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It is important to determine whether an increase in Chromogranin A levels and neuroendocrine (NE) cell activation are associated with progression towards on hormone-independent prostate-cancer. We proposed a combination of estrogens and somatostatin analogues as therapy of NE activation in hormone-independent prostate cancer. The combined therapy with ethinyl estradiol and lanreotide offered objective and symptomatic responses in patients with limited treatment options and refractoriness to conventional hormonal therapy strategies; in particular, it offered a median overall survival that was superior to the 10-month median survival in patients with hormone refractory disease. This combined therapy also sustains the new concept in cancer treatment in which therapies may target not only cancer cells but also its microenvironment, which can yield protection against apoptosis.

Neuroendocrine (NE) cells represent the third epithelial cell type on normal prostatic tissue (in addition to basal and secretory cells). They are localized in all regions of the human prostate at birth but rapidly decrease in the peripheral prostate after birth, and then reappear at puberty. After puberty, their number seems to increase until an apparently optimum level is reached, which persists between the age of 25 and 54. NE cells were defined by Pearse as APUD to refer to chemical characteristics of amine precursor uptake and decarboxylation, common to the cells of this system. The most predominant product of prostatic NE cells is Chromogranin A, but they also produce serotonin, CgB, secretogranin or CgC, thyroid-stimulating hormone-like peptide, calcitonin, katacalcin, PTHrP and a-human chorionic gonadotropin-like peptide. NE cells in normal and neoplastic prostates are devoid of androgen receptors, but they express epidermal growth factor (EGF) receptor and c-erbB-2. For these reason NE cells are androgen-insensitive. The NE component of prostate adenocarcinoma is resistant to hormone therapy; some studies showed that the number of NE tumor cells and CgA serum levels increase with the recovery of human prostate tumor from hormonal therapy. Currently there are no clinical data available to support an active role of radiotherapy in NE differentiation.

Chromogranin A (CgA) is considered as a major specific neuroendocrine tumor marker. It belongs to the secretogranin family, which is present in the gastrointestinal tract, respiratory system, endocrine glands and in a group of endocrine cells such us pancreas and thyroid. Serum levels of CgA could reflect the neuroendocrine activity and could be used when evaluating advance prostate carcinoma. Moreover, there are also several factors that may increase the serum level of CgA: treatment with proton-pump inhibitors or H2-receptor blockers, chronic atrophic gastritis, rheumatoid arthritis, liver and renal failure. Another method to evaluate NE differentiation is scintigraphy with the 111In-labeled somatostatin analogue (DTPA-D-Phe)-octrotide, (Octreoscan). This method takes advantage of the overexpression of type II somatostatin receptors on the cell surface of NE tumors. With this technique the presence of NE differentiation can be detected both at the primary (prostate) and the metastatic sites. A more specific system to detect NE cell activity is obtained by analyzing CgA gene expression in prostate tissue by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).

Purpose: The purpose of this study was to evaluate the role of magnetic resonance spectroscopic imaging (MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting tumour foci in patients with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (TRUS)-guided biopsy., Materials and Methods: This prospective randomised trial was conducted on 150 patients who underwent [¹H]MRSI and DCE-MRI and targeted biopsies of suspicious areas on MRI associated with random biopsies., Results: After the second biopsy, the diagnosis of prostate adenocarcinoma was made in 64/150 cases. On a per-patient basis, MRSI had 82.8% sensitivity, 91.8% specificity, 88.3% positive predictive value (PPV), 87.8% negative predictive value (NPV) and 85.7% diagnostic accuracy. The sensitivity, specificity, PPV, NPV and accuracy for DCE-MRI was 76.5%, 89.5%, 84.5%, 83.7% and 82%, respectively. The combination of MRSI and DCE-MRI yielded 93.7% sensitivity, 90.7% specificity, 88.2% PPV, 95.1% NPV and 90.9% accuracy in detecting prostate carcinoma., Conclusions: The combined study with [¹H]MRSI and DCE-MRI showed promising results in guiding the biopsy of cancer foci in patients with an initial negative TRUS-guided biopsy.