In a Dutch study reported in the Journal of Clinical Oncology, Groot et al found that the risk of subsequent malignant neoplasms was increased in the long-term follow up of patients receiving cisplatin or radiotherapy for testicular germ cell cancer.
Risk vs General Population
The study involved 5,848 testicular cancer 1-year survivors treated before the age of 50 years between 1976 and 2007 in 13 Dutch hospitals. After a median follow-up of 14.1 years, 350 solid subsequent malignant neoplasms were observed, representing a 1.8-fold increased risk of solid cancers compared with the general population. Solid subsequent malignant neoplasm risk was increased in patients with seminoma (standardized incidence ratio = 1.52) and in those with nonseminoma (standardized incidence ratio = 2.21). Patients with nonseminoma had an increased risk of thyroid, lung, stomach, pancreatic, colon, and bladder cancers, as well as melanoma and soft-tissue sarcoma. Patients with seminoma had an increased risk of small intestine, pancreatic, and urinary bladder cancers. Overall, the 25-year cumulative incidence of solid subsequent malignant neoplasms was 10.3%.
In a multivariable analysis, receipt of platinum-based chemotherapy was associated with an increased risk of any solid subsequent malignant neoplasm (hazard ratio [HR] = 2.40, 95% confidence interval [CI] = 1.58–3.62), colorectal subsequent malignant neoplasm (HR = 3.85, 95% CI = 1.67–8.92), and noncolorectal gastrointestinal (GI) subsequent malignant neoplasm (HR = 5.00, 95% CI = 2.28–10.95). Receipt of a platinum chemotherapy dose of 400 to 499 mg/m2 (HR = 2.43, 95% CI = 1.40–4.23) or ≥ 500 mg/m2 (HR = 2.42, 95% CI = 1.50–3.90) was associated with an increased risk of solid subsequent malignant neoplasm vs receipt of surgery alone; no increased risk of subsequent malignant neoplasm was associated with the use of lower platinum doses (HR = 1.75, 95% CI = 0.90–3.43). The hazard ratio for GI subsequent malignant neoplasms increased by 53% per 100 mg/m2 increase in platinum dose (P < .001 for trend). The hazard ratio for an infradiaphragmatic subsequent malignant neoplasms increased by 8% per Gy of infradiaphragmatic radiation dose vs no para-aortic radiation therapy (P < .001) for trend.
The investigators concluded, “Radiotherapy and platinum-containing chemotherapy are associated with increased solid [subsequent malignant neoplasm] risk, specifically with GI [subsequent malignant neoplasms].”
The study was supported by a grant from the Dutch Cancer Society.
Michael Schaapveld, PhD, of the Department of Epidemiology, Netherlands Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
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