Can ultrasensitive PSA at 3 years post-surgery project delayed BCR?

A research team at New York University School of Medicine has reported data suggesting that a single ultrasensitive PSA test result may be able to project risk for delayed biochemical recurrence (BCR) of prostate cancer at 3 years after a radical prostatectomy.

Malik et al. were able to use Lepor’s series of 1,197 consecutive open radical retropubic prostatectomy patients (all initially diagnosed with clinically localized prostate cancer) to test the idea that a single ultrasensitive PSA test result at 3 years post-surgery might be able to accurately predict risk for biochemical recurrence in a carefully characterized group of patients.

From this series of 1,197 patients, the researchers excluded the following patients “for cause:”

  • 107 men (8.9 percent) who had developed a PSA level of ≥ 0.2 ng/ml or who underwent hormone therapy or radiation therapy within the first 3 years after their surgery
  • 98 men (8.2 percent) who had PSA levels between 0.1 and < 0.2 at 3 years post-surgery

An additional 191 men (16.0 percent) did not receive an ultrasensitive PSA assay at 3 years post-surgery and were therefore als0 excluded.

This left a total of 801 men, all of whom had been given an ultrasensitive PSA test at 3 years post-surgery and who were eligible for study analysis. The researchers stratified these 801 patients into two groups based on their ultrasensitive PSA level at 3 years after their surgery:

  • Group 1: Patients whose PSA was ≤ 0.04 ng/ml (n = 765)
  • Group 2: Patients whose PSA was > 0.04 and <0.10 ng/ml (n = 36).

For these 801 men, delayed BCR was defined as the development of a PSA level ≥ 0.2 ng/ml or administration of salvage radiation therapy for a persistently rising PSA level more than 3 years after their original surgery.

The results of the follow-up analysis are as follows:

  • The 7-year, cumulative BCR-free survival rates were
    • 0.957 (range, 0.920-0.978) for patients in Group 1.
    • 0.654 (range, 0.318-0.855) for patients in Group 2.
  • In multivariate analysis, the ultrasensitive PSA level at 3 years remained the only significant predictor of delayed BCR

The good news appears to be that men with an ultrasensitive PSA value of ≤ 0.04 ng/ml at 3 years post-surgery are (perhaps not surprisingly) at minimal risk for a subsequent BCR.

A limitation of this study, however,  is that “no uniform PSA assay was obtained.” Unfortunately it is not entirely clear what the authors mean by this statement, but if the implication is that the ultrasensitive PSA tests were taken using different ultrasensitive tests evaluated at different laboratories, then the validity of the study data does have some significant problems.

The other questions raised by this study are the clinical significance of a PSA value between 0.04 and < 0.2 ng/ml at 3 years post-surgery and the clinical validity of the actions subsequently taken.

To exemplify this, let’s consider a man of 65 who has a radical prostatectomy today. Three years from now, in 2014, at age 68, he has an ultrasensitive PSA test that shows a value of 0.06 ng/ml — placing him at a 35 percent risk for biochemical recurrence within 7 years based on these study data. Six years later (i.e., in 2020, 9 years post-surgery, when he is 74 years of age) his PSA is 0.2 ng/ml and he is nominally in biochemical failure … but his PSA doubling time can be estimated at something of the order of 4 years or higher! If his PSA goes on doubling at that rate, it might well be significantly less than 15 ng/ml by the time he is 80 years of age (in 2026). So the question then becomes, is it appropriate (or perhaps even ethical) to give salvage radiation to this man who has no symptoms in 2020, when he is 74 years of age, to prevent the possibility that he might have measurable metastatic disease some time in his mid to late 80s?

These are not easy questions to answer. What is the probability of this man living to (say) 95 years of age at the time that he is 74? If he is liable to live to such an age, then salvage radiation in 2020 might be appropriate in order to prevent subsequent hormone therapy. But what if the biochemical recurrence isn’t local? In that case the salvage radiation is going to be a waste of time anyway.

