Gleason Grade Group 3 Represents a Spectrum of Disease: Results from a Large Institutional Cohort.

[BACKGROUND AND OBJECTIVE] A biopsy diagnosis of Gleason grade group (GG) 3 prostate cancer (PC) automatically classifies patients as having at least unfavorable intermediate-risk disease warranting definitive treatment. We hypothesized that GG3 PCs are not equally unfavorable.

[METHODS] The Urologic Outcomes Database at University of California-San Francisco was queried for men with localized, nonmetastatic PC diagnosed after 2000 who underwent radical prostatectomy (RP). The primary outcome was recurrence, defined as either biochemical failure (two prostate-specific antigen results ≥0.2 ng/ml) or salvage treatment. Multivariable Cox proportional-hazards regression models were used to calculate associations with the risk of recurrence, adjusted for clinicodemographic and postoperative factors.

[KEY FINDINGS AND LIMITATIONS] We included 4934 men who underwent RP in the analysis, of whom 862 (17%) were diagnosed with GG3 PC on biopsy. Cancer of the Prostate Risk Assessment postsurgery (CAPRA-S) scores overall increased over time, but remained broadly distributed. Multivariable analysis controlled for postoperative factors with CAPRA-S revealed that favorable biopsy Gleason histology (not expansile cribriform or intraductal carcinoma) was the strongest factor associated with lower risk of recurrence after RP (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41-0.91), independent of the percentage of pattern 4. A higher percentage of positive cores (PPC) was also significantly associated with the risk of recurrence (HR per 10% increment: 1.06, 95% CI 1.01-1.11). Limitations include the retrospective nature of the single-institution study and the homogeneous study population.

[CONCLUSIONS AND CLINICAL IMPLICATIONS] Patients with GG3 PC on diagnostic biopsy have heterogeneous risk. Unfavorable biopsy histology and higher PPC were significantly associated with the risk of recurrence after RP after controlling for CAPRA-S scores. Not all GG3 cancers are equally unfavorable, and differential management may be warranted.