Early Recurrence of Neuroendocrine Liver Metastasis After Curative Hepatectomy: Risk Factors, Prognosis, and Treatment

Abstract

Background Early tumor recurrence after curative resection typically indicates a poor prognosis. The objective of the current study was to investigate the risk factors, treatment, and prognosis of early recurrence of neuroendocrine tumor (NET) liver metastasis (NELM) after hepatic resection. Methods A total of 481 patients who underwent curative-intent resection for NELM were identified from a multiinstitutional database. Data on clinicopathological characteristics, intraoperative details, and outcomes were documented. The optimal cutoff value to differentiate early and late recurrence was determined to be 3 years based on linear regression. Results With a median follow-up of 60 months, 223 (46.4%) patients developed a recurrence, including 158 (70.9%) early and 65 (29.1%) late recurrences. On multivariable analysis, pancreatic NET, primary tumor lymph node metastasis, and a microscopic positive surgical margin were independent risk factors for early intrahepatic recurrence. While recurrence patterns and treatments were comparable among patients with early and late recurrences, early recurrence was associated with worse diseasespecific survival than late recurrences (10-year NELM-specific survival, 44.5 vs 75.8%, p < 0.001). Among the 34 (21.5%) patients who underwent curative treatment for early recurrence, post-recurrence disease-specific survival was better than noncuratively treated patients (10-year NELM-specific survival, 54.2 vs 26.3%, p = 0.028), yet similar to patients with late recurrences treated with curative intent (10-year NELM-specific survival, 54.2 vs 37.4%, p = 0.519). Conclusions Early recurrence after surgery for NELM was associated with the pancreatic type, primary lymph node metastasis, and extrahepatic disease. Re-treatment with curative intent prolonged survival after recurrence, and therefore, operative intervention even for early recurrences of NELM should be considered.

Early recurrence of well‐differentiated (G1) neuroendocrine liver metastasis after curative‐intent surgery: Risk factors and outcome

“…37 Despite this, an R0 resection should still be the goal of resection of NELM, as a microscopically positive margin has been associated with an increased risk of recurrence. 16 In fact, R1 surgical margin status was associated with a higher risk of late recurrence. R1 status after surgical resection of NELM may, however, be a surrogate for more extensive disease at the time of surgery.…”

“…In contrast to primary liver tumors and other metastatic cancers to the liver, NELM tends to grow expansively by pushing the surrounding liver parenchyma rather than invading it . Despite this, an R0 resection should still be the goal of resection of NELM, as a microscopically positive margin has been associated with an increased risk of recurrence . In fact, R1 surgical margin status was associated with a higher risk of late recurrence.…”

“…6 Tumor characteristics, such as tumor number and size, surgical margin, lymph node metastasis, and tumor grade are established prognostic factors following surgery for NELM. 13,[16][17][18] In addition to the presence of recurrent disease, the timing of recurrent disease has become increasingly recognized as an important prognostic factor. For example, a shorter time between surgery and recurrence among patients with primary liver cancer 20,21 and colorectal liver metastasis 22 has been associated with worse survival.…”

Surgical strategy for neuroendocrine liver metastases

“…Even when all detectable liver disease has been resected at the index hepatecomy, recurrence is frequently seen. The majority of hepatic recurrence occurs in the first 3 years after resection, and is associated with worse overall disease‐specific survival . In this situation, the options are for repeat liver resection, debulking hepatectomy or non‐resectional therapies.…”

“…Surgical resection is advised for selected patients with low‐volume recurrent or symptomatic disease . Curative resection for early recurrent liver disease was associated with improved post‐recurrence survival . Early recurrence of NET–liver metastases was more likely in younger patients (age <50 years), and in the presence of adverse tumour biology, primary pancreatic NET and primary NET lymph nodal metastases .…”