Survival Gains After Surgery for Small Pancreatic NETs?

Liam Davenport

April 11, 2023

Some patients with small, nonfunctional pancreatic neuroendocrine tumors (NETs) may benefit from surgery, an analysis of US nationwide data suggests.

Overall, researchers found that surgical resection was associated with a 42% improvement in overall survival among patients with small tumors of 1.1–2.0 cm, but not tumors 1 cm or smaller. Among those with 1.1- to 2.0-cm tumors, the survival benefit following surgery was most notable among patients aged 64 years or younger and those with no comorbidities.

The findings were published in JAMA Network Open on March 28.

While surgical resection has been the first-line treatment for patients with functional or symptomatic localized, low-grade pancreatic NETs, surgery for asymptomatic low-grade nonfunctional pancreatic NETs of 2 cm or less "remains unclear even in consensus guidelines," study author Richard D. Schulick, MD, MBA, of the University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, and colleagues write.

Consensus guidelines from the European Neuroendocrine Tumor Society, for instance, indicate surveillance for these smaller tumors, while those from the Japan Neuroendocrine Tumor Society recommend surgery. The National Comprehensive Cancer Network (NCCN), which recently updated its guidelines, suggests observation as an option for patients with tumors as large as 2.0 cm but who are strongly considering resection.

To determine whether surgical resection of these smaller lesions influences overall survival, the team combed the US National Cancer Database and identified 4641 patients with nonfunctional pancreatic NETs ≤2.0 cm in size.

Researchers divided patients by tumor sizes of ≤1 cm (group 1a) and 1.1–2.0 cm (group 1b) and examined a range of variables, including age, comorbidities, tumor location and differentiation, and overall survival.

Overall, 1278 patients had tumors measuring ≤1.0 cm (group 1a), and 3363 had tumors measuring 1.1–2.0 cm (group 1b). The mean age across both groups was 60.5 years; about half were men, and most (77.4%) were White.

Over a median follow-up of 47.1 months, the surgical resection rate was significantly lower among patients in group 1a (82.0%) than in group 1b (87.0%). Patients who underwent resection, on average, were younger and were more likely to have tumors located in the pancreas tail and to have clinical lymph node metastasis.

Overall, the team found that surgical resection was associated with longer overall survival for patients with tumors of 1.1–2.0 cm (hazard ratio [HR], 0.58) but not 1 cm or smaller (HR, 0.68; P = .12).

Among patients in group 1b (those with 1.1- to 2.0-cm tumors), the team also found that age 64 years or younger (adjusted HR [aHR], 0.34), treatment at academic institutions (aHR, 0.40), absence of comorbidities (aHR, 0.53), absence of clinical lymph node metastasis (aHR, 0.54), as well as tumors in the body (aHR, 0.36) and tail(aHR, 0.37) of the pancreas were significantly associated with increased survival after surgical resection.

Among patients with resected small nonmetastatic nonfunctional pancreatic NETs, pathologic lymph node metastasis (HR, 1.28; P = .43) and lymphovascular invasion (HR, 0.85; P = .75) were not associated with overall survival.

The results of the study "support an association between surgical resection and increased survival in select patients" among those with tumors 1.1–2.0 cm, Schulick and colleagues write.

James R. Howe, MD, who was not involved in the research, highlighted that the study tries to answer an important clinical problem:What should we do with small, nonfunctional pancreatic NETs?

However, he noted "significant selection bias" among patients included in the dataset.

More than 80% of patients with tumors <1 cm underwent surgery, which "is not consistent with what most people would do in practice," said Howe, of the Division of Surgical Oncology and Endocrine Surgery, University of Iowa Hospitals and Clinics, Iowa City. "Most would be observed and might not make it into the National Cancer Database."

Howe pointed to an even larger group of patients with pancreatic NETs who were not included in the database — those with CT evidence of a pancreatic NET but without biopsy confirmation.

With many patients potentially missing from the data, "it is very difficult to know that patients with tumors 1.1–2.0 cm in size are really benefiting from surgery, as suggested in the article," he said.

Howe highlighted a recent interim analysis that indicated that active surveillance is the "preferred approach" for tumors no larger than 2 cm.

Schulick and the research team acknowledge limitations in their dataset, including the potential for coding errors and lack of information on the Ki-67 index, symptoms, incidental diagnosis, and recurrence.

Overall, though, the authors conclude that the findings "support the recommendations of the NCCN guidelines to resect small [nonfunctional pancreatic] NETs for selected patients" but need "to be further investigated to verify the results."

The study was supported by a grant from the Japan Society for the Promotion of Science Overseas Challenge Program for Young Researchers and a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research. Schulick is the inventor of a patent licensed to DynamiCure and has received laboratory equipment from Haemonetics Inc outside the submitted work. Other authors also have relevant financial relationships.

JAMA Netw Open. Published online March 28. Full text

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