We are delighted to share the results of our "MASTER" systematic review and meta-analysis of local salvage therapies for radiorecurrent prostate cancer.
We know that approximately one-third of all prostate cancer patients will ultimately undergo definitive radiotherapy to cure their disease. Unfortunately, for the subset of these patients who experience a biochemical recurrence, optimal management is poorly defined. Much of this uncertainty stems from trepidation over perceived high rates of toxicity resulting from local salvage. And until now, toxicity rates were akin to Forrest Gump’s box of chocolates: “you never know what you’re gonna get”.
We thus set out to perform this meta-analysis in an effort to amass the data on local salvage across many modalities to quantify the benefits and potential tradeoffs of each modality.
After reviewing 150 studies reporting outcomes for 11,322 patients, we examined a number of salvage modalities, including radical prostatectomy, cryoablation, high-intensity focused ultrasound, low dose rate (LDR) brachytherapy, high dose rate (HDR) brachytherapy, and stereotactic body radiation therapy (SBRT). We found that efficacy was quite similar among these ablative and non-ablative salvage treatments, with non-significant recurrence-free survival (RFS) differences ranging from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT. However, when we examined toxicity from each of these modalities, differences started to emerge. Here, we found that re-irradiation with SBRT, HDR brachytherapy, and LDR brachytherapy, in particular, offered favorable toxicity profiles, with 5.6%, 9.6%, and 9.1% adjusted rates of severe toxicity, respectively.
The implications of this work are multifaceted. First, it encourages much-needed prospective clinical trials in this space to more rigorously and definitively delineates benefits and tradeoffs for each salvage modality so that patients can be appropriately counseled on therapeutic options for their radiorecurrent prostate cancer. In that same vein, this study also opens the door for counseling patients on the possibility of receiving local therapy after definitive radiation, with the knowledge that salvage therapies, and salvage re-irradiation in particular, do not come with the sequelae of severe toxicity.
It is also worth noting that until recently, identifying true local recurrence was a challenge, which further hindered success with local salvage. However, as newer molecular PET tracers such as prostate-specific membrane antigen (PSMA) continue to be investigated and approved by regulatory agencies, we believe that patient selection for local salvage will continue to improve.
We would like to take this opportunity to thank our co-investigators for their contributions to this work and most importantly to the patients who allowed their outcomes to be studied by the investigators whose publications allowed us to make our conclusions.
Written by: Luca F Valle, Eric J Lehrer, Daniela Markovic, David Elashoff, Rebecca Levin-Epstein, R Jeffery Karnes, Robert E Reiter, Matthew Rettig, Jeremie Calais, Nicholas G Nickols, Robert T Dess, Daniel E Spratt, Michael L Steinberg, Paul L Nguyen, Brian J Davis, Nicholas G Zaorsky, Amar U Kishan
Department of Radiation Oncology, University of California, Los Angeles, CA, USA., Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA., Department of Medicine, Statistics Core, University of California, Los Angeles, CA, USA., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Urology, University of California, 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., Ahmanson Translational Theranostics Division, Department of Molecular & Medical Pharmacology, University of California, Los Angeles, CA, USA., 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., Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA., Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA., Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA., Department of Radiation Oncology, Penn State Cancer Institute, Hershey, PA, USA., Department of Radiation Oncology, University of California, Los Angeles, CA, USA; Department of Urology, University of California, Los Angeles, CA, USA. Electronic address: .
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