What To Do When Study Results Are So Different:

Radical Prostatectomy Versus Watchful Waiting: Scandinavian vs PIVOT Study

Categories: Winter 2012
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Dr. Catalona responding to questions from a patient. ©photo by Cissy Lacks

In 2011, the New England Journal of Medicine published updated results on a Scandinavian Study* reporting on: Radical Prostatectomy Versus Watchful Waiting in Early Prostate Cancer.

The article concluded that, overall, compared to men managed with watchful waiting, men treated with radical prostatectomy after a median follow-up of 10 years had a 35% lower prostate cancer death rate.

Among men with “low-risk” prostate cancer (PSA less than 10 and a Gleason score of 6 or lower), the relative risk of death from prostate cancer was 47% lower and the relative risk of developing metastases was 57% lower.

In contrast, the PIVOT Trial (Prostate Cancer Intervention Versus Observation Trial, a US study) reported that death was not reduced among men with PSA values of less than 10ng/mL or those with low-risk tumors and was widely portrayed as showing that observation is as good as radical prostatectomy for men with lowrisk prostate cancer.

Making Decisions

How are men to make decisions about their health and tests with such opposing information?

We are talking about life and death.

I can only imagine the confusion from reading reports in the media.

The Scandinavian Study, with its longer follow up, has more reliable results and its conclusions should be considered in making any prostate cancer treatment decision.

I, along with respected colleagues and the American Urological Association, am convinced the PIVOT Study has so many flaws that its recommendations are worse than useless. If followed, they could shorten the lives of many men diagnosed with prostate cancer.

Flaws in PIVOT

PIVOT is statistically underpowered, which means that it was too small to adequately answer the question of whether or not surgery was better than observation in the patient group studied.

The only participants were VA (Veterans Administration) patients, and studies show VA patients have more health issues and are more likely to die of another cause before prostate cancer compared to non-VA patients.

In order for surgery to be curative, the cancer has to be confined to the prostate gland; however, only half of PIVOT surgical patients, with a mean PSA of 10 ng/mL, had potentially curable prostate cancer with organ-confined disease at diagnosis.

The median follow-up was 10 years, which is insufficient to assess prostate cancer as a cause of death.

An important eligibility criterion for enrollment in PIVOT was a 10-year life expectancy, which is also a key criterion for a patient being a good candidate for radical prostatectomy. But by 10 years, nearly half the men had died of causes other than prostate cancer. Thus, instead of recruiting healthy men who were candidates for either surgery or observation, PIVOT recruited men with a limited life expectancy who were candidates only for observation. Then they randomly assigned half of them to surgery.

Despite all of PIVOT’s flaws, a careful examination of PIVOT results showed that 60% fewer men assigned to surgery developed metastases, and the prostate cancer death rate was 37% lower, virtually the same as in the Scandinavian study.

AUA Response

The American Urological Association is critical of the new data from PIVOT.

For example, the AUA release says: “While the study demonstrates that some men with low-grade disease may not benefit from surgical intervention, it does not add to our understanding of who exactly these men are…due, in no small part, to the fact that only 10% of the men in PIVOT were under age 60 and only half of the patients had no other condition that could cause death.”

My Conclusion: Setting Back Progress

Active surveillance is appropriate for selected patients with low-risk disease based upon biopsy and PSA data and who have a limited life expectancy of less than 10 years or are too ill for treatment or who just don’t want to accept treatment. Even then, those patients should be carefully monitored by an experienced urologist with expertise in managing prostate cancer patients.

Misinterpretation of the results of the PIVOT trial could set back the progress that has been made with prostate cancer.

Prostate cancer is the second-leading cause of cancer death in U.S. men. With early diagnosis and improvements in treatment during the past 20 years, the prostate cancer death rate has decreased by 44% in the US.

All PIVOT tells us is that for a man who has a life expectancy of less than 10 years and has a low-volume, low-Gleason grade tumor, surgery is not an ideal option.

* Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer, Anna Bill-Axelson, M.D., Ph.D., N Engl J Med 2011; 364:1708-1717 May 5, 2011.

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