Patient-reported outcomes and quality of life in the ProtecT trial

We have already commented on the oncologic outcomes of patients enrolled in the ProtecT trial and published in today’s issue of the New England Journal of Medicine. In this commentary we shall comment on the separate paper that addresses patient-reported outcomes from that trial. For those who are interested in reading the full text of this paper, please just click here.

The paper by Donovan et al. was designed to address issues related to the health-related quality of life of the 1,643 men with clinically localized prostate cancer who agreed to be randomized in the ProtecT trial to active monitoring, to surgery, or to external beam radiation therapy (EBRT) as their initial form of management.

The patients in this trial were all asked to complete questionnaires

  • At biopsy, before their diagnosis
  • At 6 and 12 months after initial randomization, and
  • Annually thereafter for another 5 years (i.e., 6-year follow-up data in total)

The questionnaires used a variety of validated measures to assess patients’ urinary, bowel, and sexual function as well as other specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years.

All data were analyzed on an “intent-to-treat” basis although, as we noted in the prior article, a significant percentage of patients in each arm of the trial decided not to have treatment according to the arm of the trial to which they had been randomized. As we said before, this does raise questions about the validity of the decision to analyze these data on an “intent-to-treat” basis as opposed to on a “per protocol treatment” basis.

Here is the summary of the study findings:

  • For most measure, the rate of completion of the questionnaires was > 85 percent, which is high for a study like this.
  • 55/1,643 men (3.3 percent) stopped completing questionnaires, and some men did not complete all the questionnaires at every time point.
  • In the surgically treated group of patients
    • Radical prostatectomy had high impact on sexual function and urinary continence.
    • Urinary and sexual function did recover somewhat, over time, but these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial.
    • There was no apparent effect on bowel function.
  • In the EBRT-treated group of patients
    • The negative effect of treatment on sexual function was greatest at 6 months.
    • Sexual function recovered somewhat after 6 months and was stable thereafter.
    • There was little effect on urinary continence.
    • Urinary voiding and nocturia were worse at 6 months than at diagnosis.
    • After 6 months urinary voiding and nocturia generally recovered and were similar to the other groups after 12 months.
    • Bowel function was worse at 6 months than in the other groups.
    • Bowel function recovered somewhat after 6 months, except for an increased frequency of bloody stools.
  • In the active monitoring group
    • Sexual and urinary function declined gradually over time.
    • Bowel function was unchanged over time.
  • In general, effects on quality of life mirrored the reported changes in function.
  • No significant differences were observed among the groups with respect to measures of anxiety, depression, or general health-related or cancer-related quality of life.
  • Treating 4 men with surgery or 8 men with EBRT rather than active monitoring was estimated to cause 1 additional case of erectile dysfunction at 2 years.
  • Treating 5 men with surgery or 143 men with EBRT rather than active monitoring was estimated to cause 1 additional case of urinary incontinence at 2 years.
  • After 6 years of follow-up,
    • Urinary and sexual function had stabilized in the EBRT group after improving for 2 or 3 years.
    • The quality of life outcomes became similar in the active monitoring group and the radiotherapy group but remained worse in the prostatectomy group.

The authors conclude, rather blandly, that:

In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups.

We would note that conducting measurements at 6 months and 12 months after randomization (as opposed to at 6 and 12 months after completion of  first-line treatment or formally enrolling into the active monitoring arm of the trial) seems a little strange because the trial protocol only required patients being actively treated on protocol to have such treatment within 9 months of randomization. Thus, some evaluations carried out at 6 months may have occurred before a patient received treatment of any type.

On the other hand, the results of the trial are very closely correlated to what one would expect at up to 5 or 6 years post-treatment. Surgery has the most significant impact on urinary and sexual function (and men don’t recover erectile and sexual function as well as they may be expecting based on what they are told by some urologists); radiation therapy has the worst effect on bowel function; and there are no significant side effects associated with active monitoring other than those that would normally be expected in an aging male.

We would emphasize that this trial does not tell men that “no treatment” is just as good as surgery or radiation therapy for low-risk prostate cancer. What it does tell us, arguably, is that high quality active monitoring and consequent treatment as needed may well be equivalent to surgery or radiation therapy since it comes with a lower risk for side effects in the short to medium term and it comes with no clear increase in risk for either prostate cancer-specific or all-cause mortality.

The patients in this trial with probably need to be followed for another 10 to 15 years (20 to 25 years in total) before we are able to get any further insights into any differences in real risk for disease-specific mortality — and if these exist we suspect that they are going to be small.

7 Responses

  1. I’m always surprised at the number of women online, whose husbands have been adversely affected sexually by prostate cancer, who report that they are very unhappy with their situations, but that their husbands are resigned and seem just fine with everything.

    I know there can be a lot of reasons for this … denial, emotional protection, helplessness, focused on being cured of cancer … but, honestly, for my own husband (and probably many others) I think he genuinely doesn’t care that that part of our relationship is over forever (and we are only in our 50s). When they assess quality of life I can just picture him reporting that things are fine and dandy, when honestly, our marriage is ruined.

  2. Dear Clara:

    I have to say that I tend to agree with you that men will commonly downplay a decline in or loss of sexual function and activity (or just lie about it) for the very simple reason that it can be extremely hard for them to admit that they are no longer the “man” that they were (or at least thought they were) 10, 20, or 30 years earlier.

    Having said that, I don’t think it’s because they “don’t care”. I think it is most commonly a matter of denial, helplessness, and preservation of our egos.

    Perceptions about “malehood” (as opposed to “manhood”) — among most men and many women too — are learned early, and are so closely tied to the idea of the male as a sexually potent being that they can come to be the defining characteristic of “being a man”. Take away that sexual potency (because of any one of many possible causes, prostate cancer treatment specifically included) and it can be a devastating psychological blow to a man’s self-perception — and an even bigger one to how he thinks others would perceive him if they only knew (which he therefore will avoid at all costs if he can).

  3. Dear Mark:

    We do not post personal comments or opinions like the one you sent in for the simple reason that only the parties involved can really know how their marriages or other long-term relationships “worked” prior to the impact of the prostate cancer. There are many, many factors at play here that are best explored by the couple in question (with professional counseling as and when appropriate). Neither you nor I could possibly really have any idea what has actually happened in an individual case between a specific man and his wife or partner. We are missing far too much information.

  4. Fair comment.

  5. Mark:

    Thank you. We appreciate your understanding.

  6. Can I just add that I think this site is fantastic and a great resource. It has certainly helped me with my decision making about treatment options.

  7. It’s especially sad when a man gets this disease at a young age and loses potency😥 after treatment. It’s equally sad when the spouse declares the marriage is over as a result. I don’t think physicians adequately explain the side effects of their treatments.


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