Issue: June 25, 2018
Perspective from
May 08, 2018
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Task force recommendation ‘step toward harmonizing’ prostate cancer screening approaches

Issue: June 25, 2018
Perspective from
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David F. Penson
Alex H. Krist

The choice to undergo PSA screening for prostate cancer should be left up to individual men and their health care providers, according to a final recommendation statement issued today by the U.S. Preventive Services Task Force.

The final statement is consistent with a draft recommendation issued last year.

In a C-grade recommendation, the task force stated men aged 55 to 69 years should discuss the potential benefits and harms of PSA-based screening with their clinicians, taking their personal values and clinical circumstances into account before making a decision.

“The USPSTF final recommendation represents an important step toward harmonizing our clinical approach to prostate cancer screening,” David F. Penson, MD, MPH, professor and chair in the department of urologic surgery, Hamilton and Howd chair in urologic oncology, and director of Center for Surgical Quality and Outcomes Research at Vanderbilt University Medical Center, told HemOnc Today. “With one or two exceptions, most societies now recommend explaining the pros and cons of prostate cancer screening and allowing men to make their own decisions about whether to be tested. Some men may choose to be tested, whereas others may not, depending upon their personal preferences.”

Further, the task force issued a grade D recommendation for PSA-based screening among men aged 70 years or older, meaning the benefits do not outweigh the harms for this group, who should not undergo routine screening for prostate cancer.

“One of the biggest benefits that we hope this recommendation provides to men who are aged 55 to 69 years is to ensure that their values and other individual factors, such as family history, are reflected in their decision on whether to be screened for prostate cancer,” Alex H. Krist, MD, MPH, vice chair of the task force and associate professor of family medicine and population health at Virginia Commonwealth University, told HemOnc Today. “Based on what the science tells us, men in this age group who are willing to accept potential harms may choose to be screened, and those who would rather avoid those harms may choose not to be screened.”

The new guidance marks a change from USPSTF’s 2012 recommendation — based on contradictory results from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial and European Randomized Study of Screening for Prostate Cancer (ERSPC) trial — against PSA screening for all asymptomatic men based on the belief that the benefits of annual testing do not outweigh the potential harms, such as infection, incontinence and impotence, associated with treatment.

“I am delighted about this change,” Otis W. Brawley, MD, MACP, chief medical officer at the American Cancer Society and a HemOnc Today Editorial Board member, told HemOnc Today when the draft guidance was first released last year. “It brings the USPSTF into line with the American Cancer Society 2010 recommendation and the American Urological Association 2013 recommendation, as well as those from the American College of Physicians and European Association of Urology.”

Risk vs. benefit

PSA screening offers a “small potential benefit” of reducing the risk for death among some men with prostate cancer, the task force wrote in their statement.

However, this potential benefit comes with an array of possible harms. These range from false-positive results, leading to further testing and prostate biopsies, to overtreatment and adverse effects, such as erectile dysfunction and incontinence.

The final recommendation is based on a systematic review of 63 studies in 104 publications conducted by Joshua J. Fenton, MD, MPH, professor in the department of family and community medicine at University of California, Davis, and colleagues. The researchers gathered literature from PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on Feb. 1, 2018. Reviewed studies included:

Fenton and colleagues reported the following in their review:

  • Random assignment to PSA screening appeared associated with reduced risk for prostate cancer mortality in ERSPC, but not in trials conducted in the U.S. or the U.K.;
  • In ERSPC, however, 17.8% of 61,604 men received false-positive results;
  • Overdiagnosis occurred in an estimated 20.7% to 50.4% of cancers detected by screening;
  • The randomized controlled ProtecT trial found that neither radiation therapy nor radical prostatectomy significantly reduced prostate cancer mortality compared with active surveillance among men with screening-detected prostate cancer, although both radiation and radical prostatectomy significantly lowered risk for metastatic disease; and
  • Radical prostatectomy appeared linked with an increased risk for incontinence in three trials (pooled RR = 2.27; 95% CI, 1.82-2.84) and erectile dysfunction in two trials (pooled RR = 1.82; 95% CI, 1.62-2.04) compared with conservative management, and radiation appeared associated with increased risk for erectile dysfunction compared with conservative management in eight cohort studies (pooled RR = 1.31; 95% CI, 1.2-1.42).

