TY - JOUR
T1 - Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM)
T2 - A Pooled Analysis of 12 Randomized Trials
AU - Ma, Ting Martin
AU - Sun, Yilun
AU - Malone, Shawn
AU - Roach, Mack
AU - Dearnaley, David
AU - Pisansky, Thomas M.
AU - Feng, Felix Y.
AU - Sandler, Howard M.
AU - Efstathiou, Jason A.
AU - Syndikus, Isabel
AU - Hall, Emma C.
AU - Tree, Alison C.
AU - Sydes, Matthew R.
AU - Cruickshank, Claire
AU - Roy, Soumyajit
AU - Bolla, Michel
AU - Maingon, Philippe
AU - de Reijke, Theo
AU - Nabid, Abdenour
AU - Carrier, Nathalie
AU - Souhami, Luis
AU - Zapatero, Almudena
AU - Guerrero, Araceli
AU - Alvarez, Ana
AU - Gonzalez San-Segundo, Carmen
AU - Maldonado, Xavier
AU - Romero, Tahmineh
AU - Steinberg, Michael L.
AU - Valle, Luca F.
AU - Rettig, Matthew B.
AU - Nickols, Nicholas G.
AU - Shoag, Jonathan E.
AU - Reiter, Robert E.
AU - Zaorsky, Nicholas G.
AU - Jia, Angela Y.
AU - Meta-Analysis of Randomized Trials in Cancer of the Prostate (MARCAP) Consortium Investigators
AU - Garcia, Jorge A.
AU - Spratt, Daniel E.
AU - Kishan, Amar U.
N1 - Funding Information: The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. N.G.Z. is supported by the National Institutes of Health Grant LRP 1 L30 CA231572-01 (2018-2022). Funding Information: Funding support for this study comes from the Prostate Cancer Foundation and ASTRO to AUK. AUK also thanks generous donations from the DeSilva, McCarrick, and Bershad families. A.T. acknowledges support from Cancer Research UK (C33589/A28284 and C7224/A28724) the National Institute for Health Research (NIHR) Cancer Research Network. This project represents independent research supported by the National Institute for Health research (NIHR) Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London. N.G.Z. is supported by the American Cancer Society – Tri State CEOs Against Cancer Clinician Scientist Development Grant, CSDG‐20‐013‐01‐CCE (2020). Publisher Copyright: © American Society of Clinical Oncology.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85146509510&partnerID=8YFLogxK
U2 - https://doi.org/10.1200/JCO.22.00970
DO - https://doi.org/10.1200/JCO.22.00970
M3 - Article
C2 - 36269935
SN - 0732-183X
VL - 41
SP - 881
EP - 892
JO - Journal of clinical oncology
JF - Journal of clinical oncology
IS - 4
ER -