Prognostic Impact and Clinical Implications of Unfavorable Upgrading in Low-Risk Prostate Cancer after Robot-Assisted Radical Prostatectomy: Results of a Single Tertiary Referral Center

SIMPLE SUMMARY: Unfavorable pathology in low-risk prostate cancer (PCa) is one of the most controversial subjects for the implications in clinical decision making when counseling patients. In the present study, we tested the hypothesis that unfavorable tumor upgrading, which we defined as International Society of Urological Pathology (ISUP) tumor grade groups greater than 2, might have a different prognostic impact when compared with no (ISUP 1) or favorable (ISUP 2) upgrading. Study findings show that low-risk patients with unfavorable tumor upgrading were more likely to have disease relapse, which occurred in 8.4% of cases and was associated with older age, PSA density ≥ 0.15 ng/mL/cc, and tumors being larger and extending beyond the gland. Unfavorable tumor upgrading is an issue to consider when counseling low-risk patients in order to avoid delayed treatments, which may impair cancer-specific survival. These findings represent a novelty for either urologists or radiation oncologists when counseling low-risk PCa patients. ABSTRACT: Objective: to evaluate predictors and the prognostic impact of favorable vs. unfavorable tumor upgrading among low-risk prostate cancer (LR PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: From January 2013 to October 2020, LR PCa patients treated with RARP at our institution were identified. Unfavorable tumor upgrading was defined as the presence of an International Society of Urological Pathology (ISUP) grade group at final pathology > 2. Disease relapse was coded as biochemical recurrence and/or local recurrence and/or presence of distant metastases. Regression analyses tested the association between clinical and pathological features and the risk of unfavorable tumor upgrading and disease relapse. Results: Of the 237 total LR PCa patients, 60 (25.3%) harbored unfavorable tumor upgrading. Disease relapse occurred in 20 (8.4%) patients. Unfavorable upgrading represented an independent predictor of disease relapse, even after adjustment for other clinical and pathological variables. Conversely, favorable tumor upgrading did not show any statistically significant association with PCa relapse. Unfavorable tumor upgrading was associated with tumors being larger (OR: 1.03; p = 0.031), tumors extending beyond the gland (OR: 8.54, p < 0.001), age (OR: 1.07, p = 0.009), and PSA density (PSAD) ≥ 0.15 ng/mL/cc (OR: 1.07, p = 0.009). Conclusions: LR PCa patients with unfavorable upgrading at final pathology were more likely to be older, to have PSAD ≥ 0.15 ng/mL/cc, and to experience disease relapse. Unfavorable tumor upgrading is an issue to consider when counseling these patients to avoid delayed treatments, which may impair cancer-specific survival.