Persistence of adverse effects for up to 10 years after treatment for localized prostate cancer


A new article just published by Taylor et al. in the Journal of Clinical Oncology provides detailed information about the persistence of clinically significant, long-term, prostate cancer-specific, treatment-related sexual and urinary adverse effects up to 10 years post-diagnosis. Coverage of this article also appears in a report on Reuters.com.

Taylor and her colleagues used data from prostate cancer patients who participated in the the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening study to assess long-term disease-specific functioning of the survivors compared to men with no cancer (controls) and other factors.

They collected data from prostate cancer survivors (n = 529), 5 to 10 years post-diagnosis and matched these data to similar data from the control patients (n = 514) based on race, screening center, year of enrollment, and trial arm. All participants were asked to complete a telephone interview regarding prostate cancer-specific symptomatology.

The basic results of the study were actually based on data from 269 men who’d had prostate cancer detected and treated after screening and 260 men who’d also been screened but remained cancer-free. They showed that:

  • At up to 10 years post-treatment, prostate cancer survivors had poorer sexual and urinary function compared with controls (P< 0.001).
    • More than 95 percent of survivors had some degree of sexual dysfunction.
    • About 50 percent of survivors had urinary symptoms.
  • There was no significant relationship between trial arm and clinical outcome (P > 0.31).
  • Patients treated with radiation therapy of some type (n = 110) reported poorer bowel function (P < 0.05) but better sexual (P < 0.05) and urinary (P < 0.001) function than radical prostatectomy patients (n = 201).
  • Patients who received androgen deprivation therapy (ADT) as part of a treatment combination (n = 207) reported poorer hormone-related symptoms than men treated with radical prostatectomy alone (P < 0.05).

According to Taylor and her colleagues:

  • This is the first study to clearly show “the persistence of clinically significant, long-term [prostate cancer-specific] treatment-related sexual and urinary adverse effects up to 10 years postdiagnosis.”
  • This is the first study to directly compare prostate-related dysfunction among screened survivors versus screened, non-cancer controls.
  • This is the first study to clearly show that these long-term problems are attributable to prostate cancer treatment and not just to aging or co-morbidities.

The authors are also careful to note that “differences in long-term adverse effects between treatment modalities are particularly relevant for patients and clinicians when making treatment decisions.”

However, we do need to be very clear that some of the participants in the PLCO trial were treated as long ago as 1994, and that treatment has improved a great deal in the intervening 15 or so years. It would certainly be inappropriate to conclude that patients treated today would necessarily have the same risk for side effects and complications as similar patients treated 10 to 15 years ago.

5 Responses

  1. FRESH INSIGHT INTO PREMATURE PLCO RESULTS FLAW?

    (Sitemaster – welcome back from vacation! I hope you had a good one!)

    While not the point of this analysis of results of the PLCO trial, it appears that the full paper will give us information about a key aspect of the premature PLCO (and USPSTF) conclusions regarding the effectiveness of screening, information not covered in the “13 Years” update published in JNCI 2012;104:1-8. Briefly, with accepted figures showing survival of low-risk men since diagnosis at virtually 100% in the US now, and with about 95% of high-risk men surviving at at that point, it is clear that follow-up from diagnosis in the PLCO study must be much longer than 10 years to give us some indication of the impact of screening (ignoring other issues in this more-intense-screening versus usual care/plenty of screening PLCO study). Unfortunately, prior PLCO papers have not provided results showing median follow-up since diagnosis. However, even brief analysis suggests that such follow-up is likely to have been well short of 10 years, and that elevates prematurity as a critical issue, suggesting, if confirmed, that the USPSTF recommendations are profoundly flawed and worthless.

    This study presumably looked at all prostate cancer survivors in the study who were 5 to 10 years post-diagnosis, finding 529 in the greater emphasis screening group and matching them with 514 non-cancer controls. Assuming the time cut-off is the same for this study and the 13 Years result paper (i.e., 13 years follow-up since study enrollment, not since diagnosis!), there were 4,250 men in the emphasis group who had been diagnosed (3,815 in the control arm).

    These figures suggest that a substantial majority of diagnosed men had not been followed for 5 to 10 years since diagnosis; subtracting 529 from 4,250 yields 3,721 diagnosed men outside the 5 to 10 year bracket of the greater emphasis arm of the study. It is likely that some were diagnosed and followed for more than 10 years, but my hunch is that a substantial majority had fewer than 5 years of follow-up. (I’m thinking enrollment would have been relatively light during the first 3 years compared with total enrollment, and, on the other side, that diagnosis in screening studies is typically relatively somewhat heavier during the first year when existing disease is discovered as a result of the first screening.) If that hunch is right, then the median follow-up in the whole study since diagnosis in the screening emphasis arm might well be less than 5 years! Perhaps I’m missing something here, but I think this is a reasonable line of thought.

    Does anyone know whether we can get some usable figures for follow-up since diagnosis from this paper? I’m thinking the figures would not have been directly provided, but perhaps they can be gleaned with a few calculations.

  2. So relentless in the pursuit of over-treatment and its entirely predictable and substantiated hugely negative outcomes on men’s quality of life.

  3. I am not sure in what way the surgical treatment has changed significantly since 1994 other than the rapid rise of robotic surgery. However, no study has shown better outcomes with that technique compared with open surgery so one cannot conclude that the risk of side effects will be largely different in men treated today. More importantly, these men were mostly treated at major medical centers by surgeons recognized as experts in their field. That means that the risks are unlikely to be any better in the general population of urologists treating these patients outside of the the PLCO trial. Radiation techniques, however, have improved which means that patients should be now told that in general incontinence and impotence is lower with radiation than with surgery, something surgeons are not likely to find agreeable.

  4. Dear Gerry:

    Regardless of whether one uses a robot or not, I think there is a strong argument that there has been a significant expansion in the number of surgeons and the technical skill level of those surgeons who are really focused on radical prostatectomy since the early 1990s (when people like Tom Stamey and Pat Walsh were still having to explain the technical realities of nerve-sparing radical prostatectomy to many community-based and academic physicians — at educational programs run by people like me).

    If one takes the position that a patient is unwise to even consider having a radical prostatectomy carried out by someone who doesn’t have a clear track-record of focus on this procedure, then I think it is reasonable to argue that the standard of RP — as carried out by such focused sub-specialists, in the community or in academic medical centers — has risen significantly since the mid 1990s, and that that has come with some improvements in the likelihood of more rapid recovery of good continence and an increased potential for recovery of “decent” (not just “stuffable”) erectile function.

    I would agree with you, however, that the proviso of demonstrated skill, experience, and focus (more often found at major, specialized, academic centers) is a necessary criterion for expectation of good surgical outcomes.

  5. I won’t be able to download the full text for free until I go to my university next week. But I do wish that both the abstract and the Reuters report gave more information about “poorer hormone-related symptoms.” I have three reasons for this desire: (1) I have just completed a 3-year course of ADT and am curious about possibilities. (2) This week I read two survey articles about side effects of ADT. Both were inadequate with respect to my interests and seemed to be mutually contradictory on some points. That of course left me no wiser. (3) I am part of the international drive for open access to all publications. This can save lives, since non-academics often have to pay to read a full text; an abstract is often insufficiently informative. Any reader of this will do well to sign on to PLoS One (Public Library of Science), a growing source of peer-reviewed, freely-downloadable articles.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: