Radiotherapy for prostate cancer may result in an increased risk of secondary malignancies of the bladder, colon, and rectum, according to findings of a systematic review and meta-analysis.
The unadjusted odds ratios for secondary bladder, colorectal, and rectal cancers in patients exposed to radiotherapy, compared with those not exposed, were 1.39 (95% CI, 1.12-1.71), 1.68 (1.33-2.12), and 1.62 (1.26-2.08), respectively. Differences in absolute risks for cases and controls were low, ranging from –0.9 to 1.9 cancers per 100 patients, and arose from variation in type of radiotherapy, comparator group, and lag time.
The findings, based on a relatively small number of studies with limited adjustments made for confounders, point to the need for future studies, according to the investigators. They described the implications of the findings for making treatment decisions with patients.
“In particular, for patients with a long life expectancy of 20 years or more, the possibility of secondary malignancy related to radiation needs to be included in management discussions. We acknowledge, however, that further studies are required before conclusive implication of the association between radiotherapy and secondary malignancy in these patients,” wrote Dr. Christopher J.D. Wallis of the University of Toronto and his colleagues (BMJ 2016 March 2. doi: 10.1136/bmj.i851).
Evidence suggests that irradiation of the prostate may contribute to carcinogenesis outside the irradiated area by radiation scatter, as well as the bystander effect, described as changes in gene expression due to an increase in reactive oxygen species. The researchers examined the association between radiotherapy and secondary malignancies of the bladder, colorectal tract, lung, and hematologic systems, and found no consistent evidence for associations with lung and hematologic cancers.
The systematic review and meta-analysis involved 9 studies (n = 555,873) for bladder cancer, 10 (n = 228,965) for colorectal cancer, and 8 (n = 157,239) for rectal cancer. Of the 21 reports total, 18 were multi-institutional and 3 were single-center studies. The lag period before outcome determination varied considerably, as did the comparator groups, with 13 studies (62%) designating patients treated with surgery as comparators, and 8 studies designating patients with no radiation or no radiation and no surgery as controls.
The results were similar when the analysis was restricted to studies with 5-year or 10-year lag periods. Notably, for bladder and rectal cancers, risk increased with longer lag time: from 1.3 to 1.89 for a 5-year and 10-year period, respectively, for bladder cancer and from 1.68 to 2.2 for rectal cancer.
Risks associated with brachytherapy were lower than for external beam radiotherapy.