The role of chromogranin A determination in the treatment of patients with castration-resistant prostate cancer.

Abstract

Introduction. Chromogranin A has the greatest diagnostic value in detecting neuroendocrine differentiation (NED) of a tumor. This work is devoted to the study of the therapy of castration-resistant prostate cancer (CRPC) using somatostatin (AS) analogues based on the assessment of the neuroendocrine status of the tumor. Material and methods. The study included 89 patients with CRPC aged 72.2±1.4 years. Localized prostate cancer was diagnosed in 6 (6.7%), locally distributed prostate cancer (T3-4N0M0) in 12 (13.5%) patients, metastatic (T3-4N0-1M1)–in 71 (79.8%). An increase in CgA was observed in 31.5% (n=28) of CRPC patients. Combination therapy was performed with Octreotide depot (Pharm–Sintez, Russia) according to the scheme: 20 mg n/a once every 28 days in combination with dexamethasone at a dose of 4 mg per day for 1 month. Then the dose of dexamethasone was reduced. Patients were monitored every 28 days. The effectiveness was evaluated by the dynamics of PSA and CgA, as well as (ultrasound, abdominal MSCT, pelvic MRI and osteoscintigraphy). According to PSA, the answer was considered to be a decrease in the median PSA, or a lack of growth of more than 10%. Results. In patients with normal levels of CgA after 3 months of treatment, the median PSA significantly increased: from 57.0 [29.8; 94] ng/ml initially to 89.0 [47.4; 131.9] ng/ml, which was 56.1%, the decrease in CgA was 9.5% (from 2.1 to 1.9 nmol/l). In patients with elevated levels of CgA, there was a decrease in the median PSA value by 35.7%, from 169.5 [66.3; 235.3] ng/ml to 109.0 [44.8; 236.9] and CgA by 25% – from 5.2 [3.6; 7.1] to 3.9 [2.3; 5.2]. The median values and the proportion of PSA reduction in the group of «responders» stratified by CgA levels before and after 3 months of treatment were, respectively: in the group with normal CgA values – 43.0 [16.5; 154.3] nmol/l and 15.2 [7.2; 48.8] nmol/l or 64.7%; with CgA 3-7 nmol/l – 160.5 [35.1; 278.6] nmol/l and 42.4 [14.1; 88.4] nmol/l or 73.6%; in patients with CgA more than 7 nmol/L – 166.5 [28.0; 222.0] nmol/l and 81.7 [16.4; 151.0] nmol/l or 50.9%. Conclusion. Early detection of NED in CRPC with the use of the CgA marker makes it possible to stratify patients according to its severity and off r combination therapy with the inclusion of AS. An analysis of the immediate results of treatment with octreotide depot in combination with GnRH agonists and dexamethasone showed significantly higher efficacy in patients with initially increased levels of CgA, and the results achieved look preferable in patients with a moderate increase in this marker (within 3-7 nmol/l).