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Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials
- 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
- et al.
Published Web Location
https://doi.org/10.1200/jco.22.00970Abstract
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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