“In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes and other health needs,” the task force wrote in the final recommendation.

Along these lines, the task force identified several research gaps that remain to be addressed. These include a comparison of screening strategies, developing new methods for longer follow-up of screening and diagnostic techniques, specifically addressing screening and treatment of African-American men, how to best inform men with a family history of prostate cancer about the benefits and harms of screening, and how to better understand patient values about the benefits and harms.

“Importantly, the USPSTF rightly calls for more research into the effectiveness of screening in men at higher risk for the disease,” Penson told HemOnc Today. “This is a glaring deficit in our knowledge and one that needs to be filled so we can best serve men who are most likely to be afflicted with this common malignancy.”

Ongoing conversations

Several aspects changed since 2012 that led the USPSTF to update its recommendation for men aged 55 to 69 years, H. Ballentine Carter, MD, professor of urology at James Buchanan Brady Urologic Institute at Johns Hopkins University School of medicine, wrote in an accompanying editorial.

With longer follow-up for ERSPC, the absolute reduction in prostate cancer mortality increased from seven per 10,000 men at 9 years to 13 per 10,000 men at 13 years, attributed to a reduction in the rate of metastatic disease. Also, after accounting for differences in PLCO and ERSPC, researchers still observed a 25% to 30% reduction in deaths from prostate cancer.

Other new research includes that a single PSA screen is unlikely to be optimal for identifying harmful disease, and morbidity associated with prostate cancer remains substantial, “despite claims that technological advances have improved quality-of-life outcomes, although the harms of screening have been reduced,” Carter wrote.

The recommendation is a “timely and careful approach” to reassessing the value of PSA screening, for which primary care providers have a unique role to ensure the reduction in harms, Carter added. This includes a careful assessment of who PCPs offer screening to, at what interval, and with consideration of family history and African-American race.

Also, “primary care physicians are in a unique position to help ensure that men diagnosed with favorable-risk disease are presented a balanced message regarding management options,” Carter added.

This message should focus on the fact that active surveillance is the preferred option for patients with favorable-risk disease, Carter wrote.

“PSA-based screening for prostate cancer will continue to evolve as more data emerge from the pivotal screening trials, new measures are developed to identify men at risk [for] developing an aggressive phenotype who could then be targeted for screening, staging of disease evolves and treatment for prostate cancer improves,” Carter wrote. “It is incumbent on patients and physicians to be informed of these changes as they become available.”

Certain factors could make PSA screening worthwhile for some men, according to Krist.

“By having a conversation with their doctor about the potential benefits and harms of prostate cancer screening, we hope more men are able to make an informed decision that’s right for them,” Krist said. “Longer term, we hope to see this recommendation benefit men who are at increased risk for prostate cancer, such as African-American men and those with a family history, by making it clear that we need more quality research that can help them understand how best to stay healthy.” – by Andy Polhamus

 

For more information:

Alex H. Krist , MD, MPH, can be reached at mediarelations@jamanetwork.org.

David F. Penson, MD, MPH, can be reached at david.penson@vanderbilt.edu.

 

Disclosures: Krist and the authors of the systematic review report no relevant financial disclosures. One member of the task force has reported extensive work on prostate cancer, as well as strong feelings about the disease, and was recused from the topic. Penson and Carter report no relevant financial disclosures.

 

References:

USPSTF. JAMA. 2018;doi:10.1001/jama.2018.3710.

Fenton JJ, et al. JAMA. 2018;doi:10.1001/jama.2018.3712.

Carter HB, et al. JAMA. 2018;doi:10.1001/jama.2018.4914.