Refined PSA Screening Strategies May Catch More Aggressive Cases

The number of new cases of metastatic prostate cancer climbed 72 percent from 2004 to 2013, according to a controversial new study published July 19 in Prostate Cancer and Prostatic Diseases. The investigators say they can’t definitively link the increased cases to reduced prostate cancer screening and the rise could reflect the disease becoming more aggressive. However, the largest increase in new cases was among men 55 to 69 years old, which rose 92 percent.

While data shows metastatic disease began rising in 2008, before the 2012 change in screening recommendations by the U.S. Preventive Services Task Force, the authors say the sharp rise in advanced disease in 55- to 69-year old men is “particularly troubling” because these men may be most affected by changing screening guidelines and may benefit most from screening and early treatment.

“The results indicate that screening guidelines and treatment need to be refined based on individual patient risk factors,” said lead author Adam Weiner, M.D., a Northwestern University urology resident. “This may help prevent the growing occurrence of metastatic prostate cancer and potential deaths associated with the disease. This also can help minimize overdiagnosing and overtreating men with low-risk prostate cancer who do not need treatment.

Separate studies are beginning to assess new screening strategies.

Single mid-life measurement
A single midlife prostate-specific antigen (PSA) measurement may be a good predictor of subsequent development of lethal prostate cancer, according to a study published online June 13 in the Journal of Clinical Oncology. Since men with PSA below the median at age 60 years are unlikely to develop lethal disease, the authors recommend subsequent risk-stratified screening on the basis of results of a midlife PSA test between the age of 45 and 59 years.

The researchers analyzed findings from men (mean age, 55 years) who gave blood before participation in the Physicians’ Health Study, initiated in 1982. Baseline PSA levels were available for 234 patients with prostate cancer and 711 age-matched controls. The 71 participants who developed lethal prostate cancer were rematched to 213 controls. The median follow- up time from blood draw to cancer diagnosis was 9.0 years overall and 8.6 years for lethal cases.

The researchers found that men with PSA above the age-specific median had consistently and significantly increased risk of total prostate cancer across all age groups versus men with PSA at or below the median. The majority of lethal cases occurred in men with PSA above the median at all ages (82 percent lethal cases seen in men above the median at ages 40 to 49 years; 71 percent at 50 to 54 years; and 86 percent at 55 to 59 years).

The authors sought to investigate how these findings should inform screening strategies. Given the nine cases of lethal prostate cancer among men with the lowest quartile of baseline PSA across all age groups, the authors say it would be prudent to conduct another PSA test during the lifetime of men age 40 to 49 years, even if the first measure is exceptionally low, because of the lingering small risk of prostate cancer-related death. Additionally, the researchers sought to determine whether it is safe to stop PSA screening at age 60 years. They found that men aged 55 to 59 years with PSA levels below the median (0.96 ng/mL) were at low risk of lethal prostate cancer, with a cumulative incidence of lethal cases in this age group of 0.59 percent over 30 years. Thus, the authors recommend white men with PSA level below 1.0 ng/mL at age 60 years could “reasonably forgo” further PSA screening.

“We found that risk of developing lethal prostate cancer in the next 30 years among those with baseline PSA levels below the median was less than 2 percent at ages 40 to 59 years. Although risk was small, it remained present, and so screening should be continued, albeit with longer intervals,” writes lead author Mark Preston, M.D., from Brigham and Women’s Hospital in Boston. “It seems that baseline PSA level below the median at age 45 years followed by repeat measurements at 5-year intervals would capture most lethal cases, given that the 15-year cumulative incidence for lethal prostate cancer at age 40 to 44 years is zero and in the 45 to 49 year age group only 0.07 percent.”

Takeaway: A single midlife PSA screening for prostate cancer may be adequate to identify men at risk for lethal prostate cancer later in life. The midlife measurement can inform the need for subsequent personalized, risk-based screening.