Neuroendocrine Carcinoma In Conjunction With Gleason Score 8-10 Prostate Cancer: Clinical Implications For Patients Treated With Radiotherapy

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. Chromogranin A (CgA) staining was attempted by a single pathologist on core biopsies from 176 patients from the William Beaumont Hospital prostate cancer database. 143 had evaluable biopsy material. Patients received external beam RT (EBRT) alone or pelvic EBRT combined 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 presence/frequency of NE cells in core biopsy specimens correlated with clinical endpoints. Median follow-up was 5.5 years. 40 patients (28%) had at least focal positive CgA staining (< 1% n = 21, 1-10% n = 11, >10% n = 8). No significant differences existed between patients with or without staining in terms of age, pretreatment PSA, tumor stage, hormone therapy administration, percentage biopsy core involvement, mean Gleason score, or RT modality. Multivariate analysis including T-stage, PSA, Gleason score, and percentage biopsy core involvement showed CgA staining to independently predict for PSA failure, distant metastases (DM), and cause-specific survival (CSS). At 10 years, DM rates were 14.0% for patients without and 35.3% for those with any level of staining (p = 0.01). CSS was 92.4% and 74.5%, respectively, for patients without and with CgA staining (p = 0.001). Local recurrence was 14.4% without and 5.1% with CgA positivity (p = 0.58). When comparing patients by < 1% vs. > 1% staining, the DM rates were 13.4% vs. 55.3%, respectively (p = 0.001). CSS was 91.7% vs. 58.9% favoring patients with < 1% staining (p < 0.001). Overall survival was 49.1% vs. 41.9% at 10 years in favor of < 1% staining (p = 0.13). When increasing concentration of CgA staining was modeled as a continuous variable, it was significantly associated with inferior rates of DM, CSS, biochemical control, and any clinical failure. For Gleason score 8-10 prostate cancer, the presence of NE carcinoma cells as well as their increasing concentration 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.