Oral estramustine therapy in serum chromogranin A-positive stage D3 prostate cancer patients

Abstract

Neuroendocrine (NE) differentiation in prostate cancer (PC) has attracted much attention since it has been shown to be associated with androgen independence and bad prognoses. In this study 34 patients with hormone refractory prostate cancer and elevated Chromogranin A (CgA) serum values were treated with estramustine for 15 months. The results were evaluated by analyzing clinical data and the serially measured total PSA and Chromogranin A serotest concentration, as well as bone scan recordings. In responders to therapy a sharp decline in CgA level was recorded as well as a slight decrease in the number of metastatic lesions in the bone. However, in 6- and 12-month nonresponders, supranormal serum CgA concentrations were measured (mean 305 +/- 122 ng/ml/ and 284 +/- 101 ng/ml, respectively). Statistical significance was found between neither of these groups (p > 0.05). Mean bone lesions data were practically identical in nonresponding groups (9.6 and 9.5) but were much lower in the respective responders (4.9 and 4.1). Twelve patients were found to be nonresponders 3 months after therapy initiation (12 out of 34, 35.3%). From the remaining 22 studied subjects a positive response patients continued in 17 patients during the next 3 months or overall in a six-month period (17 out of 34, 50%, or 17 out of 22, 77.3% from 3-month responders). After 9 months of therapy, 15 responding, patients were found (15 out of 34, 44.1%, or 15 out of 17, 88.2% from 6-month responders) while, after a full year of estramustine administration, 8 patients responded to therapy (8 out of 34, 23.5%, or 8 out of 15, 53.3% from responders after 9 months of treatment). Finally, after 15 months of treatment, only 3 responding patients found (3 out of 34, 8.8% or 3 out of 8, 37.5% from responders after 12 months of treatment). Mean response periods after 12 and 15 months of estramustine treatment were 5.5 and 5.7 months, respectively. In conclusion, the reported results indicate a 12-15 month responding period for estramustine therapy in patients with a slight initial elevation in CgA serotest (up to 150 ng/ml) and less than 10 metastatic osseous lesions. Thus, serum CgA assessment has definitely found a role in monitoring PC patients with NE positive stage D3 disease. This specially holds true as the population of aged men is rapidly increasing, posing a great challenge to urologists and oncologists in treating difficult-to-manage hormone-independent prostatic carcinoma.