Interplay Between Duration of Androgen Deprivation Therapy and External Beam Radiotherapy With or Without a Brachytherapy Boost for Optimal Treatment of High-risk Prostate Cancer: A Patient-Level Data Analysis of 3 Cohorts.

Autor:	Kishan AU; Department of Radiation Oncology, University of California, Los Angeles.; Department of Urology, University of California, Los Angeles., Steigler A; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia., Denham JW; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia., Zapatero A; Hospital Universitario de la Princesa, Madrid, Spain., Guerrero A; Hospital Son Espases, Palma de Mallorca, Spain., Joseph D; Sir Charles Gairdner Hospital, Perth, West Australia, Australia.; Department of Medicine and Surgery, University of Western Australia, Perth, West Australia, Australia., Maldonado X; Hospital Universitari Vall d'Hebron, Barcelona, Spain., Wong JK; Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania., Stish BJ; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota., Dess RT; Department of Radiation Oncology, University of Michigan, Ann Arbor., Pilar A; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada., Reddy C; Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio., Wedde TB; Oslo University Hospital, Oslo, Norway., Lilleby WA; Oslo University Hospital, Oslo, Norway., Fiano R; Schiffler Cancer Center, Wheeling Hospital, Wheeling Jesuit University, Wheeling, West Virginia., Merrick GS; Schiffler Cancer Center, Wheeling Hospital, Wheeling Jesuit University, Wheeling, West Virginia., Stock RG; Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, New York., Demanes DJ; Department of Radiation Oncology, University of California, Los Angeles.; California Endocurietherapy Cancer Center, Oakland., Moran BJ; Chicago Prostate Cancer Center, Westmont, Illinois., Tran PT; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., Martin S; Department of Radiation Oncology, Program in Solid Tumors, Clínica Universidad de Navarra, Pamplona, Spain., Martinez-Monge R; Department of Radiation Oncology, Program in Solid Tumors, Clínica Universidad de Navarra, Pamplona, Spain., Krauss DJ; William Beaumont School of Medicine, Oakland University, Royal Oak, Michigan., Abu-Isa EI; Department of Radiation Oncology, University of Michigan, Ann Arbor., Pisansky TM; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota., Choo CR; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota., Song DY; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., Greco S; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., Deville C; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., McNutt T; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., DeWeese TL; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland., Ross AE; Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Ciezki JP; Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio., Tilki D; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.; Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany., Karnes RJ; Department of Urology, Mayo Clinic, Rochester, Minnesota., Tosoian JJ; Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland., Nickols NG; Department of Radiation Oncology, University of California, Los Angeles.; Department of Radiation Oncology, West Los Angeles Veterans Health Administration, Los Angeles, California., Bhat P; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California., Shabsovich D; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California., Juarez JE; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California., Jiang T; Department of Radiation Oncology, University of California, Los Angeles., Ma TM; Department of Radiation Oncology, University of California, Los Angeles., Xiang M; Department of Radiation Oncology, University of California, Los Angeles., Philipson R; Department of Radiation Oncology, University of California, Los Angeles., Chang A; Department of Radiation Oncology, University of California, Los Angeles., Kupelian PA; Department of Radiation Oncology, University of California, Los Angeles., Rettig MB; Division of Medical Oncology, Ronald Reagan UCLA Medical Center, University of California, Los Angeles.; Department of Medical Oncology, West Los Angeles Veterans Health Administration, Los Angeles, California., Feng FY; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco., Berlin A; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada., Tward JD; Department of Radiotherapy Oncology, Huntsman Cancer Institute at the University of Utah, Salt Lake City., Davis BJ; Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota., Reiter RE; Department of Urology, University of California, Los Angeles., Steinberg ML; Department of Radiation Oncology, University of California, Los Angeles., Elashoff D; Division of General Internal Medicine and Health Services Research, University of California, Los Angeles., Boutros PC; Department of Urology, University of California, Los Angeles.; Department of Human Genetics, University of California, Los Angeles., Horwitz EM; Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania., Tendulkar RD; Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio., Spratt DE; Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio., Romero T; Division of General Internal Medicine and Health Services Research, University of California, Los Angeles.
Jazyk:	angličtina
Zdroj:	JAMA oncology [JAMA Oncol] 2022 Mar 01; Vol. 8 (3), pp. e216871. Date of Electronic Publication: 2022 Mar 17.
DOI:	10.1001/jamaoncol.2021.6871
Abstrakt:	Importance: Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. Objective: To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). Design, Settings, and Participants: This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. Exposures: High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). Main Outcomes and Measures: The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). Results: This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to <6, 6 to <18, and ≥18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS. In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio [HR], 1.01; 95% CI, 0.65-1.57); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P = .01). For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P = .01). Conclusions and Relevance: These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.
Databáze:	MEDLINE
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