Prostate-Specific Antigen Response to Androgen Deprivation Therapy in the Neoadjuvant Setting for High-risk Prostate Adenocarcinoma (PIRANHA): Pooled Analysis of Two Randomized Clinical Trials - International Journal of Radiation Oncology, Biology, Physics
Abstract
Purpose
A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiotherapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor (AR) signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer.
Methods and Materials
This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiotherapy, at least 18 months of ADT, and had a pre-radiotherapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival (MFS), biochemical recurrence (BCR), prostate-cancer specific mortality (PCSM), and overall survival (OS).
Results
930 men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89–154 months). After a median of 3 months (IQR, 3–4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29–1.59). Overall, 535 men (57%) had a PSA>0.5 ng/mL. Poor PSA response was associated with significantly worse MFS (hazard ratio [HR], 3.93; P=0.02), worse BCR (subdistribution hazard ratio [sHR], 2.39; P=0.003), worse PCSM (sHR, 1.50; P=0.005), and worse OS (HR, 4.51; P=0.05).
Conclusions
Patients with PSA>0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.
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