Testicular cancer in the cisplatin era: Causes of death and mortality rates in a population-based cohort.

Abstract

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.

Mortality and Second Cancer Incidence After Treatment for Testicular Cancer: Psychosocial Health and Lifestyle Are Modifiable Prognostic Factors

“…The condition should be viewed as an indication of underlying socioeconomic problems, an unhealthy lifestyle, and/or neurotoxicity, with the latter condition in part amendable. 53-54 Our recently reported 65% excess suicide risk after PBCT 7 further supports the need for greater and early psychosocial support during and after TC treatment and during follow-up of TCSs.…”

“…In our study, rising age and treatment modality [5][6][7] are known nonmodifiable risk factors for overall mortality, supplemented by major comorbidity and modifiable AHOs. Several intertwined pathways explain the role of depression.…”

“…The introduction of platinum-based chemotherapy (PBCT) in the late 1970s has transferred testicular cancer (TC) into a curable malignancy, 1 with a 95% five-year relative survival rate. 2 However, recent studies have shown increased mortality and non-germ cell second cancer (SecCa) incidence, [3][4][5][6][7][8] both associated with nonmodifiable prognostic factors (eg, rising age and PBCT).…”

Cisplatin for cancer therapy and overcoming chemoresistance

“…Cisplatin was first synthesized by the Italian chemist, Michele Peyrone in 1844 and was named the Peyrone's chloride [9]. The synthesis of cisplatin was incidental to his experimentation with the magnus green salt, a platinum compound given the chemical formula PtCl 2 (NH 3 ) 2 or C12H6N2Pt [10,11,12]. Cisplatin was extracted by adding excess ammonia to an acidified PtCl 2 solution that yielded yellow and green compounds based on the insolubility of the magnus green salt in hydrochloric acid [13].…”

Risk-adapted modulation through de-intensification of cancer treatments: an ESMO classification

“…It can reduce treatment burden, rates of short-term and life-threatening adverse events, chronic, long-term toxicities, and lessen health-related financial distress. 3 Since long-term or late adverse events can adversely impact overall life expectancy, 4 there may be long-term survival benefits. Importantly, this approach could increase or preserve the quality of life of patients, with equivalent oncology outcomes or with an acceptable trade-off.…”