USPSTF changes recommendation on prostate cancer screening

Today — 5 years after the U.S. Preventive Services Task Force issued a recommendation against PSA screening for prostate cancer in all men — the task force amended its stance in a draft statement, determining that the decision about whether to be screened should be an individual one.

The new recommendation — which changed the grade for PSA screening from D to C — states the potential benefits and harms of PSA–based screening are closely balanced in men aged 55 to 69 years. As a result, the U.S. Preventive Services Task Force (USPSTF) recommends clinicians talk to these men about the potential benefits and harms of screening.

Otis W. Brawley
Donald L. “Skip” Trump

For men aged 70 years and older, the USPSTF maintained the D recommendation, based on the position that the potential benefits of PSA–based screening do not outweigh the harms, and these men should not be screened for prostate cancer.

“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.”

Donald L. “Skip” Trump, MD, FACP, executive director of Inova Schar Cancer Institute and a HemOnc Today Editorial Board member, also said he supports the new USPSTF recommendation, adding he thought the 2012 D recommendation led to patients deciding to “just forget about” screenings.

“This recommendation indicates the USPSTF is continuing to think about this important issue, and they are moving to a position many of us in the field support,” Trump 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.”

The task force’s draft recommendation statement and evidence reviews have been posted for public comment on the USPSTF website from April 11 to May 8. All public comments will be considered as the task force develops its final recommendation and evidence review.

Evidence of harms, 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% percent of screen-detected prostate cancers.

Additionally, active treatments for prostate cancer are frequently associated with sexual, urinary and bowel difficulties. 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.

Alex H. Krist

“What this recommendation means is 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 member of the USPSTF, told HemOnc Today. “What we’re really encouraging is that 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 with screenings.”

The USPSTF revised its 2012 recommendation based on data from three large randomized controlled studies: Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening, European Randomized Study of Screening for Prostate Cancer (ERSPC), and Prostate Testing for Cancer and Treatment (ProtecT).

After a median follow-up of 14.8 years in PLCO and 13 years in ERSPC, there was no difference in the risk for prostate cancer mortality in the screening vs. control arms in the PLCO trial (RR = 1.04; 95% CI, 0.87 to 1.24) but a 21% relative reduction in prostate cancer mortality in the ERSPC trial (RR = 0.79; 95% CI, 0.69 to 0.91).

Based on ERSPC incidence and mortality data, an estimated 27 men (95% CI, 17-66) needed 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 randomly assigned.

In neither trial was screening associated with significantly reduced all-cause mortality.

In the ERSPC trial, there also was 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%). Data from both trials suggested that between 20.7% and 50.4% of screen-detected cancers were over-diagnosed and would not have come to clinical attention in the absence of screening.

The ERSPC trial showed more than 15% of men who underwent PSA screenings received a false-positive result. Another data review by the USPSTF showed that one in five men who had radical prostatectomies developed long-term urinary incontinence requiring diaper use, and more than two in three men experienced long-term sexual 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 who chose radical prostatectomy, radiation therapy with neoadjuvant androgen deprivation therapy, or active surveillance, and there were no statistically significant differences in prostate cancer mortality.

Jim C. Hu

However, metastatic disease occurred less frequently among men randomly assigned radical prostatectomy (2.3%) or radiation therapy (1.9%) than men assigned active surveillance (6%).

These guidelines are more in line with the task force’s C recommendation on breast cancer screening for women, according to Jim C. Hu, MD, MPH, professor of urologic oncology at Weill Cornell Medicine, who also applauded the change.

“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 from 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. So, relatively speaking, this is more concordant with other professional guidelines.”

It is still not appropriate to routinely screen all men, Krist added.

“Likewise, in some men it is very appropriate,” Krist 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 the higher-risk men as well.”

Use of active surveillance

Many men with prostate cancer never experience symptoms, and without screening, would never know they have the disease. In autopsy studies of men who died of other causes, more than 20% of men aged 50 to 59 years, and more than one third of men aged 70 to 79 years, were found to have prostate cancer.

“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 is that, in actual practice, there are data showing that active surveillance is used more often than it was in 2012.”

In its 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 an 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 will not. Because there is no good way to identify men who will have high-risk cancers, many men receive surgery or radiation to treat prostate cancer, including those who do not benefit.

“The task force was clearly moved by the fact that in American medicine, we are starting to surveil a lot of prostate cancer,” Brawley said. “The immediate treatment days have gone by the wayside.”

Although there may be more prostate cancer diagnoses and use of active surveillance with screening changes, there should not be higher rates of treatment, Hu said.

“I think 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.”

High-risk populations

Although the USPSTF’s new recommendation applies to all men aged 55 to 69 years, evidence indicates black men are more likely to develop prostate cancer compared with white men (203.5 vs. 121.9 cases per 100,000 men) and 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 men, and the ERSPC trial did not report race-specific subgroup information. In the PLCO trial, black men were significantly more likely to have major infections after prostate biopsy than white men (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 with prostate cancer than men without a family history.

“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 over exuberant with prostate cancer screening in the 1990s,” Brawley said. “We had celebrities, sports figures, even politicians getting paid to endorse it. We had free screenings at state fairs, shopping malls, even in vans parked in grocery store parking lots and on the floor of the 1996 Republican National Convention. 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.

“Then the pendulum started swinging too far away from screening,” Brawley added. “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 said. “Some promotion of screening for profit is still going on, but hopefully, this recommendation will stop it.” – by Chuck Gormley

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.

For additional reading :

Draft statement available for comment at www.screeningforprostatecancer.org.

