The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT).
Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality.
Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT.
ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022 Oct 21 [Epub]
Ting Martin Ma, Yilun Sun, Shawn Malone, Mack Roach, David Dearnaley, Thomas M Pisansky, Felix Y Feng, Howard M Sandler, Jason A Efstathiou, Isabel Syndikus, Emma C Hall, Alison C Tree, Matthew R Sydes, Claire Cruickshank, Soumyajit Roy, Michel Bolla, Philippe Maingon, Theo De Reijke, Abdenour Nabid, Nathalie Carrier, Luis Souhami, Almudena Zapatero, Araceli Guerrero, Ana Alvarez, Carmen Gonzalez San-Segundo, Xavier Maldonado, Tahmineh Romero, Michael L Steinberg, Luca F Valle, Matthew B Rettig, Nicholas G Nickols, Jonathan E Shoag, Robert E Reiter, Nicholas G Zaorsky, Angela Y Jia, Jorge A Garcia, Daniel E Spratt, Amar U Kishan, Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium Investigators
Department of Radiation Oncology, University of California, Los Angeles, CA., Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH., The Ottawa Hospital Cancer Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., Department of Radiation Oncology, University of California San Francisco, San Francisco, CA., Academic Urology Unit, Royal Marsden Hospital, London, United Kingdom., Department of Radiation Oncology, Mayo Clinic, Rochester, MN., Department of Radiation Oncology, Cedars Sinai, Los Angeles, CA., Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA., Clatterbridge Cancer Centre, Bebington, Wirral, United Kingdom., Clinical Trials and Statistics Unit (ICR-CTSU), The Institute of Cancer Research, London, United Kingdom., The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom., MRC Clinical Trials Unit at UCL, London, United Kingdom., Department of Radiation Oncology, Rush University Medical Center, Chicago, IL., Radiotherapy Department Grenoble, Grenoble Alpes University, Centre Hospitalier Universitaire de Grenoble, Grenoble, France., Sorbonne University, APHP Sorbonne University, La Pitié Salpêtrière, Paris, France., Department of Urology, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands., Department of Radiation Oncology, Centre Hospitaler Universitaire de Sherbrooke, Sherbrooke, Canada., Division of Radiation Oncology, McGill University Health Center, Montreal, Canada., Department of Radiation Oncology, University Hospital La Princesa, Health Research Institute, Madrid, Spain., Hospital Son Espases, Palma de Mallorca, Spain., Department of Radiation Oncology, University Hospital Gregorio Maranon, Complutense University, Madrid, Spain., Hospital Universitari Vall d'Hebron, Barcelona, Spain., Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, CA., Department of Urology, University of California, Los Angeles, CA., Department of Urology, University Hospitals Seidman Cancer Center, Cleveland Medical Center, Cleveland, OH., Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Cleveland Medical Center, Cleveland, OH., Department of Hematology Oncology, University Hospital Cleveland Medical Center, Cleveland, OH.