Impact of Extracapsular Lymph Node Involvement After Neoadjuvant Chemoradiation Therapy Followed by Surgery in Carcinoma of the Esophagus: A Multicenter Study.

OBJECTIVES: The current study aims to examine the impact of extracapsular lymph node involvement (EC-LNI) on survival for both esophageal adenocarcinoma (AC) and squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery. BACKGROUND: Studies have demonstrated the negative prognostic value of EC-LNI in primary surgery, but its impact after nCRT remains unclear. METHODS: From the databases of 6 European high-volume centers 1505 patients with R0 resections were withheld. Oncologic variables, including ypT, ypN, number of positive lymph nodes, and lymph node capsular status: EC-LNI and intracapsular lymph node involvement (IC-LNI), were examined. Statistical analysis was performed by Cox proportional hazards modeling. RESULTS: In SCC 182 patients (31.6%) had positive lymph nodes, of whom 60 (33.0%) showed EC-LNI. In AC 391 patients (42.1%) had positive lymph nodes, of whom 147 (37.6%) showed EC-LNI. Overall 5-year survival (O5YS) in SCC was 42.0%. Presence of EC-LNI meant a significantly worse O5YS than IC-LNI or pN0 (10.6%, 39.5%, and 47.4%, respectively; P < 0.05). O5YS in AC was 41.2%. No significant difference was observed between EC-LNI and IC-LNI (P = 0.322). In the multivariate analysis, among the examined possible prognosticators, presence of EC-LNI showed the highest hazard ratio (2.29, confidence interval: 1.52-3.47) as an independent prognosticator for overall survival in SCC, but it was not in AC. CONCLUSIONS: Based on this international multicenter study, the presence of EC-LNI after nCRT is at least as important as N-stage for survival and EC-LNI is the strongest prognosticator for overall survival in SCC but not in AC.

International Multicenter Study on the Impact of Extracapsular Lymph Node Involvement in Primary Surgery Adenocarcinoma of the Esophagus on Overall Survival and Staging Systems.

OBJECTIVE: The current pathological lymph node (pN) staging is based on the number of positive lymph nodes but does not take into consideration characteristics of the involved lymph nodes itself. The current study aims to examine the prognostic value of extracapsular lymph node involvement (EC-LNI) and intracapsular lymph node involvement (IC-LNI) for esophageal adenocarcinoma treated by primary surgery. METHODS: From the databases of five European high volume centers, 1639 adenocarcinoma patients with primary R0-resection were withheld after excluding 90-day mortality. Oncologic variables, including number of resected lymph nodes, number of resected positive lymph nodes, and EC-LNI/IC-LNI were examined. The Union Internationale contre le Cancer (UICC) 7th edition prognostic staging was used as baseline staging system. Statistical analysis was performed by Cox proportional hazards modeling and verified using the Random Survival Forest technique. RESULTS: EC-LNI showed significantly worse overall 5-year survival compared with IC-LNI overall (13.4% vs 37.2%, P < 0.0001), including in each pN-category [16.4% vs 45.6% in pN1 (P < 0.0001), 16.1% vs 23.8% (P = 0.047) in pN2 (P = 0.065), and 8.7% vs 26.3% in pN3 categories, respectively]. pN1 IC-LNI patients show a 5-year overall survival comparable (P = 0.92) with stage IIB (ie, pT3N0). Reclassifying the UICC prognostic stages according to these findings into an adapted staging model showed a significant (P < 0.0001) increase in homogeneity, discriminatory ability, and monotonicity compared with the original UICC TNM 7th edition prognostic staging. CONCLUSIONS: These data suggest that lymph node capsular status is an important prognostic factor and should be considered for the future edition of the TNM staging system for esophageal cancer.

Signet ring cells in esophageal and gastroesophageal junction carcinomas have a more aggressive biological behavior.

OBJECTIVE: To clarify the biologic behavior of esophageal signet ring cell (SRC) carcinomas of the esophagus and gastroesophageal junction (GEJ). To evaluate the accuracy of pretreatment biopsies in diagnosing true SRC carcinoma. BACKGROUND: In contrast with gastric cancer, little is known about the biologic behavior and prognosis of SRC. METHODS: All adenocarcinomas (ADC) of the esophagus and GEJ-patients undergoing primary resection between 1990 and 2009 were included (n = 920). Specimens containing SRCs (n = 114) were classified according to World Health Organization criteria (>50% SRC or <50% SRC). RESULTS: Thirty-two patients showed more than 50% SRC and 71 patients showed less than 50% SRC. Overall cancer-specific 5-year survival was worse for SRC (22.4%, P < 0.0001) and for SRC > 50% (13.6%, P = 0.0001) compared with ADC. Complete resection was achieved in 86.5% of patients (n = 697) in ADC, 69.5% (n = 57) in SRC < 50%, and 78.1% (n = 25) in SRC > 50% (vs ADC, respectively, P < 0.0001 and P = 0.1801). In 379 pN + R0 patients, the median number of positive lymph nodes was comparable between ADC and SRC < 50% (4 vs 5, P = 0.207) or SRC > 50% (4 vs 8, P = 0.077). Compared with ADC, SRC > 50% showed more pN3's (30% vs 61%, P = 0.006), higher recurrence (56% vs 42% for ADC, P = 0.003), and local-regional recurrences (29% vs 16%, P = 0.002). Pretreatment biopsies were unreliable to define the presence of SRC > 50% (sensitivity = 56.3%, positive predictive value = 43.9%). CONCLUSIONS: SRCs are aggressive neoplasms associated with poorer prognosis than other ADCs after primary esophagectomy. Because our data suggest that pretreatment biopsies failed to reliably define presence of SRC > 50%, presence of SRCs in pretreatment biopsies seems to be of no use to define treatment strategy or prognosis.

Palliative esophagectomy in unexpected metastatic disease: sense or nonsense?

Background Despite integrated positron emission tomography and computed tomography screening before and after neoadjuvant treatment in patients with locally advanced esophageal cancer, unexpected metastatic disease is still found in some patients during surgery. Should then esophagectomy be aborted or is there a place for palliative resection? Methods Between 2002 and 2015, 681 patients with potentially resectable esophageal cancer were sheduled for neoadjuvant therapy and subsequent esophagectomy. In 552 patients, a potentially curative esophagectomy was performed. In 12 patients, unexpected disease was discovered during surgery but esophagectomy was performed with synchronous resection of metastases; 10 of them had oligometastatic disease (≤4 single-organ metastases). Esophagectomy was not performed in 117 patients (because of disease progression in 50); 14 were also single-organ oligometastatic. Data of 10 single-organ oligometastatic patients who underwent esophageal resection (group 1) were compared those of 10 non-resected but treated counterparts (group 2) and with 228 patients who underwent potentially curative esophagectomy with persistent pathological lymph nodes (group 3). Results Five oligometastatic esophagectomy patients had lung metastases: 1 peritoneal, 2 adrenal, 1 pleural, and 1 pancreatic. Two oligometastatic non-resected patients had lung, 5 liver, and 3 brain metastases. Median overall survival was 21.4, 12.1, and 20.2 months in the respective groups (group 1 vs. group 2 p = 0.042; group 2 vs. group 3 p = 0.002; group 1 vs. group 3 p = 0.88). Conclusions Survival is longer in patients undergoing palliative esophagectomy with unexpected single-organ oligometastatic disease and comparable to survival in patients with persistent pathological lymph nodes. Palliative resection in these patients seems to be justified.