Today — 5 years after the U.S. Preventive Services Task Force issued a recommendation against PSA screening for prostate cancer in all men — the task force amended its stance in a draft statement, determining that the decision about whether to be screened should be an individual one.

The new recommendation — which changed the grade for PSA screening from D to C — states the potential benefits and harms of PSA–based screening are closely balanced in men aged 55 to 69 years. As a result, the U.S. Preventive Services Task Force (USPSTF) recommends clinicians talk to these men about the potential benefits and harms of screening.

Otis W. Brawley
Donald L. “Skip” Trump

For men aged 70 years and older, the USPSTF maintained the D recommendation, based on the position that the potential benefits of PSA–based screening do not outweigh the harms, and these men should not be screened for prostate cancer.

“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.”

Donald L. “Skip” Trump, MD, FACP, executive director of Inova Schar Cancer Institute and a HemOnc Today Editorial Board member, also said he supports the new USPSTF recommendation, adding he thought the 2012 D recommendation led to patients deciding to “just forget about” screenings.

“This recommendation indicates the USPSTF is continuing to think about this important issue, and they are moving to a position many of us in the field support,” Trump 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.”

The task force’s draft recommendation statement and evidence reviews have been posted for public comment on the USPSTF website from April 11 to May 8. All public comments will be considered as the task force develops its final recommendation and evidence review.

Evidence of harms, 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.

PAGE BREAK

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% percent of screen-detected prostate cancers.

Additionally, active treatments for prostate cancer are frequently associated with sexual, urinary and bowel difficulties. 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.

Alex H. Krist

“What this recommendation means is 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 member of the USPSTF, told HemOnc Today. “What we’re really encouraging is that 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 with screenings.”

The USPSTF revised its 2012 recommendation based on data from three large randomized controlled studies: Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening, European Randomized Study of Screening for Prostate Cancer (ERSPC), and Prostate Testing for Cancer and Treatment (ProtecT).

After a median follow-up of 14.8 years in PLCO and 13 years in ERSPC, there was no difference in the risk for prostate cancer mortality in the screening vs. control arms in the PLCO trial (RR = 1.04; 95% CI, 0.87 to 1.24) but a 21% relative reduction in prostate cancer mortality in the ERSPC trial (RR = 0.79; 95% CI, 0.69 to 0.91).

Based on ERSPC incidence and mortality data, an estimated 27 men (95% CI, 17-66) needed 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 randomly assigned.

In neither trial was screening associated with significantly reduced all-cause mortality.

In the ERSPC trial, there also was 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%). Data from both trials suggested that between 20.7% and 50.4% of screen-detected cancers were over-diagnosed and would not have come to clinical attention in the absence of screening.

PAGE BREAK

The ERSPC trial showed more than 15% of men who underwent PSA screenings received a false-positive result. Another data review by the USPSTF showed that one in five men who had radical prostatectomies developed long-term urinary incontinence requiring diaper use, and more than two in three men experienced long-term sexual 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 who chose radical prostatectomy, radiation therapy with neoadjuvant androgen deprivation therapy, or active surveillance, and there were no statistically significant differences in prostate cancer mortality.

Jim C. Hu

However, metastatic disease occurred less frequently among men randomly assigned radical prostatectomy (2.3%) or radiation therapy (1.9%) than men assigned active surveillance (6%).

These guidelines are more in line with the task force’s C recommendation on breast cancer screening for women, according to Jim C. Hu, MD, MPH, professor of urologic oncology at Weill Cornell Medicine, who also applauded the change.

“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 from 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. So, relatively speaking, this is more concordant with other professional guidelines.”

It is still not appropriate to routinely screen all men, Krist added.

“Likewise, in some men it is very appropriate,” Krist 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 the higher-risk men as well.”

Use of active surveillance

Many men with prostate cancer never experience symptoms, and without screening, would never know they have the disease. In autopsy studies of men who died of other causes, more than 20% of men aged 50 to 59 years, and more than one third of men aged 70 to 79 years, were found to have prostate cancer.

“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 is that, in actual practice, there are data showing that active surveillance is used more often than it was in 2012.”

PAGE BREAK

In its 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 an 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 will not. Because there is no good way to identify men who will have high-risk cancers, many men receive surgery or radiation to treat prostate cancer, including those who do not benefit.

“The task force was clearly moved by the fact that in American medicine, we are starting to surveil a lot of prostate cancer,” Brawley said. “The immediate treatment days have gone by the wayside.”

Although there may be more prostate cancer diagnoses and use of active surveillance with screening changes, there should not be higher rates of treatment, Hu said.

“I think 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.”

High-risk populations

Although the USPSTF’s new recommendation applies to all men aged 55 to 69 years, evidence indicates black men are more likely to develop prostate cancer compared with white men (203.5 vs. 121.9 cases per 100,000 men) and 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 men, and the ERSPC trial did not report race-specific subgroup information. In the PLCO trial, black men were significantly more likely to have major infections after prostate biopsy than white men (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 with prostate cancer than men without a family history.

“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.”

PAGE BREAK

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 over exuberant with prostate cancer screening in the 1990s,” Brawley said. “We had celebrities, sports figures, even politicians getting paid to endorse it. We had free screenings at state fairs, shopping malls, even in vans parked in grocery store parking lots and on the floor of the 1996 Republican National Convention. 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.

“Then the pendulum started swinging too far away from screening,” Brawley added. “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 said. “Some promotion of screening for profit is still going on, but hopefully, this recommendation will stop it.” – by Chuck Gormley

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.

For additional reading :

Draft statement available for comment at www.screeningforprostatecancer.org.