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.
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).
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).
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.
International journal of radiation oncology, biology, physics. 2023 Dec 25 [Epub ahead of print]
John Nikitas, Wee Loon Ong, Nathalie Carrier, Tahmineh Romero, Jeremy Millar, Michael L Steinberg, Matthew B Rettig, Paul C Boutros, Robert Reiter, Nicholas G Nickols, Luca Valle, Sean E McGuire, Daniel E Spratt, Luis Souhami, Soumyajit Roy, Jarad M Martin, David Joseph, Abdenour Nabid, Amar U Kishan
Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA., Alfred Health Radiation Oncology, Central Clinical School, Monash University, Melbourne, VIC, Australia; Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Heath Sciences Centre, University of Toronto, Toronto, ON, Canada., Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada., Department of Medicine Statistics Core, University of California, Los Angeles, Los Angeles, CA, USA., Alfred Health Radiation Oncology, Central Clinical School, Monash University, Melbourne, VIC, Australia., Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Hematology-Oncology Section, Medicine Service, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, USA., Department of Urology, University of California, Los Angeles, Los Angeles, CA., Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Radiation Oncology Service, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, USA., Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA., Department of Radiation Oncology, University Hospital Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 44106, USA., Department of Radiation Oncology, McGill University Health Centre, Montreal, QC, Canada., Department of Radiation Oncology, Rush University, Chicago, IL, USA., Department of Radiation Oncology, Calvary Mater Newcastle & School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia., University of Western Australia, Perth, WA, Australia; Genesis Cancer Care, Perth, WA, Australia; 5D Clinics, Perth, WA, Australia., Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: .