Factors thought linked to a higher or lower risk of prostate cancer may be seriously flawed due to detection bias, according to a study published in the Journal of Medical Oncology. According to the findings, men with certain personal characteristics and conditions, including benign prostatic hyperplasia (BPH), are more likely to get tested for cancer than others.
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,” has important implications for cancer research and prevention.
“We assumed that prostate cancers are diagnosed uniformly, but that’s not true,” the study’s first author, Dr. Catherine Tangen with the Fred Hutchinson Cancer Research Center in Seattle, Washington, said in a press release.
The study, which is the first systematic review of bias in prostate cancer biopsy, is based on data obtained during two major clinical trials: the Prostate Cancer Prevention Trial (PCPT) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Both studies are from the Southwest Oncology Group (SWOG), which is part of the National Cancer Institute’s National Clinical Trials Network.
Researchers led by Dr. Ian Thompson, who was also the principal investigator in the PCPT and a co-investigator in the SELECT trial, analyzed data from more than 17,000 men in the placebo arm of the two studies. They then calculated the association between the risk of developing prostate cancer and factors such as age, ethnicity, family history, body mass index, and use of medications like statins.
At the end of the PCPT trial, all participants underwent a biopsy regardless of the level of prostate-specific antigen (PSA) in their blood. This provided unbiased data on the risk of developing prostate cancer. However, for the SELECT trial, a biopsy was performed at the discretion of the physician and in accordance with the preference of the patients, reflecting practices found in the general population.
The researchers then divided participants into groups, using comparisons that provide information about the impact of biopsy detection bias on prostate cancer risk estimates.
They found that some risk factor estimates varied significantly across the groups. Men who were younger, married, had benign prostatic hyperplasia (BPH), or a family history of prostate cancer were more likely to undergo biopsy regardless of the level of PSA level in their blood, compared to men who smoked, had diabetes, and/or had a body mass index of 25 or higher.
“We found a lot of variation in who got a biopsy. Risk and reality often didn’t line up,” Tangen said. “Risk factors for prostate cancer derived from epidemiologic studies not only may be erroneous but may lead to misdirected research efforts.”
“In medicine, we don’t want to do the wrong thing, and in research, we don’t want to look in the wrong places. Our work shows we may be doing both in prostate cancer,” Thompson added.
Dr. Alexander Kutikov, a urology surgeon at Fox Chase Cancer Center in Philadelphia who was not involved in the study, said: “This is an extremely elegant study that nicely illustrates the pitfalls that abound with interpretation of observational data. Primary care physicians should interpret any observational studies that report on associations with prostate cancer risk with extreme caution.”