Role of tumor markers before or during chemotherapy for digestive neuroendocrine carcinomas as an exploratory analysis of JCOG1213

The clinical utility of tumor markers such as neuron-specific enolase (NSE) and progastrin-releasing peptide (ProGRP) in digestive neuroendocrine carcinoma (NEC) remains unclear. This exploratory analysis aimed to evaluate whether pretreatment and changes of tumor marker levels can predict treatment efficacy. In 137 of the 170 patients enrolled in JCOG1213 with digestive NECs (WHO 2010), we evaluated the association between treatment response and pretreatment NSE and ProGRP levels as well as the changes of these tumor markers from baseline to 6 weeks after chemotherapy. Pretreatment NSE and ProGRP were elevated in 127 and 74 patients. The objective response rate was 58.3%/55.6% in patients with high/normal NSE, and 60.8%/56.7% in patients with high/normal ProGRP. Any decline in tumor markers at 6 weeks tended to be associated with response, particularly for NSE than for ProGRP. The odds ratios for response in decreased NSE and ProGRP at 6 weeks of chemotherapy were 3.231 (P = 0.0198) and 1.652 (P = 0.2247) in multivariable analysis. Pretreatment NSE and ProGRP levels were not associated with tumor response. NSE and ProGRP have potential roles in treatment monitoring, especially changes in NSE were more relevant to tumor response than changes in ProGRP.