Quest Winter 2015 : Page 1

A Publication of Dr. William J. Catalona Assessing the Impact of PSA Testing Q uest Winter 2015 • Volume 23, Number 3 and the Urological Research Foundation ©Dan Oldfield Looking to the Future 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. PSA testing ushered in a new era of diagnosing The mixed results prostate cancer. have led to some screening reduces the number of men controversy over PSA testing, including who have advanced cancer at the time the U.S. Preventive Services Task Force of diagnosis better than screening for eginning within 5 years of the (USPSTF) 2012 recommendation breast cancer with mammography and widespread acceptance of PSA against PSA screening. Critics of the physical examination. 1 screening in the U.S., there was USPSTF recommendation say that it Their essay could reflect a positive what to date has amounted to an 80% was based on incomplete, flawed data change in attitude about PSA testing. It decrease in the percentage of men with and inaccurate estimates of the benefits sends a message to primary care metastatic cancer at diagnosis and a and harms of screening. physicians and internal medicine 50% decrease in the U.S. prostate Still, the USPSTF recommendation specialists that the USPSTF cancer mortality rate. has impacted clinical practice. Fewer recommendation does not benefit men are being tested, which will likely Randomized clinical trials and patients. lead to more men having metastatic controversy prostate cancer at diagnosis. See page 3 Comparing breast cancer and The prospective, randomized for a recent study on the effects of the prostate cancer screening clinical trials used to evaluate prostate USPSTF recommendation. The article’s authors, H. Gilbert cancer screening have generated mixed Despite the controversy over PSA Welch, M.D., M.P .H., David H. Gorski, results. A high-quality trial in Sweden screening, most major professional M.D., Ph.D, and Peter C. Albertsen, reported a 44% lower mortality rate in organizations currently recommend M.D., found that the incidence of the PSA screening group. In contrast, shared decision making between doctor metastatic breast cancer hasn’t changed the U.S. Prostate, Lung, Colorectal, and patient concerning PSA since 1975, but the incidence of testing. metastatic prostate cancer has he URF needs and appreciates your decreased by half since 1988. To A shift in perspective support for its groundbreaking research explain the dramatic difference in these In a NEJM essay published trends, the authors examined screening on the prevention, detection and treatment in October, three prominent strategies for breast and prostate cancer experts—and critics of of prostate cancer. Please consider an end-cancers. PSA testing in the past— of-year donation to the URF. acknowledged that PSA ( Continued on page 2.) 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. B T

Assessing the Impact of PSA Testing

Looking to the Future

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.

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.

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.

Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers

Men with mutations in the breast cancer genes BRCA1 and BRCA2 have a higher risk of developing prostate cancer than men who don’t carry these genetic mutations. IMPACT is an international study evaluating the use of targeted prostate cancer screening in men with BRCA1/2 mutations. The researchers recently reported the first year’s screening results.

All study subjects were 40-69 years of age. Of the 2,481 men in the study, 791 were BRCA1 carriers and 731 were BRCA2 carriers. The biopsy threshold was PSA >3 ng/ml.

Fifty-nine men were diagnosed with prostate cancer (18 BRCA1 carriers and 24 BRCA2 carriers), and 66% of the cancers were intermediate or high-risk. The positive predictive value for biopsy in BRCA2 carriers was 48%—double the value reported in population screening studies. There was a significant difference in detecting intermediate- or high-risk disease in BRCA2 carriers.

The early results from the IMPACT study suggested that targeting screening at men with BRCA mutations could result in the finding the tumors that are more likely to require treatment.

Read the full article at http://epubs.democratprinting.com/article/Assessing+the+Impact+of+PSA+Testing/2325074/281285/article.html.

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