The First Prostate Specific Antigen Value after Androgen Deprivation Therapy Initiation and after Definitive Radiation Therapy Completion As a Biomarker For Disease Relapse and Mortality in Intermediate and High Risk Prostate Cancer

Abstract

To determine whether the first Prostate Specific Antigen (PSA) value after initiation of neoadjuvant androgen deprivation therapy (ADT) or initially after radiation therapy (RT) completion may serve as a prognostic biomarker of recurrence, cause specific and overall survival in prostate cancer. We performed a single-institution, retrospective review of 648 patients with intermediate and high risk prostate cancer treated with neoadjuvant, adjuvant, and concurrent ADT and definitive external beam radiation therapy (EBRT) (n=477), brachytherapy (n=93), or combination RT (n=78) between 2003-2013. Patients were excluded if PSA was performed at an outside facility. Median follow-up time was 6 years. A 6-18 month total course of ADT was used (3 months during the neoadjuvant period, 2-3 months concurrently with RT). Data collected included NCCN risk group, Gleason score, radiation treatment type, first PSA value measured within 8 weeks after ADT initiation (post-ADT PSA, n=437, median=2 ng/mL), and first PSA value measured at 3 months after RT completion (post-RT PSA, n=614, median=0.1 ng/mL). Patients were divided into groups based on post-ADT PSA (0-2 ng/mL, 2-5 ng/mL, >5 ng/mL) and post-RT PSA (0 ng/mL, 0.01-0.2 ng/mL, >0.2 ng/mL) values. Primary outcome measures were biochemical recurrence free survival (BRFS), distant metastasis free survival (DMFS), prostate cancer specific mortality (PCSM), and overall survival (OS); time to event analysis was performed in multivariable Cox regression models including the aforementioned variables. A first post-ADT PSA of >5 ng/mL was strongly associated with increased hazard for each outcome measure in multivariate analysis (HR for BRFS: 1.97; DMFS: 2.24; PCSM: 3.32, and OS: 2.26, p<.01 for all). A first post-RT PSA of >0.2 ng/mL was also significantly associated with increased hazard across all outcome measures in multivariate analysis (HR for BRFS: 3.70, p<.001; DMFS: 4.99, p<.001; PCSM: 3.73, p<.01, and OS: 1.65, p<.05). A higher first PSA value (>5 ng/mL) after ADT initiation and before RT, as well as a higher first PSA value (>0.2 ng/mL) after RT completion significantly correlates with increased risk of biochemical relapse, distant metastases, prostate cancer specific death, and decreased overall survival in this cohort. These findings support the early use of PSA values after initiation of therapy as a potential biomarker for mortality after prostate cancer treatment.