Precision-Medicine Approach Could Revive Prostate Cancer Test


“A new study led by researchers at UC San Francisco and Kaiser Permanente has identified genetic predictors of normal prostate-specific antigen (PSA) levels in healthy men, which could be used to improve the accuracy of PSA-based prostate cancer screening tests.

“Until recently, PSA tests for prostate cancer were considered an exemplar of successful early cancer detection leading to improved treatment outcomes. But over the past five years, a series of studies has suggested that the tests are not sensitive enough: frequent false positives lead to too many unnecessary medical procedures, and false negatives give men a false sense of security. In 2012, the was given a ‘D’ rating by the U.S. Preventive Task Force, and the test is no longer covered by some insurers.”

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Questioning Medicine: Breast Cancer Screening (CME/CE)

Joe Weatherly, DO, and Andrew Buelt, DO, are family medicine residents in St. Petersburg, Fla. Together, they co-produce the podcast Questioning Medicine, where they deconstruct issues confronting today’s clinicians. In this guest blog, Weatherly gives his take on breast cancer screening

“In 2014, there will be an estimated 1,665,540 cancer diagnoses, and approximately 585,720 deaths from cancer or complications from the treatment of cancer. Estimates are that 3% to 35% of cancer patients avoid premature death by screening alone.

“This sounds wonderful. Those individuals and their stories are the poster children for preventive medicine. The cost and collateral impact on their lives is well worth it to those who prolong life and obtain ‘remission.’

“What we don’t talk about are the potential harms false positives can have on the majority of those screened. The Susan G. Komen foundation website states ‘…. goal is to find cancer, not to avoid false- positive results.’ But false positives have consequences.

“The screening machine spits out false positives, false negatives, and identifies positive cancer diagnoses that will not benefit from treatment.

“We have sold America on the notion that breast cancer screening will reduce the risk of breast cancer death by more than 50%. And it will prevent death in more than 8% of the participants.

“But according to Biller-Andorno et al., the screening process on its best day can provide a relative risk reduction of 20% and, in absolute terms, one breast cancer death per 1,000 women.”

Lung Cancer Screening of Medicare-Eligible Patients Associated with Greater Benefits, Risks

“Screen-detected lung cancer prevalence, as well false-positive results, were higher among Medicare-eligible participants compared with younger participants, according to results of a secondary analysis of the National Lung Screening Trial.

“Initial results of the National Lung Screening Trial (NLST) demonstrated a 20% reduction in the risk for lung cancer with annual low-dose CT compared with chest radiography in high-risk adults aged 55 to 74 years. The findings served, in part, as the basis for the US Preventive Services Task Force’s recommendation — issued in December 2013 — that high-risk individuals aged 55 to 80 undergo annual lung cancer screening with low-dose CT.

“However, experts have debated whether the annual screens should be covered for Medicare beneficiaries, who comprised approximately 25% of the trial’s population (age 55 to 64 years, n=19,612; age 65 to 74 years, n=7,110). In April, the Medicare Evidence Development & Coverage Advisory Committee expressed low to intermediate confidence that the benefits of annual screening outweighed the potential risks in the Medicare population.”

Professional Recommendations Against Routine Prostate Cancer Screening Have Little Effect

“The effect of guidelines recommending that elderly men should not be routinely screened for prostate cancer ‘has been minimal at best,’ according to a new study led by researchers at Henry Ford Hospital.

“The study, published as a research letter online in JAMA Internal Medicine, focused on the use of PSA — prostate-specific antigen — to test for prostate cancer. ‘We found that the effect of the guidelines recommending against the routine screening of elderly men in particular has been minimal at best,’ says Jesse Sammon, D.O., a researcher at Henry Ford’s Vattikuti Urology Institute and lead author of the study.

“The researchers found an estimated 17 million men age 50 or older without a history of prostate cancer or prostate problems who reported undergoing PSA screening. Though credited with a significant improvement in 5-year cancer survival rates during the first decade after the FDA approved PSA testing of men without symptoms, its use for routine screening is controversial.

” ‘The concern is that the test often provides false-positives, leading subjects who do not have a prostate malignancy to undergo treatment they don’t need and suffer such side effects as impotence and urinary incontinence,’ says Dr. Sammon.

“Nearly three years ago, the debate led the U.S. Preventative Services Task Force to recommend against routine PSA screening in any age group.

” ‘But in the time since, nationwide patterns of PSA screening were largely unknown,’ says Dr. Sammon. ‘We sought to examine those patterns to determine the effects of the most recent USPSTF recommendation.’ “

Informed Consent: False Positives Not a Worry in Lung Cancer Study

“The U.S. Preventive Services Task Force recently recommended computerized tomography (CT) lung screening for people at high risk for cancer, but a potential problem with CT is that many patients will have positive results on the screening test, only to be deemed cancer-free on further testing. Many policymakers have expressed concern that this high false-positive rate will cause patients to become needlessly upset. A new study of National Lung Screening Trial participant responses to false positive diagnoses, however, finds that those who received false positive screening results did not report increased anxiety or lower quality of life compared with participants who received negative screen results.

” ‘Most people anticipated that participants who were told that they had a positive screen result would experience increased anxiety and reduced quality of life. However, we did not find this to be the case,’ said Ilana Gareen, assistant professor (research) of epidemiology in the Brown University School of Public Health and lead author of the study published in the journal Cancer.

“The NLST’s central finding, announced in 2010, was that screening with helical CT scans reduced lung cancer deaths by 20 percent compared to screening with chest X-rays. The huge trial spanned more than a decade, enrolling more than 53,000 smokers at 33 sites.”

MicroRNA Signature Classifier May Reduce False Positives in Lung Cancer

“A noninvasive plasma microRNA signature classifier combined with low-dose CT was associated with a fivefold reduction in the false-positive rate for lung cancer detection compared with CT alone, according to results of a retrospective study.

“The analysis included 939 smokers enrolled in the Multicenter Italian Lung Detection trial who had been assigned low-dose CT (n=652) or observation (n=287).”

Editor’s Note: Sometimes a doctor believes he/she has detected lung cancer in a patient, but the patient is later found not to have lung cancer. This is known as a “false positive.” Scientists tested a new lung cancer detection procedure to see if it reduced the risk of false positives. The procedure combines CT scans with molecular testing of a patient’s blood sample for substances that could indicate the presence of lung cancer. It found that the new procedure worked better than CT scans alone.