Lack of persuasive data continues to plague PSA testing

Is the era of PSA screening coming to an end? Proponents say the test saves lives, but a growing number of critics contend that widespread screening does more harm than good. The ongoing controversy over the clinical value of PSA screening has long been perpetuated by a lack of persuasive data, leaving doctors and their patients with difficult conversations and a host of perplexing decisions.

The much-anticipated results from two large randomized trials—the U.S. PLCO trial and the Europe-based ERSPC study—fostered more ambiguity than clarity (New Engl J Med 360:1310- 1328, 2009). Experts extrapolated what these study results mean in routine practice for Oncology News International.

Risk reduction vs quality of life “We’re not left knowing much more than we did before the studies,” said Peter Bach, MD, an associate attending physician at New York’s Memorial Sloan-Kettering Cancer Center. “The U.S. study appears to be negative, but there’s a meaningful amount of contamination and there may be insufficient follow-up. However, the European study looks like it’s positive to the tune of a 20% reduction in mortality.”

But in order to put the PSA issue into a population-based health perspective, “we need to fully understand the trade-off between mortality risk reduction and the obvious detriment to quality of life in men who were treated earlier than necessary or to those who shouldn’t have been treated at all,” Dr. Bach added.

“We need better quality-of-life information in order to figure out how to balance the trade-off between potential benefits and overdiagnosis. On a population health basis, we can’t go by mortality statistics and say that serious harms associated with too-early or unnecessary treatments don’t matter,” he said.

“If the European study was also negative, then we’d have a different problem. We’d say, ‘OK, we now realize that PSA doesn’t work, but how do we get the PSA genie back in the bottle?’” Dr. Bach said.

Dr. Bach stressed that the European study’s long lag time to benefit and multicountry design raise certain design questions, but if the reported 20% mortality reduction is proven valid, then PSA screening confers about the same survival advantage as does mammography.

“If this were a painless pill, then PSA screening is a no-brainer. But since we can’t accurately describe the clinical trade-offs well enough for individual men to make an informed decision, we certainly can’t cast a broader PSA screening policy,” Dr. Bach said.

Is more focus on high risk needed?
Susceptibility to developing prostate cancer has a highly heritable component men who have a first-degree relative with the disease are at much higher risk than those who do not have a family history. True believers in PSA will cite the European study’s report that lives may be saved by screening and the true nonbelievers will cite the U.S. study’s lack of survival benefit, said Derek Raghavan, MD, PhD.

“However, right now we should discuss and advise our patients without being zealots and confusing them. Without good data, I continue to be extra careful with my patients who have a family history (especially those with deaths from prostate cancer) and African Americans, who reportedly have a worse survival,” said Dr. Raghavan, who is chair of The Cleveland Clinic’s Taussig Cancer Institute.

Dr. Raghavan noted that a crucial piece of the prostate cancer conundrum is the cancer itself. “There are two different types of prostate cancer, one that progresses very slowly and is less dangerous, and one that can progress quickly, causing widespread and potentially lethal disease,” he said. “The vexing problem is that it is very difficult to differentiate the indolent from the aggressive types.”