Local Failure and Survival After Definitive Radiotherapy for Aggressive Prostate Cancer: An Individual Patient-level Meta-analysis of Six Randomized Trials |
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| Affiliation: | 1. Department of Radiation Oncology, University of California, Los Angeles, CA, USA;2. Department of Urology, University of California, Los Angeles, CA, USA;3. NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA;4. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA;5. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA;6. Department of General Internal Medicine and Health Services Research, University of California, Los Angeles, CA, USA;7. Department of Radiation Oncology, Centre Hospitalier Universitaire de Grenoble, Grenoble, France;8. Centre Georges-François Leclerc, Dijon, France;9. Sorbonne Université Paris, Paris, France;10. Department of Urology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands;11. Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA;12. Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA;13. Division of Hematology and Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA;14. Departments of Radiation Oncology, Urology, and Medicine, University of California, San Francisco, CA, USA;15. Department of Pathology, University of California, Los Angeles, CA, USA;p. Department of Radiation Oncology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA;q. Department of Human Genetics, University of California, Los Angeles, CA, USA;r. European Organization for Research and Treatment of Cancer Headquarters, Brussels, Belgium;s. Department of Radiation Oncology, Cedars Sinai, Los Angeles, CA, USA;1. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan;2. Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan;3. Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima, Japan;4. Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine and School of Public Health, Kyoto, Japan;1. Division of Surgery and Interventional Science, University College London, London, UK;2. Department of Urology, University College London Hospitals NHS Foundation Trust, London, UK;3. British Urology Researchers in Surgical Training (BURST) Research Collaborative, London, UK;4. Institute of Applied Health Research, University of Birmingham & NIHR Birmingham Biomedical Research Centre, Birmingham, UK;5. NIHR UCLH/UCL Comprehensive Biomedical Research Centre, London, UK;1. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York;2. Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California (ZSZ) |
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| Abstract: | BackgroundThe importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown.ObjectiveTo evaluate the clinical implications of LF after definitive RT.Design, setting, and participantsIndividual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials.Outcome measurements and statistical analysisMultivariable Cox proportional hazard models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), and distant metastasis (DM)-free survival (DMFS) and LF as a time-dependent covariate. Markov proportional hazard models were developed to evaluate the impact of specific transitions between disease states on these endpoints.Results and limitationsMedian follow-up was 6.4 yr overall and 7.2 yr for surviving patients. LF was significantly associated with OS (hazard ratio [HR] 1.70 [95% confidence interval {CI} 1.37–2.10]), PCSS (3.10 [95% CI 2.33–4.12]), and DMFS (HR 1.92 [95% CI 1.54–2.39]), p < 0.001 for all). Patients who had not transitioned to the LF state had a significantly lower hazard of transitioning to a PCa-specific death state than those who transitioned to the LF state (HR 0.13 [95% CI 0.04–0.41], p < 0.001). Additionally, patients who transitioned to the LF state had a greater hazard of DM or death (HR 2.46 [95% CI 1.22–4.93], p = 0.01) than those who did not.ConclusionsLF is an independent prognosticator of OS, PCSS, and DMFS in high-grade localized PCa and a subset of DM events that are anteceded by LF events. LF events warrant consideration for intervention, potentially suggesting a rationale for upfront treatment intensification. However, whether these findings apply to all men or just those without significant comorbidity remains to be determined.Patient summaryMen who experience a local recurrence of high-grade prostate cancer after receiving upfront radiation therapy are at significantly increased risks of developing metastases and dying of prostate cancer. |
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| Keywords: | Local failure Radiotherapy High grade |
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