Increased Risk of Non-Germ Cell Second Cancer (SC) after Cisplatin-Based Chemotherapy (CBCT) in 1-Year Testicular Cancer (TC) Survivors (TCS)

Background: Previous studies have documented that TCS have a 1.7 to 3.5-fold increased risk of developing SC compared with an age-matched general population after chemotherapy (CT) and/or radiotherapy (RT), but no increased risk after surgery only. Previous studies lack treatment details, and/or include patients treated before the introduction of cisplatin. Methods: All Norwegian 1-year TCS diagnosed with their first TC 1980-2009 and with no prior history of cancer (n = 5625), were identified through the Cancer Registry of Norway (CRN). Clinical parameters, including detailed information on all cancer treatment given initially and in case of a relapse, were extracted from medical records and linked with data from CRN. The TCS were categorized into treatment groups: Surgery only (24.8%), CT (43.9%), RT (27.4%) and CT and RT combined ((CT + RT) 3.9%). Age-adjusted Cox regression models were performed to evaluate the impact of cancer treatment on the risk of SC, stratified according to decade of diagnosis. Results: Median observation time was 16.6 years (IQR 10.9-23.8), during which 572 TCS (10.2%) were diagnosed with a non-germ cell SC. Median time to SC was 18.1 years (IQR 11.1-24.2). Overall, compared with surgery only, there was an elevated risk of SC after RT (Hazard Ratio (HR) 1.36, 95% CI 1.07-1.73) and RT + CT (HR 1.64 95% CI 1.10-2.46). When excluding TCS with <10 years observation time, all treatment groups had increased risks for SC (CT: HR 1.57, 95% CI 1.14-2.16; RT: HR 1.77, 95% CI 1.31-2.39; RT + CT: HR 1.83, 95% CI 1.14-2.96). There was an increased risk for SC with increasing number of cisplatin-based CT (CBCT), significant for 4 cycles (HR 1.35, 95% CI 1.01-1.81) and ≥5 cycles (HR 1.69, 95% CI 1.06-2.70). The risk for bladder cancer increased after CBCT (HR 3.81, 95% CI 1.29-11.21) and RT (HR 2.93, 95% CI 1.00-8.60). RT + CT was associated with elevated risks for leukemia (HR 13.82, 95% CI 1.20-159.67) and cancers of the stomach (HR 6.79, 95% CI 1.60-28.70) and thyroid (HR 8.71, 95% CI 1.56-52.08). Conclusions: Cytotoxic treatment increases the risk of SC in TCS. After CBCT, the risk significantly increases after ≥4 cycles. Long-term follow-up of TCS focusing on prevention and early detection of SC seem to be important. Legal entity responsible for the study: Translational Cancer Research Group, Deapartment of Clinical Medicine, UiT The Arctic University of Norway. Funding: Helse Nord RHF. Disclosure: All authors have declared no conflicts of interest.