Benjamin A Greenberger1, Nicholas G Zaorsky2, Robert B Den3. 1. Department of Radiation Oncology, Sidney Kimmel Medical College & Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: benjamin.a.greenberger@gmail.com. 2. Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA. 3. Department of Radiation Oncology, Sidney Kimmel Medical College & Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA.
Abstract
CONTEXT: There is little level 1 evidence regarding the relative efficacy of radical prostatectomy (RP) compared with radiotherapy (RT) combined with androgen deprivation therapy (ADT) for high-risk prostate cancer. OBJECTIVE: To conduct a systematic review and meta-analysis comparing overall and prostate cancer-specific mortality (OM and PCM) among patients with high-risk prostate cancer treated with RP or RT/ADT. EVIDENCE ACQUISITION: We searched PubMed, Scopus, and the Cochrane Library through July 2019 covering a period since 2009. We report the results of our systematic search according to recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Adjusted hazard ratios (aHRs) were extracted for each endpoint. The risk of bias was assessed using the Newcastle-Ottawa Scale. EVIDENCE SYNTHESIS: A total of 23 studies with low to moderate risk of bias were found to meet the inclusion criteria. In keeping with prior studies, external beam radiation therapy (XRT) without specification of ADT was associated with worse OM and PCM (aHR 1.65, 95% confidence interval [CI] 1.42-1.91, p < 0.0001: I2 = 53.4%) and (aHR 1.90, 95% CI 1.61-2.23, p < 0.0001: I2 = 50.4%). These associations were weaker although not entirely eliminated when comparing RT/ADT versus RP (PCM aHR 1.54, 95% CI 1.16-2.04, p = 0.002: I2 = 61.5%). Combination of RT and brachytherapy (MaxRT), on the contrary, was associated with improved PCM compared with RP (aHR 0.48, 95% CI 0.30-0.78, p = 0.003: I2 = 23.8%), an effect that was not significant when comparing MaxRT with the combination RP/adjuvant RT (aHR 0.81, 95% CI 0.59-1.11, p = 0.197: I2 = 0%). CONCLUSIONS: Evidence demonstrating definitive superiority of either modality is lacking. Recent studies show improved consideration of ADT, radiation dose, brachytherapy boost, and utilization of postoperative adjuvant radiation. Residual confounding continues to limit the interpretation of observational data. PATIENT SUMMARY: In the treatment of high-risk prostate cancer, many observational studies reporting higher mortality for radiotherapy demonstrate potential for confounding. More recent studies with current standard of care radiation regimens using androgen deprivation therapy or brachytherapy boost demonstrate approaching equivalence of prostatectomy and radiation modalities. Prospective randomized trials are needed to confirm these findings.
CONTEXT: There is little level 1 evidence regarding the relative efficacy of radical prostatectomy (RP) compared with radiotherapy (RT) combined with androgen deprivation therapy (ADT) for high-risk prostate cancer. OBJECTIVE: To conduct a systematic review and meta-analysis comparing overall and prostate cancer-specific mortality (OM and PCM) among patients with high-risk prostate cancer treated with RP or RT/ADT. EVIDENCE ACQUISITION: We searched PubMed, Scopus, and the Cochrane Library through July 2019 covering a period since 2009. We report the results of our systematic search according to recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Adjusted hazard ratios (aHRs) were extracted for each endpoint. The risk of bias was assessed using the Newcastle-Ottawa Scale. EVIDENCE SYNTHESIS: A total of 23 studies with low to moderate risk of bias were found to meet the inclusion criteria. In keeping with prior studies, external beam radiation therapy (XRT) without specification of ADT was associated with worse OM and PCM (aHR 1.65, 95% confidence interval [CI] 1.42-1.91, p < 0.0001: I2 = 53.4%) and (aHR 1.90, 95% CI 1.61-2.23, p < 0.0001: I2 = 50.4%). These associations were weaker although not entirely eliminated when comparing RT/ADT versus RP (PCM aHR 1.54, 95% CI 1.16-2.04, p = 0.002: I2 = 61.5%). Combination of RT and brachytherapy (MaxRT), on the contrary, was associated with improved PCM compared with RP (aHR 0.48, 95% CI 0.30-0.78, p = 0.003: I2 = 23.8%), an effect that was not significant when comparing MaxRT with the combination RP/adjuvant RT (aHR 0.81, 95% CI 0.59-1.11, p = 0.197: I2 = 0%). CONCLUSIONS: Evidence demonstrating definitive superiority of either modality is lacking. Recent studies show improved consideration of ADT, radiation dose, brachytherapy boost, and utilization of postoperative adjuvant radiation. Residual confounding continues to limit the interpretation of observational data. PATIENT SUMMARY: In the treatment of high-risk prostate cancer, many observational studies reporting higher mortality for radiotherapy demonstrate potential for confounding. More recent studies with current standard of care radiation regimens using androgen deprivation therapy or brachytherapy boost demonstrate approaching equivalence of prostatectomy and radiation modalities. Prospective randomized trials are needed to confirm these findings.