Luca F Valle1, Eric J Lehrer2, Daniela Markovic3, David Elashoff3, Rebecca Levin-Epstein1, R Jeffery Karnes4, Robert E Reiter5, Matthew Rettig6, Jeremie Calais7, Nicholas G Nickols8, Robert T Dess9, Daniel E Spratt9, Michael L Steinberg1, Paul L Nguyen10, Brian J Davis11, Nicholas G Zaorsky12, Amar U Kishan13. 1. Department of Radiation Oncology, University of California, Los Angeles, CA, USA. 2. Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA. 3. Department of Medicine, Statistics Core, University of California, Los Angeles, CA, USA. 4. Department of Urology, Mayo Clinic, Rochester, MN, USA. 5. Department of Urology, University of California, Los Angeles, CA, USA. 6. 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. 7. Ahmanson Translational Theranostics Division, Department of Molecular & Medical Pharmacology, University of California, Los Angeles, CA, USA. 8. 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. 9. Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA. 10. Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 11. Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA. 12. Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA. 13. Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA. Electronic address: aukishan@mednet.ucla.edu.
Abstract
CONTEXT: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality. OBJECTIVE: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities. EVIDENCE SYNTHESIS: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified. CONCLUSIONS: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted. PATIENT SUMMARY: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
CONTEXT: Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality. OBJECTIVE: To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities. EVIDENCE SYNTHESIS: A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified. CONCLUSIONS: Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted. PATIENT SUMMARY: In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
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