When to Start ADT With A PSA Only Recurrence

We know that the overall survival (OS) in prostate cancer is usually prolonged and we also know that long-term hormone therapy (ADT) is associated with significant side effects as well as having an economic cost. 

Catherine Marshall, MD, MPH, and colleagues from The Johns Hopkins Hospital evaluated the overall survival (OS) as well as other outcomes for men with recurrent prostate cancer when they deferred ADT until they developed metastasis. They hypothesized that men who delayed starting ADT until they developed metastases would also have a prolonged OS. 

This study, which was reported at the 2019 ASCO meeting was a retrospective review of 2,636 men who had a radical prostatectomy (surgery) between 1981-2017 and then went on and developed a biochemical recurrence (their PSA began to climb, but they had negative scans).  

After excluding men inappropriate for this study, including any man who had prior ADT exposure, 1,686 men deferred the use of ADT until they developed metastasis. The median age of the participants was 60 years, median follow-up was ten years, median PSA doubling time was 33 months, 78% had Gleason <= 7 disease, and 41% received salvage radiotherapy. 

The median metastasis free survival (MFS) was 21 years, and median overall survival (OS) was 22 years. 

Among the men with PSA doubling time <=6 months (n=283), the median MFS was nine years, and median OS was 13 years. Among men who developed metastasis (n=489), the median MFS was ten years, and the median OS was 15 years. Among men who developed metastasis and had a PSA doubling time <=6 months (n=172), the median MFS was six years, and the median OS was ten years.

In multivariable models, age, Gleason < 8 vs ≥8, radical prostatectomy stage (organ confined vs. not), PSA doubling time, and salvage radiation therapy were associated with OS. 

 Dr. Marshall concluded from this study the following: 

•    Deferred ADT in relapsing M0 (negative scans) patients is associated with prolonged OS measured from the time of local treatment, comparable to OS with salvage ADT in the contemporary experience.

•    Drug approval trials in non-metastatic castrate resistant prostate cancer (nmCRPC) should focus on patients at high risk for metastasis and death before ADT, and determine standardized criteria for the initiation of ADT.

•    Prolongation of MFS in nmCRPC requires further validation and may not necessarily reflect a net OS benefit.