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Radiotherapy, chemotherapy increase risks of second malignancy, cardiovascular disease similar to smoking in patients with testicular cancer, researchers report

Monday, November 12 2007 | Comments

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What's This? Previous radiotherapy and chemotherapy may increase the risk of developing a second malignant neoplasm (SMN) and cardiovascular disease (CVD) among survivors of testicular cancer, according to data from a study conducted in the Netherlands.

To compare the effects of radiotherapy and chemotherapy on the long-term risks of SMNs and CVD in survivors of testicular cancer, researchers examined data from a nationwide cohort of 2,707 individuals who had survived testicular cancer for >=5 years. Rates of SMNs and CVD in these individuals were compared with those of the general population, as determined from Danish population registries.

After a median follow-up of 17.6 years, 287 SMNs, 357 CVDs (myocardial infarction, angina pectoris, and congestive heart failure), and 79 peripheral vascular diseases occurred in the survivor cohort. When compared with the general population, testicular cancer survivors had a 70% greater risk of an SMN (HR, 1.7; 95% CI, 1.5-1.9) and a 10% greater risk of CVD (HR, 1.1; 95% CI, 1.0-1.3).

The incidence of SMNs was greater in organs located in areas commonly irradiated during testicular cancer treatment, including the stomach, pancreas, urinary bladder, and kidneys, most noticeably when radiotherapy was combined with chemotherapy, the authors noted. Furthermore, the survivors who were treated only with surgery had no increased risk of an SMN, except for melanoma.

In multivariate analyses, subdiaphragmatic radiotherapy was associated with a significant 2.6-fold increase in the risk of an SMN, but no increase in the risk of CVD, whereas treatment with cisplatin-containing chemotherapy was associated with a significant 2.1-fold increase in the risk of an SMN and a significant 1.7-fold increase in the risk of CVD.

Overall, the risk of developing an SMN or CVD was 1.8-fold greater following subdiaphragmatic radiotherapy and 1.9-fold greater following cisplatin-based chemotherapy, which were similar to the 1.7-fold increase in risk observed in smokers. Among the patients who developed an SMN and CVD (n=34), smoking (HR, 3.4) and mediastinal radiotherapy (HR, 7.1) were especially strong risk factors, the authors noted.

"In view of the observed risks, surveillance is preferable for the majority of future stage I seminomas and nonseminomas," the authors suggested.

"In accordance with other groups of cancer survivors, we recommend the development of guidelines on follow-up management that include monitoring for late effects of testicular cancer treatment in collaboration with primary care professionals," they added. (van den Belt-Dusebout AW, et al. J Clin Oncol 2007;25:4370-4378.)

In an accompanying editorial, Dr. Dean Bajorin of the Memorial Sloan-Kettering Cancer Center agreed that oncologists should take these increased long-term risks into account when recommending therapies to patients with early testicular cancer who are likely to live for several decades after treatment.

"[T]his study ... should serve as a platform for the academic oncology community to re-examine how we weigh risks and benefits in creating chemotherapy recommendations for patients with stage I testis cancer," Dr. Bajorin wrote. (J Clin Oncol 2007;25:4341-4343.)

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