What should one do if one’s PSA remains detectable after radical prostatectomy?

After surgery, PSA should become “undetectable” on a normal PSA test (i.e., < 0.1 ng/ml) within a month or two, but sometimes it remains elevated. The primary purpose of the ARO 96-02 randomized clinical trial was to determine whether there was an advantage to treating stage T3-4N0 patients while PSA was still undetectable, or whether they could wait to be treated. Waiting has the advantage of allowing better healing of recently cut and handled tissues, and avoiding over-treatment. In that study, there was a significant advantage to immediate treatment in preventing eventual clinical recurrence. However, the study also included 74 patients whose PSA never became undetectable, and they all received immediate radiation therapy. Wiegel et al. did a 10-year follow-up analysis of that group to see how they fared.

Among the 74 patients:

  • The median PSA after surgery was 0.6 ng/ml (range, 0.05 to 5.6 ng/ml).
  • They were checked for distant metastases with a bone scan and X-rays.
  • They all received 66 Gy of 3D-CRT to the prostate fossa at a median of 86 days after surgery; 58 percent received adjuvant hormone therapy.
  • Compared to those who reached undetectable PSA, they had higher pre-surgery PSA levels, stages, Gleason scores, and incidence of positive surgical margins.
  • Among 48 patients for whom data was available, only 15 percent achieved an undetectable PSA following radiotherapy.
  • Their 10-year clinical relapse-free survival was 63 percent.
  • Their 10-year metastasis-free survival was 67 percent, compared to 83 percent among patients who had undetectable PSAs initially.
  • Their 10-year overall survival was 68 percent, compared to 84 percent among patients who had undetectable PSAs initially.
  • There were no Grade 3 or higher acute toxicities, but 7 percent experienced Grade 3 late urinary toxicity.

Wiegel et al. conclude:

A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups will benefit most from which treatment option.

This seems a reasonable conclusion. Some patients with persistent PSA after surgery will enjoy a long-term survival benefit from adjuvant radiation aimed at the prostate fossa, but a third will develop metastases and die in spite of such treatment. It seems that only 15 percent were actually cured, or at least had a PSA that became undetectable, by the therapy. It was not the purpose of the study to detect a survival benefit in this subset of patients who had persistent PSA, so there are no conclusions that can be drawn about the strategy of immediate treatment. We cannot yet reliably identify through imaging or biochemical tests those men who will benefit from immediate radiation, although some men with high or quickly rising PSA levels may have PET-detectable metastases.

In spite of this, Wiegel is quoted in an ASTRO press release as saying:

Our analysis demonstrates that patients who have detectable PSA post-prostatectomy may benefit from more aggressive, early and uniform treatment that could improve survival outcomes.

This conclusion seems unwarranted based on the data. However, it is certainly a reasonable decision, and one that many patients will make in consultation with their radiation oncologists.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

24 Responses

  1. There is a big difference between a pT3a patient with a post-surgery PSA of 0.05, and pT4 with a PSA of 5.6. pT3a might be a single focal EPE, whereas pT4 might be invasion of bladder or rectum, etc. The cancer might no longer confined to any practical CTV and would not respond to sRT. Not clear if the study considered this.

    Agree that the conclusion seems unwarranted. I would be tempted to at least wait for some indication of rising PSA before pulling the trigger on RT (but not very long).

  2. 58% of the 74 patients received hormone therapy in addition to radiation. 15% overall (with the data available) got to an undetectable PSA. I would think this number would have been lower (probably more like 5%) if none of them were on hormone therapy (just radiation).

    “What should one do if one’s PSA remains detectable after radical prostatectomy?”

    In this scenario, I would say that one should consult with a medical oncologist, preferably one that specializes in prostate cancer and works with all tools, including radiation, especially to treat aggressive prostate cancer.

  3. I would be interested to see a parallel assessment of quality of life and survival here. Immediate radiation and ADT following surgery has the potential for stacking a lot of misery on the front end. It might be worth that price if it meant more good quality years later.

  4. In response to Jerry’s comment: The abstract of the article says that 43 of 74 (58%) had hormone therapy, but it doesn’t say when they had it. I would guess that in many cases it was after the post-RT PSA had been measured. Also, post-RT PSA data was available for only 48 of 74 patients — so if some patients had hormone therapy concurrent with RT, they might be among the ones for whom post-RT PSA was not available.

  5. I suppose that a persistent PSA for a T3 or T2 patient does not have the same meaning as for a T1c patient with a pathology report of the dissected prostate which revealed no signs of any cancer anywhere.

  6. Radical prostatectomy for PSA 15, Gleason 7, PSA 0.3, 3 months after prostatectomy. What are the best options and prognosis?

  7. Dear Mohammad:

    If you join our social network, that site is specifically designed for discussion of individual patients’ cases and their clinical options.

