Study Shows Surgery Does Not Significantly Reduce Mortality among Patients with Prostate Cancer versus Observation after 20 Years of Follow-up

BACKGROUND:
In light of the protracted course of prostate cancer and extended survival of many patients, treatment decisions often require information about additional treatments received, patient-reported outcomes, and very long-term mortality. This study reports on all-cause and prostate cancer mortality through nearly 20 years of follow-up and describes disease progression, treatments received, and patient-reported outcomes during follow-up. Between November 1994 and January 2002, investigators randomly assigned 731 men with localized prostate cancer to radical prostatectomy or observation at VA and National Cancer Institute medical centers. Patients had to have a PSA value <50ng per milliliter, be 75 years old or younger, have a bone scan negative for metastatic disease, and a life expectancy of >10 years. Investigators assessed all-cause and prostate cancer mortality through August 2014, a minimum of 12 years and maximum of 19.5 years or until death. Disease progression, treatment received (i.e., surgery, radiation therapy, chemotherapy), and patient-reported health outcomes were based on follow-up through January 2010.

FINDINGS:

• Surgery (radical prostatectomy) did not significantly reduce all-cause mortality or prostate cancer mortality compared with observation in men with localized prostate cancer diagnosed in the early PSA era. During 19.5 years of follow-up (median=12.7 years), 223 of 364 men (61%) assigned to surgery died compared to 245 of 367 men (67%) assigned to observation. Prostate cancer mortality occurred in 27 men (7%) randomized to surgery vs. 42 men (11%) randomized to observation.
• "Any progression" of prostate cancer occurred in 41% of men randomized to surgery versus 68% randomized to observation. Most disease progression was local, and about half asymptomatic.
• Surgery may reduce mortality in men with intermediate-risk prostate cancer, depending on the pathological classification. However, surgery resulted in large long-term increases in urinary, erectile, and sexual dysfunction and smaller shorter-term adverse effects on physical function and activities of daily living.
• Patient-reported overall health and "worry about health" did not differ between groups.

IMPLICATIONS:

• The authors suggest reducing overtreatment in men with localized prostate cancer, especially those with low-risk disease.
• This study is an example of how VA implements multisite clinical trials with practice implications on a national level.

AUTHOR/FUNDING INFORMATION:
This study was partly funded by HSR&D and by VA's Cooperative Studies Program. Dr. Wilt is part of HSR&D's Center for Chronic Disease Outcomes Research (CCDOR), Minneapolis, MN.

Wilt T, Jones K, Barry M, et al. Follow Up of Prostatectomy Versus Observation for Early Prostate Cancer. The New England Journal of Medicine. July 13, 2017;377(2):132-42.