Neuroendocrine carcinoma in conjunction with Gleason score 8-10 prostate cancer: Clinical implications for patients treated with radiotherapy.

Abstract

4649 Background: Neuroendocrine (NE) carcinoma cells may be associated with prostate cancer, more often in high grade tumors. Their significance in localized disease treated with radiotherapy (RT) remains uncertain. We conducted a clinicopathologic study to determine if RT patients with Gleason score 8-10 and a NE component are at risk for inferior outcomes vs. patients without NE features. Methods: Chromogranin (chromo) staining was attempted on core biopsies from 126 patients from the William Beaumont Hospital prostate cancer database. 99 had evaluable tumor in biopsy material. Patients received external beam RT alone or with high dose rate brachytherapy boost. Staining was quantified as 0%, < 1% (focal), 1-10%, or > 10% of tumor cells. Cox regression and Kaplan Meier estimates determined if the frequency of NE cells in core biopsy specimens correlated with clinical endpoints. Results: Median follow- up was 5.4 years. 27 patients had at least focal positive chromo staining. No significant differences existed between patients with or without staining in terms of age, pretreatment PSA, tumor stage, hormone therapy administration, % biopsy core involvement, or RT modality. Mean Gleason score was higher for the patients with absent chromo staining (8.4 vs. 8.2, p=0.04). Multivariate analysis showed chromo staining to adversely predict for PSA failure, distant metastases (DM), and cause-specific survival (CSS). At 10 years, DM rates were 13.1% for patients without and 51.3% for those with staining (p=0.005). CSS was 89.3% and 73.4%, respectively, for patients without and with chromo staining (p=0.001). Local recurrence was 7.3% without and 3.8% with chromo positivity (p=0.62). A trend toward an overall survival advantage was seen for patients without chromo staining with 5-year rates of 77.8% vs. 59.5% but 46.3% vs. 45.0% at 10 years (p=0.09). Results were similar when patients were grouped as < 1% vs. > 1% staining. Conclusions: For Gleason score 8-10 prostate cancer, the presence of NE carcinoma cells is associated with inferior clinical outcomes for patients treated with radiotherapy. This appears to relate most directly to an increase in distant as opposed to local failures. No significant financial relationships to disclose.