We are in no position to make the decision what an individual patient like the one in this example should or shouldn’t do if he has biochemical recurrence. However, what we are sure about is that every patient in that position should be thinking really hard about every decision he takes. For older men with slowly progressive prostate cancer after first-line therapy, as they age, every additional treatment comes with a significant risk for complications and loss of quality of life … and with limited evidence for and no guarantee of any real survival benefit.

3 Responses

  1. I have been a believer in ultrasensitive testing, using versions with reliable accuracy down to < 0.01 in a practical clinical/lab setting, since the fall of 2000. At that time I attended one of the "National Conferences on Prostate Cancer" (at Long Beach, CA), and presenter/moderator Dr. Stephen B. Strum, MD, discussed the importance of ultrasensitive testing, including about a dozen abstracts of pertinent studies that found it valuable. It has been a key tool in managing my own challenging case, enabling me and my doctor to observe PSA nadirs after courses of triple androgen deprivation therapy of < 0.01 for the first cycle, < 0.01 again for the second cycle, and 0.02 ng/ml for the third (using the Roche ECLIA as opposed to the earlier Immulite 2000 assays). This evidence has enabled me to enjoy three long periods off the heavier duty drugs (Lupron and bicalutamide).

    As for usefulness in the scenario discussed, doctors whose advice I track are enthusiastic about low-key tactics to slow the PSA if needed. As noted by Sitemaster, the PSA doubling time may be too slow to warrant any intervention. However, as an example of a practical low-key intervention, we now have accumulating evidence that quality pomegranate juice or extract is able to slow, halt or reverse the rate of PSA doubling for men with a significant PSA doubling time, for example a doubling every 15 months. Despite the FDA's misguided view of the 5-alpha-reductase inhibitor drugs, finasteride and dutasteride (Avodart) most likely also have an important role to play as an option for men facing a significant PSA velocity. There are additional low-key tactics.

    Thanks for highlighting this study of the usefulness of an ultrasensitive snapshot at 3 years post-RP, and thanks for your thoughtful comments.

  2. Pre-op Gleason 4 + 5 = 9; 7/7 cores positive; RP 4/2010.

    Surgical pathology results: pT3a; extraprostatic extension and invasion of the bladder neck; no lymph node invasion; Gleason 5 + 4 = 9.

    Adjuvant treatment: 38 external beam radiation treatments 8-9/2010.

    Outcome to date: Four post-op PSAs all < 0.1 ng/ml.

    Should I consider ultrasensitive PSA assay and if so where can I obtain it?

  3. Dear Dean:

    You certainly could consider asking your managing physician to order ultrasensitive PSA tests. Whether they would really make any difference to your future care if your PSA started to rise is very questionable, however.

    Look at it this way … If your PSA remains at < 0.1 ng/ml, you are clearly in remission. Most doctors would tell you that biochemical failure in your case would occur when your PSA reached 0.2 ng/ml or higher. If that happened, your next course of treatment would likely need to be some form of hormonal therapy — and there is no real consensus about whether it is appropriate to start that as soon as your PSA reaches 0.2 ng/ml or to wait until it gets significantly higher. A lot would depend on your PSA doubling time.

    Now, if you were to get ultrasensitive PSA tests, you might be able to discover that your PSA had started rising as much as a year or so before it exceeded 0.1 ng/ml, but (a) calculating PSA doubling times on the basis of PSA levels below 0.1 ng/ml is not generally recommended and (b) the clinical value of starting hormone therapy before your PSA reaches a minimum of 0.2 ng/ml is still very questionable. So … What is getting ultrasensitive PSA testing going to do for you? Probably very little.

    If you had had just the surgery, without the adjuvant radiation, the situation might be considered to be different. In that case, arguably, using ultrasensitive PSA testing might have allowed you to spot disease recurrence early and therefore have salvage radiation early, which would probably have been a good thing. But since you had adjuvant radiation, that is no longer an issue.

    You can discuss all this with your doctors, who can certainly order ultrasensitive PSA tests for you (assuming your insurance provider covers the costs), but if I was in your shoes I would just go on smiling for as long as my PSA test results kept coming back at < 0.1 ng/ml. Sometimes less information offers better knowledge!

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