학술논문
Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials
Document Type
article
Author
Martin, Ting; Sun, Yilun; Malone, Shawn; Roach, Mack; Dearnaley, David; Pisansky, Thomas M; Feng, Felix Y; Sandler, Howard M; Efstathiou, Jason A; Syndikus, Isabel; Hall, Emma C; Tree, Alison C; Sydes, Matthew R; Cruickshank, Claire; Roy, Soumyajit; Bolla, Michel; Maingon, Philippe; De Reijke, Theo; Nabid, Abdenour; Carrier, Nathalie; Souhami, Luis; Zapatero, Almudena; Guerrero, Araceli; Alvarez, Ana; San-Segundo, Carmen Gonzalez; Maldonado, Xavier; Romero, Tahmineh; Steinberg, Michael L; Valle, Luca F; Rettig, Matthew B; Nickols, Nicholas G; Shoag, Jonathan E; Reiter, Robert E; Zaorsky, Nicholas G; Jia, Angela Y; Garcia, Jorge A; Spratt, Daniel E; Kishan, Amar U; Investigators, on behalf of the Meta-Analysis of Randomized Trials in Cancer of the Prostate Consortium
Source
Journal of Clinical Oncology. 41(4)
Subject
Language
Abstract
PurposeThe 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).Materials and methodsIndividual 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.ResultsOverall, 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.ConclusionADT 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.