Screening for PSA Cuts Death Rate, But Pitfalls Remain

Oliver Sartor, MD

Oliver Sartor, MD

Screening for prostate-specific antigen (PSA) significantly cuts the death rate from prostate cancer, so America’s medical community should continue to offer the test to appropriate men, but at the same time should work harder to avoid the screen’s potential pitfalls—undertreatment or overtreatment of patients with the disease, said Oliver Sartor, MD, in a talk during the 7th Annual Interdisciplinary Prostate Cancer Congress (IPCC) Saturday in New York City.

“What did the pre-PSA era look like? The American College of Surgeons cancer databases from 1986 through 1988 show that 20% to 21% of patients with prostate cancer were walking in with metastatic disease,”¹said Sartor, Laborde Professor of Cancer Research at Tulane University Medical School in New Orleans, Louisiana, and medical director of the Tulane Cancer Center. “I started [treating] prostate cancer in 1989, and having all these people walk in with metastatic disease was just heartbreaking. We really wanted to do something better than just wait for metastasis to occur.”

Sartor admitted that PSA testing results in both harm and benefit, but said the true concern is not the value of the testing itself, but the undertreatment of men with high-risk prostate cancer and the overtreatment of men with low-risk prostate cancer. In fact, he said, several studies have shown that active surveillance is underutilized and treatment is the norm in low-risk patients in the United States.

“If they are diagnosed,” he said of patients with lower-grade prostate cancers, “they should consult with a physician who is comfortable with surveillance before they decide to be treated.”

PSA screening has long been controversial, and debate has intensified over the past 2 years, since the US Preventive Services Task Force discouraged PSA testing across the board by giving the technique a “D” rating. Sartor questioned that guidance, noting that the USPSTF panel that evaluated the value of PSA testing was led by a pediatric hematologic/oncologist who ostensibly had little or no experience treating prostate cancer.

Meanwhile, a guideline issued by the American Urological Association last year does support PSA testing for certain men between 55 and 69 years of age, and the National Comprehensive Cancer Network last week released a guideline that calls for an initial PSA test between ages 45 and 50, with later testing based on risk factors, and more stringent rules for when biopsy is indicated.

Sartor pointed out that prostate cancer has a high incidence rate as compared to other cancers, at least in part because PSA screening has led to more biopsies being conducted to check men for the disease. Also due to screening, the death rate from prostate cancer has been declining, he said.

While prostate cancer is the second leading cause of cancer death among men, resulting in 28,000 deaths per year, the mortality rate from the condition in men over 50 years is fairly low, at 2% to 3%—and may yet prove to be even lower than that, Sartor said.

“The vast majority of men with prostate cancer will not die from their disease,” he said.

That’s why there’s concern about screening for PSA, which can often result in the diagnosis of prostate cancer long before it is clinically evident—in men 51—56 years old, the lead time was about 12 years, according to one study.²If men are unnecessarily treated, they often must live with long-term side effects, “a huge issue in prostate cancer,” Sartor said.

Still, he said that a large randomized trial known as the European Randomized Study of Screening for Prostate Cancer (ERSPC)^3,4—an aggregation of data from a host of trials—supported the value of PSA testing.

ERSPC included 182,000 men, with a core group aged 55—69 years. The study compared men whose PSAs were screened every 2 to 7 years against men whose PSAs were not checked. In the unscreened group, prostate cancers were found later and were more likely to be high-risk when they were discovered. The likelihood of men to die of their disease during a follow-up period of more than 10 years was 0.4% in the screened group and 0.5% in the unscreened group.

According to Sartor, the study demonstrated a 60% increase in the prostate cancers detected in the screened vs the non-screened group, and at 9 years of follow-up, prostate cancers with a Gleason score of ≤6—considered low-volume and often not worth treating—totaled 72.2% in the screened group vs 54.8% in the control group.

After 11 years of follow-up in the intent-to-treat population, Sartor said, there was a 21% reduction in the risk of death from prostate cancer in the screened group. He added that the death rate in the control group seemed to accelerate at about year 14, and he postulated that the trend would continue if follow-up were pursued, demonstrating a greater benefit to PSA screening over time.

The doctor pointed out that 74% of the men in the screened group who died of prostate cancer were diagnosed in the first round of screening, which for many of the patients was likely their first screening ever. He suggested that the age range of the patients in the study was older than it should have been in order to derive the most benefit from PSA screening.

The age issue was elucidated in a Swedish subset of ERSPC, published by Hugosson et al in 2010,⁵which showed that “younger men (aged 50 to 64 upon enrollment in the study) with longer follow-up have a 44% reduction in prostate cancer-specific mortality” if their PSA is screened, Sartor said. He added that the unscreened cohort in this subset, as well, began to demonstrate a more accelerated death rate at about 14 years.

Sartor noted that results from ERSPC were not quite as reliable as physicians might have hoped. In the Dutch subset of the trial, for example, it was found that 19.4% of men in the non-screening group did, in fact, have their PSA tested; meanwhile, 5.4% of the men in the Dutch screening arm never underwent PSA screening.

However, a paper correcting for those issues was published this year by Bokhorst et al,⁶Sartor said. It showed that unadjusted results from the study’s intent-to-treat analysis demonstrated a hazard ratio of 0.68 in favor of screening at a median follow-up of 13 years; after correction for both non-attendance and contamination, the study demonstrated a hazard ratio of 0.49 in favor of screening, Sartor said.

Sartor concluded that PSA “screening as conducted in the Dutch center of the ERSPC can reduce the risk of prostate cancer death by up to 51%.”

The doctor mentioned that another large trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial,^7,8was conducted to test the value of PSA screening, with results suggesting that testing increases the risk of discovery of a prostate cancer, but does not decrease the risk of death. However, Sartor said that contamination was so rampant in the trial that its results should be ignored. In all, 52% of the participants in the study’s non-screening group had their PSA checked, while 44% of men in the trial had PSA tests prior to randomization.

Sartor summed up his beliefs on the issue of PSA screening by noting that they are reflected in his own medical choices.

“I get my own PSA,” he said, “so I think you know where I stand on the issue.”

References

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3. Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study.N Engl J Med. 2009;360:1320—1328.
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6. Bokhorst LP, Bangma CH, van Leenders GJLH, et al. Prostate specific antigen-based prostate cancer screening: reduction of prostate cancer mortality after correction for nonattendance and contamination in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.European Urology. 2014;65(2):329—336.
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8. Andriole GL, Crawford ED, Grubb RL 3^rd, et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up.J Natl Cancer Inst. 2012;104(2):125—132.