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Radiotherapy slightly increases risk for secondary malignancies among men with prostate cancer
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Patients who underwent radiotherapy during treatment for prostate cancer demonstrated a greater risk for second malignancies than those who did not receive radiotherapy, according to results of a systematic review and meta-analysis.
However, absolute rates of secondary malignancies appeared low.
Secondary malignancy is an established potential complication for patients who undergo radiotherapy for prostate cancer, but results of prior studies designed to assess the extent of this risk have been inconsistent.
Robert Nam, MD, MSc, FRCS(C), associate scientist and head of genitourinary oncology at Sunnybrook Research Institute at University of Toronto, and colleagues evaluated 21 cohort and case–control studies — 18 multi-institutional reports and three single-center studies — of patients with prostate cancer designed to evaluate the association between radiotherapy receipt and development of secondary malignancies of the bladder, colorectal tract, lung and hematological system.
Thirteen of these studies used patients treated with surgery as controls, and eight studies used patients who did not undergo radiotherapy as controls.
The researchers deemed most of the studies to be of moderate risk for bias. Common concerns included a lack of explicit demonstration that the outcome was not present at the start of the study, variations in the length of follow-up and attrition bias.
Nam and colleagues observed an association between radiotherapy receipt and increased risk for bladder cancer (four studies; adjusted HR = 1.67, 95% CI, 1.55-1.8), colorectal cancer (three studies; adjusted HR = 1.79, 95% CI, 1.34-2.38) and rectum cancer (three studies; adjusted HR = 1.79, 95% CI, 1.34-2.38), but not for cancers of the lung (two studies; adjusted HR = 1.45, 95% CI, 0.7-3.01) or hematological system (one study; adjusted HR = 1.64, 95% CI, 0.9-2.99).
When researchers restricted for 5- or 10-year lags between treatment and the development of secondary malignancies, they observed similar results. Odds ratios for bladder cancer (1.3 vs. 1.89) and rectal cancer (1.68 vs. 2.2) increased with longer lag time.
Among study participants who received radiotherapy, absolute rates of secondary malignancies ranged from 0.1% to 3.8% for bladder cancer, 0.3% to 4.2% for colorectal cancer, and 0.3% to 1.2% for rectal cancer.
“It must be noted that many of the results were obtained from a small number of studies, and the
absolute risk of secondary malignancy remains low,” Nam and colleagues wrote. “Variation in the crude incidence of secondary cancers is, at least in part, due to differences in follow-up between the included studies.”
Most studies limited to external beam radiotherapy showed an increased risk for secondary malignancy after radiotherapy; however, studies limited to brachytherapy did not suggest this association.
The researchers acknowledged their analysis may have been limited by the number of studies; the lack of important information on cofounders, comorbidities and other risk factors associated with cancers other than prostate cancer; the small number of studies in individual subgroup analyses; and the need for high-quality, minimally biased studies.
Although additional studies are necessary to confirm these results, the findings may be helpful in clinician and patient decision-making, researchers wrote.
“This information could be particularly important to a large proportion of patients where treatment is recommended and according to treatment guidelines where surgery or radiation would be equal options for them to choose,” Nam said in a press release.
Despite the recognized association between radiation exposure and carcinogenesis, the development of secondary malignancies also can depend on the primary malignancy, the dose to tissues at risk and specific characteristics of patients, Christine E. Eyler, MD, clinical fellow in the Harvard Radiation Oncology Program, and Anthony L. Zietman, MD, professor of radiation oncology at Massachusetts General Hospital, wrote in an accompanying editorial.
“Ultimately, clinicians and patients must decide together whether, for example, the roughly [1.4- to 1.7-fold] increase in relative risk of a second malignancy after a 10-year lag period justifies
alternative treatments,” Eyler and Zietman wrote. “Young patients with few comorbidities might be more likely to factor this risk into their decision-making, whereas older patients or those with competing health risks might not and, indeed, should not.”
Eyler and Zietman recommended prospective analyses with large multi-institutional databases and registries be conducted to “identify the predisposing characteristics of patients and culpable technical factors associated with radiation-associated malignancies.”
“Perhaps most important, this study confirms our belief that second malignancy should be added to the already long list of avoidable hazards associated with treatment for those men with low-risk prostate cancer who simply need no treatment at all,” they wrote. “Concern about second malignancies should not, however, stand in the way of an effective and well-studied treatment being given to men with higher-grade, lethal prostate cancer for whom the potential benefit simply dwarfs the risk.” – by Kristie L. Kahl
Disclosure: The researchers report no relevant financial disclosures. Eyler and Zietman report no relevant financial disclosures.
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