Tertiary Gleason pattern in radical prostatectomy specimens is associated with worse outcomes than the next higher Gleason score group in localized prostate cancer

Abstract

Aim: To assess the predictive value of TGP on biochemical recurrence (BCR) and its association with clinicopathological outcomes in a large, multicenter cohort of patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP).

Materials and methods: Records of 6,041 patients who were treated with RP between 2000 and 2011 for clinically nonmetastatic PCa were, retrospectively, analyzed from prospectively collected datasets. BCR-free survival rates were assessed using univariable and multivariable cox-regression analyses.

Results: Median patient age was 61 years (interquartile range [IQR]: 57-66) with a median preoperative prostrate specific antigen of 6ng/ml (IQR: 4-9). Overall, 28% of patients had Gleason score (GS) 6, 0.3% GS 6 + TGP, 33% GS 7 (3 + 4), 0.2% GS 7 (3 + 4) + TGP, 22% GS 7 (4 + 3), 0.2% GS 7 (4 + 3) + TGP, 0.1% GS 8 and 0.4% GS 9 or 10. Median follow-up was 45 months (IQR: 31-57). Harboring a TGP was associated with higher rates of positive surgical margins, lymphovascular invasion, extraprostatic extension, and seminal vesicle invasion than their counterparts within the same GS group as well as in the next higher GS group (all P ≤ 0.05). At 5 years post-RP, BCR estimates were 5% for patients with GS 6, 13% for patients with GS 6 + TGP, 6% for patients with GS 7 (3 + 4), 22% for patients with GS 7 (3 + 4) + TGP, 16% for patients with GS 7 (4 + 3), 41% for patients with GS 7 (4 + 3) + TGP, 38% for patients with GS 8 (4 + 4) and 46% for patients with GS 9 or 10. Patients harboring a TGP had higher BCR rates than the patients in the next higher GS group: GS 6 + TGP vs. GS 7 (3 + 4), HR = 1.6, P = 0.02 and GS 7 (3 + 4)+TGP vs. GS 7 (4 + 3), HR = 1.4, P = 0.03. Patients with a TGP in the GS 7 (4 + 3) group had comparable BCR rates as patients with GS = 8 (P = 0.4) and GS 9 to 10 (P = 0.2). On multivariable analysis that adjusted for the effects of preoperative prostrate specific antigen, nodal involvement, positive surgical margin, extraprostatic disease (pT3a), seminal vesicle invasion (pT3b) and different institution, harboring a TGP showed higher risk of developing BCR within the same GS group and comparable risk of developing BCR with the next higher GS group.

Conclusion: Patients with TGP at RP have adverse clinicopathological features when compared to their counterparts in the same and the next higher GS group without TGP. Risk of developing BCR increases with the presence of TGP within the same GS group. This risk seems to be comparable between patients with TGP and their counterparts in the next higher GS group without TGP. Knowledge of TGP in RP specimens is likely to improve risk stratification, patient counseling and follow-up scheduling. Further prospective studies that control significant clinical endpoints such as metastasis and mortality are necessary for more significant predictions.

Keywords: Biochemical recurrence; Gleason score; Prostate cancer; Radical prostatectomy; Tertiary Gleason pattern.