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

PURPOSE: To evaluate whether selected modifiable patient-reported adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) represent prognostic factors of overall mortality, cancer mortality, and first-time non-germ cell second cancer (SecCa) incidence. PATIENTS AND METHODS: In 775 long-term TCSs (diagnosis: 1980-1994) who previously participated in a quality-of-life survey, 20-year mortality and SecCa incidence were compared between the surgery group (n = 272) and TCSs after platinum-based chemotherapy (PBCT; n = 503). A PBCT standard group (total cisplatin: ≤ 630 mg: n = 124) was separated from a PBCT high subgroup (total cisplatin: > 630 mg; n = 379). Univariate and multivariate analyses (Kaplan-Meier; Cox proportional hazard analyses) included age, treatment, and prior major physical comorbidity as nonmodifiable factors, whereas low socioeconomic status, unhealthy lifestyle, probable depression disorder, and neurotoxicity were modifiable AHOs. RESULTS: For all TCSs, the cumulative overall 20-year mortality was 14% (95% CI, 11.8 to 16.8). Rising age, PBCT high, and comorbidity significantly increased the risk of overall mortality rate. Compared with a low-risk group (no AHO; n = 446) and with exception of neurotoxicity, this risk was further significantly enhanced by 80% in TCSs of a medium-risk group (one or two AHOs; n = 278). In men of a high-risk group (three AHOs; n = 47), the probability of overall mortality and of cancer mortality was eight-fold and five-fold increased, respectively. Risk grouping did not influence on SecCa incidence. CONCLUSION: Self-reported unfavorable modifiable AHO concerning lifestyle and psychosocial health are in TCSs independently and significantly associated with increased overall mortality and cancer mortality. Health professionals and the TCSs themselves, particularly those after PBCT high, should continuously be aware of these risk factors attempting maximal reduction of these AHOs and thereby supporting long-term survival.

Testicular Cancer in the Cisplatin Era: Causes of Death and Mortality Rates in a Population-Based Cohort.

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.

Metachronous Contralateral Testicular Cancer in the Cisplatin Era: A Population-Based Cohort Study.

PURPOSE: It is hypothesized that cisplatin-based chemotherapy (CBCT) reduces the occurrence of metachronous contralateral (second) germ cell testicular cancer (TC). However, studies including treatment details are lacking. The aim of this study was to assess the second TC risk, emphasizing the impact of previous TC treatment. PATIENTS AND METHODS: Based on the Cancer Registry of Norway, 5,620 men were diagnosed with first TC between 1980 and 2009. Treatment data regarding TC were retrieved from medical records. Cumulative incidences of second TC were estimated, and standardized incidence ratios were calculated. The effect of treatment intensity was investigated using Cox proportional hazard regression. RESULTS: Median follow-up was 18.0 years, during which 218 men were diagnosed with a second TC after median 6.2 years. Overall, the 20-year crude cumulative incidence was 4.0% (95% CI, 3.5 to 4.6), with lower incidence after chemotherapy (CT) (3.2%; 95% CI, 2.5 to 4.0) than after surgery only (5.4%; 95% CI, 4.2 to 6.8). The second TC incidence was also lower for those age ≥ 30 years (2.8%; 95% CI, 2.3 to 3.4) at first TC diagnosis than those age < 30 years (6.0%; 95% CI, 5.0 to 7.1). Overall, the second TC risk was 13-fold higher compared with the risk of developing TC in the general male population (standardized incidence ratio, 13.1; 95% CI, 11.5 to 15.0). With surgery only as reference, treatment with CT significantly reduced the second TC risk (hazard ratio [HR], 0.55). For each additional CBCT cycle administered, the second TC risk decreased significantly after three, four, and more than four cycles (HRs, 0.53, 0.41, and 0.21, respectively). CONCLUSION: Age at first TC diagnosis and treatment intensity influenced the second TC risk, with significantly reduced risks after more than two CBCT cycles.

Continuing increased risk of second cancer in long-term testicular cancer survivors after treatment in the cisplatin era.

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 2.0- to 3.7-fold increased risks for cancers of the small intestine, bladder, kidney and lung. There was a 1.6- to 2.1-fold increased risk of SC after ≥2 cycles of cisplatin-based CT. Radiotherapy (RT) was associated with 1.5- to 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.

Long-term serum platinum changes and their association with cisplatin-related late effects in testicular cancer survivors.

BACKGROUND: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. MATERIAL AND METHODS: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment. Information about second cancers after SII was retrieved from the Norwegian Cancer Registry. RESULTS: A larger Pt decline from SI to SII was associated with a decreased risk of a second cancer diagnosis (HR 0.78, 95% CI 0.62-0.99 per 10 ng/L/year), and worsening of paresthesias in hands (OR 1.98, 95% CI 1.09-3.59 per 10 ng/L/year) and tinnitus (OR 1.51, 95% CI 1.01-2.27 per 10 ng/L/year). CONCLUSION: 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.