The importance of local failure (LF) after treatment of high-grade prostate cancer (PCa) with definitive radiotherapy (RT) remains unknown.
To evaluate the clinical implications of LF after definitive RT.
Individual patient data meta-analysis of 992 patients (593 Gleason grade group [GG] 4 and 399 GG 5) enrolled in six randomized clinical trials.
Multivariable 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.
Median 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.
LF 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.
Men 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.
European urology. 2019 Nov 09 [Epub ahead of print]
Amar U Kishan, Fang-I Chu, Christopher R King, Wendy Seiferheld, Daniel E Spratt, Phuoc Tran, Xiaoyan Wang, Stephanie E Pugh, Kiri A Sandler, Michel Bolla, Philippe Maingon, Theo De Reijke, Nicholas G Nickols, Matthew Rettig, Alexandra Drakaki, Sandy T Liu, Robert E Reiter, Albert J Chang, Felix Y Feng, Dipti Sajed, Paul L Nguyen, Patrick A Kupelian, Michael L Steinberg, Paul C Boutros, David Elashoff, Laurence Collette, Howard M Sandler
Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA. Electronic address: ., Department of Radiation Oncology, University of California, Los Angeles, CA, USA., NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA., Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Department of General Internal Medicine and Health Services Research, University of California, Los Angeles, CA, USA., Department of Radiation Oncology, Centre Hospitalier Universitaire de Grenoble, Grenoble, France., Centre Georges-François Leclerc, Dijon, France; Sorbonne Université Paris, Paris, France., Department of Urology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands., Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA., Division of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Division of Hematology and Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA., Division of Hematology and Oncology, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA., Department of Urology, University of California, Los Angeles, CA, USA., Departments of Radiation Oncology, Urology, and Medicine, University of California, San Francisco, CA, USA., Department of Pathology, University of California, Los Angeles, CA, USA., Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Department of Urology, University of California, Los Angeles, CA, USA; Department of Human Genetics, University of California, Los Angeles, CA, USA., European Organization for Research and Treatment of Cancer Headquarters, Brussels, Belgium., Department of Radiation Oncology, Cedars Sinai, Los Angeles, CA, USA.