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From the Winter 2015 Quest
PSA testing ushered in a new era of diagnosing prostate cancer. © Dan Oldfield
In 1991, Dr. Catalona published an article in The New England Journal of Medicine that was the first to show that prostate-specific antigen (PSA) testing is useful for the early diagnosis of prostate cancer. It was one of the most influential articles in the field of prostate cancer. Prior to the article, the only method of early detection was the digital rectal examination.

Beginning within 5 years of the widespread acceptance of PSA screening in the U.S., there was what to date has amounted to an 80% decrease in the percentage of men with metastatic cancer at diagnosis and a 50% decrease in the U.S. prostate cancer mortality rate.

Randomized clinical trials and controversy

The prospective, randomized clinical trials used to evaluate prostate cancer screening have generated mixed results. A high-quality trial in Sweden reported a 44% lower mortality rate in the PSA screening group. In contrast, the U.S. Prostate, Lung, Colorectal, Ovarian Cancer (PLCO) trial reported no benefit. However, the PLCO trial was flawed because of extensive screening of controls and poor compliance with biopsy recommendations.

The mixed results have led to some controversy over PSA testing, including the U.S. Preventive Services Task Force (USPSTF) 2012 recommendation against PSA screening. Critics of the USPSTF recommendation say that it was based on incomplete, flawed data and inaccurate estimates of the benefits and harms of screening.

Still, the USPSTF recommendation has impacted clinical practice. Fewer men are being tested, which will likely lead to more men having metastatic prostate cancer at diagnosis. See page 3 for a recent study on the effects of the USPSTF recommendation.

Despite the controversy over PSA screening, most major professional organizations currently recommend shared decision making between doctor and patient concerning PSA testing.

A shift in perspective

In a NEJM essay published in October, three prominent cancer experts—and critics of PSA testing in the past— acknowledged that PSA screening reduces the number of men who have advanced cancer at the time of diagnosis better than screening for breast cancer with mammography and physical examination. 1

Their essay could reflect a positive change in attitude about PSA testing. It sends a message to primary care physicians and internal medicine specialists that the USPSTF recommendation does not benefit patients.

Comparing breast cancer and prostate cancer screening

The article’s authors, H. Gilbert Welch, M.D., M.P.H., David H. Gorski, M.D., Ph.D, and Peter C. Albertsen, M.D., found that the incidence of metastatic breast cancer hasn’t changed since 1975, but the incidence of metastatic prostate cancer has decreased by half since 1988. To explain the dramatic difference in these trends, the authors examined screening strategies for breast and prostate cancers.

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Over the past 40 years, mammography screening has been unable to identify cancers at an earlier stage (before symptoms appear). The authors argue that the steady rates of metastatic breast cancer rates could be due to either mammography screening not being “sensitive” enough to find the cancers early, or that breast cancer can’t be detected before it has spread.

In comparison, the advent of PSA screening in the early 1990s led to a sharp uptick in prostate cancer diagnoses, “one that’s unrivaled in U.S. cancer data,” wrote the authors. They hypothesized that the steep decline in metastatic prostate cancer rates was most likely the result of PSA screening.

The authors cautioned that the dramatic reduction in metastatic prostate cancer does not necessarily mean that death rates will decline. They cited the 21% reduction in prostate cancer-specific mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). However, the ERSPC median follow-up was only 6.4 years in the screened group and 4.3 years in the control group. The natural course of early prostate cancer is usually approximately 15-25 years. Thus, the relative mortality reduction in ERSPC might increase with longer follow-up.

Looking to the future

The next step is learning to identify the men who have life-threatening prostate cancer, as treating these men early will save their lives. For men who do not have life-threatening prostate cancer, active surveillance is a reasonable option.

This is the basis of Dr. Catalona’s SPORE research project. Dr. Catalona and his colleagues are examining the use of genetic testing to identify which men are more likely to succeed with active surveillance, and which men are destined to fail active surveillance and thus need immediate treatment. In the next issue of QUEST, Dr. Catalona will be seeking patients who have been involved in active surveillance to participate in this important study.

1- N Engl J Med 373;18; 1685-1687

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