eprintid: 10157968 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/15/79/68 datestamp: 2022-10-26 15:13:47 lastmod: 2022-10-26 15:13:47 status_changed: 2022-10-26 15:13:47 type: article metadata_visibility: show sword_depositor: 699 creators_name: Ma, Ting Martin creators_name: Sun, Yilun creators_name: Malone, Shawn creators_name: Roach, Mack creators_name: Dearnaley, David creators_name: Pisansky, Thomas M creators_name: Feng, Felix Y creators_name: Sandler, Howard M creators_name: Efstathiou, Jason A creators_name: Syndikus, Isabel creators_name: Hall, Emma C creators_name: Tree, Alison C creators_name: Sydes, Matthew R creators_name: Cruickshank, Claire creators_name: Roy, Soumyajit creators_name: Bolla, Michel creators_name: Maingon, Philippe creators_name: De Reijke, Theo creators_name: Nabid, Abdenour creators_name: Carrier, Nathalie creators_name: Souhami, Luis creators_name: Zapatero, Almudena creators_name: Guerrero, Araceli creators_name: Alvarez, Ana creators_name: Gonzalez San-Segundo, Carmen creators_name: Maldonado, Xavier creators_name: Romero, Tahmineh creators_name: Steinberg, Michael L creators_name: Valle, Luca F creators_name: Rettig, Matthew B creators_name: Nickols, Nicholas G creators_name: Shoag, Jonathan E creators_name: Reiter, Robert E creators_name: Zaorsky, Nicholas G creators_name: Jia, Angela Y creators_name: Garcia, Jorge A creators_name: Spratt, Daniel E creators_name: Kishan, Amar U creators_name: Meta-Analysis of Randomized Trials in Cancer of the Prostate (MA, title: Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials ispublished: inpress divisions: UCL divisions: J38 divisions: D65 divisions: B02 note: Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/ 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. date: 2022-10-21 date_type: published publisher: American Society of Clinical Oncology (ASCO) official_url: https://doi.org/10.1200/JCO.22.00970 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1983774 doi: 10.1200/JCO.22.00970 lyricists_name: Sydes, Matthew lyricists_id: MRSYD21 actors_name: Payne, Roxanne actors_id: RPAYN74 actors_role: owner full_text_status: public publication: Journal of Clinical Oncology event_location: United States issn: 0732-183X citation: Ma, Ting Martin; Sun, Yilun; Malone, Shawn; Roach, Mack; Dearnaley, David; Pisansky, Thomas M; Feng, Felix Y; ... Meta-Analysis of Randomized Trials in Cancer of the Prostate (MA; + view all <#> 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; Meta-Analysis of Randomized Trials in Cancer of the Prostate (MA; - view fewer <#> (2022) Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials. Journal of Clinical Oncology 10.1200/JCO.22.00970 <https://doi.org/10.1200/JCO.22.00970>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10157968/1/jco.22.00970.pdf