Outcomes of Second Cancers in Men with Histories of Testicular Cancer

In his memorable manuscript, Testicular cancer: A model for a curable neoplasm (Cancer Res 1981; 41:3275), Dr. Lawrence Einhorn laid the groundwork for the remarkable change in management of testicular cancer that, in 2007, results in about 95% of patients receiving curative treatment. Given this remarkable cure rate and the young age at which most patients receive therapy, late effects of testicular cancer therapy — including risk for hypertension and other cardiovascular problems — are being recognized. Second cancers are among the leading causes of death in testicular cancer survivors; previous work has demonstrated a substantial increase in risk for developing solid tumors in various tissues, including lung, pancreas, colon, and mesothelioma (J Natl Cancer Inst 2005; 97:1354). Although ample evidence supports a high risk for second cancers, few data are available about whether therapy for these second cancers remains effective: That is, does primary therapy for testicular cancer compromise our ability to deliver potentially curative therapy for a second cancer?

Using SEER (Surveillance, Epidemiology, and End Results) data, NIH investigators compared cancer-specific and all-cause mortality rates for 621 testicular cancer survivors who developed second cancers (these were the second-cancer patients) with mortality rates for a sample of 12,420 age- and race-matched patients with first cancers at the same stage and anatomic site as the identified second cancers and with the same calendar year of diagnosis (these were the first-cancer patients). Seventy-six percent of the testicular cancers had been seminomas; initial management of testicular cancer had included radiotherapy in 389 patients (63%) and chemotherapy alone in 84 (14%).

Compared with cancers in first-cancer patients, second cancers in second-cancer patients were diagnosed at an earlier age (mean, 66 vs. 55) and during a later calendar year (mean, 1992 vs. 1995). Overall, 284 second-cancer patients died during follow-up, with 191 (67%) of the deaths attributed to second cancers; 5443 first-cancer patients died during follow-up, with 3929 (72%) of the deaths attributed to cancer. Compared with the cancer-related mortality rate for first-cancer patients, the rate for second-cancer patients was similar, except for the rate related to tumors in the radiotherapy field for patients with testicular cancers that were diagnosed from 1973 to 1979 (rate ratio, 1.29) — during that time, high radiotherapy doses were used for treatment of testicular cancer, and chest irradiation was common practice.