Assessing the clinical utility of pro-gastrin releasing peptide on the monitoring of medullary thyroid carcinoma

Abstract Objectives Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy monitored with serum calcitonin (CT) and carcinoembryonic antigen (CEA), whose doubling times guide imaging and treatment decisions. CT interpretation is constrained by analytical and biological variability, prompting interest in complementary biomarkers. Pro-gastrin releasing peptide (ProGRP) shows a low within-subject biological variation, making it attractive for serial monitoring. Methods In this single-centre retrospective study, 43 post-thyroidectomy MTC patients (complete response [CR], n=20; partial response [PR], n=10; progressive disease [PD], n=13) with serial ProGRP, CT and CEA were analysed using patient-level median concentrations. Groups were compared using the Kruskal–Wallis test with Dunn–Holm correction, and biomarkers were correlated at patient level (Spearman). Reference change values (RCV95) were derived from EFLM within-subject biological variation and local analytical imprecision. Biomarker-specific doubling times were estimated in PD as an exploratory analysis. Results All three biomarkers increased stepwise across CR, PR and PD (p<0.001). On single-timepoint comparison, CT showed the broadest discrimination, separating CR from PR and PR from PD, whereas ProGRP and CEA separated only PD from CR. ProGRP correlated strongly with CT (ρ=0.80). RCV95 was narrowest for ProGRP (16.6 %) vs. CEA (25.1 %) and CT (38.2 %). Doubling times were estimable in only a few patients and did not clearly distinguish biomarkers. Conclusions ProGRP behaves as a disease burden biomarker that tracks calcitonin and, through its narrow RCV95, may serve as a fine-grained longitudinal complement for CT and CEA. These hypothesis-generating findings warrant prospective, multicentre validation.