Progastrin is abnormally released in the blood of patients with different cancers (colorectal, gastric, ovarian, breast, uterus, melanoma…), as the progastrin gene is a direct target of the WNT/ß-catenin oncogenic pathway involved in tumorigenesis of many organs (ASCO 2017, Prieur et al CCR 2017). The value of progastrin as a diagnostic, and as a therapeutic monitoring marker, was assessed in patients treated for peritoneal carcinomatosis from gastro-intestinal (GI) cancers in the prospective BIG-RENAPE study (NCT02823860).
Patients were enrolled during management of peritoneal carcinomatosis (before or after neo-adjuvant chemotherapy, or surgery) and then regularly sampled for blood. Progastrin was measured using the ELISA DECODE LAB test®. The diagnostic value of progastrin concentrations at inclusion in 190 GI cancer patients (test set) was assessed against 80 samples from French donors (control set with non-cancer subjects). The longitudinal therapeutic monitoring value of progastrin test was also investigated.
The Area Under the ROC curve of prograstrin for cancer diagnosis was 0.87, 95% CI [0.83-092]. Progastrin was significantly elevated at inclusion in all GI tumor subtypes (p < 0.0001; median 3.08, 95% CI [1.15-7.23], including colo-rectal & small bowel (n = 151; median 2.78) and oeso-gastric (n = 33; median 4.75) carcinomas). During monitoring, progastrin levels decreased after neoadjuvant treatment (median value 2.20, n = 23), decrease that became significant after surgery (p < 0.0001, median value 1.57, n = 84), with patients going back to normal value and others not. A trend for better PFS was observed in patients with progastrin decline after surgery. Progastrin baseline value did not correlate with renal function.
Progastrin assay is a simple and inexpensive blood test exhibiting high diagnostic accuracy in patients with GI carcinomas, along with promising therapeutic longitudinal changes across sequential managements. Assessment of progastrin value as a multi-tumor screening assay, and as a monitoring test, is on-going.
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A. Prieur, P. Liaud, M. Flaceliere, D. Joubert: Employee: ECS-Screening. All other authors have declared no conflicts of interest.