Risk factors for prostate cancer may not be what researchers believed. According to a study published recently in the Journal of Clinical Oncology, biases exist in screening and biopsy patterns, and those biases strongly influence the assessment of prostate cancer risk factors.
The study, “Biases in Recommendations for and Acceptance of Prostate Biopsy Significantly Affect Assessment of Prostate Cancer Risk Factors: Results From Two Large Randomized Clinical Trials,” suggests that risk factors derived from epidemiologic studies, where not all participants are equally likely to undergo screening, may be erroneous and lead to misdirected research efforts.
Prostate cancer is the second most common cause of cancer death in men, and efforts that aim to control it include prevention, screening and improved treatment. Usually, prostate cancer prevention and early detection rely on the assessment of a patient’s risk to determine how often he should undergo PSA screening or a prostate biopsy.
But such risk factors are identified in epidemiologic studies and implemented in the clinic without confirmatory clinical trials. As a result, researchers in this study learned that even risk factors that are not associated with prostate cancer will be found to increase cancer risk. That is because men with the risk factor are more likely to undergo screening and be diagnosed with prostate cancer.
“We assumed that prostate cancers are diagnosed uniformly, but that’s not true,” Catherine Tangen, DrPH, of the Fred Hutchinson Cancer Research Center, and the lead author of the study, said in a press release. “We found a lot of variation in who got a biopsy. Risk and reality often didn’t line up. As a public health researcher, this concerns me. Bias can warp our understanding of the prostate cancer disease process — and misdirect our efforts to test new risk factors and prevention strategies in future research,” she said.
Tangen and her team reviewed data from more than 17,000 men, including more than 2,200 diagnosed with prostate cancer, who were included in two major trials: the Prostate Cancer Prevention Trial (PCPT) and the Selenium and Vitamin E Chemoprevention Trial (SELECT). Each trial screened participants with different patterns, which led to differences in risk factors.
The PCPT trial included a biopsy in all men in the end of the study, regardless of their PSA test, which provided an unbiased data on cancer risk. The SELECT trial, however, included a PSA test, a digital rectal exam, or a biopsy based only on the doctor’s recommendations or patient’s preferences, which was similar to what happens in the general population.
Researchers found that men who were healthier, younger, better-educated, married, or with a family history of prostate cancer, all were more likely to undergo a prostate biopsy, irrespective of their PSA levels.
Looking at the risk factors for prostate cancer in both trials, the researchers found major differences. As an example, while the SELECT trial suggested that statin administration reduced the risk of prostate cancer, no association was found in the PCPT study.
Researchers concluded that such differences likely were being caused by differences in screening. Indeed, although the PCPT study indicated that vasectomy increased the risk for prostate cancer in 12%, the team saw a reduction to only 4% when the biased detection was taken into account.
A similar trend was observed in family history of prostate cancer and elevated PSA levels, which both were associated with higher risk for prostate cancer, but whose association decreased when the researchers controlled for the biopsy bias.
“The research community sometimes makes faulty conclusions about prostate cancer risk — assumptions that may lead to flawed screening decisions and incorrect choices about research directions,” Tangen said. “Detection bias is introduced when screening information is not acted upon uniformly. That is a reasonable strategy for a doctor who is assessing an individual’s risk profile and preferences. However, at the population level it can lead us to screen and biopsy men who are at low risk, and lead us to fail to screen and biopsy men who are at higher risk, Tangen said. “In research, bias can cause us to waste precious time and money investigating the wrong risk factors. One wrong assumption can have a huge domino effect.”
The researchers believe their findings have great implications for cancer care research, not only in prostate cancer, but in other cancers, too.
“In medicine, we don’t want to do the wrong thing and in research, we don’t want to look in the wrong places,” said Ian Thompson, MD, of the University of Texas Health Science Center at San Antonio, principal investigator on the PCPT trial and a leader in SELECT. “Our work shows we may be doing both in prostate cancer. As there are similar issues in other cancers such as breast and thyroid, this issue may occur for these tumors as well. So, the message is this: Risk factors for cancer are very complex. Before we all leap to conclusions, we need to collect very detailed research data on who is screened and why, and be very rigorous in our analysis of that data and what it might mean for clinical care.”
“In cancer research, we all want the truth,” Tangen agreed. “But we’ve found that we may just have to work harder to find it. There is a lot of noise out there,” she said.