Updated PIVOT data seem to support recent AUA/ASTRO/SUO guidelines


A new article in this week’s New England Journal of Medicine has given us follow-up data from the PIVOT trial of radical prostatectomy vs. simple observation in treatment of localized prostate cancer. The original results of the PIVOT trial were first presented at the annual meeting of the American Urological Association in 2011 to what your sitemaster can remember as being a “stunned” audience.

We are not going to try to repeat the complete and very detailed discussions about this trial that took place some 6 years ago now. Suffice it to say that that was not a trial of radical prostatectomy compared to modern active surveillance. It was, however, a randomized trial of radical prostatectomy compared to just “observing” the patients until it was determined that they needed treatment to manage symptoms of their prostate cancer.

A summary of the original, published results of the PIVOT trial can be found if you click here. There is general understanding that the PIVOT trial was not a “perfect” trial for a number of reasons, but it was certainly ground-breaking.

In the new article by Wilt et al. in this week’s NEJM, the authors report the following:

  • That although the original data (at 12 years of follow-up) showed no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only (and especially so for men with low-risk forms of prostate cancer), there is still “uncertainty” about the non-lethal health outcomes and long-term mortality of men with localized prostate cancer treated by observation as opposed to surgery.
  • The newly published data are based on follow-up of all 731 men in the trial through August 2014, equating to an actual follow-up over 19.5 years and an average (median) follow-up of 12.7 years.
  • Patient deaths overall have now occurred in
    • 223/364 patients (61.3 percent) assigned to radical prostatectomy
    • 245/367 patients (66.8 percent) assigned to observation
  • This equates to an absolute difference in mortality rates of 5.5 percent in favor of surgery and a hazard ratio [HR] of 0.84 (P = 0.06).
  • Patients deaths attributable to prostate cancer or to treatment for prostate cancer have now occurred in
    • 27/364 patients (7.4 percent) assigned to radical prostatectomy
    • 42/367 patients (11.4 percent) assigned to observation
  • This equates to an absolute difference in prostate cancer-specific mortality rates of 4.05 percent in favor of surgery and an HR of 0.63 (P = 0.06).

The authors further state that:

  • Surgery may have been associated with
    • Lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percent)
    • No lower-cause mortality than observation among men with low-risk disease (absolute difference, 0.7 percent)
    • No lower cause mortality than observation among men with high-risk disease (absolute difference, 2.3 percent)
  • Treatment for disease progression
    • Was less frequent among men treated with radical prostatectomy than with observation (absolute difference, 26.2 percent)
    • Was primarily for asymptomatic, local, or biochemical (PSA-based) progression.
  • Urinary incontinence and erectile and sexual dysfunction were each greater among men treated by radical prostatectomy than those managed on observation (through 10 years of follow-up).
  • Disease-related or treatment-related limitations in activities of daily living were also greater among men treated by radical prostatectomy than those managed on observation (but only through the first 2 years of follow-up; these limitations were not assessed after the first 2 years).
 The authors conclude that:

After nearly 20 years of follow-up among men with localized prostate cancer, surgery was not associated with significantly lower all-cause or prostate-cancer mortality than observation. Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression, mostly for asymptomatic, local, or biochemical progression.

The data from this study (at an average of just under 13 years of follow-up) appear to confirm for us that:

  • At least for most men with low-risk disease, even on just “observation” as opposed to true active surveillance, there is no significant increase in risk of death from prostate cancer.
  • The vast majority of the men in this trial (90.6 percent) had not died of their prostate cancer at nearly 13 years of follow-up.

Now in assessing these data we do have to remember that all the men enrolled in this trial were 60+ years of age (with a median age of 67 years) and that they were all military veterans being treated at VA hospitals. It is fair to state that veterans being treated at VA hospitals do tend to have rather higher levels of underlying and comorbid clinical health issues than the average American being treated in non-military facilities. The extent to which this may play into the outcomes of this study is unknown.

The “New” Prostate Cancer InfoLink wishes to carefully note that the data from this study do not tell us that all men diagnosed with low-risk prostate cancer should simply be monitored as opposed to having immediate treatment (by surgery or any other technique) for their disease. Rather, they help to confirm the recommendations recently issued in a joint AUA/ASTRO/SUO guideline on the management of localized prostate cancer, which, in its very first recommendation, states that:

Counseling of patients to select a management strategy for localized prostate cancer should incorporate shared decision making and explicitly consider cancer severity (risk category), patient values and preferences, life expectancy, pre-treatment general functional and genitourinary symptoms, expected post-treatment functional status, and potential for salvage treatment.

There is no “right” way to treat localized prostate cancer today. There are simply a wide range of options. And just monitoring patients (on some form of active surveillance) is an excellent option for appropriately selected individuals with very low-risk, low-risk, and, in some cases, even “favorable” intermediate-risk disease.

4 Responses

  1. Possible edit needed to below?

    • Surgery may have been associated with
    ◦ Lower all-cause mortality than observation among men with intermediate-risk disease (absolute difference, 14.5 percent)
    ◦ No lower-cause mortality than observation among men with low-risk disease (absolute difference, 0.7 percent)
    ◦ No lower cause mortality than observation among men with high-risk disease (absolute difference, 2.3 percent)

  2. Dear blogollum:

    Actually no. These numbers are correct. Only the absolute difference of 14.5% is statistically significant. The absolute differences of 0.7% and 2.3% are not statistically significant and thus could have occurred from pure chance.

    Can I explain why there was no real difference among the men with high-risk disease? I suspect it was because there just weren’t very many of them, but I haven’t seen the full text of this paper

  3. Exactly my question when I read this on MedPage earlier in the week, Sitemaster … I am thinking the study was just underpowered? Other thoughts? …

  4. Dear Rick:

    The study was massively underpowered. We have known this for years. My memory is that it was orginally meant to enroll more like 1,500 or 2,000 patients.

    As an associated consequence, it took far longer to enroll the patients than had initially been projected. More than 13,000 patients had to be screened, of whom about 5,500 were eligible, to enroll the 731 men who actually agreed to participate.

    You also need to bear in mind that this study was designed about 25 years ago — in 1992. Just think what we know now that we didn’t know then!

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