%0 Journal Article
%@ 0732-183X
%A Ma, Ting Martin
%A Sun, Yilun
%A Malone, Shawn
%A Roach, Mack
%A Dearnaley, David
%A Pisansky, Thomas M
%A Feng, Felix Y
%A Sandler, Howard M
%A Efstathiou, Jason A
%A Syndikus, Isabel
%A Hall, Emma C
%A Tree, Alison C
%A Sydes, Matthew R
%A Cruickshank, Claire
%A Roy, Soumyajit
%A Bolla, Michel
%A Maingon, Philippe
%A De Reijke, Theo
%A Nabid, Abdenour
%A Carrier, Nathalie
%A Souhami, Luis
%A Zapatero, Almudena
%A Guerrero, Araceli
%A Alvarez, Ana
%A Gonzalez San-Segundo, Carmen
%A Maldonado, Xavier
%A Romero, Tahmineh
%A Steinberg, Michael L
%A Valle, Luca F
%A Rettig, Matthew B
%A Nickols, Nicholas G
%A Shoag, Jonathan E
%A Reiter, Robert E
%A Zaorsky, Nicholas G
%A Jia, Angela Y
%A Garcia, Jorge A
%A Spratt, Daniel E
%A Kishan, Amar U
%A Meta-Analysis of Randomized Trials in Cancer of the Prostate (MA
%D 2022
%F discovery:10157968
%I American Society of Clinical Oncology (ASCO)
%J Journal of Clinical Oncology
%T Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials
%U https://discovery.ucl.ac.uk/id/eprint/10157968/
%X 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.
%Z Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/