Prostate-specific antigen doubling time predicts the development of distant metastases for patients who fail 3-dimensional conformal radiotherapy or intensity modulated radiation therapy using the Phoenix definition

Abstract

PurposeProstate-specific antigen doubling time (PSADT) is commonly used as an indication for salvage androgen deprivation therapy (ADT) for PSA failure following radiotherapy (RT). Previously, we had shown that PSADT of <12 months is an important predictor of distant metastasis following 3-dimensional conformal RT (3DCRT) using the American Society for Therapeutic Radiology and Oncology definition of biochemical failure. We sought to determine if this approach is still valid using the Phoenix definition. Methods and MaterialsEligible patients included 432 men with T1-3N0M0 prostate cancer who demonstrated PSA failure after completing definitive 3DCRT or intensity modulated radiotherapy from 1989 to 2005. Endpoints included freedom from distant metastasis (FDM), prostate cancer specific survival (CSS), and overall survival (OS). PSADT was stratified by 0-6, 6-12, 12-18, 18-24, and >24 months. The median follow-up was 95 months (6-207 months). ResultsThe 7-year FDM, CSS, and OS rates for the entire group were 73%, 77%, and 52%, respectively. Seven-year FDM was 50% for PSADT <6 months versus 83% for PSADT >6 months (P = .0001). Seven-year CSS was 61% for PSADT <6 and 85% for PSADT >6 (P = .0001). Seven-year OS was 47% for PSADT <6 and 53% for PSADT >6 (P = .04). The proportion of men with BF receiving salvage ADT with a PSADT <6 months was 59%, 6-12 was 45%, 12-18 was 42%, 18-24 was 36%, and >24 was 28%. ADT was associated with improved 7-year CSS (68% vs 46%, P = .015). Of the 314 men with PSADT >6 months, 124 received ADT and 190 were observed. With a median follow-up of 38 months from biochemical failure (BF), there was no demonstrable benefit to ADT in the 7-year CSS (87% vs 79%, respectively; P = .758). Independent predictors of FDM were PSADT (P < 0.0001), Gleason Score (P = .011), and the use of initial ADT (P = .005). ConclusionsPSADT remains a significant predictor of clinical failure and CSS for men treated with 3DCRT or intensity modulated radiotherapy who fail according to the Phoenix definition. Immediate use of ADT in patients with PSADT <6 months is significantly associated with improved CSS, although the benefit is less apparent in patients with longer PSADT. These results further refine the role of PSADT in predicting which patients may benefit from salvage ADT and those who may be observed expectantly.