Secondary Cancers Linked to Radiotherapy in Men With Prostate Cancer

Robert K. Nam, MD, MSc

Men with prostate cancer treated with radiotherapy were at higher risk for developing second malignancies in the bladder, colon, and rectum compared with men who were not exposed to radiotherapy, according to a systemic review and meta-analysis from the University of Toronto, Canada.

Overall, 21 studies were selected for analysis. Robert K. Nam, MD, MSc, division of urology, and colleagues reported an increased risk of cancers of the bladder (4 studies; adjusted HR 1.67, 95% CI 1.55-1.80), colorectum (3 studies; adjusted HR 1.70; 95% CI 1.34-2.38), and rectum (3 studies; adjusted HR 1.79, 95% CI 1.34-2.38).

In contrast, secondary hematologic cancers (1 study; adjusted HR 1.64, 95% CI 0.90-2.99) or lung cancers (2 studies; adjusted HR 1.45, 95% CI 0.70-30.01) were not associated with exposure to radiotherapy. In addition, the researchers found that patients who received external beam radiotherapy had higher odds of developing a second malignancy as compared with patients who received brachytherapy. The researchers reported that the absolute rates, however, were low.

“We found a positive risk association,” said Nam. “This study clearly shows that physicians need to discuss the possibility of a second cancer after radiation treatment.”

The researchers focused on sites that are closest to the prostate gland: bladder, rectum, and colon. “Those are the vulnerable areas that are susceptible to radiation exposure when treating the prostate gland. We also looked at distant areas that could be susceptible because of radiation scatter. These sites include the bone and lung. Our study did not show an association for those distant sites.”

Treatment options for patients with a diagnosis of prostate cancer can include surgery or radiotherapy. Each option is associated with side effects including urinary incontinence and erectile dysfunction. Secondary cancers related to treatment represent perhaps the most serious of all complications, but previous studies have led to conflicting results.

Meta-analysis cannot establish cause and effect, but those involving observational research are useful for pulling evidence together. These results were consistent when the researchers restricted analyses to studies using five- or 10-year lag periods between treatment and the development of a secondary cancer.

The researchers noted in the analysis that odds ratios for bladder and rectal cancer increased with a longer lag time (odds ratio at 5-year lag versus 10-year lag: 1.3 versus 1.89 for bladder cancer and 1.68 versus 2.2 for rectal cancer), suggesting a potential association between radiotherapy and the development of secondary malignancy of the bladder and rectum.

“This information could be particularly important to a large proportion of patients in which treatment is recommended and according to treatment guidelines in which surgery or radiation would be equal options for them to choose,” said Nam.

Armed with this information from the study, urologists are in a better position to discuss treatment options with their patients, said Nam. “Informed decision making is so important. It’s important for patients to be aware of this risk and to understand the complications that could arise from treatment.”

Nam explained that for patients who are at low-risk and candidates for active surveillance, second malignancies are not an issue. At the other end of the spectrum, those patients with high-risk, aggressive disease will likely die from it, before the development of a second malignancy.

“But the group who might require treatment, where treatment provides long-term cancer control, these survivors could suffer the ill effects of radiation treatment. It is these patients who are at risk for developing these types of cancers and it’s important for urologists to discuss the risk with them.”

Wallis CJD, Mahar AL, Choo R, et al. Second malignancies after radiotherapy for prostate cancer: systemic review and meta-analysis. BMJ. 2016;352:i851. doi:10.1136/bmj.i851.