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PSA levels in midlife predict future prostate cancer mortality
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Middle-aged men with elevated PSA levels experienced an increased risk for lethal prostate cancer, according to the results of a nested case–control study.
“We found that a single baseline PSA level measured during midlife predicted subsequent development of lethal prostate cancer with good accuracy over 30 years of follow-up,” Mark A. Preston, MD, MPH, instructor in surgery at Brigham and Women’s Hospital, and colleagues wrote. “Assuming that opportunistic screening was at least somewhat effective in reducing mortality, our results are likely to underestimate the association between baseline PSA and lethal prostate cancer in the absence of any screening.”
Stacy Loeb
Although PSA screening is known to reduce prostate cancer mortality, it also is associated with overdiagnosis and overtreatment, and controversy exists as to whether the benefits outweigh the risks.
In an unscreened Swedish population, PSA level at midlife predicted prostate cancer mortality and risk for metastases. Preston and colleagues sought to evaluate the association between midlife PSA level and lethal prostate cancer in men in the United States using opportunistic screening.
Researchers used data from the Physicians’ Health Study, a placebo-controlled trial of 22,071 midlife male physicians (aged 40 to 59 years) that evaluated aspirin and beta-carotene and was initiated in 1982. From that trial, 234 patients with prostate cancer and 711 age-matched controls (1:3) had data on baseline PSA levels.
The mean age at blood draw was 55 years.
Median follow-up from blood draw to overall prostate cancer diagnosis was 9 years.
Researchers evaluated participants according to age: 40 to 49 years (cancer, n = 34; control, n = 104), 50 to 54 years (cancer, n = 70; control, n = 202) and 55 to 59 years (cancer, n = 130; control, n = 405).
Median PSA was 0.68 ng/mL in the 40 to 49 group, 0.88 ng/mL in the 50 to 54 group and 0.96 ng/mL in the 55 to 59 group.
Men with PSA levels above the median had a significantly increased risk for prostate cancer in the 40 to 49 group (OR = 7.3; 95% CI, 2.4-21.8), 50 to 54 group (OR = 7.6; 95% CI, 3.4-17.2) and 55 to 59 group (OR = 10.1; 95% CI, 5.2-19.6). Researchers noted this risk was significantly pronounced across age groups among men whose PSA level was above the 90th percentile.
Seventy-one patients (cancer, 60; control, 11) from the original cohort developed lethal disease, and the researchers subsequently rematched them with 213 controls at a 1:3 ratio (cancer, control) and analyzed in the same age subgroups: 40 to 49 years (n = 11; n = 31), 50 to 54 years (n = 17; n = 51) and 55 to 59 years (n = 43; n = 131).
Median follow-up from blood draw to lethal prostate cancer was 8.6 years.
Participants who had PSA levels above the 90th percentile had a significantly increased risk for lethal prostate cancer compared with men with PSA levels less than or equal to median PSA levels in the 40 to 49 group (OR = 8.7; 95% CI, 1-78.2), 50 to 54 group (OR = 12.6; 95% CI, 1.4-110.4) and 55 to 59 group (OR = 6.9; 95% CI, 2.5-19.1).
Of all lethal prostate cancer events, men with PSA levels above the median accounted for 82% of deaths in the 40 to 49 group, 71% of deaths in the 50 to 54 group and 86% of deaths in the 55 to 59 group. Researchers noted nine cases of lethal prostate cancer occurred among men with the lowest quartile of baseline PSA.
Men with PSA below the median experienced low 30-year absolute risk for developing lethal prostate cancer across age groups (40-44, 0.19%; 45-49, 0.51%; 50-54, 1.62%; 55-59, 0.59%).
“These findings do not necessarily imply that prostate biopsy or definitive treatment is immediately required in younger men with higher PSA levels at baseline because this could lead to overdiagnosis,” Preston and colleagues wrote. “[These findings do imply] that they undergo more intensive PSA screening to enable earlier identification of cancer and potential cure while still possible.”
A conflict exists between personalized and evidence-based medicine regarding the risks and benefits of prostate cancer screening, Stacy Loeb, MD, assistant professor of urology and population health at Langone Medical Cancer of New York University, wrote in an accompanying editorial.
“Because the baseline PSA level is a stronger predictor of future prostate cancer risk than either race or family history, it seems reasonable to use these values to tailor the screening protocol on the basis of the individual’s level of risk,” Loeb wrote. “A one-size-fits-all approach to prostate cancer screening ignores the large variation in prostate cancer risk. ... Only through the judicious application of screening, detection and treatment can we further reduce morbidity from prostate cancer at a lower cost and without causing undue harm.” – by Nick Andrews
Disclos ure: Preston reports no relevant financial disclosures. Loeb reports honoraria and travel expenses from and consultant/advisory roles with Bayer HealthCare Pharmaceuticals and Sanofi. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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