Definition of high-risk prostate cancer impacts oncological outcomes after radical prostatectomy

To examine the impact of different pretreatment definitions on biochemical recurrence (BCR)-free survival, metastasis-free survival, and cancer-specific survival after radical prostatectomy.

Overall, 26,364 patients with clinically localized disease who underwent radical prostatectomy at a single institution (1992-2017) were retrospectively analyzed. Seven pretreatment definitions of high-risk CaP (prostate-specific antigen [PSA] ≥20 ng/ml, clinical stage ≥T2c, clinical stage T3 [cT3], biopsy Gleason score [GS] 8-10 [Grade Group {GG} IV-V], biopsy GS 9 to 10 [GG V], D'Amico risk definition, National Comprehensive Cancer Network risk definition) were evaluated. Kaplan-Meier, as well as multivariable Cox regression analyses were used.

Depending on the definition, patients with high-risk CaP comprised between 0.9% (cT3) and 20.3% (D'Amico high-risk) of the population. Ten-year BCR-free survival rates varied from 36.0% (≥cT2c) to 47.4% (National Comprehensive Cancer Network high-risk). Ten-year metastasis-free survival rates varied from 56.6% (GS 9-10/GG V) to 77.5% (PSA ≥ 20 ng/ml). Ten-year cancer-specific survival rates varied from 86.6% (cT3) to 94.5% (PSA ≥ 20 ng/ml). In multivariable analysis, all high-risk definitions were associated with significantly higher risk of BCR (hazard ratio [HR]: 3.4-3.9), metastatic progression (HR: 3.9-8.8), and cancer-specific mortality (HR: 2.8-11.2).

Variety in outcomes exists, depending on the pretreatment definition of high-risk CaP. Among the tested, GS 9 to 10 (GG V), cT2c, and cT3 were the strongest predictor for higher BCR risk, cT3 was the strongest predictor for higher metastatic progression risk and GS 9 to 10 (GG V) was the strongest predictor for higher cancer-specific mortality risk in multivariable analyses.