  8. Radical prostatectomy 13 months ago; Gleason 4 + 3 = 7; NO; focally positive margin; T2a. PSA was 0.126 at 3 months post surgery. PSA 0.1 undectable 6 months post surgery; PSA 11 monnths post-surgery 0.116. Would this be a persistent PSA or a recurrence? Oncologist suggests start radiation and hormone treatment soon.

  9. Dear Chris:

    This seems to be a rather odd situation since — even though your PSA has never really dropped to less than 0.1 ng/ml — it also seems to be relatively stable at about 0.1 ng/ml or slightly higher. The variation of 0.026 ng/ml between the highest and the lowest PSA levels at up to 11 months after surgery is well within the levels of possible variance for an ultrasensitive PSA test, and there is no clear signal that your PSA is rising significantly.

    If I was in your situation, I would wait another 3 months and get another PSA test then before I “did anything”. If it has risen again, you could decide on a short course of androgen deprivation therapy (ADT, also known as hormone therapy) at that time along with radiation to try to eliminate any remaining cancer. On the other hand, if it is still stable at around 0.1 or a tad higher, you could just wait another 3 months.

    Decisions in situations like this are very much a matter of personal opinion and discussion between the doctor and the patient. There really is no really “right” and no “wrong” response, but waiting for another 3 months is unlikely to affect your risk for progressive prostate cancer. A formal “biochemical failure” would only occur when your PSA had risen to 0.2 ng/ml.

  10. Thank you for your insight on my situation. I did have another PSA taken at another lab 1 month later at 12 months. PSA was 0.170. I still have concern since there is a positive margin. I will take your advice though and wait and test in 3 months.

  11. Chris:

    Please don’t just “take my advice.” I’m not a doctor. You want to make sure your doctor is OK with this suggestion too.

    Also, do make sure you get all your PSA tests done by the same lab if you possible can, otherwise all you are doing is adding to the number of reasons why you may not be able to know whether your PSA is really rising or not. Data from PSA tests can vary significantly from lab to lab for all sorts of reasons.

  12. Yes, I will talk to Doctor first and will be sure to use the same lab. Thank you.

  13. Chris,

    It appears that your second PSA test was not an ultrasensitive test, which explains the discrepancy. In a study at UCLA last year among men with unfavorable pathology like yours, researchers found that a first PSA < 0.03 ng/ml always predicted eventual full biochemical failure. Click here for a discussion of the study:.

    The fact that your PSA is not rapidly rising yet should provide some comfort that salvage radiation may still be curative for you. I would not delay in discussing this with your radiation oncologist. No one can predict whether your cancer is indolent for a long time or a short time, but it is certainly still there, and may at any time progress from indolent to metastatic. I can’t see any advantage in waiting.

  14. Allen:

    For Chris, the advantage in waiting is the opportunity to maximize recovery of continence and erectile function after the original surgery.

  15. I agree that avoiding toxicity is a persuasive argument against adjuvant radiation, especially within the first 3 months. I also agree that radiation compounds the side effects of surgery. Doctors tell me that the anastomosis has healed by 3 months. However, Chris has already waited 12 months — I haven’t seen anything yet that indicates that the prospects of salvage RT-related urinary or sexual toxicity improve by waiting longer after that. In fact, a SEER database analysis last year indicated that there was no difference in urinary and sexual toxicity between men receiving adjuvant radiation (which they defined as within 9 months of prostatectomy) vs. those receiving salvage radiation (12 or more months following surgery). The prospect of any improvement in toxicity seems slight in comparison with the risk of progression.

  16. Allen:

    Yes … but Chris’s PSA doesn’t actually seem to be rising. Within the limits of accuracy of any PSA test I know of, it appears to be stable, so what is is he loosing by just monitoring his PSA for as long as he can?

    As you have observed previously, we have no data at all that has ever shown any clinical benefit associated with giving salvage radiation before his PSA gets to 0.2 ng/ml.

    If his PSA was clearly rising, it would be a different issue, but it isn’t. His PSA doubling time appears to be way greater than 12 months.

  17. What Kang et al. showed is that it will rise – it always did in every single case they looked at. Waiting until it has proved to be rising carries the risk that it is rising because it has metastasized. Getting it while it is still indolent is a lot less risky. We will have to wait at least 10 years before we know the clinical benefit of early salvage, if there is one. You may disagree, but I think there is general consensus that early salvage has better outcomes than wait-and-see. So the way I look at it, he has nothing to gain by waiting any longer, and something to lose by it.

  18. This is Chris. All PSAs were performed at the same lab with exception to the last one of 0.170. The first PSA was explained as source maybe periurethral glands. The second PSA was explained as undetectable 0.100. The PSA of 0.125 at 11 months was still explained as possible benign tissue and not expected as BCR so quickly, given the pathology report.

