ASCO 2019: Outcomes of Men with Recurrent M0 Prostate Cancer who Defer Androgen Deprivation Therapy until Metastasis - Medical Oncologist Perspective

Chicago, IL (UroToday.com) A substantial portion of patients with localized prostate cancer who are treated with definitive local therapy (surgery, radiation) will develop biochemical recurrence, defined as two PSAs ≥0.4 ng/mL. This population is estimated to be over 25,000 patients in the United States every year. The management of these patients is complex and depends on a variety of tumor and patient characteristics. Some of these patients may have a very indolent recurrence and never have clinical progression. Others may develop symptomatic, metastatic disease. For some low-risk patients, it is reasonable to defer systemic disease and follow PSA doubling times to decide on when to initiate treatment, in the absence of radiographic progression. In a prior retrospective analysis of 450 men who had been treated with prostatectomy and then followed after PSA recurrence without therapy until metastasis, median follow up was 8.0 years and median metastasis-free survival was 10.0 years.1 The most predictive factors for metastases were Gleason score and PSA doubling time.  This study examines the outcomes of men who deferred treatment until the development of metastases. 

This abstract retrospective reviews 2,636 men who had radical prostatectomy between 1981 and 2017 and then subsequently developed biochemically recurrent prostate cancer. All patients who had received androgen deprivation therapy prior to the development of metastases were excluded. After excluding those patients, a total of 1,686 men were included in the final analysis. The majority of these patients had Gleason 7 disease or lower (79%) and 41% of patients had received salvage radiotherapy.
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29% of patients developed metastases during this time frame. While the majority of patients who developed metastases had a PSA doubling time of 6 months or less, 45% of patients had a PSA doubling time of greater than 10 months at the time of metastases. The median metastasis-free survival (MFS) was 21 years and median overall survival (OS) was 22 years. Age, Gleason score, and stage at the time radical prostatectomy, and receipt of salvage radiation therapy were most associated with overall survival.
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In this retrospective study, patients with deferred androgen deprivation therapy for biochemical recurrence may live for decades before the development of metastases. Delayed androgen deprivation therapy (ADT) may be appropriate for carefully selected patients (Low Gleason score, limited life expectancy) and based on the results of this study, the median overall survival was 22 years from radical prostatectomy. This study excludes patients who started ADT before metastases (as this was the point of the study) but by doing so, there may have been many patients who were high risk who were likely excluded. What was surprising from this study is how similar median MFS and OS were. One would expect that the median OS would be several years after median MFS given the addition of abiraterone and docetaxel to treat metastatic castration sensitive prostate cancer. It is interesting to note that patients with a PSA DT<10 months had an MFS of 8 years from radical prostatectomy and OS of 12 years, and the author notes that these numbers are not too different than what was seen with treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) in SPARTAN and ARAMIS.
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Presented by: Catherine Handy Marshall, MD, MPH, Assistant Chief of Service, Osler Medical Housestaff Training Program, Assistant Professor of Oncology, Johns Hopkins Medicine, Baltimore, MD 

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu, at the 2019 ASCO Annual Meeting #ASCO19, May 31-June 4, 2019, Chicago, IL USA

References:
  1. Antonarakis ES, Feng Z, Trock BJ, et al. The natural history of metastatic progression in men with prostate‐specific antigen recurrence after radical prostatectomy: long‐term follow‐up. BJU international 2012;109:32-9.