TY - JOUR
T1 - Second Malignant Neoplasms and Cause of Death in Patients With Germ Cell Cancer
T2 - A Danish Nationwide Cohort Study
AU - Kier, Maria Gry Gundgaard
AU - Hansen, Merete K
AU - Lauritsen, Jakob
AU - Mortensen, Mette S
AU - Bandak, Mikkel
AU - Agerbaek, Mads
AU - Holm, Niels V
AU - Dalton, Susanne O
AU - Andersen, Klaus K
AU - Johansen, Christoffer
AU - Daugaard, Gedske
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Importance: 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.Design, Setting, and Participants: 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).Main Outcomes and Measures: 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 and Relevance: 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.
AB - Importance: 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.Design, Setting, and Participants: 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).Main Outcomes and Measures: 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 and Relevance: 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.
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Bleomycin
KW - Cisplatin
KW - Cohort Studies
KW - Denmark
KW - Etoposide
KW - Humans
KW - Male
KW - Neoplasms, Germ Cell and Embryonal
KW - Neoplasms, Second Primary
KW - Proportional Hazards Models
KW - Risk Factors
KW - Treatment Outcome
KW - Journal Article
U2 - 10.1001/jamaoncol.2016.3651
DO - 10.1001/jamaoncol.2016.3651
M3 - Journal article
C2 - 27711914
SN - 2374-2437
VL - 2
SP - 1624
EP - 1627
JO - JAMA Oncology
JF - JAMA Oncology
IS - 12
ER -
