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Task force ‘got it right’ with revised prostate cancer screening recommendation
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The U.S. Preventive Services Task Force’s updated recommendation on PSA screening reflects the increasing emphasis physicians and patients place on shared decision-making, according to several key opinion leaders in oncology.
The draft guidance also demonstrates a deeper understanding of the risks and benefits of prostate cancer screening, as well as the increased use of active surveillance among men diagnosed with low-risk disease, they added.
“This recommendation indicates the U.S. Preventive Services Task Force [USPSTF] is continuing to think about this important issue, and it is moving to a position many of us in the field support,” Donald L. “Skip” Trump, MD, FACP, executive director of Inova Schar Cancer Institute and a HemOnc Today Editorial Board member, told HemOnc Today. “That is, to evaluate a person’s risk because of family history and race; to evaluate competing causes of morbidity and mortality; and to discuss options with patients, realizing that if PSA is measured and found to be increased, then substantial conversation needs to ensue to help the patient decide on the next step.”
In 2008, the USPSTF recommended against PSA–based screening for men aged older than 75 years and stated there was insufficient evidence to recommend for or against screening for men aged 75 years and younger. Four years later, the panel broadened its recommendation to include all men based on the belief that the harms of annual testing — such as infection, incontinence and impotence — outweigh the benefits associated with treatment.
That recommendation caused patients to “just forget about” screenings, Trump said.
The updated draft recommendation — released April 11 — states the potential benefits and harms of PSA–based screening are closely balanced among men aged 55 to 69 years. As a result, the task force determined the decision about whether to be screened should be an individual one, and clinicians should talk to men in this age group about the potential benefits and harms of screening.
“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. “It brings the USPSTF into line with the ACS 2010 recommendation and the American Urological Association 2013 recommendation, as well as those from the American College of Physicians and European Association of Urology.
“The task force was clearly moved by the fact that in American medicine, we are starting to surveil a lot of prostate cancer,” Brawley added. “The immediate treatment days have gone by the wayside.”
The task force’s updated recommendation still discourages PSA–based screening for men aged 70 years and older, contending the potential benefits do not outweigh the harms.
The task force accepted comments on the draft recommendation until early May, and it is expected to issue final recommendation and evidence review later this year.
Harms vs. benefits
The CDC estimates that more than 2.5 million American men were diagnosed and living with prostate cancer in 2013. More than 25,000 men in the United States died of prostate cancer in 2016, and the median age of death from prostate cancer was 80 years.
The USPSTF concluded that PSA screening may reduce risk for prostate cancer mortality but is associated with harms, including false-positive results, biopsy complications, and overdiagnosis in 20% to 50% of screen-detected prostate cancers.
Additionally, active treatments for prostate cancer frequently are associated with sexual, urinary and bowel dysfunction.
“This recommendation means that overall, on a population level, there is a small net benefit from prostate cancer screenings,” Alex H. Krist, MD, MPH, associate professor of family medicine and population health at Virginia Commonwealth University and a member of the USPSTF, told HemOnc Today. “We’re really encouraging men aged 55 to 69 have discussions with their doctors about the benefits and harms of prostate cancer screening, and that they make an individual decision based on their values and preferences about what’s right for them.”
The USPSTF revised its 2012 recommendation based on data from three large randomized controlled studies: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial, the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, and the Prostate Testing for Cancer and Treatment (ProtecT) trial.
After median follow-up of 14.8 years in PLCO, researchers reported no difference in prostate cancer mortality risk between the screening and control arms (RR = 1.04; 95% CI, 0.87 to 1.24). However, after a median follow-up of 13 years in ERSPC, investigators observed a 21% relative reduction in prostate cancer mortality in the screening group (RR = 0.79; 95% CI, 0.69 to 0.91).
Based on ERSPC data, an estimated 27 men (95% CI, 17-66) need to be diagnosed with prostate cancer to avert one prostate cancer death. Screening was associated with 3.1 (95% CI, 1.8-4.4) fewer cases of metastatic prostate cancer per 1,000 men.
Neither trial revealed a significant association between screening and reduced all-cause mortality.
The ERSPC trial also showed a high rate of positive screening (32.3 per 100 men) and biopsy (27.7 per 100 men). Biopsy-related harms included moderate to severe pain at 35 days (7.3%; 95% CI, 5.7-9.1), infectious complications (2% to 7%), and hospitalization (approximately 1%). The ERSPC trial showed more than 15% of men who underwent PSA screenings received false-positive results.
Another data review by the USPSTF showed one in five men who underwent radical prostatectomies developed long-term urinary incontinence requiring diaper use, and more than two-thirds of men experienced long-term impotence. Additionally, one in six men experienced long-term bothersome bowel symptoms, including bowel urgency and fecal incontinence.
In the ProtecT trial, prostate cancer survival was approximately 99% at 10-year follow-up among men with screen-detected prostate cancer, whether they chose radical prostatectomy, radiation therapy with neoadjuvant androgen deprivation therapy, or active surveillance, and there were no statistically significant differences between the three options in prostate cancer mortality.
The USPSTF’s updated guidelines are more in line with the task force’s recommendation on breast cancer screening for women, according to Jim C. Hu, MD, MPH, professor of urologic oncology at Weill Cornell Medicine and NewYork–Presbyterian Hospital.
“After 13 years of follow-up, the European Randomized Study for Prostate Cancer showed that 781 men needed to be invited to screening to prevent one death of prostate cancer,” Hu said. “If you look at breast cancer for women aged 50 to 59, it takes 1,339 women to be screened to prevent one death. This received a grade B from the USPSTF so, relatively speaking, this is more concordant with other professional guidelines.”
