LH-receptor polymorphisms and response to androgen deprivation therapy in prostate cancer.

Abstract

4597 Background: Androgen deprivation therapy (ADT) is the cornerstone of treatment for advanced prostate cancer. Our recent data demonstrates an integral role of luteinizing hormone (LH) signaling in androgen synthesis in prostate cancer cells. We therefore hypothesized that genetic variation in the LH receptor may impact the efficiency of signal transduction and influence the degree of castration, the duration of response to ADT and overall course. We now report the association between LH receptor genotype and response to ADT. Methods: Fifty eligible patients had a histopathological diagnosis of prostate cancer and had received ADT for advanced prostate cancer. The blood was collected from each patient after obtaining informed consent. DNA was extracted from blood and genotypes for LHR were assayed using the TaqMan method. The time to castration resistance and level of testosterone suppression were obtained by linking to clinical records. Genotype groups were compared using ANOVA or Kruskal-Wallis tests. Results: The median age at diagnosis was 59 (range 48-69). Of the 50 patients enrolled, 29 were treated for primary metastatic disease, 18 at biochemical recurrence (BCR) and 12 with BCR accompanied by radiographic metastases. The median PSA at initiation of ADT was 109.4 ng/ml for primary metastatic disease and 9.8 ng/ml for recurrent disease. The median time to castration resistance was 12 months in the primary metastatic group and 32.4 months in the recurrent group. In the recurrent group, the presence of minor alleles in the LH receptor genotype was associated with a shorter time to castration resistance with a median of 39 months in men with no minor alleles, 23 months in men with 1 minor allele and 16 months in men with 2 minor alleles (p<.05). Median testosterone levels (T) during ADT were higher for men carrying any minor alleles. Median nadir T was 7 ng/dL for men with no minor alleles compared to 22.5 ng/dL for those with 1-2 minor alleles (p=0.07) with median peak T of 19 ng/dL vs. 43 ng/dL, respectively (p=0.01). Conclusions: Genetic variation in the LH receptor was clearly linked with time to castration resistance and depth of castration and warrants further analysis to define its role as a prognostic and predictive marker.