Findings from a recent study may challenge the early use of androgen deprivation therapy (ADT) for men who experience biochemical recurrence of prostate cancer following radical prostatectomy (RP).
“We found that the median overall survival and metastasis-free survival from time of diagnosis of prostate cancer is quite long in men with biochemically recurrent prostate cancer and is comparable to the overall survival estimated in contemporary clinical trials,” lead investigator Catherine Handy Marshall, MD, of Johns Hopkins University School of Medicine in Baltimore, told Renal & Urology News. “Early ADT, at time of biochemical relapse, does not clearly prolong overall survival or improve quality of life, and when to start this therapy is still a matter of debate.”
Dr Handy Marshall’s team retrospectively studied 2930 men with a median age of 61 years and median follow-up of 10 years. Metastasis developed in 595 men (20%), and all of them received ADT. As measured from the time of RP, median metastasis-free survival (MFS) for the entire study population was not reached, she and her colleagues reported in a poster presentation at the European Society for Medical Oncology 2019 Congress in Barcelona. In the metastasis-only group, median MFS was 6 years. Median overall survival for the study population as a whole was 21 years.
“We did this retrospective analysis because 3 recent clinical trials [PROSPER, SPARTAN, and ARAMIS] showed improvement in MFS for men with non-metastatic castration resistant prostate cancer treated with novel anti-androgens,” Dr Handy Marshall said. “We were interested in this because those trials, and the non-metastatic castration-resistant state, result from the non-validated initial implementation of ADT for biochemically recurrent prostate cancer.”
Kevin Courtney, MD, PhD, Associate Professor of Internal Medicine in the Division of Hematology/Oncology and Co-Leader of the Genitourinary Oncology Disease Oriented Team at the University of Texas Southwestern Medical Center in Dallas, said 81% of the men in this study had low- or intermediate-risk disease, which may need to be taken into account in future analyses. Various studies have looked at whether ADT should be started in patients with biochemical recurrence in the absence of tumor. “This [study] shows you can safely delay ADT in men with biochemical recurrence after prostatectomy. That is consistent with what has been found in previous work. However, there are challenges in extrapolating these findings to patients with nonmetastatic castration-resistant prostate cancer (M0 CRPC). Further work is needed to validate metastasis-free survival as an end point for those patients.”
Paul Mathew, MD, a genitourinary oncologist at Tufts Medical Center in Boston, said the findings of Dr Handy Marshall’s group are relevant, but he is concerned that the men in the study may not be biologically comparable to the men who participated in the trials of novel antiandrogens. “It is difficult to know if these populations are equivalent,” Dr Mathew said. “There is probably a subgroup of patients with BCR for whom early implementation of ADT would impact overall survival favorably, but this is likely to be a small fraction of the overall population for which we do not have reliable tools for definition.”
Clinicians already are concerned about using the novel antiandrogens because they are extremely expensive and can adversely impact quality of life with adverse effects such as chronic fatigue. “Another criticism is that there is no overall survival advantage documented, although this may materialize with more mature follow-up,” Dr Mathew said. “If I had started a patient on ADT for BCR, and their PSA was rising rapidly, I would use a first-generation antiandrogen such as bicalutamide first because it is cheap and has few side-effects.”
“It is going to take better head-to-head trials looking at deferred ADT and defining the true benefits of these novel agents and at what stage they should be implemented in terms of overall survival,” said Soroush Rais-Bahrami, MD, Associate Professor of Urology and Radiology at the University of Alabama at Birmingham and Co-Director of the UAB Program for Personalized Prostate Cancer Care. Advances in targeted imaging techniques, such as prostate-specific positron emission tomography tracers, that pinpoint tumor sites also could help clinicians decide when to begin ADT, he said.
Amar U. Kishan, MD, Assistant Professor in the Department of Radiation Oncology at the University of California, Los Angeles, said an important finding from the new study is that many men who have BCR after RP and are managed expectantly until developing metastases still have excellent overall survival outcomes, suggesting that a large proportion of men may be “overtreated” if they are started on hormonal therapy.
“I think the guidelines as they currently are, which do not mandate ADT, but rather allow either ADT or observation depending the clinical circumstance and patient preference, are reasonable, though this work certainly underscores that most men may not need ADT,” Dr Kishan said.
Handy Marshall C, Chen Y, Cullen J, et al. Overall survival (OS) and metastasis free survival (MFS) in men with biochemically relapsed (BCR) prostate cancer after radical prostatectomy (RP) managed with deferred androgen deprivation therapy (ADT): A combined Johns Hopkins and CPDR study. Presented at the European Society for Medical Oncology 2019 Congress held September 27-October 1, 2019 in Barcelona. Poster 852P