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

Abstract

Development of hormone-refractory prostate cancer (HRPC) may be due to outgrowth of neuroendocrine cells in the prostate gland. Increase 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). 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). At least 3 serum samples 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) throughout 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. 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.