Introduction: Gleason Score 7 prostate cancer (including Grade Group (GG) 2 and GG3) represents a widely heterogenous disease process, and precise sub-stratification of this cohort is paramount. Our group previously demonstrated that the total length of Gleason pattern 4 (GP4) across all biopsy cores has been shown to be associated with adverse pathologic outcomes after radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy on post-prostatectomy oncologic outcomes.
Methods: We compared four GP4 quantification methods including: maximum %GP4 in any single core, overall %GP4 (mm of GP4/total mm of cancer), total length GP4 (mm) across all cores, and length GP4 (mm) in the core with the greatest volume of GP4. for prediction of biochemical recurrence–free survival after radical prostatectomy using multivariable Cox proportional hazards regression.
Results: A total of 457 men with Grade Group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy at our institution. The 3-year biochemical recurrence–free survival probability was 85% (95% CI 81–88%). On multivariable analysis, all four GP4 quantification methods—maximum %GP4 (HR=1.30; 95% CI 1.07–1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21–2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36–4.52; p=0.003), and total length GP4 in highest core (HR=1.32; 95% CI 1.11–1.57; p=0.001)—were significantly associated with BCR. Models including all methods of GP4 quantification resulted in a meaningful increase in discrimination of BCR risk, with similar gains in Harrell’s C-index ranging from 0.017 to 0.019.
Conclusions: These findings further support routine reporting of and inclusion of GP4 quantification in pathology reports and risk prediction models for patients with Grade Group 2 prostate cancer. These data also support studying GP4 quantification as a surrogate endpoint for disease progression for trials, including those of men managed with active surveillance.
Source of Funding: This work was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers at MSK, the NIH/NCI grant P50 CA092629, and the NIH/NCI Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748). Marlon Perera is sponsored by the Australian-America Fulbright Commission administered through a 2021-2022 Fulbright Future Scholarship funded by The Kinghorn Foundation. Sigrid Carlsson is supported by a NIH/NCI grant K22-CA234400.