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One of the most frustrating and frightening things that can happen to a prostate cancer patient is for there to be a recurrence of the PSA after he thought he had been cured by surgery, radiation therapy, or both. This is entirely understandable. It is no picnic to go through those treatments in the first place, and when the PSA is clearly going up, it can only mean (with very rare exception) that there are still cancer cells lurking somewhere in the body. The rate of the PSA rise can predict how long it will be until something shows up on a scan, and on average, this is about EIGHT years. The median time to death from prostate cancer after a PSA recurrence is 16 years.
For >95% of patients there is something that CAN be done to stem the rise in PSA. That is to go on hormonal therapy (androgen deprivation, ADT) which will drop the PSA, often all the way to undetectable levels, in over 95% of patients. Voila! Both patient and physician feel much better emotionally. But for the patient, there is a significant price to pay. Namely the hot flashes, loss of energy, weight gain, bone calcium loss, lack of libido and further decrease in sexual function to name a few. The question is whether this is “worth it”.
A study to be presented in the next few weeks at ASCO’s annual meeting, suggests it won’t make much difference if you start ADT early versus waiting until metastases, or perhaps even symptoms occur. Utilizing the CaPSURE database, the investigators evaluated over 2000 men who had PSA relapse. The estimated 5 year overall survival (87% vs 85%) and 10 year overall survival (72% vs 72%) were the same regardless of whether the men received immediate or delayed ADT. The same was true for death from prostate cancer…no significant difference. There are of course other considerations that may come into play like treating those patients who have highly aggressive disease earlier because one knows that there will be metastases within a year, or the patient simply can’t live with himself knowing his PSA is going up.
In my experience, it is the exceptional patient who is willing to go play golf or travel or enjoy his grandchildren and forgo PSA testing on a regular basis. I have trouble even convincing my patients to extend their PSA testing to 6 months from 3 months. The question is, does it make any sense to watch this “number”, any more than it would to have cardiac catheterization every 3 months to follow the slow but inexorable accumulation of calcium in your coronary artery? Or what about the 0.01 mm increase in your abdominal aortic aneurysm? Or the accumulation of two more tangles in the Alzheimer plaque in your brain. Just because we CAN measure PSA so easily certainly doesn’t mean we SHOULD, and I have seen far too many men let this number ruin their otherwise healthy lives.
prost8blog 
Another excellent comment although this one hits me in the gut a bit. I am “that guy” you describe who gets tested monthly and lets the number dominate his life. In my defense I did not start ADT until I had the mets. Your point though is excellent especially if they now have numbers to show it does not make a difference in outcome for those with rising PSA and no mets.
Very good information as I head to the post ADT PSA testing phase
It is counter-intuitive that it doesn’t make any difference to treat cancer early.
True, but it is equally counter-intuitive that screening for prostate cancer doesn’t make much difference, and NONE of the studies have shown an advantage for screening in men over 70. For this disease, it is a matter of the competing causes of death vs. a generally slow moving cancer. The older you get, the more and varied are the slow moving things that are creeping up on you…
Dr. Glode – – thank you very much for your insights on this topic. Very helpful in my consideration process. Even though my PSA has hit 0.90 I’d sure like to get a couple of more years without ADT because of all the travel we have planned. We’ll see how it rolls out.
Billy,
The information included in this blog is worth absorbing. Glode knows his stuff. Betty
Betty Gerstley bjmdaspen@gmail.com
Please note my new email address and update your address book.
Dr. Glode,
Quote: “The estimated 5 year overall survival (87% vs 85%) and 10 year overall survival (72% vs 72%) were the same regardless of whether the men received immediate or delayed ADT. The same was true for death from prostate cancer…no significant difference.”
Does this apply, also, to men with high risk disease recurrence (Gleason 8, 9, or 10)? Also, the RADAR working group up in Vail last February apparently issued a recommendation that if no mets are found then another scan at a PSA of 5 is recommended. If no mets are found then another scan is not recommended until the PSA hits 20. If no mets are found at that point, then the RADAR working group recommends ongoing scans at every doubling point based on PSA testing every three months. I believe the group recommends no ADT until mets are discovered. Is this a match with your thinking relative to your comments on ADT initiation? Thanks.
I sat in on the RADAR group meeting. It is a bunch of experts whose recommendations are certainly reasonable. That said, there really aren’t any data that reliably tell us exactly when to start ADT or why to use one clinical indicator vs. another. There are no data that I am aware of to support the RADAR recommendations or choice of those PSA values versus some other set of numbers. Logical benchmarks could include some arbitrary doubling time, an arbitrary PSA point, the appearance of first metastases, or the appearance of first pain. Generally, of course, the patients with the highest Gleason scores or shortest doubling times will reach any one of these endpoints before someone with less aggressive disease.
Would you mind commenting on recent studies ( May 21st 2014 Cancer Connect) on prognosis with PSA doubling time <18 months prior to treatment?
Dan Gallagher’s question is intriguing. I’ve often wondered how much statistical results can be applied to a discrete individual. For example, my pre-treatment PSA only went up 0.20 or 0.30 per year, on average for a long period of time. I even had a few instances where it would drop by 0.40 or 0.50, year to year. I finally topped out at 4.40, at time of treatment. Yet, my Gleason score was 9. Seems like only the Gleason score was meaningful in the long run.
It shows how different everyone’s case is. I had a 2.2 to 2.4 PSA for years and then jumped to 5.6 in one year. Biopsy showed all cores 4:3 and and lowest percentage was 65% cancerous with extra capsular extension. So the premise that high velocity change in PSA may carry forward in post treatment (radiation) PSA levels may well be a game changer from the overall survival statistics.
There have been numerous studies on psa kinetics that demonstrate just what we all know. Short doubling times = bad; Long doubling times = better.
That said, there is still not enough 1:1 correlation between PSA and survival to allow the FDA to use it as a surrogate endpoint for approving drugs. It is also true that patients with a “low” PSA may have a bad cancer, yet another fly in the ointment of dong PSA screening – it can easily miss the tumors we would most like to catch early. Here is but one of MANY references on the topic: http://onlinelibrary.wiley.com/doi/10.1002/cncr.26437/full
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