Study: Prophylactic Up-Front Locoregional Surgery Has No Survival Advantage

The study found that prophylactic locoregional surgery (LRS) for asymptomatic patients with small intestinal neuroendocrine tumors (SI-NETs) provided no survival advantage compared with delayed LRS.

A new study found that prophylactic surgery for asymptomatic patients with small intestinal neuroendocrine tumors (SI-NETs) provided no survival advantage.

“SI-NETs have an indolent clinical course, and are often diagnosed at a late stage,” wrote the authors. “Sixty percent of patients with SI-NETs present with distant metastases, most commonly in the liver; thus a high proportion of patients are diagnosed with stage IV tumors.”

For SI-NETS patients without local tumor-related symptoms, prophylactic locoregional surgery (LRS) has been encouraged in order to prevent future intestinal obstruction, ischemia, perforation, or bleeding. However, there is a lack of data comparing benefit of prophylactic upfront LRS compared to delayed LRS.

The study, published in JAMA Oncology, analyzed the outcome of LRS in asymptomatic patients with stage IV SI-NETs compared with delayed LRS as needed. Authors collected data from 363 patients documented in the SI-NET prospective database of Uppsala University Hospital in Sweden. Patients must have had a histopathologically confirmed diagnosis of SI-NET, radiologically confirmed distant metastases, and no abdominal symptoms to be included.

Patients were split up between those who were selected for and underwent prophylactic up-front surgery within 6 months of diagnosis combined with oncologic treatment (LRS group), and those who underwent no surgery or delayed surgery as needed combined with oncologic treatment (delayed LRS group).

Of the 363 patients, 161 were in the LRS group, and 202 were in the delayed LRS group. Patients in the unmatched delayed LRS group were older and had a more advanced disease. Eighty-nine of those patients underwent delayed LRS, and 113 never underwent LRS.

A 1:1 nearest-neighbor propensity score match with a caliper width of 0.1 was implemented between the LRS and delayed LRS groups using the variables such as age, sex, calendar year at baseline, carcinoid symptoms, and the Charlson comorbidity index, a predictive factor for survival, ranging from zero to 31 points.

The results of the propensity score matching identified 2 isonumerical groups with similar baseline variables and propensity score distributions. The LRS and delayed LRS groups were comparable in median overall survival (OS) and cancer-specific survival. There was no difference in 30-day mortality or postoperative mortality rates. There was also no difference in median length of hospital stay (LOS), or LOS due to local tumor-related symptoms. Patients in the LRS group underwent more re-operative procedures.

Overall, there was no survival benefit found for patients with initial prophylactic LRS compared with delayed LRS.

While there is value in the use of LRS for patients with SI-NETs when radical resection is feasible or when symptomatic disease is present, results of this study challenge the appropriateness of the use in patients with distant metastases in the absence of local tumor-related symptoms.

“In the era of personalized treatment, maximalist surgery should be reconsidered and replaced by a comprehensive multidisciplinary approach for the optimal treatment of patients with SI-NETs,” concluded the authors.