Diagnostic imaging: assessing the testicular cancer risk

A

lthough testicular cancer is a relatively rare diagnosis, it is the most common cancer in young men in Europe and the US. In the last 40 years, cases of the most prevalent form of the disease, testicular germ cell tumour (TGCT), have spiked. No one can explain why. A number of experts believe an environmental factor must be the culprit, but no studies have yet been able to determine a definitive link.

In 1975, three out of 100,000 men were diagnosed with TGCT. Today, it’s six out of 100,000. Over the same period, there has been a 20-fold increase in the use of diagnostic radiation, such as X-rays and CT scans. And the doses of radiation used in these tests have increased seven-fold. Researchers at the University of Pennsylvania School of Medicine wondered if the figures could be related.

Radiation is a known risk factor for cancer due to its ability to damage DNA. When cells are unable to appropriately repair the broken genetic material, cancer-causing mutations may occur.

While much research on possible environmental risk factors in testicular cancer has focused on cannabis smoking, imaging below the waist might be a neater explanation for the increasing prevalence of TGCT, reasoned Katherine L Nathanson, an oncology professor at the University of Pennsylvania’s medical school.

“There’s a whole story about cannabis use and cancer risk which frankly I’ve never really understood biologically,” she says. “Testicular tumours come from foetal germ cells so why would later-life cannabis use make any difference? But diagnostic imaging very early on might have an impact. The biological mechanism there was more sensible to me.”

Studies on the role that diagnostic radiation might play in TGCT have been limited. Past reports looking at the relationship between developing this cancer and radiation have looked at occupational, rather than medical exposure, and focused mostly on atomic bomb survivors. 

Nathanson and colleagues invited 1,246 men between the ages of 18 and 55 to take part in a study to explore the role of diagnostic radiation in testicular cancer risk. Participants completed a questionnaire that asked about their experience of medical imaging during their lifetime, including the location on the body and number of exposures. The researchers also collected tumour samples from the men with cancer.

The findings, published in​​​​​​​ PLOS ONE, showed a correlation between medical imaging and testicular cancer risk once the data was adjusted for known risks of testicular cancer, including family history, race and age.

Men who reported at least three exposures of X-ray and CT procedures below the waist had a 59% increased risk of developing TGCT compared to men with no exposure. The risk was also elevated for those exposed to diagnostic radiation during the first decade of their life.

More research with a larger study population is needed to confirm the Penn Medicine results. But the findings suggest health professionals should do what they can to limit a patient’s testicles being exposed to medical radiation. This could be achieved by reducing the dose of radiation as much as possible or using gonad shields. However, audits of paediatric diagnostic scans have found that health professionals correctly use and position testicular shields just 25% of the time.

Not everyone has agreed with the PLOS ONE findings. There has been some pushback from other experts in the field, reveals Nathanson. “We’ve had a lot of reaction from the paediatric imaging community because they want to move away from shielding and this suggests it’s not a good idea.”

Nathanson does admit, however, that there are several limitations to the study. Men with testicular cancer might be more likely to recall prior exposure to diagnostic radiation, for instance. And the researchers didn’t collect information on the exact age of first exposure to diagnostic imaging.

“It’s really hard to do a perfect study because it would have to be a prospective study where you follow people for long periods of time and track their imaging,” explains Nathanson. “You have to make the decision that either you’re never going to look at the question or you do what is admittedly an imperfect study.”

She points out that research has also linked diagnostic radiation to other cancers. For instance, women undergoing X-rays for scoliosis may have an increased risk of breast cancer. And a 2012 study of 175,000 children linked brain tumours and leukaemia to CT scans. Given a readily available intervention exists for testicular shielding, the PLOS ONE study could help radiologists make a more informed decision about how best to protect their patients.

“I’m not saying it’s enough to change guidelines. But I do think it should raise some additional consideration in this field because there was no data before,” Nathanson adds. “You have to think about the cost-benefit ratio.”

Nathanson doesn’t have immediate plans to explore this specific link further. But she will continue to explore risk factors for testicular cancer in her role as leader of the Testicular Cancer Consortium.

In this project, researchers around the world pool together resources of genome-wide association studies to identify new genetic markers of risk for the disease. Nathanson’s mission is to improve our understanding of testicular cancer, which will hopefully lead to improved treatments and better ways of preventing the disease in the future.