PIVOT: Latest Data on Surveillance Versus Surgery for Prostate Cancer

Gerald Chodak, MD


August 30, 2017

Hello. I am Dr Gerald Chodak, speaking for Medscape. Today I want to talk about a recent update to PIVOT, the Prostate Intervention Versus Observation Trial. Wilt and colleagues[1] began this trial in 1994 and they are now reporting the results with a follow-up of about 19.5 years. In this study, 731 men were randomly assigned to watchful waiting or radical prostatectomy. The following are the key results.

First, overall survival favored the prostatectomy group by 5.5%. This compared with a difference in survival of 3% favoring surgery when results were last reported in 2012.[2] The change was not very significant during this period of time. The absolute difference in prostate cancer mortality was 4% in favor of the surgery group, compared with 1.1% when they last reported the findings. Of importance, for men with low-risk disease, the difference in prostate cancer mortality was only 0.7%, but it was 14.5% for men with intermediate-risk disease. Somewhat surprising, the men with high-risk disease had only a 2.3% improvement in cancer mortality with surgery. Overall, more men in the watchful-waiting group experienced disease progression in various ways, but in a high percentage, progression was biochemical only, with increases in levels of prostate-specific antigen.

Before coming to any conclusions about this trial, we must understand the potential limitations. First, to reach the enrollment of 731, the investigators screened 5000 eligible patients, introducing the possibility of selection bias, with so many men refusing to participate. In addition, of the men who were assigned to receive radical prostatectomy, 15% did not have that surgery, and for the men assigned to watchful waiting, 20% actually received some other form of definitive therapy. Most of these factors could have biased the results toward watchful waiting.

Another potential limitation is that one third of the men were African American, which is a higher proportion than in the general population. We know that prostate disease in general is worse in African Americans, and thus, that bias could have worked in favor of radical surgery. Finally, the overall health of the study population was less than that of the general population when compared with aged-matched controls. If less-healthy people were enrolled in the trial, their participation may have removed the opportunity to help them improve their cancer-specific survival.

Knowing all of this, what can we take away from this trial? First, the results clearly emphasize—again—that for low-risk disease, the possibility of benefiting from definitive therapy is extremely low. This has been confirmed in other trials as well. Thus, men with low-risk disease need to be presented with this information so they have the opportunity to decide whether definitive therapy is what they want. This trial clearly did show that men who had definitive therapy had a worse quality of life in terms of impotence and incontinence.

Men who had definitive therapy had a worse quality of life in terms of impotence and incontinence.

The greatest benefit occurred for the men with intermediate-risk disease, and they too need to understand the potential differences in outcomes. Many men with intermediate-risk disease are being offered active surveillance, but that should be done with some degree of caution.

The surprising results for men with high-risk disease leave us with two possible explanations. It is possible that more of the men in that group did not comply with their assigned treatment, meaning that men assigned to surgery did not undergo definitive therapy while men assigned to watchful waiting did undergo definitive therapy. Both of those possible factors could have skewed the results for high-risk disease, making surgery less advantageous than it should have been. Another interpretation is that, for men with high-risk disease, the PSA level may not be a good enough screening test, meaning that some cancer cells may have already spread by the time the disease is discovered. We may need a better screening test to find those men early enough to make a difference.

The bottom line is, we have good information—as best as can be expected—from a large trial with long follow-up, demonstrating that the impact of surgery on low-risk disease is very small and the impact for intermediate risk-disease is significantly higher. Going forward, patients need to be provided with this information, and physicians need to be assured that they have this information when counseling patients.

Ultimately, the decision will come down to a patient's personal choice, considering their risk for tolerating side effects in order to have a small difference in cancer mortality. For the low-risk group, that risk seems to favor conservative treatment.

I look forward to your comments. Thank you.


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