It is still not appropriate to routinely screen all men, Krist said.
“Likewise, in some men it is very appropriate,” he said. “We would have liked to have made a separate recommendation for higher-risk men but, the fact is, there aren’t enough studies that include higher-risk men for us to be able to make that assessment. That’s why these discussions and shared decisions apply to higher-risk men, as well.”
Active surveillance
Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease.
Autopsy studies of men who died of other causes detected prostate cancer in more than 20% of those aged 50 to 59 years, and more than one-third of men aged 70 to 79 years.
Data from both the PLCO and ERSPC trials suggested that between 20.7% and 50.4% of screen-detected cancers were overdiagnosed and would not have come to clinical attention in the absence of screening.
Because these data suggest some men may not require treatment — and because of the harms associated with treatment — the use of active surveillance may counteract the potential for overtreatment with greater PSA testing.
“What’s changed [from 2012] is that we have a greater understanding of the balance of those benefits and harms,” Krist said. “When we have these discussions with our patients, we can incorporate this new evidence into these discussions. The other shift in balance to a small net benefit [from PSA–based screenings] is that, in actual practice, there are data showing that active surveillance is used more often than it was in 2012.”
A study by Cooperberg and Carroll, published in 2015 in JAMA, showed the proportion of men aged 75 years or older who chose active surveillance nearly tripled from the period between 2000 and 2004 (21.9%) to the period between 2010 and 2013 (76.2%).
In its updated recommendation, the USPSTF noted that when a man has an elevated PSA, it may be caused by prostate cancer, but it could also be caused by other conditions, such as an enlarged prostate or inflammation of the prostate.
PSA–based screening and follow-up prostate biopsies cannot tell for sure which cancers are likely to be aggressive and which are not. Because there is no good way to identify men who have high-risk cancers, many men — including those who may not need treatment — undergo surgery or radiation.
Although revised screening guidance may lead to more prostate cancer diagnoses and greater use of active surveillance, the treatment rate should not increase, Hu said.
“The task force got it right,” he said. “We need longer follow-up to see if, ultimately, these MRIs and these biomarkers are accurate in stratifying whether an elevated PSA is due to background noise or enlargement vs. prostate cancer. Already, approximately half of men diagnosed with prostate cancer turn to active surveillance. We’re also more sophisticated with using MRIs before we do a biopsy. So, if the MRI looks normal with an elevated PSA, we may not automatically order a biopsy. The field has gotten more sophisticated, and it’s good to have options.”
Still, although active surveillance of low-risk cancer can reduce treatment harms, the USPSTF acknowledged surveillance may be associated with higher risk for prostate cancer metastasis.
In ProtecT, metastatic disease occurred less frequently among men randomly assigned radical prostatectomy (2.3%) or radiation therapy (1.9%) than men assigned active surveillance (6%).
High-risk populations
Although the USPSTF’s new draft recommendation applies to all men aged 55 to 69 years, evidence indicates black men are more likely than white men to develop prostate cancer (203.5 vs. 121.9 cases per 100,000 men), and they are more than twice as likely to die of prostate cancer (44.1 vs. 19.1 deaths per 100,000 men).
However, only 4% of the PLCO trial’s population were black, and the ERSPC trial did not report race-specific subgroup information. In the PLCO trial, black men were significantly more likely than white men to have major infections after prostate biopsy (OR = 7.1; 95% CI, 2.7-18).
The USPSTF also noted that, in the Finnish arm of the ERSPC trial, men with at least one first-degree relative with prostate cancer were 30% more likely to be diagnosed than men without a family history of the disease.
“In our recommendation statement, we went through a lot of effort to call out the need for more research in high-risk groups,” Krist said. “It’s a real national priority to understand the balance of the risks and benefits and how it’s different in higher-risk groups than in average-risk men. We should be able to do more of these types of studies.”
It is important for physicians and patients to put into context the significance of the USPSTF’s new recommendation on PSA screenings, Brawley said.
“The medical world was overexuberant with prostate cancer screening in the 1990s,” Brawley said.
Celebrities, sports personalities and politicians made paid endorsements. Free screenings were offered at state fairs, shopping malls, and even on the floor of the Republican National Convention in 1996, he said.
“There was an epidemic of prostate cancer, and a man who was diagnosed was immediately told he had to get treated with a radical prostatectomy or radiation,” Brawley said. “Then the pendulum started swinging too far away from screening. More and more people started realizing the harms were better proven than the benefits, if any benefits truly existed. That was when the task force and other organizations recommended against routine screening.
“Now, I see all these organizations coming to what I consider the wise moderate position,” Brawley added. “Some promotion of screening for profit is still going on, but hopefully this recommendation will stop it.” – by Chuck Gormley
References:
Cooperberg MR and Carroll PR. JAMA. 2015;doi:10.1001/jama.2015.6036.
U.S. Preventive Services Task Force prostate cancer screening draft recommendations. Available at: screeningforprostatecancer.org. Accessed April 11, 2017.
For more information:
Otis W. Brawley, MD, MACP, can be reached at otis.brawley@cancer.org.
Jim C. Hu, MD, MPH, can be reached at jch9011@med.cornell.edu.
Alex H. Krist, MD, MPH, can be reached at alexander.krist@vcuhealth.org.
Donald L. “Skip” Trump, MD, FACP, can be reached at donald.trump@inova.org.
Disclosure: Brawley, Hu, Krist and Trump report no relevant financial disclosures.