Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer.
OBJECTIVE
To compare radiotherapy and chemotherapy effects on long-term risks of second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) in testicular cancer (TC) survivors.


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.


CONCLUSIONS
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.
van den Belt-Dusebout
Alexandra W
AW
Department of Epidemiology, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
de Wit
Ronald
R
Gietema
Jourik A
JA
Horenblas
Simon
S
Louwman
Marieke W J
MW
Ribot
Jacques G
JG
Hoekstra
Harald J
HJ
Ouwens
Gabey M
GM
Aleman
Berthe M P
BM
van Leeuwen
Flora E
FE
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D002945:Cisplatin / Q000009:adverse effects*; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology; D009426:Netherlands / Q000453:epidemiology; D016016:Proportional Hazards Models; D011878:Radiotherapy / Q000009:adverse effects; D012306:Risk; D017741:Survivors / Q000706:statistics & numerical data; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
D000970:Antineoplastic Agents; D002945:Cisplatin