Liquid Biopsy Blood Biomarker Possible Predictor of Tumor Recurrence, Cost Savings

A study concluded that use of a multigene liquid biopsy blood biomarker for diagnosis of neuroendocrine tumors was over 94% effective at predicting tumor recurrence compared with other commonly used biomarker, Chromogranin A.

The NETest, a multigene liquid biopsy blood biomarker test used to diagnose neuroendocrine tumors (NETs), was found to be more accurate at predicting recurrence in patients who had undergone NET resection surgery than other standard postsurgery imaging techniques, such as Chromogranin A (CgA), investigators concluded in a study.

The prospective multicenter evaluation of NET resections over 24 months, published in Annals of Surgery, found that NETest could be an important clinical tool and a real-time, noninvasive molecular strategy to determine whether a patient is disease free after surgery and aid providers in facilitating the surgical management of NETs.

“NETest provides a highly accurate preoperative diagnostic and post operatively as a predictor of disease recurrence. This liquid biopsy may have value for stratifying patients for surgical follow-up and could result in a decrease in postoperative management costs,” wrote the investigators.

A main issue with determining poor outcomes associated with NETs is that they are often diagnosed at an advanced stage, meaning that curative surgical resection options are limited. Additionally, symptoms usually present late and there are currently no effective pan-NET biomarkers, making developing diagnostic and prognostic tools imperative.

Because NETs are frequently indolent and carry an average survival rate of 5 to 10 years, follow-up represents a significant clinical and financial component of NET management. Recent reports have concluded that CgA, a pan-NET biomarker that has long been considered effective for diagnosis and management, only presents minimal value because of problems with assay reproducibility, overall sensitivity, and limited clinical applicability.

The investigators included 103 patients from Milan, Italy (n = 28); London, United Kingdom (n = 27); Turin, Italy (n = 26); Silesia, Poland (n = 13); and New Haven, Connecticut (n = 9) who had undergone surgery and postoperative biomarker assessment for gastroenteropancreatic or bronchopulmonary NETs. The median age was 59 years, and 63 of the patients were women. The patients’ surgical sites were the lung (n = 26), pancreas (n = 47), small bowel (n = 26), appendix (n = 2), stomach (n = 1), and duodenum (n = 1).

The NETest results were elevated in all of the patients, and the median level was 73, yielding positive overall results. This was considerably higher than the CgA results, which were positive in only 22% of patients (n = 23). Additionally, all surgical resection types presented with reduced NETest levels, which was also seen with CgA levels; however, the CgA reduction was considered insignificant.

In total, 30% of the patients experienced recurrences, which occurred in 81 out of 83 R0 resections (resection without any microscopic evidence of residual disease) during the 24-month follow-up period. The investigators found that the per patient cost for each recurrence would cost health systems $987,000, and the cost per recurrence detection would $82,800. The authors concluded that if the NETest strategy was utilized, the cost would drop to a per-patient cost of $535,000 and a per-recurrence cost of $47,700.

The study had some limitations, including that cost-scaling assessments were used to assess the potential US health care impact and that cost savings were largely reflected in the decrease in imaging because a positive NETest would aid providers in figuring out when to image and what modality to use.

“Further studies are required to define the accuracy and cost-effectiveness of the NETest in the detection of postoperative recurrent disease,” wrote the investigators.


Modlin, IM, Kidd M, Frilling A, et al. Molecular genomic assessment using a blood-based mRNA Signature (NETest) is cost-effective and predicts neuroendocrine tumor recurrence with 94% accuracy. Ann Surg. 2021;274(3):481-490. doi:10.1097/SLA.000000000000502