There is an unmet need for a tool that could predict early favorable prostate-specific antigen (PSA) response in metastatic hormone sensitive prostate cancer (mHSPC) patients receiving androgen receptor pathway inhibitor (ARPI). Here, we train and validate a multivariable logistic regression model to predict early favorable PSA response (≤0.2 ng/mL by 6 months) in these patients. Patients randomly allocated to the ARPI arms of the LATITUDE (abiraterone), TITAN (apalutamide), and ARASENS (darolutamide) trials, are split 60:40 into training (n = 1030) and internal validation (n = 688) cohorts. The locked model is validated in an independent external validation cohort - the enzalutamide arm of the ENZAMET trial (n = 540). The area under curve and Brier score for the locked model in the external validation cohort are 0.82 (95% confidence interval [CI] = 0.78-0.85) and 0.16, respectively. Stratification by predicted probability tertiles show PSA response rates of 92% (95% CI = 88-96), 74% (95% CI = 68-81), and 39% (95% CI = 32-47), respectively. Pending prospective validation, our model predicts early favorable PSA response supporting its potential role in guiding treatment decisions.
Nature communications. 2025 Dec 17 [Epub ahead of print]
Soumyajit Roy, Yilun Sun, Maha Hussain, Kim N Chi, Karim Fizazi, Ian D Davis, Susan Halabi, Neeraj Agarwal, Simon Chowdhury, Bertrand Tombal, Scott C Morgan, Shawn Malone, Pedro C Barata, Michael Ong, Christopher J D Wallis, Alejandro Berlin, Umang Swami, Amar U Kishan, Angela Y Jia, Nicholas G Zaorsky, Jorge A Garcia, Prateek Mendiratta, Jason R Brown, Vinod V Subhash, Martin R Stockler, Hayley Thomas, Rana R McKay, Eric J Small, Neal D Shore, Fred Saad, Christopher J Sweeney, Daniel E Spratt
Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine Cleveland, Cleveland, OH, USA. ., Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA., Division of Hematology Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., BC Cancer and Vancouver Prostate Centre, Vancouver, BC, Canada., Department of Cancer Medicine, Institut Gustave Roussy, Centre Oscar Lambret, University of Paris-Saclay, Villejuif, France., Cancer Services, Eastern Health, Melbourne, VIC, Australia., Departemnt of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA., Division of Medical Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA., Guy's, King's and St. Thomas' Hospitals and Sarah Cannon Research Institute, London, UK., Department of Surgery, Université Catholique de Louvain (UCL), Cliniques Universitaires Saint-Luc, Brussels, Belgium., Department of Radiation Oncology, Radiology, and Medical Physics, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada., Department of Internal Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA., Department of Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada., Division of Urology, Department of Surgery, Mount Sinai Hospital and University Health Network, University of Toronto, Toronto, ON, Canada., Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada., Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine Cleveland, Cleveland, OH, USA., Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Sydney, NSW, Australia., Moores Cancer Center, University of California San Diego, La Jolla, CA, USA., Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA., Carolina Urologic Research Center, Myrtle Beach, SC, USA., Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada., South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine Cleveland, Cleveland, OH, USA. .