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

Abstract

Background The objective of the current study was to identify the risk of early vs late recurrence of well‐differentiated (G1) neuroendocrine liver metastasis (NELM) after curative‐intent resection. Methods Patients who underwent curative‐intent resection for well‐differentiated NELM were identified from a multi‐institutional database. Clinicopathological details, as well as the long‐term overall (OS) and recurrence free survival (RFS) were obtained and compared. The optimal cutoff value to differentiate early and late recurrence was determined to be 1 year based on trend curve analysis. Results Among the 548 patients undergoing curative resection for NELM, 162 patients had a well‐differentiated NELM. After a median follow‐up of 69 months, 59 (36.4%) patients had tumor recurrence; 23 (39.0%) patients recurred within 1 year (early recurrence) after surgery, while 36 (61.0%) recurred after 1 year (late recurrence). Early recurrence was associated with worse outcome vs late recurrence (5‐year OS, 72.4% vs 92.0%; P = 0.020) and no recurrence (5‐year OS, 72.4% vs 100.0%; P < 0.001). In addition, postrecurrence survival was worse within 36 months after recurrence among patients who recurred early compared with patients who recurred late (survival after recurrence at 36 months: early recurrence, 71.6% vs late recurrence, 91.4%; P = 0.047), although survival was comparable at 60 months (early recurrence, 71.6% vs late recurrence, 70.0%; P = 0.304). On multivariable analysis, nonfunctional neuroendocrine tumors (hazard ratio [HR], 4.4; 95% confidence interval [CI], 1.2‐16.7; P = 0.029) and lymph node metastasis (HR, 3.6; 95% CI, 1.1‐11.1; P = 0.028) were independent risk factors for early recurrence, whereas lymph node metastasis (HR, 3.0; 95% CI, 1.2‐7.8; P = 0.020) and R1 resection (HR, 3.9; 95% CI, 1.4‐10.5; P = 0.008) were independently associated with late recurrence. Conclusions Roughly, one‐third of patients with well‐differentiated NELM experienced a recurrence following curative‐intent surgery. Among patients who recurred, two out of five patients recurred within 1 year after surgery. Early recurrence of well‐differentiated NELM was associated with the hormone functional status and lymph node metastasis.

Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence

“…However, the prognostic impact of the combination of these features into a risk score for DR has been poorly investigated, with data derived from heterogeneous series, with relatively short follow-up after resection, and most studies focused exclusively on pancreatic NETs (PanNETs). [6][7][8][9][10][11][12][13][14][15][16][17][18][19] The absence of a risk score for DR results in two major issues in post-surgical management. First, the efficacy of adjuvant treatments in radically resected EP-NETs still represents an unexplored option.…”

Risk Factors and Predictive Score Model for Early Recurrence After Curative Surgery in Patients With Poorly Differentiated Gastrointestinal Neuroendocrine Neoplasms

“…It has been well-documented that early recurrence after surgery leads to dismal prognosis (10)(11)(12). Because there is no consensus on the optimal threshold for differentiating early and late recurrence of GI-PDNEN, early recurrence was defined as recurrence within the 1st year after surgery, which is in line with that used in previous studies (10)(11)(12). With a relatively large sample size from one single-center institution in China, we demonstrated that the rate of early recurrence after curative surgery in GI-PDNEN was 30.7% and the median overall survival was 12 months.…”

“…It has been well-documented that early recurrence after surgery leads to dismal prognosis ( 10 – 12 ). Because there is no consensus on the optimal threshold for differentiating early and late recurrence of GI-PDNEN, early recurrence was defined as recurrence within the 1st year after surgery, which is in line with that used in previous studies ( 10 – 12 ).…”

Neuroendocrine liver metastases: a contemporary review of treatment strategies

“…While long-term OS generally is excellent, recurrence following hepatic resection of NELM can approach 50-95%, and the majority of recurrences will occur in the liver (21,40). Among patients who develop intrahepatic recurrence, >70% will occur within 3 years of surgery, and approximately 40% within 1 year (34,43). Multiple studies have highlighted the safety and relative efficacy of repeat hepatectomy for recurrent primary and metastatic liver disease (44,45); repeat hepatic resection for recurrent NELM has similarly been demonstrated to be feasible and associated with good long-term survival outcomes in wellselected patients (46).…”