PURPOSE Using complete information regarding testicular cancer (TC) treatment burden, this study aimed to investigate cause-specific non-TC mortality with impact on previous treatment with platinum-based chemotherapy (PBCT) or radiotherapy (RT). METHODS Overall, 5,707 men identified by the Cancer Registry of Norway diagnosed with TC from 1980 to 2009 were included in this population-based cohort study. By linking data with the Norwegian Cause of Death Registry, standardized mortality ratios (SMRs), absolute excess risks (AERs; [(observed number of deaths − expected number of deaths)/person-years of observation] ×10,000), and adjusted hazard ratios (HRs) were calculated. RESULTS Median follow-up was 18.7 years, during which non-TC death was registered for 665 (12%) men. Overall excess non-TC mortality was 23% (SMR, 1.23; 95% CI, 1.14 to 1.33; AER, 11.14) compared with the general population, with increased risks after PBCT (SMR, 1.23; 95% CI, 1.07 to 1.43; AER, 7.68) and RT (SMR, 1.28; 95% CI, 1.15 to 1.43; AER, 19.55). The highest non-TC mortality was observed in those < 20 years at TC diagnosis (SMR, 2.27; 95% CI, 1.32 to 3.90; AER, 14.42). The most important cause of death was non-TC second cancer with an overall SMR of 1.53 (95% CI, 1.35 to 1.73; AER, 7.94), with increased risks after PBCT and RT. Overall noncancer mortality was increased by 15% (SMR, 1.15; 95% CI, 1.04 to 1.27; AER, 4.71). Excess suicides appeared after PBCT (SMR, 1.65; 95% CI, 1.01 to 2.69; AER, 1.39). Compared with surgery, increased non-TC mortality appeared after 3 (HR, 1.47; 95% CI, 0.91 to 2.39), 4 (HR, 1.41; 95% CI, 1.01 to 1.99), and more than four (HR, 2.04; 95% CI, 1.25 to 3.35) cisplatin-based chemotherapy cycles after > 10 years of follow-up. CONCLUSION TC treatment with PBCT or RT is associated with a significant excess risk of non-TC mortality, and increased risks emerged after more than two cisplatin-based chemotherapy cycles after > 10 years of follow-up.
Using complete information on total treatment burden, this population-based study aimed to investigate second cancer (SC) risk in testicular cancer survivors (TCS) treated in the cisplatin era. The Cancer Registry of Norway identified 5,625 1-year TCS diagnosed 1980-2009. Standardized incidence ratios (SIRs) were calculated to evaluate the total and site-specific incidence of SC compared to the general population. Cox regression analyses evaluated the effect of treatment on the risk of SC. After a median observation time of 16.6 years, 572 TCS developed 651 nongerm cell SCs. The SC risk was increased after surgery only (SIR 1.28), with site-specific increased risks of thyroid cancer (SIR 4.95) and melanoma (SIR 1.94). After chemotherapy (CT), we observed 2.0to 3.7-fold increased risks for cancers of the small intestine, bladder, kidney and lung. There was a 1.6to 2.1-fold increased risk of SC after ≥2 cycles of cisplatin-based CT. Radiotherapy (RT) was associated with 1.5to 4.4-fold increased risks for cancers of the stomach, small intestine, liver, pancreas, lung, kidney and bladder. After combined CT and RT, increased risks emerged for hematological malignancies (SIR 3.23). TCS treated in the cisplatin era have an increased risk of developing SC, in particular after treatment with cisplatin-based CT and/or RT.Additional Supporting Information may be found in the online version of this article.
5006 Background: Previous studies have reported an increased risk of premature mortality in testicular cancer (TC) survivors, probably associated with previous platinum-based chemotherapy (PBCT) or radiotherapy (RT). However, complete data regarding PBCT cycles are lacking in available literature. Using complete TC treatment data, this population-based cohort study aimed to investigate non-TC mortality in relation to TC treatment. Methods: Overall, 5,707 men diagnosed with TC 1980-2009 were included, identified from the Cancer Registry of Norway. Clinical parameters and treatment data were abstracted from medical records and linked with the Norwegian Cause of Death Registry. Causes of death were classified by the European Shortlist. Standardized mortality ratios (SMRs) were calculated to compare the cause-specific mortality in the cohort to an age-matched general population. Age-adjusted hazard ratios (HRs) were estimated to evaluate the impact of number of PBCT cycles on non-TC mortality. Results: During a median follow-up of 18.7 years, 665 (12%) men were registered with non-TC death. The overall excess non-TC mortality was 23% (SMR 1.23, 95% CI 1.14-1.33) compared with the general population, with increased risks after PBCT (SMR 1.23, 95% CI 1.06-1.42) and RT (SMR 1.28, 95% CI 1.15-1.43), but not after surgery (SMR 0.95, 95% CI 0.79-1.14). SMRs increased significantly with increasing follow-up time ≥10 years, and the overall risk of non-TC death reached a maximum after ≥30 years follow-up (SMR 1.64, 95% CI 1.31-2.06). The most important cause of death was non-TC second cancer with an overall SMR of 1.53 (95% CI 1.35-1.73). Increased risks appeared after PBCT (SMR 1.43, 95% CI 1.12-1.83) and RT (SMR 1.59, 95% CI 1.34-1.89). Treatment with PBCT was associated with significantly 1.69-6.78-fold increased SMRs for cancers of the oral cavity/pharynx, esophagus, lung, bladder, and leukemia. After RT, significantly 3.02- 4.91-fold increased SMRs emerged for cancers of the oral cavity/pharynx, stomach, liver, pancreas and bladder. Non-cancer mortality was also increased by 15% (SMR 1.15, 95% CI 1.04-1.27), and excesses appeared after PBCT (1.23, 95% CI 1.03-1.47) and RT (SMR 1.17, 95% CI 1.01-1.34). Importantly, we report excess suicides after PBCT (SMR 1.65, 95% CI 1.01-2.69). Long-term overall cardiovascular mortality was not increased in the study cohort nor according to treatment modality. Compared with surgery, the overall non-TC mortality was increased after 4 (HR 1.41, 95% CI 1.00-1.98) and >4 (HR 2.03, 95% CI 1.24-3.33) PBCT cycles after >10 years of follow-up. Conclusions: TC treatment with PBCT or RT is associated with significantly increased long-term non-TC mortality, with non-TC second cancer being the most important cause of death. Significantly elevated risks for non-TC mortality emerged after ≥4 PBCT cycles after >10 years of follow-up.
In summary, we found a significant association between a larger Pt decline and a reduced risk of second cancers and deterioration of paresthesias in hands and tinnitus.
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