July 12, 2017
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Early prostate cancer survival similar after radical prostatectomy, observation

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Radical prostatectomies for localized prostate cancer did not significantly reduce all-cause or prostate cancer–specific mortality compared with observation over 20 years of follow-up, according to study results published in The New England Journal of Medicine.

“Our study provides convincing evidence that supports at least three other large, long-term randomized trials in men with localized prostate cancer, demonstrating that observation or PSA–based active monitoring results in similar long-term overall and cancer-specific mortality for the large majority of men and especially for men with PSA–detected and low-risk disease or in older men with higher-risk disease,” Timothy Wilt, MD, MPH, professor of medicine at Veterans Affairs Center for Chronic Disease Outcomes Research in Minneapolis, told HemOnc Today. “Further, observation avoids large, long-term and sometimes serious treatment-related harms, including urinary, erectile and sexual dysfunction, treatment-related bother and reductions in daily activities.”

Photo of Timothy Wilt
Timothy Wilt

Researchers of the PIVOT trial randomly assigned 731 men (mean age, 67 years; median PSA value, 7.8 ng/mL) with localized prostate cancer and a life expectancy of at least 10 years to radical prostatectomy (n = 364) or observation (n = 367) from November 1994 through January 2002.

All-cause mortality and prostate-cancer mortality served as the primary endpoints. Researchers extended follow-up through August 2014 for the primary outcome.

After 19.5 years of follow-up (median, 12.7 years) death occurred in 223 men (61.3%) assigned surgery and in 245 (66.8%) assigned observation (absolute difference in risk, 5.5 percentage points; 95% CI, –1.5 to 12.4; HR = 0.84; 95% CI, 0.7-1.01).

Median survival was 13 years (95% CI, 12.5-13.5) with surgery compared with 12.4 years (95% CI, 11.4-12.8) with observation.

Death attributed to prostate cancer or its treatment occurred in 27 men (7.4%) assigned surgery and in 42 men (11.4%) assigned observation (absolute difference in risk, 4 percentage points; 95% CI, –0.2 to 8.3; HR = 0.63; 95% CI, 0.39-1.02).

Surgery reduced risk for all-cause mortality compared with observation among men with intermediate-risk disease (absolute difference, 14.5 percentage points; 95% CI, 2.8-25.6) but not among those with low-risk disease (absolute difference, 0.7 percentage points; 95% CI, –10.5 to 11.8) or high-risk disease (absolute difference, 2.3 percentage points; 95% CI, –11.5 to 16.1).

Photo of Michael Brawer
Michael K. Brawer

“My view when we started the study was that radical prostatectomy worked, but it didn’t work as well as everybody was saying,” study researcher Michael K. Brawer, MD, vice president of medical affairs at Myriad Genetics Laboratories, told HemOnc Today. “With these new data, we now see that there is some separation, particularly in the intermediate-risk group and in men with a PSA greater than 10. This is a case where we needed a very long follow-up to provide answers.”

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Any progression occurred in 40.9% of men assigned surgery and 68.4% of men assigned observation.

Fewer men assigned surgery than observation experienced disease progression or received additional treatment, which mostly consisted of treatment for asymptomatic, local or PSA progression (33.5% vs. 59.7%; absolute difference, 26.2 percentage points; 95% CI, 19-32.9).

At 10 years’ follow-up, more men who underwent surgery experienced urinary incontinence (17.3% vs. 4.4%) and erectile and sexual dysfunction (14.6% vs. 5.4%).

“Physicians and patients now have high-quality information to confidently recommend and choose observation as a preferred treatment option for most men with PSA–detected localized prostate cancer, especially men with low-risk disease, older men or men with serious health conditions who have higher-risk disease, or those wishing to avoid treatment harms,” Wilt said. “Observation results in similar overall mortality, low and similar prostate cancer mortality and avoids early treatment harms. Observation is an excellent, wise and often preferred treatment choice.”

These findings are consistent with those of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) and the Prostate Testing for Cancer and Treatment (ProtecT) trial, according to the researchers.

“Clinical practice guidelines and performance incentives should be developed to encourage widespread use of observation or PSA–based active monitoring,” Wilt said. “Informed decision tools and media messages should support patient choice regarding observation as a wise and quality health care choice.”

The results of this study, along with the U.S. Preventive Services Task Force’s recommendation that clinicians speak to men about the benefits and harms of PSA screening, could lead more men to elect observation over surgery, Brawer said, especially if their cancers are diagnosed at earlier stages.

“It’s worth noting the cancers we have found have become more and more favorable,” Brawer said. “We’re starting to see the pendulum swing backward, and there is more testing and that would suggest we’ll find prostate cancers in an even more favorable stage than we saw in the early 1990s.”

There has been a slow adoption of observation, PSA–based monitoring and biopsy-based active surveillance in recent years. Wilt said his team’s findings — along with the recent ProtecT trial showing evidence that observation and PSA–based monitoring result in similar mortality to radical intervention — will result in greater awareness and increased implementation of observation.

“There remains skepticism of the scientific facts from these studies, fear regarding a cancer diagnosis, and widely held treatment beliefs and incentives that will make widespread adoption of these best practices challenging,” Wilt said. “However, the fact that men with tumors detected currently by PSA testing have lower PSA and smaller-volume tumors with better long-term natural history than those enrolled in our study makes observation even a better option for more men currently diagnosed with localized cancer.” – by Chuck Gormley

For more information:

Michael K. Brawer, MD, can be reached at Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT 84108; email: mbrawer@myriad.com.

Timothy Wilt, MD, MPH, can be reached at Minneapolis VA Health Care System Center for Chronic Disease Outcomes Research (CCDOR), Mail code: 152, Bldg. 9, One Veterans Drive, Minneapolis, MN 55417; email: tim.wilt@va.gov.

Disclosure: The Department of Veterans Affairs, the Agency for Healthcare Quality and Research, and the NCI funded this study. Wilt reports no relevant financial disclosures. Brawer is vice president of medical affairs at Myriad Genetics Laboratories. Please see the full study for a list of all other researchers’ relevant financial disclosures.