Screening Remains Critical to Optimal Management of Prostate Cancer

Leonard G. Gomella, MD

The mortality rate from prostate cancer has declined significantly in the past few decades; however, there is much debate over how much PSA screening contributed to that decline. At the 2013 IPCC®, Leonard G. Gomella, MD, discussed his view that PSA screening, while not solely responsible for the reduction, is a critical component of prostate cancer management and should continue to be used with the appropriate patients.

“We have seen that the mortality [from prostate cancer] since the 1990s has continued to go down. And, in fact, if you look at the interval from about 1991 and you move it forward to about 2010- 2011, you’ll see almost a 50% decline in mortality [Figure],” said Gomella, professor and chairman of the Department of Urology, and director of Clinical Affairs at the Jefferson Kimmel Cancer Center, Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. “We are starting to see metastatic cancer go away, and PSA has led to stage migration—earlier and more treatable cancers, and we’ve seen the survival rate go up dramatically, so PSA screening is doing something good.”

What Does the Literature Show?

Gomella stressed that screening alone did not produce the mortality decline. Rather, the synergistic effect from combining screening with treatment has improved outcomes. “[Screening is] one of the pieces of the puzzle that is improving the mortality from prostate cancer. It’s not all about screening—there are treatment effects [as well].”Gomella’s support for screening is rooted in clinical studies that have examined PSA testing. While initial trial results have varied, Gomella said the longer you follow-up and the closer you examine even the negative trials, the support is there for PSA screening. Of the three largest trials, the European Randomized Study of Screening for Prostate Cancer (ERSPC; N Engl J Med. 2009;360:1320-1328) and the Göteborg trial (Lancet Oncol. 2010;11[8]:725-732) showed that PSA screening reduced prostate cancer mortality rates.

Figure. The PSA Dilemma

According to Leonard G. Gomella, MD, PSA screening is part of a group of factors including better therapy, earlier use of hormones, changes in death assignment, lifestyle changes, and medication use (statins/COX-2 inhibitors), that has led to a reduction in the overall prostate cancer mortality rate. However, the US Preventive Services Task Force has recommended against using PSA screening in any asymptomatic male.

Source: Gomella LG. Screening for prostate cancer: the PSA controversy. Presented at: 6th Annual Interdisciplinary Prostate Cancer Congress; March 16, 2013; New York, NY.

The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (N Engl J Med. 2009;360:1310- 1319) did not demonstrate a reduction in mortality; however, “In post-hoc analysis [of the PLCO data], it showed that if a man had more than one PSA test done, that he had a 25% reduction in his risk of prostate cancer death.” There was also contamination in the PLCO, as many men in the control group had PSA screening done outside of the trial. Additionally, Gomella said that a reanalysis of the PLCO data showed that if you “looked at men who had comorbidities and took them out, the study was positive.”

Gomella also noted that with screening studies, long-term follow-up is critical to demonstrating the true benefit of PSA testing. The data show that “as time goes on, the benefit of screening becomes greater and greater,” he said. For example, with the 11-year follow-up of the ERSPC (N Engl J Med. 2012;366[11]:981-990), the number of men who needed to be screened to prevent one prostate cancer death dropped from 1440 to 1055. Additionally, the number of men who needed to be treated to prevent one death dropped from 48 to 37.

Is PSA Screening in Jeopardy?

Gomella said the bottom line with the clinical trial evidence is that screening is effective; however, the data do not support general population screening. To avoid overtreatment, screening should be targeted to specific individuals, according to Gomella. “[Screening]…makes sense in certain populations—those at high risk for the disease, those at high risk for death or morbidity from the disease, and those in good health [few comorbidities and a life expectancy of at least 10-15 years].”Gomella’s staunch defense of screening came amid concern from him and many of his colleagues that the use of PSA testing may be in jeopardy.

Historically, the authoritative US organizations—the US Preventive Services Task Force (USPSTF), the National Comprehensive Cancer Network, the American Cancer Society (ACS), and the American Urological Association—recommended some form of screening. However, in 2012, the USPSTF gave PSA screening a “D” rating, recommending against screening any asymptomatic male for prostate cancer.

Practical Advice

At the 2013 IPCC®, Leonard G. Gomella, MD, offered advice for physicians making screening decisions on the frontline of care:

• Having an informed discussion with the patient is critical. “Talk to the patient. Don’t just order the PSA test. Explain to the patient why they’re getting it,” Gomella said.
• Use the nomograms in the NCCN Guidelines for Prostate Cancer.
• PSA is not perfect—when screening patients, also use other tools, including the digital rectal exam, and especially the Gleason score.
• Reach out to your peers—multidisciplinary care is critical. Outcomes can be improved when medical oncologists, urologists, and radiation oncologists work together.
• Active surveillance (see page 32) is critical to maximizing the efficacy of the screening/ treatment paradigm. “It will address the overtreatment issue that is caused by screening for prostate cancer,” said Gomella.

“The thing that [upset] most of us was the fact that they said, ‘Don’t screen someone until they have symptoms.’ Well that completely breaks our principle of screening men for prostate cancer who are symptomatic, when it’s most curable,” said Gomella.

The recommendation is particularly disconcerting to Gomella and his colleagues because of its implications under the Affordable Care Act. Medicare is only required to cover “A”- and “B”-rated services. Unless an exception is made, or individual states decide to cover screening, the USPSTF rating would mean Medicare would not be required to cover PSA testing, which would lead to a drastic reduction in screening rates overall.

Gomella is concerned that this could lead to a return to when almost every man diagnosed with prostate cancer had advanced/metastatic disease. “To abandon PSA screening completely is going to take a lot of these men who are benefiting from screening and basically throw them out the window.”

Gomella noted that Kathleen Sebelius, secretary of the Department of Health and Human Services, is on record as stating that PSA screening would still be covered; however, he remains concerned that the “letter of the law” could still be implemented.