Adjuvant versus neoadjuvant androgen deprivation with radiation therapy for prostate cancer: Does sequencing matter?

Abstract

37 Background: Androgen deprivation therapy (ADT) is typically given neoadjuvantly and concurrently with radiation therapy (RT) rather than adjuvantly in the management of intermediate and high risk prostate cancer. Our objective is to compare outcomes between patients who receive adjuvant ADT (ADJ), i.e. immediately after the completion of RT, with those who receive a neoadjuvant and concurrent regimen (NEO). Methods: From 1995-2002, 515 patients with CaP were definitively treated with RT and ADT. ADT was given for a duration of 6 months in all cases. NEO was given 2-3 months prior to the start of RT. ADJ was initiated immediately following the completion of RT. ADT sequencing was NEO in 311 (60%) and ADJ in 204 (40%). The distribution by NCCN risk classification for NEO was high in 67%, intermediate in 26%, and low in 7%. The risk group distribution for ADJ was high in 69%, and intermediate in 31%. RT dose was either 78 Gy at 2 Gy/fx (n=168) or 70 Gy at 2.5 Gy/fx (n=347). Kaplan-Meier analysis was used to calculate biochemical relapse free survival (bRFS, Phoenix definition), distant metastasis free survival (DMFS) and overall survival (OS). Cox proportional hazards regression was used to examine the impact of ADT timing on outcomes. Results: The median follow up for all patients was 8 years. For the entire cohort, the 10-yr bRFS, DMFS and OS rates were 61%, 80% and 66%, respectively. The 10-yr bRFS rates for ADJ vs. NEO were 63% vs. 60% (p=0.98). The 10-yr DMFS rates for ADJ vs. NEO were both 80% (p=0.60). The 10-yr OS rates for ADJ vs. NEO were 65% vs. 67% (p=0.98). There were no statistically significant differences in bRFS, DMFS or OS between the two groups after accounting for patient, tumor and treatment characteristics on both univariate and multivariate analyses. Conclusions: There is no difference between neoadjuvant vs. adjuvant ADT in the setting of dose-escalated RT for localized prostate cancer. This suggests that the synergy between radiation therapy and androgen deprivation is independent of the sequencing of both modalities and that the initiation of RT does not need to be delayed for a course of neoadjuvant ADT.