Presentation Authors: Kosuke Takemura*, Masaya Ito, Yasukazu Nakanishi, Madoka Kataoka, Kazumasa Sakamoto, Hiroaki Suzuki, Noriyuki Iida, Ken-ichi Tobisu, Fumitaka Koga, Tokyo, Japan
Introduction: Gamma-Glutamyltransferase (GGT) is a well-established serum biomarker for hepatobiliary dysfunction. GGT is also known as a membrane-bound enzyme implicated in neutralizing reactive oxygen compounds and free radicals. The elevation of serum GGT has recently been reported to be linked to decreased survival in various malignancies. However, there is no report on prognostic roles of GGT in castration-resistant prostate cancer (CRPC). The aim of this study is to evaluate the prognostic significance of serum GGT in CRPC patients treated with enzalutamide.
Methods: A total of 50 consecutive CRPC patients treated with enzalutamide at a single cancer center between 2014 and 2018 were retrospectively evaluated. Overall survival (OS) was defined as the time from the initiation of enzalutamide to either death or the last follow-up. Other variables collected included age, performance status, Gleason score, pretreatment, opioid usage, lymph node/visceral metastases, hemoglobin (Hgb), albumin, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), C-reactive protein, and prostate-specific antigen (PSA) at the initiation of enzalutamide. The difference in the Kaplan-Meier curves was evaluated by log-rank test. Associations of variables with OS were analyzed by Cox proportional hazard model. The accuracy of prognostic models was assessed by Harrellâ€™s c-index.
Results: Median serum GGT was 27 U/L and the appropriate cut-off value for GGT was set at 38 U/L. Serum GGT was elevated in 19 patients (38%). During follow-up period (median, 1.2 years), 21 patients died (2-year OS rate, 72%). Patients with elevated GGT showed significantly worse prognosis than those with normal GGT with respective 2-year OS rates of 47% and 87% (P = 0.002). On multivariate analysis, elevated GGT was a significant and independent factor for shorter OS (hazard ratio, HR = 4.20; P = 0.005) as were high PSA (HR = 5.50; P = 0.004) and low Hgb (HR = 4.18; P = 0.006). Incorporation of GGT into an MSKCC's prognostic model, consisting of age, performance status, Hgb, PSA, LDH, ALP, and albumin, increased its Harrell's c-index from 0.836 to 0.870.
Conclusions: The present study for the first time demonstrated that elevated serum GGT was an adverse prognostic factor in CRPC patients treated with enzalutamide.