Biopsy biases may influence prostate cancer risk factor assessment

Last Updated: 2016-11-03

By Reuters Staff

NEW YORK (Reuters Health) - A new analysis of two large prostate cancer prevention trials has identified "profound" differences in characteristics between men who did and did not undergo prostate biopsy, raising the possibility of detection bias.

"The overarching implication of our data is obvious: evidence from observational studies suggesting that certain factors reduce/increase the risk of prostate cancer may be seriously flawed because of detection bias," Dr. Catherine Tangen of Fred Hutchinson Cancer Research Center in Seattle and colleagues state in their report, online October 28 in the Journal of Clinical Oncology.

Epidemiologic studies may identify risk factors that are implemented into practice without confirmatory trials, the researchers note. However, biopsy-detectable prostate cancers are common in aging men, they add, and usually do not cause symptoms until they spread.

"As a result, if a risk factor, even one unassociated with prostate cancer, is incorporated into clinical practice, it will be found to increase cancer risk because men with the risk factor will be more likely to undergo screening," the researchers note. Those who screen positive tend to undergo biopsy, and so, "Ultimately, men with the risk factor will then be more likely to be diagnosed with prostate cancer."

To investigate whether biases in biopsy recommendations might influence risk factor-prostate cancer associations, the researchers analyzed data from the Prostate Cancer Prevention Trial (PCPT) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT) to identify groups of men with incident prostate cancer.

After the researchers adjusted for age, longitudinal prostate-specific antigen, and digital rectal examination, they found that men in their 60s, men with benign prostatic hyperplasia, and men with a family prostate cancer history were more likely to undergo biopsy, while those with a body mass index of 25 or above, diabetes, or a history of smoking were less likely to have a biopsy.

Odds ratios for some risk factors varied across the cohorts, the researchers found. For example, black men's OR for prostate cancer compared with other ethnicities was 1.20 in SELECT and 1.83 in PCPT. In SELECT, statins were associated with decreased odds of prostate cancer (OR, 0.65), while this was not the case in PCPT (OR, 0.99).

Several studies have linked statins, vasectomy and aspirin to prostate cancer risk, Dr. Tangen and her team note.

"Without detailed data about screening and biopsy verification, it is not possible to tease out whether there is a biopsy detection bias or a true association of a risk factor with prostate cancer, or a combination of both," they add. "Adjusting for PSA screening alone is not adequate."

These biases can have a number of negative effects, the researchers note, for example if men begin to use interventions that do not actually reduce prostate cancer risk, but carry adverse effects.

"A second unfortunate result is that precious research resources may be directed to preclinical and clinical studies, only to find the original observation to be flawed," the team notes.

The results could extend to other types of cancer in which patients often have asymptomatic, slow-growing diseases, the researchers add. "We encourage further study of this area to develop a better understanding of the true relationship between risk factors and cancer," they conclude.

Dr. Tangen did not respond to an interview request by press time.

SOURCE: http://bit.ly/2ffKAr3

J Clin Oncol 2016.