The Significance of Primary Biopsy Gleason 5 in Patients with Grade Group 5 Prostate Cancer.

The five-tier grade group (GG) classification for prostate cancer (PCa) does not differentiate between primary (5+4) or secondary (4+5) histological Gleason 5 pattern in GG 5. We addressed the prognostic value of primary versus secondary biopsy Gleason 5 for GG 5 among 18 555 PCa patients treated with radical prostatectomy (RP) between 1992 and 2014. Of these, 922 patients had GG 5 PCa with primary (n=295) or secondary (n=627) Gleason 5 on biopsy. Prediction of biochemical recurrence (BCR), metastasis, and cancer-specific mortality (CSM) was assessed using Kaplan-Meier curves and univariable/multivariable Cox regression controlling for known prognosticators. Median follow-up was 74.8 mo (interquartile range [IQR] 49.2-120.2). BCR developed in 24.3% of patients (n=4508) at a median of 23.6 mo (IQR 7.1-48.6). Metastasis developed in 4.5% (n=827) and 2.0% (n=370) died of PCa. When stratifying GG 5 by primary versus secondary Gleason 5, the estimated 5-yr metastasis-free survival was 80.4% (95% confidence interval [CI] 76.1-85.0%) versus 86.9% (95% CI 84.2-89.7%; p= 0.002) and cancer-specific survival was 90.9% (95% CI 87.5-94.4%) versus 96.3% (95% CI 94.7-98.0%; p< 0.001). On multivariable analysis, the negative impact of primary biopsy Gleason 5 among GG 5 patients remained significant for metastasis (hazard ratio [HR] 1.58; p< 0.001) and CSM (HR 2.44; p< 0.001). Therefore, stratifying GG 5 into primary (5 + 4, 5 + 5) and secondary (4 + 5) Gleason 5 may be warranted. PATIENT SUMMARY: We recorded worse oncological outcomes for patients with a primary histological Gleason 5 pattern on prostate biopsy compared to patients with a secondary biopsy Gleason 5 pattern.