    My own confusion and concerns led me to see oncologist who recommends SRT along with ADT. This would seem like a persistant PSA except that the PSA went undetectable at 6 months. I have regained continence as well as erectile function. I am on board for aggressive treatment if possible cure or longer survival.


  19. And Chris … For all my and Allen’s slightly different and nuanced perceptions of how to address your problem, in the end only you can decide what you feel you need to do!


  20. My husband’s PSA is 3 years post-surgery. His doctor has suggested radiation. He also has a hernia, which needs surgery. Which do you think he should have first — the radiation or the hernia surgery? Or will opening him up cause more problems?

    Please help.

    Frightened Wife

  21. Dear Cynthia:

    There are a whole bunch of questions that are important to making the decision about whether your husband should have radiation first or the hernia surgery first. They include things like how fast your husband’s PSA has been rising, exactly where the hernia is (and whether the area where the hernia is will be within the radiation field when he has the radiation), etc.

    These are really questions that you need to be discussing with your husband’s primary care physician, his urologist, the doctor who would do the hernia surgery, and the doctor who would be doing the radiation therapy. It is simply not possible for us to answer a question like this. However, in general, unless there is some really good reason not to do this. I would have thought it would be wisest for you husband to have the hernia surgery first and then the radiation therapy.

    One other thing that it might help to do if you are going to have to delay the radiation therapy until your husband has recovered from the hernia surgery (which is going to take a little while) would be for him to have a short course of androgen deprivation therapy (ADT, also known as “hormone” therapy) to control the cancer for a few months. This is also something to discuss with the doctors. The radiation oncologist may want him to have this anyway along with the radiation, depending on other factors like how fast your husband’s PSA has been rising and what his Gleason score was at the time of his original prostate cancer surgery.

    While I understand your concern, it should be perfectly possible for the doctors to cope with both of these problems without any serious difficulty. It should just take a little careful planning.

  22. Dear Sir …

    Thank you so much for taking the time to answer my question … even tho it stated on your site … Comment.

    It gives my husband and I another necessary question to ask his doctor and something else to read up on.

    Naval Doctors come and go … so while one may have his chart and background information on his problems the new doctor may not … so at least this gives us one more question to ask and with which to make decisions about his own body.

    Thank you and God bless you.

  23. My husband had a radical prostatectomy 2 years ago and recently a hernia op. He had radiation therapy post prostatectomy and PSA was 0.02. Recently his PSA has more than doubled to 0.05 and his oncologist said to wait 3 months.

    He phoned his oncologist with two questions and spoke to a nurse as he was busy.

    1. Whether a recent hernia op could of raised PSA?
    2. Could he start hormone therapy sooner rather than later?

    The nurse said no to op question and said his oncologist knew what he was doing and so on. … She said his PSA rise was tiny and not to worry about it. Her tone was rude, abrupt, and uncaring, and this upset us both.

    My husband was told his cancer was very aggressive; it filled up his prostate quickly and infiltrated to being outside. He had nerves removed thus affecting erectile function but this is the least of his worries.

    Should we get a second opinion?

    Worried wife.

  24. Dear Elaine:

    First, I am sorry to hear that the nurse was rude and uncaring. She should know better.

    Second, while I definitely understand why you and your husband are concerned by the rise in his PSA, I think that (a) this apparent rise in his PSA is extraordinarily unlikely to have anything to do with the hernia operation and that (b) almost any good urologist is going to say that your husband should wait a little while and get a repeat PSA test before thinking he should be “doing something”.

    PSA levels can show this sort of small, apparent rise at levels below 0.1 ng/ml for all sort of reasons. It is perfectly possible that the next PSA value could come back at something like 0.03 ng/ml or maybe even 0.02 again.

    So … what to do?

    You could go and get a second opinion, but I believe that any good urologist is going to tell you to wait for at least couple of months and get a repeat PSA before making any decisions.

    You could call your urologist’s office again and ask if the doctor could please return your phone call himself, and then do two things: (1) Explain that you are very worried about the PSA level (even though you understand why he thinks your should wait 3 months to get a repeat PSA level) and ask him if you could have it done in 2 months’ time as a compromise. (2) Tell him that when you spoke to his nurse about this she was “rude, abrupt, and appeared to be completely uncaring”. Your husband’s situation may appear routine to her, but she needs to understand that it is by no means “routine” for the patient (and his spouse).

    The question of whether you want to go to see a different doctor depends on how you feel about the doctor you have been seeing. If he has seemed to be caring and interested and helpful, then you probably want to stay with him. By now he knows more about your husband’s prostate than anyone else in the world. However, he does need to be told that his nurse is not demonstrating the same level of care for his patients.

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