Platinum Exposure May Increase Mortality Risk in Testicular Cancer Patients

A new study analyzed the association between exposure to platinum through certain types of chemotherapy and mortality in patients with testicular cancer.

“The prognosis of testicular cancer (TC) has greatly improved since the late 1970s because of the introduction of cisplatin‐containing combination chemotherapy for disseminated TC, improvements in radiation techniques, and better supportive care,” the study authors wrote, adding, “TC treatment may, however, cause detrimental long‐term health effects for TC survivors.”

“Therefore, we examined cause‐specific mortality within a large, multicenter Dutch cohort of patients with TC diagnosed in the cisplatin era between 1976 and 2006.” The researchers’ findings were published in Cancer.

The study included testicular cancer patients treated at 13 Dutch hospitals between 1976 and 2006. All patients received their diagnosis at younger than 50 years old. Data were available on the primary treatment for all patients.

Final analysis included 6,042 testicular cancer patients in the full cohort and 1,138 patients randomly selected for a subcohort analysis.

Patients were followed for a median 17.6 years, during which time 800 patients time. Of the patients who died, 40.3% died due to testicular cancer. Twenty-five years following testicular cancer treatment, the cumulative mortality was 9.6% (95% CI, 8.5% to 10.7%). Patients with nonseminoma, compared to general population mortality rates, were 2.0 to 11.6 times more likely to die from lung, stomach, pancreatic, rectal, and kidney cancers; soft-tissue sarcomas; and leukemia; they were nearly twice (1.9) as likely to die from ischemic heart disease (95% CI, 1.3 to 2.8), and almost four times (3.9; 95% CI, 1.5 to 8.4) more likely to die from pneumonia. Seminoma patients were between 2.5 and 4.6 times more likely to die from stomach, pancreatic, and bladders cancers and leukemia. Patients treated with radiotherapy had a 2.1-fold (95% CI, 1.8 to 2.5) increased risk for death due to second malignant neoplasms; chemotherapy patients were 2.5 times (95% CI, 2.0 to 3.1) more likely to die from second malignant neoplasms. Multivariable analysis observed a 2.5-fold increase hazard ratio (HR; 95% CI, 1.8 to 3.5) for mortality due to second malignant neoplasms in patients treated with platinum-containing chemotherapy compared to patients who did not have platinum-containing chemotherapy. With every 100 mg/m2 increase in platinum dose, the HR for second malignant neoplasm mortality increased 0.29 (95% CI, 0.19 to 0.39; P for trend < 0.001). Compared to patients who were not exposed to platinum, those who received platinum-containing chemotherapy had a 2.1-fold (95% CI, 1.5 to 4.2) increased risk for ischemic heart disease mortality.

“In conclusion, TC survivors treated in the platinum era experience increased mortality from [second malignant neoplasms] SMNs in comparison with the general population, and this appears in part due to exposure to platinum‐containing chemotherapy,” the researchers summarized. “This study also shows that exposure to platinum‐containing chemotherapy is associated not only with a dose‐dependent increased SMN incidence but also increased mortality from SMNs.”