Pi-Lba08 Preliminary Assessment of a Validated Urine Exosome Assay (Exdx Prostate (Intelliscore) for Predicting Biochemical Recurrence Post-Prostatectomy

Abstract

INTRODUCTION AND OBJECTIVES:The VA Cooperative Studies Group Study #553 was designed to prospectively evaluate the efficacy of early adjuvant chemotherapy added to the standard of care (SOC) for patients with prostate cancer who are potentially cured by radical prostatectomy but who are at high risk for relapse based on clinical and pathologic parameters.METHODS: Patients at high risk for relapse after prostatectomy were randomized in 1:1 ratio to the SOC group of observation or to the chemotherapy group with docetaxel and prednisone administered every 3 weeks for 18 weeks. Randomization was stratified for PSA, Gleason score, tumor stage and the presence of positive margins, within each site. The primary endpoint was progression-free survival. Secondary endpoints included overall, prostate cancer-specific, and metastasis-free survival and time to initiation of androgen deprivation. Time to event data were compared using a log-rank test in the ITT analysis. Proportional hazards regression were used to calculate estimates of hazard ratio, adjusting for stratifying variables and incorporating site via a gamma frailty.RESULTS: A total of 297 patients randomized between July 2006 and October 2011 were included in the analysis (157 randomized to SOC and 140 to chemotherapy). The median follow-up was 62.4 months (range 0.2 to 104.3 months). For the primary endpoint, the two groups did not statistically differ in progression-free survival (median time to progression 55.5 months in chemotherapy group, 45.6 months in SOC group; logrank test p¼0.26; adjusted hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.60-1.14). Subgroup analyses showed benefit in progression-free survival for patients with tumor stage T3b (HR 0.58, 95% CI 0.34-0.98, logrank test p¼0.041) and for African Americans (HR 0.54, 95% CI 0.29-1.01, p¼0.054). The secondary endpoint analyses are hampered by low event rates for all secondary endpoints. The most common adverse events Grade 3 related or possibly related to chemotherapy included neutropenia in 40%, hyperglycemia in 18%, and fatigue in 5%, with febrile neutropenia in 1.4%.CONCLUSIONS: Adjuvant chemotherapy in high-risk prostate cancer using docetaxel and prednisone was well tolerated and did not lead to statistically significant improvement in progression-free survival for the ITT population as a whole. Subgroup analyses suggest potential benefit for patients with higher risk pathology (pT3b) and African-American ancestry, supporting ongoing and planned trials of systemic chemotherapy for hormone-sensitive prostate cancer.