Serum chromogranin‐A in advanced prostate cancer

Abstract

Objective To determine the value of serum chromogranin A (CgA), a marker of neuroendocrine differentiation, for monitoring prostate cancer; CgA levels were related to three other tumour markers, i.e. total prostate‐specific antigen (tPSA), prostatic acid phosphatase (PAP), neurone‐specific enolase (NSE), and to testosterone, to assess the importance of hormone withdrawal. Patients and methods Serum samples (218) were obtained from 118 patients with prostate cancer, including 111 patients with advanced prostate cancer; 103 presented to our centre for systemic radionuclide therapy of painful skeletal metastases. CgA concentrations were measured using a new immunoradiometric assay (IRMA; Cis Bio International, Gif sur Yvette, France) and a threshold of 70 ng/mL was determined after receiver operating characteristic curve analysis. Testosterone was also measured with an IRMA assay; tPSA, PAP and NSE were assayed using the time‐resolved amplified cryptate emission. Results Serum marker levels were high in 64% of the patients for CgA, 24% for NSE, 89% for tPSA and 81% for PAP. Patients resistant to endocrine treatments and with elevated tPSA (i.e. hormone‐independent) showed increased CgA and NSE in 62% and 29%, respectively. Patients with hormone‐dependent prostate cancer (i.e. with a normal tPSA level) had elevated CgA in 59% but no abnormal NSE. All patients of the latter group except one showed clinical progression of their disease. However, the mean (sd) concentrations of CgA in hormone‐independent (146) or hormone‐dependent (22) patients, at 185.3 (449.1) and 160.9 (293.9) ng/mL, respectively, were not statistically different (P = 0.8, Mann–Whitney U‐test). For 30 patients, blood samples were drawn and markers measured before and after systemic radionuclide therapy. There was a significant increase in the CgA and tPSA concentrations after treatment (P = 0.0146 and 0.0025, respectively). Conclusions In association with tPSA, serum CgA appears to be a promising marker for monitoring patients with prostate cancer.

Beyond prostate-specific antigen: alternate serum markers

“…9,16 CgA may predict response to chemotherapy, 17,18 and as a marker of NE differentiation CgA has been shown to reflect androgen-independent disease even before evidence of PSA progression. 19,20 Some have suggested that CgA velocity may be useful in predicting time to androgen independence after hormonal therapy and have indicated that treatments variably accelerate NE differentiation (intermittent androgen deprivation oantiandrogen only ocastration only ocombined androgen blockade). 16,19 In the androgen-independent CaP patient, increased CgA levels appear to correlate with adverse outcomes and decreased overall survival, though levels indicative of a survival disadvantage are undefined (Table 2).…”

New circulating biomarkers for prostate cancer

“…As such, it may be possible to use chromogranin A to monitor metastatic PCa patients under androgen blockade. 90,91 Novel blood biomarkers for prostate cancer K Bensalah et al…”

Combination of insulin-like growth factor-1, IGF binding protein-3, chromogranin A and prostate specific antigen can improve the detection of prostate cancer

“…[39] Tumors with NE features have displayed more aggression and are more resistant to hormone therapy. [25] Some studies have claimed that CgA is an independent prognostic marker for PCa, [40] while others have conflicted with these findings. [29,41] No PCa predictive values were seen for IGF-1, IGFBP-3 or CgA; AUC were 0.58, 0.55 and 0.56, respectively.…”

“…Therefore, it is possible to use CgA to monitor metastatic PCa patients under androgen blockade. [25] Some indicate CgA utility in early diagnosis, particularly when used in combination with free/total PSA ratio, [26] however, some studies found that CgA does not precisely differentiate malignant disease. [27] Similar debate occurs regarding CgA and tumor features [28] and CgA does not show any advantage in the prognosis of PCa recurrence after radical prostatectomy or radiotherapy.…”