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Treatment-Specific Risks of Second Malignancies and Cardiovascular Disease in 5-Year Survivors of Testicular Cancer

Alexandra W. van den Belt-Dusebout, Ronald de Wit, Jourik A. Gietema, Simon Horenblas, Marieke W.J. Louwman, Jacques G. Ribot, Harald J. Hoekstra, Gabey M. Ouwens, Berthe M.P. Aleman, Flora E. van Leeuwen

From the Departments of Epidemiology, Radiotherapy, and Urology, the Netherlands Cancer Institute, Amsterdam; the Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam; the Departments of Medical Oncology and Surgical Oncology, University Medical Center Groningen, Groningen; Eindhoven Cancer Registry, Comprehensive Cancer Center South; and the Department of Radiotherapy, Catharina Hospital, Eindhoven, the Netherlands

Address reprint requests to Flora E. van Leeuwen, PhD, Department of Epidemiology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; e-mail: f.v.leeuwen{at}nki.nl

Purpose: To compare radiotherapy and chemotherapy effects on long-term risks of second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) in testicular cancer (TC) survivors.

Patients and Methods: In our nationwide cohort comprising 2,707 5-year TC survivors, incidences of SMNs and CVDs were compared with general-population rates by calculating standardized incidence ratios (SIRs) and absolute excess risks (AERs). Treatment effects on risks of SMN and CVD were quantified in multivariable Cox regression and competing risks analyses.

Results: After a median follow-up time of 17.6 years, 270 TC survivors developed SMNs. The SIR of SMN overall was 1.7 (95% CI, 1.5 to 1.9), with an AER of 32.3 excess occurrences per 10,000 person-years. SMN risk was 2.6-fold (95% CI, 1.7- to 4.0-fold) increased after subdiaphragmatic radiotherapy and 2.1-fold (95% CI, 1.4- to 3.1-fold) increased after chemotherapy, compared with surgery only. Subdiaphragmatic radiotherapy increased the risk of a major late complication (SMN or CVD) 1.8-fold (95% CI, 1.3- to 2.4-fold), chemotherapy increased the risk of a major late complication 1.9-fold (95% CI, 1.4- to 2.5-fold), and smoking increased the risk of a major late complication 1.7-fold (95% CI, 1.4- to 2.1-fold), compared with surgery only. The median survival time was 1.4 years after SMN and 4.7 years after CVD.

Conclusion: Radiotherapy and chemotherapy increased the risk of developing SMN or CVD to a similar extent as smoking. Subdiaphragmatic radiotherapy strongly increases the risk of SMNs but not of CVD, whereas chemotherapy increases the risks of both SMNs and CVDs. Prolonged follow-up after chemotherapy is needed to reliably compare the late complications of radiotherapy and chemotherapy after 20 years.

Supported by the Lance Armstrong Foundation and the Dutch Cancer Society.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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