There remains a lack of clarity regarding the influence of sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) on outcomes in prostate cancer (PCa). Herein, we evaluate the optimal sequencing of ADT with prostate-directed RT in localized PCa.
MEDLINE (1966-2018), Embase (1982-2018), ClinicalTrials.gov, and conference proceedings (1990-2018) were searched to identify randomized trials evaluating the sequencing, but not duration, of ADT with RT. Two randomized phase III trials were identified, and individual patient data were obtained: Ottawa 0101 and NRG Oncology's Radiation Therapy Oncology Group 9413. Ottawa 0101 randomly assigned patients to neoadjuvant or concurrent versus concurrent or adjuvant short-term ADT. Radiation Therapy Oncology Group 9413, a 2 × 2 factorial trial, included a random assignment of neoadjuvant or concurrent versus adjuvant short-term ADT. The neoadjuvant or concurrent ADT arms of both trials were combined into the neoadjuvant group, and the arms receiving adjuvant ADT were combined into the adjuvant group. The primary end point of this meta-analysis was progression-free survival (PFS).
The median follow-up was 14.9 years. Overall, 1,065 patients were included (531 neoadjuvant and 534 adjuvant). PFS was significantly improved in the adjuvant group (15-year PFS, 29% v 36%, hazard ratio [HR], 1.25 [95% CI, 1.07 to 1.47], P = .01). Biochemical failure (subdistribution HR [sHR], 1.37 [95% CI, 1.12 to 1.68], P = .002), distant metastasis (sHR, 1.40 [95% CI, 1.00 to 1.95], P = .04), and metastasis-free survival (HR, 1.17 [95% CI, 1.00 to 1.37], P = .050) were all significantly improved in the adjuvant group. There were no differences in late grade ≥ 3 gastrointestinal (2% v 3%, P = .33) or genitourinary toxicity (5% v 5%, P = .76) between groups.
The sequencing of ADT with prostate-directed RT has significant association with long-term PFS and MFS in localized PCa. Our findings favor use of an adjuvant over a neoadjuvant approach, without any increase in long-term toxicity.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020 Dec 04 [Epub ahead of print]
Daniel E Spratt, Shawn Malone, Soumyajit Roy, Scott Grimes, Libni Eapen, Scott C Morgan, Julia Malone, Julia Craig, Robert T Dess, William C Jackson, Holly E Hartman, Amar U Kishan, Rohit Mehra, Samuel Kaffenberger, Todd M Morgan, Zachery R Reichert, Joshi J Alumkal, Jeff Michalski, W Robert Lee, Thomas M Pisansky, Felix Y Feng, William Shipley, Howard M Sandler, Mathew J Schipper, Mack Roach, Yilun Sun, Colleen A F Lawton
Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI., The Ottawa Hospital Cancer Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada., University of California Los Angeles, Los Angeles, CA., Department of Pathology, University of Michigan, Ann Arbor, MI., Department of Urology, University of Michigan, Ann Arbor, MI., Department of Medicine, University of Michigan, Ann Arbor, MI., Washington University St. Louis, St. Louis, MO., Duke University, Durham, NC., Mayo Clinic, Rochester, MN., UCSF, San Francisco, CA., Mass General Hospital, Boston, MA., Cedars-Sinai Hospital, Los Angeles, CA., Medical College of Wisconsin, Milwaukee, WI.