Androgen Deprivation Therapy In Prostate Cancer Patients Research Articles

Abstract 3616: Androgen deprivation therapy and second primary lung cancer risk in prostate cancer patients in the US Veterans.

Abstract Background Previous observational studies have consistently reported decreased risk of lung cancers among prostate cancer patients. Recent literature suggests a role of estrogen receptor (ER) beta and aromatase, which can convert testosterone to estrogen, in development and progression of non small cell lung cancers. Second primary lung cancer risk among breast cancer patients appears to be higher in ER negative patients compared to ER positive patients probably from estrogen receptor blockade. As androgen deprivation therapy (ADT) has been well established for more than 70 years as an effective treatment modality for prostate cancer, we hypothesized the hormone modulation may decrease lung cancer risk and investigated the effect of ADT on second primary lung cancer risk among patients with prostate cancer. Methods We identified 62,589 men in VA Central Cancer Registry (VACCR) who were diagnosed with prostate cancer between 1999 and 2008, with follow-up available through 2010. The primary outcome was development of lung cancer, determined by VACCR. Descriptive statistics were used to compare basic characteristics between the groups. Cox proportional hazards model was used to assess the influence of ADT on the lung cancer incidence, adjusted for patient characteristics and prostate cancer stage. All the statistical analyses were performed using STATA 10 (Stata Corp, College Station, TX). Results Men who had ADT as part of their treatment for prostate cancer tend to be older (median age 71.3 vs 65.7, p < 0.01) and smoke slightly more (72.5% vs 71.4%, p=0.02). As expected, ADT group tend to have higher stage prostate cancers. There were 766 secondary lung cancers diagnosed in the cohort for the follow-up period. ADT group had significantly decreased secondary lung cancer risk by approximately 20% (HR 0.83, 95%CI=0.70-0.97) when adjusted for age, smoking status and prostate cancer stage at presentation. Conclusion Our study suggests that ADT in prostate cancer patients is associated with a decreased risk of second primary lung cancers. Independent validation studies and subgroup analyses to clarify the association is warranted. This work was supported by Veteran's Health Administration 1IK2BX001283-01 and NCI 5P50CA128613-02. Citation Format: Hyunseok Kang, Rathi N. Pillai, Johann C. Brandes. Androgen deprivation therapy and second primary lung cancer risk in prostate cancer patients in the US Veterans. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3616. doi:10.1158/1538-7445.AM2013-3616

Androgens induce oxidative stress and radiation resistance in prostate cancer cells though NADPH oxidase

Androgen deprivation therapy (ADT) facilitates the response of prostate cancer (PC) to radiation. Androgens have been shown to induce elevated basal levels of reactive oxygen species (ROS) in PC, leading to adaptation to radiation-induced cytotoxic oxidative stress. Here, we show that androgens increase the expression of p22phox and gp91phox subunits of NADPH oxidase (NOX) and ROS production by NOX2 and NOX4 in PC. Pre-radiation treatment of 22Rv1 human PC cells with NOX inhibitors sensitize the cells to radiation similarly to ADT, suggesting that their future usage may spare the need for adjuvant ADT in PC patients undergoing radiation.