Conditional progression-free survival in men on active surveillance for prostate cancer stratified by NCCN risk.

Abstract

222 Background: Active surveillance (AS) is an accepted management strategy for men with very low, low, and select cases of favorable intermediate National Comprehensive Cancer Network (NCCN) risk prostate cancer (PCa). However, how patients’ risk of disease progression evolves over time during AS has not been well defined. Conditional survival measures the probability a patient will continue to survive some number of years, given that they have already survived a certain number without progression. We evaluated our AS cohort to investigate overall and conditional progression free survival on AS, stratified by the NCCN risk groups. Methods: We reviewed our institutional database of 1254 men enrolled in AS for localized PCa from 1996-2016. Our AS protocol includes prostate specific antigen (PSA) and digital rectal exam (DRE) every 4-6 months for 3 years, then annually. Mandatory confirmatory 12 core biopsy is done at 12-18 months. Multiparametric magnetic resonance imagining (mpMRI) or additional systematic or MRI-fusion biopsies are done at the discretion of physician and patient. Overall freedom from pathologic grade progression on follow-up biopsy and treatment free survival were estimated using the Kaplan-Meier method. Survival curves were compared pairwise using the Log-rank test and adjusted for false discovery rates with the Benjamini-Hochberg procedure. Three-year conditional survival estimates were derived for both outcomes from the Kaplan-Meier estimator. Results: Of 1254 men, 521 (41.6%) met criteria for very low, 606 (48.4%) for low, and 125 (10.0%) for favorable intermediate NCCN risk at diagnosis. Median follow-up time was 6.5 years (IQR 4.1-9.4). Median pathologic grade progression free survival in years was significantly longer for very low risk (7.8, 95% CI 6.8-11.2) compared to low risk men (5.6, 95% CI 4.7-6.9), however neither was significantly different from favorable intermediate risk men (5.9). There was no significant difference in treatment free survival between the three risk groups. At diagnosis, the three-year risk for pathologic grade progression (24%, 95% CI 21-27%) and progression to treatment (22%, 95% CI 20-25%) were similar. However, with increasing time of event-free AS, the conditional probability of pathologic grade progression increased, while that of progression to treatment decreased. Conclusions: Our results demonstrate that despite a mild increase in pathologic progression free survival in very low risk men, there was no clear difference in overall treatment free survival between very low, low, and select favorable intermediate NCCN risk men. Further, with increased time spent on AS, despite elevated rates of pathologic progression, patient progression to treatment decreased. This trend may be indicative of changes in goals of care as men with PCa age and should be closely monitored during AS.