Early PSA response has been found to be prognostic of outcome in metastatic hormone sensitive prostate cancer (mHSPC). We performed a secondary analysis of TITAN trial to determine if early PSA response was predictive of treatment efficacy in mHSPC patients.
Early PSA response was defined as achieving a PSA level of ≤ 0.2 ng/mL by 6 months of random assignment. A Cox proportional hazard model was constructed in a landmark population with an interaction term between the treatment and early PSA response to determine differential treatment effect on overall survival (OS). We applied multivariable Cox proportional hazard regression model with time to early PSA response fitted with restricted cubic spline to determine the association of time to early PSA response with OS.
Approximately 24% (124/524) of patients in the ADT alone group and 61% (321/524) in the apalutamide group had PSA response ≤ 0.2 ng/mL by 6 months. Longer time to early PSA response was associated with significantly superior OS in the apalutamide group. There was a significant difference in treatment effect from apalutamide on OS (p-interaction = 0.03) among 6-month PSA responders (HR: 0.66; 95% CI: 0.44-1.00) versus non-responders (HR: 1.14; 95% CI: 0.89-1.46). This difference in treatment effect was not statistically significant at 3 months (p-interaction = 0.17). Among 6-month PSA responders, 3-year confounder-adjusted OS was 84% (80-88) for the apalutamide group and 74% (66-82) for the ADT alone group. Among non-responders, 3-year adjusted OS for the two treatment arms were 58% (52-65) and 56% (51-60), respectively.
Early PSA response by 6 months was a predictor of treatment efficacy from ADT plus apalutamide on OS. Longer time to early PSA response was associated with superior OS in the apalutamide arm.
The Journal of urology. 2024 Jul 26 [Epub ahead of print]
Soumyajit Roy, Yilun Sun, Kim N Chi, Michael Ong, Shawn Malone, Christopher J D Wallis, Amar U Kishan, Julia Malone, Umang Swami, Georges Gebrael, Jason R Brown, Angela Y Jia, Scott C Morgan, Fred Saad, Simon Chowdhury, Neeraj Agarwal, Daniel E Spratt
Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois., Case Western Reserve University, Cleveland, Ohio., BC Cancer and Vancouver Prostate Centre, Vancouver, British Columbia, Canada., The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario, Canada., Department of Urology, Mount Sinai Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada., Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California., Department of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., University Hospitals, Seidman Cancer Center, Cleveland, Ohio., Department of Surgery, Centre hospitalier de l'Université de Montréal, Montreal, Quebec, Canada., Guy's and St Thomas' NHS Foundation Trust and Sarah Cannon Research Institute, London, United Kingdom.