Neuroendocrine Differentiation in Castration-Resistant Prostate Cancer: A Systematic Diagnostic Attempt

We propose a composite and reproducible neuroendocrine differentiation (NED)– assessing panel—including plasma chromogranin A (p-CgA), tissular CgA (t-CgA), somatostatin receptor 2 (SSTR2), and Ki-67— of needle biopsy specimens to be applied to patients with castration-resistant prostate cancer (CRPC). In our series, a high prevalence (85.1%) of NED was found. Neuroendocrine markers were associated with high prostatespecific antigen (PSA) levels, aggressive (high initial Gleason Score) and rapidly progressive disease, and consequent decreased overall survival (OS). Background: Assessing the neuroendocrine (NE) pattern in castration-resistant prostate cancer (CRPC) may prove useful in selecting potential responders to target therapies such as somatostatin analogues. The aim of this study was to define a panel of markers or examinations appropriate to characterize NE differentiation (NED). Methods: Forty-seven patients with CRPC underwent a systematic diagnostic attempt to characterize the NE phenotype using a plasma blood test for chromogranin A (CgA) and immunohistochemical staining of needle biopsy‐obtained specimens (CgA, somatostatin receptor 2 [SSTR2], Ki-67, and androgen receptors). In a subgroup of 26 patients, somatostatin receptor scintigraphy using 111 In-DTPA-d-Phe octreotide (octreotide scintigraphy; Octreoscan, Covidien, Hazelwood, MO) was also performed. Results: NED was found in 85.1% of patients (if serum CgA, tissular CgA, and tissular SSTR2 were considered separately: 54%, 67%, and 58%, respectively). Only 15% of the 26-patient subgroup had an abnormal octreotide scintigraphy result. Although p-CgA and t-CgA were associated with more aggressive disease with a worse prognosis, patients with positive tissular SSTR2 staining had longer overall survival (OS). Conclusion: This systematic approach to explore the NED in a quite homogeneous group of patients with CRPC seems reproducible and appropriate. Further investigations are required to validate this panel and better characterize potential responders to targeted therapy.