Comment from authors: "Despite the statistically significantly increased long-term risk of second solid tumors, it is clear that the remarkable gains in survival provided by treatments for testicular cancer far outweigh the risk of this serious late effect, and generalization of our results to modern practice should be undertaken with caution. Given current modifications in treatment that result in lower radiation doses, solid tumors in the future will probably have considerably less impact on the lives of testicular cancer survivors, although careful follow-up is necessary to reliably quantify long-term risk. "

Lois B. Travis, Sophie D. Fosså, Sara J. Schonfeld, Mary L. McMaster, Charles F. Lynch, Hans Storm, Per Hall, Eric Holowaty, Aage Andersen, Eero Pukkala, Michael Andersson, Magnus Kaijser, Mary Gospodarowicz, Timo Joensuu, Randi J. Cohen, John D. Boice, Jr., Graça M. Dores, Ethel S. Gilbert

Affiliations of authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (LBT, SJS, MLM, ESG); Norwegian Radium Hospital, Oslo, Norway (SDF); The University of Iowa, Iowa City, IA (CFL); Danish Cancer Society, Copenhagen, Denmark (HS, MA); Karolinska Institute, Stockholm, Sweden (PH, MK); Cancer Care Ontario, Toronto, Ontario, Canada (EH); The Norwegian Cancer Registry, Oslo, Norway (AA); Finnish Cancer Registry, Helsinki, Finland (EP); The Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (MG); Helsinki University Central Hospital, Helsinki, Finland (TJ); Howard Hughes Medical Institute, Chevy Chase, MD (RJC); International Epidemiology Institute, Rockville, MD and Vanderbilt University Cancer Center, Nashville, TN (JDB); Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD (GMD)

Background: Although second primary cancers are a leading cause of death among men with testicular cancer, few studies have quantified risks among long-term survivors. Methods: Within 14 population-based tumor registries in Europe and North America (1943–2001), we identified 40 576 1-year survivors of testicular cancer and ascertained data on any new incident solid tumors among these patients. We used Poisson regression analysis to model relative risks (RRs) and excess absolute risks (EARs) of second solid cancers. All statistical tests were two-sided. Results: A total of 2285 second solid cancers were reported in the cohort. The relative risk and EAR decreased with increasing age at testicular cancer diagnosis (P<.001); the EAR increased with attained age (P<.001) but the excess RR decreased. Among 10-year survivors diagnosed with testicular cancer at age 35 years, the risk of developing a second solid tumor was increased (RR = 1.9, 95% confidence interval [CI] = 1.8 to 2.1). Risk remained statistically significantly elevated for 35 years (RR = 1.7, 95% CI = 1.5 to 2.0; P<.001). We observed statistically significantly elevated risks, for the first time, for cancers of the pleura (malignant mesothelioma; RR = 3.4, 95% CI = 1.7 to 5.9) and esophagus (RR = 1.7, 95% CI = 1.0 to 2.6). Cancers of the lung (RR = 1.5, 95% CI = 1.2 to 1.7), colon (RR = 2.0, 95% CI = 1.7 to 2.5), bladder (RR = 2.7, 95% CI = 2.2 to 3.1), pancreas (RR = 3.6, 95% CI = 2.8 to 4.6), and stomach (RR = 4.0, 95% CI = 3.2 to 4.8) accounted for almost 60% of the total excess. Overall patterns were similar for seminoma and nonseminoma patients, with lower risks observed for nonseminoma patients treated after 1975. Statistically significantly increased risks of solid cancers were observed among patients treated with radiotherapy alone (RR = 2.0, 95% CI = 1.9 to 2.2), chemotherapy alone (RR = 1.8, 95% CI = 1.3 to 2.5), and both (RR = 2.9, 95% CI = 1.9 to 4.2). For patients diagnosed with seminomas or nonseminomatous tumors at age 35 years, cumulative risks of solid cancer 40 years later (i.e., to age 75 years) were 36% and 31%, respectively, compared with 23% for the general population. Conclusions: Testicular cancer survivors are at statistically significantly increased risk of solid tumors for at least 35 years after treatment. Young patients may experience high levels of risk as they reach older ages. The statistically significantly increased risk of malignant mesothelioma in testicular cancer survivors has, to our knowledge, not been observed previously in a cohort of patients treated with radiotherapy.
Journal of the National Cancer Institute, Vol. 97, No. 18, 1354-1365, September 21, 2005