Cumulative Cancer Locations is a Novel Metric for Predicting Active Surveillance Outcomes: A Multicenter Study

Background: Active surveillance (AS) of prostate cancer (PC) has increased in popularity to address overtreatment. Objective: To determine whether a novel metric, cumulative cancer locations (CCLO), can predict AS outcomes in a group of AS patients with low and very low risk. Design, setting, and participants: CCLO is obtained by summing the total number of histological cancer-positive locations in both diagnostic and confirmatory biopsies (Bx). The retrospective study cohort comprised three prospective AS cohorts (Helsinki University Hospital: n = 316; European Institute of Oncology: n = 204; and University of Münster: n = 89). Outcome measurements and statistical analysis: We analyzed whether risk stratification based on CCLO predicts different AS outcomes: protocol-based discontinuation (PBD), Gleason upgrading (GU) during AS, and adverse findings in radical prostatectomy (RP) specimens. Results: In Kaplan Meier analyses, patients in the CCLO high-risk group experienced significantly shorter event-free survival for all outcomes (PBD, GU, and adverse RP findings; all p < 0.002). In multivariable Cox regression analysis, patients in the CCLO high-risk group had a significantly higher risk of experiencing PBD (hazard ratio [HR] 12.15, 95% confidence interval [CI] 6.18–23.9; p < 0.001), GU (HR 6.01, 95% CI 2.16–16.8; p = 0.002), and adverse RP findings (HR 9.144, 95% CI 2.27–36.9; p = 0.006). In receiver operating characteristic analyses, the area under the curve for CCLO outperformed the number of cancer-positive Bxs in confirmatory Bx in predicting PBD (0.734 vs 0.682), GU (0.655 vs 0.576) and adverse RP findings (0.662 vs 0.561) and the added value was supported by decision curve analysis. Conclusions: CCLO is distinct from the number of positive Bx cores. Higher CCLO predicts AS outcomes and may aid in selection of patients for AS. Patient summary: For patients on active surveillance for prostate cancer, the cumulative number of cancer-positive locations in diagnostic and confirmatory biopsies is a predictor of active surveillance outcomes. In three independent prostate cancer active surveillance cohorts a novel metric called cumulative number of cancer locations significantly predicted active surveillance outcomes.