Editor's note: This is Part 2 of a 2-part series. Part 1 published in the April 15 issue of “CancerScope.”
Many critics have found flaws with the recent draft guidelines for prostate cancer screening released last fall by the US Preventive Services Task Force (USPSTF). The proposed guidelines, discussed in more detail in Part 1 of this series, were based on findings from 2 large screening trials: the US-based Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC). The recent guidelines issued a “D” recommendation for prostate-specific antigen (PSA) screening for men younger than age 75 years, indicating that the benefits do not outweigh the harms.1
Among the critics of the guidelines is William Catalona, MD, director of the clinical prostate cancer program at Northwestern University in Chicago, Illinois, and a pioneer of PSA screening. Specifically, Dr. Catalona believes the USPSTF's assessment of harms is inaccurate. “They used very outdated studies from 20 years ago to assess the risk of prostatectomy and radiation therapy,” he says. “They overestimated the risk of screening and treatment. For example, they said that no study has ever reported on anxiety associated with screening, but the Göteborg study [part of the ERSPC trial] found that only 6% of patients had high anxiety associated with biopsies.”
Indeed, the USPSTF stated in its study discussion that the evidence on treatment-related harms was most applicable to open retropubic radical prostatectomy and external-beam radiation therapy, although details of techniques and specific regimens were frequently lacking. Also, the task force stated that it found little evidence comparing newer techniques for prostatectomy, such as nerve-sparing approaches that use robotic-assisted or free-hand laparoscopy, with watchful waiting. Still, the task force added that it did not find a pattern suggesting that more recent studies reported different risk estimates than older studies.
Michael LeFevre, MD, MSPH, co-vice chair of USPSTF, says, “We updated our review with the most recent literature based on large, population-based studies. If people feel they have significant information on this—that the harms have declined—they should publish it.”
One of the really bad things is that [the USPSTF guideline] shuts down the discussion and shuts down the decision making. To deny patients the opportunity to make an informed decision puts them in harm's way. And to do this based on flawed science is really unconscionable. —William Catalona, MD
According to Dr. Catalona, the true extent of overdiagnosis is unknown, because if a patient is diagnosed, undergoes a radical prostatectomy, and is cured, researchers have no way of knowing whether he was overdiagnosed. Many factors can be taken into account to avoid overdiagnosis, he says, including a patient's age, race, family history, PSA velocity, and more; after diagnosis is made, physicians also can look at Gleason grade and percentage of cancer in the biopsy.
“The PCLO's protocol is not how things are done today,” he says. “If I had a 50-year-old black patient with 2 brothers [who had] aggressive prostate cancer and a 2.5 ng/mL PSA, I wouldn't wait until it got to a 4 to biopsy him. On the other hand, if I had an 80-year-old patient with a PSA around 5 that hadn't changed much in the past 10 years, I wouldn't biopsy him.”
He adds that these factors do not come out in large, randomized trials and that the trials are no longer relevant to how the field has progressed in understanding overdiagnosis and overtreatment. “I think the pendulum has swung too far,” he says. “Patients with life-threatening prostate cancer look at me and wonder if they're being overdiagnosed.”
On the other side, he says, is the risk of underdiagnosis. Although recent studies and a National Institutes of Health consensus panel have recommended active surveillance for men with low-grade prostate cancer, Dr. Catalona says there are still risks involved. There is the risk of a sampling error in which initial biopsies do not show prostate cancer (or if they do, they do not indicate how aggressive it is). As a result, some patients are later diagnosed with aggressive disease. Studies show that about 35% to 50% of men fall off active surveillance and must be treated, he says.