Chromogranin A in Diagnosing and Monitoring Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Large Series from a Single Institution

Abstract

Background/Aims: Plasma chromogranin A (CgA) is the most widely used biochemical biomarker in the diagnostic workup and follow-up of gastroenteropancreatic neuroendo- crine neoplasms (GEP-NENs). Herein, we assessed the clinical utility of CgA in diagnosing and monitoring a large series of GEP-NENs. Patients and Methods: A total of 181 GEP-NEN patients (87 males, 94 females) with pancreatic (n = 81) and gastrointestinal neoplasms (n = 100) were included; 99 patients had grade (G)1 NENs (Ki-67 ≤2%), 57 G2 NENs (Ki-67 3-20%) and 25 G3 NENs (Ki-67 >20%); 81 patients had tumor-node-metastasis (TNM) stage I, 14 stage II, 17 stage III and 69 stage IV cancer. For every patient, CgA values were assessed at diagnosis and during follow-up. Results: At diagnosis, the CgA values were above the upper reference limit in 148 patients (82%); the median CgA levels were significantly higher in functioning than in nonfunctioning tumors (295 vs. 43 U/l; p = 0.0001) as well as significantly higher in patients with metastases than in those without metastases (324.5 vs. 42 U/l; p = 0.0001). In logistic regression analysis, baseline CgA levels were significantly associated with Ki-67 index (p < 0.0001) and TNM stage (p < 0.0001) independently of the age and sex of the patient and the primary site of the tumor. The overall 5- and 10-year survival rates were 74 and 64.5%, respectively. A low Ki-67 index, the type of treatment and an early CgA decrease after treatment were positively correlated with the survival rate. After radical surgery, 15/95 patients relapsed, and an increase in CgA values anticipated the clinical and objective disease recurrence after a period of 9-12 months. Conclusions: In GEP-NENs, plasma CgA has a significant prognostic relevance.

The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors

“…36,37 CgA has been validated as a prognostic marker in midgut NET in randomized clinical trials. 38 Pancreastatin, a breakdown product of CgA, may be more specific in certain contexts, such as patients using proton pump inhibitors (which raise CgA levels).…”

NET Blood Transcript Analysis Defines the Crossing of the Clinical Rubicon: When Stable Disease Becomes Progressive

“…A variety of metrics have been assessed to evaluate the use of these markers. For example, a 30% decrease in CgA (from pretreatment levels) is considered predictive of SSA efficacy [38], while an increase in three consecutive measurements is considered to anticipate relapse after midgut surgery [39]. Some authors proposed that alterations of ≥25% in CgA may have good sensitivities (>75%) and specificities (>85%) for predicting disease events [33] while others suggested that levels twice the ULN (∼300 µg/l or 300 ng/ml) [32] or higher (≥600) [40] are effective predictors of disease progression.…”

Clinicopathological features and prognostic factors of colorectal neuroendocrine neoplasms.

“…Our data only included the Chinese population, and it is not clear whether the results could be generalized to populations worldwide. Second, additional known risk factors that could predict survival were not evaluated, including histological growth pattern, mitotic rate, Ki-67 index, and immunohistochemistry markers, such as chromogranin A (CgA) and synaptophysin (Syn) [21,[30][31][32][33]. Finally, our analysis did not adjust for treatment approaches that may impact outcomes [34].…”