Prognostic significance of neuroendocrine differentiation in patients with Gleason score 8-10 prostate cancer treated with primary radiotherapy

Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):e119-25. doi: 10.1016/j.ijrobp.2010.12.064. Epub 2011 May 17.

Abstract

Purpose: To determine the prognostic significance of neuroendocrine differentiation (NED) in Gleason score 8-10 prostate cancer treated with primary radiotherapy (RT).

Methods and materials: Chromogranin A (CgA) staining was performed and overseen by a single pathologist on core biopsies from 176 patients from the William Beaumont prostate cancer database. A total of 143 had evaluable biopsy material. Staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Patients received external beam RT alone or together with high-dose-rate brachytherapy. Cox regression and Kaplan-Meier estimates determined if the presence/frequency of neuroendocrine cells correlated with clinical endpoints.

Results: Median follow-up was 5.5 years. Forty 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 prostate-specific antigen, tumor stage, hormone therapy administration, % biopsy core involvement, mean Gleason score, or RT dose/modality. CgA staining concentration independently predicted for biochemical and clinical failure, distant metastases (DM), and cause-specific survival (CSS). For patients with <1% vs. >1% staining, 10-year DM rates were 13.4% vs. 55.3%, respectively (p = 0.001), and CSS was 91.7% vs. 58.9% (p < 0.001). As a continuous variable, increasing CgA staining concentration predicted for inferior rates of DM, CSS, biochemical control, and any clinical failure. No differences in outcomes were appreciated for patients with 0% vs. <1% NED.

Conclusions: For Gleason score 8-10 prostate cancer, >1% NED is associated with inferior clinical outcomes for patients treated with radiotherapy. This relates most directly to an increase in distant disease failure.

MeSH terms

  • Adenocarcinoma* / chemistry
  • Adenocarcinoma* / pathology
  • Adenocarcinoma* / radiotherapy
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Brachytherapy / methods
  • Chromogranin A / analysis*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neuroendocrine Cells / chemistry*
  • Neuroendocrine Cells / cytology
  • Prognosis
  • Prostate / chemistry
  • Prostate / pathology
  • Prostate-Specific Antigen / analysis
  • Prostatic Neoplasms* / chemistry
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / radiotherapy
  • Radiotherapy Dosage
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Chromogranin A
  • Prostate-Specific Antigen