compared across three time periods: 1999-2005 (pre-revision), 2006-2007 (transitional period), and 2008-2015 (post-revision). AS is usually employed in patients with GS 6 or GS 7 PC. Thus, we therefore focused on the analysis of patients with CNBs of GS ≤7.
RESULTS: Between 1999 and 2015, 380 men with GS ≤7 PC underwent RP at our institution (median age: 62y; median PSA: 5.8 ng/ml). Of these, 231 CNB specimens were classified as GS ≤6, while 149 were GS 7.46% (pre-revision), 43% (transitional), and 54% (post-revision) of CNB with original scores ≤6 were later upgraded in corresponding RP specimens (p <0.001).
CONCLUSIONS: The 2005 ISUP GS revisions did not lower the rates of GS upgrades in RP specimens when compared to corresponding initial CNBs. Thus, these revisions did not improve AS selection. Future advances in molecular diagnostics may provide additional valuable information that facilitates patient enrollment in AS programs.

To evaluate the impact that the 2012 US Preventive Services Task Force (USPSTF) prostate-specific antigen (PSA) screening guidelines have had on the diagnosis of prostate cancer, we compared the incidence and distribution of new cases diagnosed in 2011-before the USPSTF PSA screening recommendations versus 2014 at which time the guidelines were widely adopted.
We identified all prostate biopsies performed by a large urology group practice utilizing a centralized pathology lab. We examined total biopsies performed, percentage of positive biopsies, and for those with positive biopsies examined for differences in patient age, PSA, and Gleason score.
A total of 4,178 biopsies were identified - 2,513 in 2011 and 1,665 in 2014. The percentage of positive biopsies was 27% in 2011 versus 34% in 2014 (p<0.0001). Among patients with positive biopsies, we found statistically significant differences between the 2 cohorts in the median ages and Gleason scores. Patients were about 1 year younger in 2014 compared to 2011 (t-test; p=0.043). High Gleason scores (8-10) were diagnosed in 19% of the 2014 positive biopsies versus 9% in the 2011 positive biopsies (chi square; p<0.0001).
After the widespread implementation of the 2011 USPTF PSA screening guidelines, 34% fewer biopsies were performed with a 29% increase in positive biopsy rates. We found a significantly higher incidence of high grade disease in 2014 compared with 2011. The percentage of patients with positive biopsies having Gleason scores 8-10 more than doubled in 2014. The higher incidence of these more aggressive cancers must be part of the discussion regarding PSA screening.

To investigate whether the International Society of Urological Pathology (ISUP) 2005 revision of the Gleason grading system has influenced the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), as the new guideline implies that some prostate cancers previously graded as Gleason score 6 (3 + 3) are now considered as 7 (3 + 4).
A matched-pair analysis was conducted. In all, 215 patients with Gleason score 6 or 7 (3 + 4) prostate cancer on biopsy who underwent RP before 31 December 2005 (pre-ISUP group), were matched 1:1 by biopsy Gleason score, clinical tumour category, PSA level, and margin status to patients undergoing RP between 1 January 2008 and 31 December 2011 (post-ISUP group). Patients were followed until BCR defined as a PSA level of ≥0.2 ng/mL. Risk of BCR was analysed in a competing-risk model.
The median follow-up was 9.5 years in the pre-ISUP group and 4.8 years in the post-ISUP group. The 5-year cumulative incidences of BCR were 34.0% and 13.9% in the pre-ISUP and post-ISUP groups, respectively (P < 0.001). The difference in cumulative incidence applied to both patients with Gleason score 6 (P < 0.001) and 7 (3 + 4) (P = 0.004). There was no difference in the 5-year cumulative incidence of BCR between patients with pre-ISUP Gleason score 6 and post-ISUP Gleason score 7 (3 + 4) (P = 0.34). In a multiple Cox-proportional hazard regression model, ISUP 2005 grading was a strong prognostic factor for BCR within 5 years of RP (hazard ratio 0.34; 95% confidence interval 0.22-0.54; P < 0.001).
The revision of the Gleason grading system has reduced the risk of BCR after RP in patients with biopsy Gleason score 6 and 7 (3 + 4). This may have consequences when comparing outcomes across studies and historical periods and may affect future treatment recommendations.