Impact of chemotherapy on anxiety, depression, and suicidality amongst testicular cancer survivors.
Authors: Nelson Tyler J. , Meagher Margaret F , Leonard Austin , Dolendo Isabella , Deshler Leah N. , Morgan Kylie M. , Duran Elizabeth A. , Sabater Minarim Daniel , Wang Luke , Taylor Jacob , Herchenhorn Daniel , Stewart Tyler F. , Javier-Desloges Juan , Salmasi Amir , McKay Rana R. , Millard Fred , Rose Brent S , Bagrodia Aditya 
Published: March 2023

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Background: Chemotherapy for testicular cancer (TC) is highly effective yet associated with significant consequences on long-term health-related quality of life. We evaluate the impact of chemotherapy on anxiety, depression, and suicidality amongst TC survivors. Methods: We conducted a retrospective cohort study of US veterans diagnosed with TC in the Veterans Health Affairs database from 1990-2016. Patients with non-primary germ cell tumor histologies were excluded. Baseline disease characteristics and treatment received were ascertained from the VA Central Cancer Registry. Anxiety or depression was a composite endpoint comprised of diagnosis codes for anxiety, depression, or administration of medications used to treat these diagnoses. Incident suicidality was defined as a diagnosis code for suicidal ideation. Time to event was defined as time from diagnosis to event or censor at the time of last follow-up. Rates of outcomes were reported through cumulative incidences. Associations with outcomes and receipt of chemotherapy were assessed through multivariable Cox regression models. Results: In total, 1684 patients (1174 seminoma, 510 nonseminoma) were included in the cohort. Median age at diagnosis in the cohort was 40 years old. Median follow up time was 7.67 years for surviving patients. 1506 (89.4%) patients were white, 114 (6.8%) were African American, and 64 (3.8%) were another or unknown race. There were 1066 (63.3%) stage I patients, 191 (11.3%) stage II, 198 (11.8%) stage III, and 229 (13.6%) unknown stage patients. 579 (34.4%) patients received chemotherapy. At the time of diagnosis, 104 (6.2%) patients already experienced anxiety or depression. At 10 years, cumulative incidence of the diagnosis of anxiety or depression as 44.1% in the entire cohort. At 10 years, cumulative incidence of the diagnosis of suicidality was 5.5%. On multivariable Cox regression, factors associated with a higher risk of anxiety or depression were older age at diagnosis (Hazard Ratio (HR): 1.11 per standard deviation increase, p=0.01), being unemployed (HR: 1.25, p=0.01), and receipt of chemotherapy (HR: 1.43, p<0.001). Race, stage, alcohol or tobacco use and seminoma type were nonsignificant. Factors associated with increased risks of suicidality were being unemployed (HR: 2.00, p=0.01) and not being married (HR: 2.50, p=0.001). Stage, age, race, alcohol and tobacco use, seminoma type, and receipt of chemotherapy were not significantly associated with suicidality. Conclusions: Psychosocial morbidity is high among TC survivors. Despite being effective and necessary for maintaining excellent oncologic outcomes, chemotherapy appears to increase the rates of psychosocial morbidity. Socioeconomic risk factors, including employment and marriage, may also impact psychosocial health. Clinicians should be proactive in identifying support systems for TC survivors.