Elevated serum chromogranin a precedes prostate-specific antigen elevation and predicts failure of androgen deprivation therapy in patients with advanced prostate cancer

Background and Purpose: Development of hormone-refractory prostate cancer (HRPC) may be due to outgrowth of neuroendocrine cells in the prostate gland. Incease in prostate-specific antigen (PSA) levels usually precedes clinical progression in patients failing hormone therapy. The timing of changes of PSA and chromogranin A (CgA) remains unclear. We analyzed serial serum levels of CgA and PSA in prostate cancer patients receiving androgen deprivation therapy (ADT). Methods: From October 1998 through January 2003, 90 patients with locally advanced (n = 20) or metastatic (n = 70) prostate cancer receiving ADT were enrolled. Serial serum samples for PSA and CgA assay were collected before and every 3 months during ADT. The median follow-up was 35 months (range, 20 to 52 months). Results: At least 3 serum saamples were obtained during ADT in 78 patients. Among these patients, 36 (46.2%) had no PSA re-elevation (< 4 ng/mL) and their CgA remained low (<84.6 ng/mL) through the treatment period. Another 17 patients (21.8%) also had low PSA (< 4.0 ng/mL) but had progressively increasing CgA. The remaining 25 patients (32%) developed HRPC. Among them, 17 showed progressive elevation in CgA (> 100 ng/mL), which was followed by PSA elevation after a median interval of 10 months. Interestingly, CgA levels decreased again upon reaching plateaus as PSA began to rise. Conclusions: For patients with advanced prostate cancer receiving ADT, serum CgA may be a useful tumor marker that precedes PSA elevation. Elevation of CgA during ADT signals ultimate treatment failure and may have clinical implications for implementation of novel therapies.