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 - PubMed (original) (raw)

Randomized Controlled Trial

. 2024 Jul 1;119(3):826-831.

doi: 10.1016/j.ijrobp.2023.12.022. Epub 2023 Dec 25.

Wee Loon Ong 2, Nathalie Carrier 3, Tahmineh Romero 4, Jeremy Millar 5, Michael L Steinberg 1, Matthew B Rettig 6, Paul C Boutros 7, Robert Reiter 7, Nicholas G Nickols 8, Luca Valle 8, Sean E McGuire 9, Daniel E Spratt 10, Luis Souhami 11, Soumyajit Roy 12, Jarad M Martin 13, David Joseph 14, Abdenour Nabid 3, Amar U Kishan 15

Affiliations

Randomized Controlled Trial

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

John Nikitas et al. Int J Radiat Oncol Biol Phys. 2024.

Abstract

Purpose: A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor 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 radiation therapy, at least 18 months of ADT, and had a preradiation therapy 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, biochemical recurrence, prostate-cancer specific mortality, and overall survival.

Results: Nine hundred thirty 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 metastasis-free survival (hazard ratio [HR], 3.93; P = .02), worse biochemical recurrence (subdistribution HR, 2.39; P = .003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P = .005), and worse overall survival (HR, 4.51; P = .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.

Copyright © 2023 Elsevier Inc. All rights reserved.

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