Objectives

We investigated whether androgen deprivation therapy (ADT) in prostate cancer patients was associated with a decreased risk for second primary lung cancer in US veterans.

Methods

Prostate cancer diagnoses in the US Veterans Affairs Cancer Registry between 1999 and 2008 were identified. Use of hormonal therapy and diagnoses of second primary lung cancer were determined from the registry. Synchronous prostate and lung cancers, defined as 2 diagnoses made within 1 year, were excluded from the analysis. Cancer-free survival was estimated using the Kaplan-Meier method and hazard ratios were estimated using Cox proportional hazard models.

Results

Among the 63,141 identified patients with prostate cancer, 18,707 subjects were eligible for the study. Hormonal therapy was used in 38% of patients and the median follow-up period was 28 months. ADT use was associated with longer lung cancer-free survival in prostate cancer patients (log-rank p=0.01). After adjusting for age, race, smoking and prostate cancer stage, ADT use was associated with decreased lung cancer risk by 15, 21, and 24% after 1, 2, and 3 years, respectively.

Conclusions

ADT in prostate cancer patients may be associated with decreased second primary lung cancer risk among US veterans.

Background

Epigenetic events play a major role in the carcinogenesis of tobacco-related cancers. The authors conducted a retrospective cohort study to evaluate the effects of exposure to the anticonvulsant agent valproic acid (VPA), a histone deacetylase inhibitor, on the risk of developing cancers of the lung, head and neck, prostate, bladder, and colon.

Methods

The study was based on the 2002 through 2008 National Veterans Affairs (VA) medical SAS data set linked to the VA Central Cancer Registry. The cohort was defined as subjects aged>40 years who were followed in the VA system for at least 1 year for 1 of 4 diagnoses for which a VPA indication exists (bipolar disorder, posttraumatic stress disorder, migraines, and seizures). Multivariable Cox proportional hazards models were used to estimate hazards ratios (HR) and 95% confidence intervals (95% CI) reflecting the association between use of VPA and cancer incidence.

Results

VPA use was associated with a significant reduction in the risk of cancers of the head and neck (HR, 0.66; 95% CI, 0.48-0.92). Additional associations were noted with the duration of treatment and median VPA drug levels. No significant differences in cancer incidence were observed for cancers of the lung (HR, 1.00; 95% CI, 0.84-1.19), bladder (HR, 0.86; 95% CI, 0.64-1.15), colon (HR, 0.95; 95% CI, 0.74-1.22), and prostate (HR, 0.96; 95% CI, 0.88-1.12).

Conclusions

Use of VPA is associated with a lower risk of developing head and neck cancers.