Are all grade group 4 prostate cancers created equal? Implications for the applicability of the novel grade grouping

• Published in: Urologic oncology 2017-07, Vol.35 (7), p.461.e7-461.e14
• Main Authors: Gandaglia, Giorgio, M.D, Karnes, R. Jeffrey, M.D, Sivaraman, Arjun, M.D, Moschini, Marco, M.D, Fossati, Nicola, M.D, Zaffuto, Emanuele, M.D, DellʼOglio, Paolo, M.D, Cathelineau, Xavier, M.D, Montorsi, Francesco, M.D, Sanchez-Salas, Rafael, M.D, Briganti, Alberto, M.D
• Format: Article
• Language: English
• Subjects: Aged; Biochemical recurrence; Gleason score; Humans; Male; Neoplasm Grading - methods; Novel grade grouping; Prostate cancer; Prostatectomy - methods; Prostatic Neoplasms - pathology; Radical prostatectomy; Urology
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2017.02.012

Abstract Background According to the novel prostate cancer (PCa) grade grouping, men with Gleason score 8 should be included in the grade group 4 regardless of primary and secondary scores. We aimed at evaluating the effect of Gleason patterns on the risk of recurrence in men with grade group 4 PCa. Patients and methods Overall, 1,089 patients treated with radical prostatectomy with grade group 4 PCa at final pathology were identified. Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen values≥0.2 ng/ml and rising. Clinical recurrence (CR) was defined as positive imaging after BCR. Kaplan-Meier analyses assessed time to BCR and CR. Multivariable Cox regression analyses assessed the impact of Gleason patterns on the risk of BCR and CR. Results Overall, 295 (27.1%), 651 (59.8%), and 143 (13.1%) patients had pathologic Gleason pattern 3+5, 4+4, and 5+3. Overall, 435 (39.9%) patients had positive margins and 439 (30.2%), 300 (27.5%), 350 (32.1%), and 216 (19.8%) had pT2, pT3a, pT3b/4, and pN1 disease. Median follow-up was 83 months. Overall, 536 and 221 patients experienced BCR and CR. The 10-year BCR- and CR-free survival rates were 42.9% and 67.5% vs. 38.3% and 59.7% vs. 40.6% and 50.4% for patients with pathologic Gleason pattern 3+5 vs. 4+4 vs. 5+3, respectively (all P ≤0.005). In multivariable analyses, patients with Gleason pattern 3+5 were at lower risk of BCR compared to those with 4+4 ( P = 0.002). Men with Gleason pattern 3+5 were at lower risk of CR compared to those with 4+4 and 5+3 (all P ≤ 0.01). Conclusions Patients with a primary Gleason score 3 are at reduced risk of recurrence as compared to their counterparts with 4 or 5. Primary and secondary Gleason scores should be considered to stratify the risk of recurrence after surgery in patients with grade group 4 PCa.