Rising PSA – When to start therapy

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One of the most frequent situations I encounter in my small “prostate cancer only” practice is a man who has had treatment (usually surgery or radiation) several years ago and now has a rising PSA. He feels absolutely fine, may be exercising daily, and his PSA is often so low that a routine scan won’t show anything. What to do?

The options in this situation are changing. Treating oligometastatic disease (few metastases) is somewhat of a new frontier in this situation. In the “old days” when I wrote about this subject, we reviewed the non-randomized data that suggested no advantage to starting ADT earlier. More recently, the idea of treating some men with radiation or surgery directed at the mets if they have only a few has become more popular. Added to this is the increased sensitivity of the newer PET scans (choline, acetate, PSMA targeted) that may reveal metastases even with PSA values less than 1.0. While it is hoped that some men could be cured by this approach, it is also possible that one could delay the implementation of ADT and its side effects. There are multiple ongoing clinical trials looking at this issue. With such rapidly changing technology, it will be difficult to come up with a “right choice” in every situation. What may have been considered “non-metastatic rising PSA” last year could become “oligometastatic” simply by the implementation of the new scans.

Beyond this is the issue of treatment-related side effects. In an article this week in Lancet Oncology, the side effects of treating men with asymptomatic, non-curable prostate cancer (TOAD and TROG studies) was reported. This study is one of the few randomized studies in this setting. The men were about 70 years old with rising PSA’s, most having been previously treated. They were randomized 1:1 to starting ADT immediately or waiting until at least 2 years later unless “symptoms or metastases developed or PSA doubling times decreased to 6 months or less”. Earlier, the investigators published the survival data in this study, indicating some advantage to starting earlier, as shown in this graph. 

However, keep in mind that the men who were in the immediate ADT arm also experienced the ADT side effects sooner according to the new report. The most important areas of symptoms were the hot flashes and decreases in sexual activity (reported only in the men who were sexually active) which were significantly worse with the immediate treatment, as might be expected. In a “global quality of life” measurement there was also worse quality of life, although it was not significant (the score number was 72.39 for delayed therapy vs. 70.83 for the immediate group). Further, the type of ADT used varied, and included both intermittent and continuous therapy (usually intermittent therapy has at least some improvement in quality of life). Finally, none of the men in these studies received the newer (and vastly more expensive -but probably more effective) ADT agents, abiraterone or enzalutamide which have been shown to improve survival when used “up front” in the metastatic setting.

Thus, a rising PSA is obviously a reason for concern, but choosing a management strategy is quite complicated at the present time. The best news to come out of this study is that prostate cancer is a slow disease. “Overall, 18 (6%) men died from prostate cancer, 12 (8%) in the delayed treatment arm and six (4%) in the immediate arm…” This is not to say that as time goes on there will not be more prostate cancer deaths, and there was earlier metastatic progression in the delayed group, but it is equally important to realize that at age 70 there will be significant competing causes of mortality. Something will get us eventually, so the key is to not let prostate cancer (or the PSA) dominate our thinking. What other things can you work on? Stop smoking. Exercise. Improve your diet. And most of all, enjoy each day as a gift and live it to the fullest regardless of how you decide to deal with a rising PSA.