title: Second Malignant Neoplasms and Cause of Death in Patients With Germ Cell Cancer: A Danish Nationwide Cohort Study.
abstract: OBJECTIVE
  Patients given systemic treatment for testicular germ cell cancer (GCC) are at increased risk for a second malignant neoplasm (SMN). Previous studies on SMN and causes of death lacked information on the exact treatment applied or were based on patients receiving former treatment options.
  
  
  OBJECTIVE
  To evaluate the treatment-specific risks for SMN and death in a nationwide population-based cohort of patients with GCC treated with current standard regimens.
  
  
  METHODS
  This study examined a Danish nationwide cohort of 5190 men with GCC who entered the Danish Testicular Cancer database between January 1, 1984, and December 31, 2007. Treatment results were compared with a randomly sampled, age-stratified, population-based control group. Cases of gonadal and extragonadal primary were included in the nationwide cohort. The treatments were surveillance only; retroperitoneal radiotherapy (RT); bleomycin, etoposide, and cisplatin (BEP); or more than 1 line of treatment (MTOL).
  
  
  METHODS
  Cumulative incidence and hazard ratios (HRs) for SMN and death calculated by the Cox proportional hazards model were compared with those of age-matched controls.
  
  
  RESULTS
  The study population comprised 2804 patients with seminoma and 2386 with nonseminoma. The median follow-up was 14.4 years (interquartile range, 8.6-20.5 years). The 20-year cumulative incidence of SMN with death as a competing risk was 7.8% (surveillance), 7.6% (BEP), 13.5% (RT), 9.2% (MTOL), and 7.0% (controls). We found no increased risk for SMN after surveillance, while the HRs were 1.7 (95% CI, 1.4-2.0), 1.8 (95% CI, 1.5-2.3), and 3.7 (95% CI, 2.5-5.5), respectively, after BEP, RT, and MTOL. Mortality owing to non-GCC causes was decreased after surveillance, but increased by 1.3 times after BEP and RT and by 2.6 times after MTOL. Excess mortality due to SMN was found after BEP (HR, 1.6; 95% CI, 1.2-2.2), RT (HR, 2.1; 95% CI, 1.5-2.9), and MTOL (HR, 5.8; 95% CI, 3.6-9.6).
  
  
  CONCLUSIONS
  We found no increased risk for SMN or death among patients undergoing surveillance only. The risks for SMN and death due to SMN were increased after BEP alone, RT alone, and MTOL. Approaches to define patients who might benefit from less intensive treatment are needed.
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark2Unit of Survivorship, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Kier
authors.affiliation: Unit of Statistics, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Merete K
authors.initials: MK
authors.lastname: Hansen
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Lauritsen
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mette S
authors.initials: MS
authors.lastname: Mortensen
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Bandak
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Agerbaek
authors.affiliation: Department of Oncology, Odense University Hospital, Odense, Denmark.
authors.forename: Niels V
authors.initials: NV
authors.lastname: Holm
authors.affiliation: Unit of Survivorship, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Susanne O
authors.initials: SO
authors.lastname: Dalton
authors.affiliation: Unit of Statistics, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Klaus K
authors.initials: KK
authors.lastname: Andersen
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark2Unit of Survivorship, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Johansen
authors.affiliation: Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001761:Bleomycin / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005047:Etoposide / Q000009:adverse effects; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000150:complications / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D016016:Proportional Hazards Models; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin