Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials. Issue 4 (1st February 2023)

• Record Type: Journal Article
• Authors: Ma, Ting Martin; 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; Gonzalez San-Segundo, Carmen; 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.;
• Is Part Of: Journal of clinical oncology. Volume 41:Issue 4(2023)
• Page Start: 881
• Page End: 892
• Publication Date: 2023-02-01
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.22.00970
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.