Outcomes of high-risk prostate-specific antigen level during active surveillance with targeted and systematic prostate biopsy.

343 Background: National Comprehensive Cancer Network (NCCN) recommendations for very low to intermediate-risk prostate cancer (PCa) include active surveillance (AS). Patients who develop a prostate-specific antigen (PSA) level over 20 ng/mL during AS, however, are re-classified as NCCN high-risk and are recommended to undergo definitive management. In the past decade, the diagnostic accuracy for PCa has significantly improved with a combined approach to prostate biopsies (magnetic resonance imaging and ultrasound fusion targeting + systematic). This study aims to describe the outcomes of patients who continued AS following a PSA of 20 ng/mL or higher. Methods: Patient information and clinical data were obtained from a prospectively maintained database at the National Cancer Institute (NCT02594202). Patients on AS with a minimum of one subsequent combined biopsy (fusion + systematic) following a PSA of 20 ng/mL or higher were identified. Descriptive statistics were obtained using GraphPad Prism 10.1 (Boston, Massachusetts USA). Results: A total of 20 patients were identified, of whom 15 (67.7%) subsequently underwent definitive management. Patients had a median age of 72.0 [IQR 71-74.8] years, with a median of 13 [IQR 10-12] years on AS. In the continued AS cohort, the most recent PSA was below 20 ng/mL in two patients with a median of 22.9 ng/mL [IQR 15.2 -23.6], while repeat biopsy showed benign tissue or grade group (GG) 1 disease. In those who underwent definitive management, the last PSA on AS was a median of 23.2 ng/mL [IQR 21.9-32.8], with all patients having GG 2 or higher disease. Twelve patients underwent surgery and three external beam radiotherapy with long-term androgen deprivation therapy, within a median time of 2 mos [IQR 2.0 - 2.5 mos] after their last biopsy. For those who underwent surgery, 4 (33.3%) had GG upstaging, 2 (16.7%) had GG downstaging, while 6 (50.0%) had no change in overall GG on final pathology. The first post-operative PSA was undetectable in all but one patient. Conclusions: A PSA greater than 20 ng/mL is a high-risk feature that continues to have clinical significance during AS in the contemporary era of combined prostate biopsies. In our small cohort, one quarter of the patients remain on AS, while three-quarters of the patients underwent definitive management. GG upgrading occurred in one third of patients and therefore continued AS in these patients should be approached with caution and limited to those with benign findings or GG 1 disease on follow-up combined biopsy.