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Outcomes of Second Cancers in Men with Histories of Testicular Cancer

Among men who have undergone curative therapy for testicular cancer, risk for second cancers is high, but therapy for them is not compromised by previous treatment.

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.

Comment: Long-term follow-up of testicular cancer survivors (especially those with nonseminomas) is the standard of care, because in a small subset of patients, late relapses will manifest. In addition, patients who are treated for testicular cancer remain at high risk for developing therapy-related late effects, including second cancers, but our ability to deliver effective therapy for second cancers does not appear to be compromised.

— Robert Dreicer, MD, MS, FACP

Published in Journal Watch Oncology and Hematology September 4, 2007

Citation(s):

Schairer C et al. Comparative mortality for 621 second cancers in 29356 testicular cancer survivors and 12420 matched first cancers. J Natl Cancer Inst 2007 Aug 15; 99:1248-56.

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