MedicalResearch.com Interview with:
Amar U. Kishan, MD
Department of Radiation Oncology
University of California, Los Angeles
MedicalResearch.com: What is the background for this study?
Response: Patients with high risk prostate cancer have several curative treatment options: radical prostatectomy, external beam radiotherapy with androgen deprivation therapy, and external beam radiotherapy with a brachytherapy boost, also with androgen deprivation therapy (so-called extremely dose-escalated radiotherapy). Prior attempts at comparing long-term clinical outcomes between these treatment options have been hampered by the fact that standards of care have changed significantly with respect to the appropriate dose of radiation and the usage of androgen deprivation therapy. Therefore, many comparative effectiveness reports are in essence comparing apples with rotten oranges.
Further, not all high risk prostate cancers are the same. Gleason score 9-10 disease is a particularly aggressive form of prostate cancer that is much more likely to metastasize and potentially cause death. Thankfully, this is a rarer type of prostate cancer — but this also means that not much data are available specifically for this type of disease.
Therefore, we launched a multi-institutional study of men with Gleason score 9-10 disease, including 1809 men treated across 12 institutions. All men were treated between 2000 and 2013 and therefore were more likely to have treatments that would be commensurate with modern standards.
MedicalResearch.com: What are the main findings?
Response: We found that patients receiving extremely-dose escalated radiotherapy had significantly improved cancer-specific survival and were significantly less likely to develop metastases than men treated with surgery or standard external beam radiotherapy. Importantly, outcomes of men treated with surgery and external beam radiotherapy were identical. It is also important to highlight that the median duration of androgen deprivation therapy was 12 months with extreme dose-escalation, versus 22 months with radiation alone, and that nearly 40% of patients undergoing surgery ultimately underwent postoperative radiation.
Specifically, after adjusting for major imbalances in age and disease status across the three groups, the 10-year risk of prostate cancer specific death was 13% for patients receiving extremely dose-escalated radiotherapy, versus 26% for those receiving external beam radiotherapy alone and 23% for those undergoing radical prostatectomy. Similarly, the 10-year risk of distant metastasis was 13% for patients receiving extremely dose-escalated radiotherapy, versus 44% for those receiving external beam radiotherapy alone and 46% for those undergoing radical prostatectomy. This translates to a nearly 50% reduction in prostate cancer-specific death, and a 75% reduection in the rate of distant metastases.
MedicalResearch.com: What should readers take away from your report?
Response: I think there are two main “take away” messages.
First, patients with Gleason score 9-10 disease appear to benefit from a comprehensive treatment strategy that includes both intensified treatment directed at the prostate–radiation with a brachytherapy boost–and systemic treatment–a median of a year of androgen deprivation therapy.
Second, men with Gleason score 9-10 disease definitively have a curable disease and, particularly with intensified treatment upfront, few actually succumb to their disease.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Any time we see such a large treatment effect, we must ask two questions: why does this work, and who is going to benefit (that is, how can we identify the patients who will benefit the most from an intensified treatment). There are emerging genetic tools that will give us insight into both questions, and this constitutes an area of active and future research. One could and should also ask, how could outcomes have been improved in the patients who did receive radiation without brachytherapy or radical prostatectomy. That too is being investigated. Potential answers may include earlier use of radiation after prostatectomy, and/or use of androgen deprivation therapy before or after radical prostatectomy, as well as use of more powerful anti-androgen agents with radiation.
Kishan AU, Cook RR, Ciezki JP, Ross AE, Pomerantz MM, Nguyen PL, Shaikh T, Tran PT, Sandler KA, Stock RG, Merrick GS, Demanes DJ, Spratt DE, Abu-Isa EI, Wedde TB, Lilleby W, Krauss DJ, Shaw GK, Alam R, Reddy CA, Stephenson AJ, Klein EA, Song DY, Tosoian JJ, Hegde JV, Yoo SM, Fiano R, D’Amico AV, Nickols NG, Aronson WJ, Sadeghi A, Greco S, Deville C, McNutt T, DeWeese TL, Reiter RE, Said JW, Steinberg ML, Horwitz EM, Kupelian PA, King CR. Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer. JAMA. 2018;319(9):896–905. doi:10.1001/jama.2018.0587
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