Screening strategy may predict lethal prostate cancer later in life

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Prostate cancer screening with prostate-specific antigen (PSA) has been shown to reduce death and the spread of prostate cancer to other parts of the body, but the PSA test remains highly controversial as it frequently leads to over diagnosis and over treatment of men who may not be at risk. Smarter screening strategies that can improve the accuracy of diagnosing lethal prostate cancer are urgently needed. Through a prospective study of US men, investigators from Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health have found that measuring PSA levels in younger men (between the ages of 40 and 59) could accurately predict future risk of lethal prostate cancer later in life. Their findings suggest that screening PSA levels in men at mid-life may help identify those who are at greater risk and should be monitored more closely.

"We found a single baseline PSA-level measurement during midlife could accurately predict future risk of lethal prostate cancer," said co-lead author Mark Preston, MD, MPH, a physician in BWH's Division of Urology. "These data identify subgroups of men, based on their PSA levels at a given age, who could benefit from screening intervals tailored to their actual magnitude of risk."

The current study leverages data from the Physicians' Health Study (PHS), a randomized, placebo-controlled trial that tested aspirin and risk of cardiovascular outcomes. The PHS began in 1982 and US male physicians who took part in it provided blood specimens before the trial began. Those blood samples, and the detailed questionnaires filled out by the study participants over the next 30 years, gave researchers the information they needed to conduct the current research project. Using information from 234 men who were diagnosed with prostate cancer, including 60 who developed lethal prostate cancer, and 711 controls, all between 40 and 59 years of age at the start of the trial, the research team measured PSA levels from stored plasma samples and followed the men's outcomes over time.

The researchers found that this single, baseline PSA level measured at midlife could accurately predict future risk of prostate cancer: Of the lethal prostate cancer events, 82 percent, 71 percent and 86 percent occurred in men with a baseline PSA above the median at ages 40-49, 50-54 and 55-59, respectively.

The study also found that men who had a PSA below median (

"These data support the recommendation that risk-stratified screening for prostate cancer based on mid-life PSA should be considered in men aged 45 to 59," said senior author Lorelei Mucci, ScD, associate professor of Epidemiology in the Department of Epidemiology at Harvard T.H. Chan School of Public Health. "Our study does not imply prostate biopsy or definitive treatment is immediately required in younger men with higher PSA levels at baseline, as this could lead to over diagnosis. Rather, these men should undergo more intensive PSA screening to enable earlier identification of cancer and potential cure while still possible."

The authors note that study limitations include that the study population consists primarily of Caucasian men, includes limited lethal events and that an unknown proportion of participants may have undergone opportunistic screening prior to the study.

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The Physicians' Health Study was supported by the NIH (CA-097193, CA-34944, CA-40360, HL-26490 and HL-34595]. Funding support for this study was provided by the Department of Defense Prostate Cancer Research Program (W81XWH-12-1-0072), Dana-Farber Cancer Institute Mazzone Awards Program, the Prostate Cancer Foundation Young Investigator Award, the American Urological Association Urology Care Foundation, the National Cancer Institute (R33 CA127768-02, P50-CA92629, P50-CA090381), Swedish Cancer Society (34550), Fundaçion Federico, the Sidney Kimmel Center for Prostate and Urologic Cancers, David H. Koch through the Prostate Cancer Foundation and Cancer Center Support Grant P30 CA008748. The authors report no conflicts of interest.

Paper cited: Preston MA et al. "Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal Prostate Cancer," Journal of Clinical Oncology DOI: 10.1200/JCO.2016.66.7527

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare. BWH has more than 4.2 million annual patient visits and nearly 46,000 inpatient stays, is the largest birthing center in Massachusetts and employs nearly 16,000 people. The Brigham's medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in patient care, quality improvement and patient safety initiatives, and its dedication to research, innovation, community engagement and educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Brigham Research Institute (BRI), BWH is an international leader in basic, clinical and translational research on human diseases, more than 3,000 researchers, including physician-investigators and renowned biomedical scientists and faculty supported by nearly $666 million in funding. For the last 25 years, BWH ranked second in research funding from the National Institutes of Health (NIH) among independent hospitals. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative as well as the TIMI Study Group, one of the premier cardiovascular clinical trials groups. For more information, resources and to follow us on social media, please visit BWH's online newsroom.

Harvard T.H. Chan School of Public Health brings together dedicated experts from many disciplines to educate new generations of global health leaders and produce powerful ideas that improve the lives and health of people everywhere. As a community of leading scientists, educators, and students, we work together to take innovative ideas from the laboratory to people's lives–not only making scientific breakthroughs, but also working to change individual behaviors, public policies, and health care practices. Each year, more than 400 faculty members at Harvard Chan School teach 1,000-plus full-time students from around the world and train thousands more through online and executive education courses. Founded in 1913 as the Harvard-MIT School of Health Officers, the School is recognized as America's oldest professional training program in public health.

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