Surgery in oesophago-gastric cancer with metastatic disease: Treatment, prognosis and preoperative patient selection☆

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Abstract

Background

The role of surgical resection in metastatic oesophago-gastric adenocarcinomas (EGA) is not defined and regularly discussed in interdisciplinary tumour boards. Primary objective of this retrospective study was the outcome of patients after surgery. We additionally evaluated our preoperative prognostic score (PPS) based on tumour grading, clinical response to chemotherapy and presumed R-status.

Methods

123 of 811 EGA patients were evaluated as cM1, either confirmed intraoperatively or by imaging. Response evaluation after chemotherapy was performed by endoscopy, CT-scan and histopathologically. The prospectively documented patient and outcome data were analysed retrospectively.

Results

70 patients with adenocarcinoma of the oesophago-gastric junction and 53 patients with gastric cancer were included. The majority had one M1 site (n = 102). 72 received preoperative chemotherapy (CTx) and 51 underwent primary resection. 11 were explored without resection. 49/112 (40%) had multivisceral resections and 63/112 (56%) were completely resected (R0). 26/72 (36%) were clinical responders and 30 patients had a favourable PPS.

Median survival was 20.0 months. Survival was significantly prolonged by resection, especially complete resection, and by preoperative CTx (all p = 0.001). Multivisceral resection, type or number of metastases, or primary tumour localization had no impact on survival. In patients undergoing preoperative CTx, clinical response and the PPS influenced survival significantly. In R0 resected patients, preoperative CTx, clinical response and the PPS remained prognostic.

Conclusion

Primary resection without preoperative CTx is not appropriate for metastatic EGA. Subgroups of patients with a favourable PPS with response to CTx may be good candidates for surgical resection in metastatic oesophago-gastric cancer.

Introduction

The therapeutic approach in metastatic Oesophago-gastric cancer has changed significantly. Whereas formerly any M1-category was excluded from surgery, nowadays surgery for patients with metastatic disease are often discussed in multidisciplinary tumour boards.1, 2, 3 Individually for each patient, expectations have to be weighted against surgical feasibility, risk and overall benefits since so far results of randomized studies are not available.4, 5 The treatment goals in an M1 situation theoretically range from relief of symptoms and prevention of complications caused by the primary tumour to improvement of quality of life up to a significant survival benefit or cure in some patients. Surgical strategies vary from a mere resection of the primary tumour to a complete resection of the primary tumour and all metastatic sites. The problem of the literature on this topic is its extreme heterogeneity. The inclusion criteria for surgical treatment in published series are wide and often not clearly disclosed, making comparison of studies difficult. Studies include patients with syn- or metachronous metastases, with and without preoperative therapy and with different sites and number of metastases.1, 2, 6, 7, 8 Preliminary results of the FLOT-3 study suggest a benefit for resected patients with limited metastatic disease compared to patients with chemotherapy alone.9 Mariette et al. also demonstrated a survival benefit for surgically treated patients compared to non-surgical treatment in gastric cancer.10 Median survival for resected patients with metastatic disease ranges from 8 months to 20 months,6, 8, 10, 11 which is in line with the 18.6 months reported for limited metastatic patients treated with surgery or other local therapies in the FLOT trial.9 We have to be aware that results might be influenced by a selection bias of the included patients in the surgical treatment arms. Several factors have been suggested as indicators for potential benefits from resection, i.e. response to induction therapy,1, 12 number and pattern of metastasis,1, 6, 12, 13, 14, 15 performance status,6, 13 and extent of the primary tumour.2, 14 Previously published prognostic factors include the delivery of chemotherapy, resection, length of the primary tumour, number of metastatic sites and histopathological response.1, 2, 7 The primary objective of this retrospective study was to assess the outcome of patients with limited metastatic Oesophago-gastric adenocarcinoma with special emphasis on preoperative chemotherapy and response evaluation. Additionally, our preoperative prognostic score (PPS)16 was now assessed in a larger patient series.

Section snippets

Patients and methods

Between 2002 and 2012 811 patients with histopathologically proven adenocarcinoma of the Oesophago-gastric junction (AEG) or stomach were treated and continuously documented in a patient database at the department of surgery of the university hospital Heidelberg. 123 patients (15.3%) were confirmed as M1, either intraoperatively as pM1 or as cM1 by imaging (Figure S1). 32 of the M1 patients were already included in the paper of Blank et al.16 with shorter follow-up. The institutional review

Results

In this study 123 patients with cM1 metastatic Oesophago-gastric cancer undergoing surgery were included. 107 patients were staged cT3/4 and 111 cN+. The primary tumour was localized at the Oesophago-gastric junction in 70 (56.9%) patients and in the stomach in 53 patients (43.1%). 72 patients were treated with preoperative chemotherapy. 112 patients underwent resection of the tumour, 11 patients were explored without resection. Of the 112 resected patients 63 underwent a complete resection

Prognostic factors

The median overall survival of all 123 patients was 20.0 months (±1.49 95%CI 17.1–22.9). The 2-year overall survival rate was 31.8%, 3-year overall survival rate 28.0% and 5-year overall survival rate 20.7%. Surgical resection, complete resection and preoperative CTx prolonged survival (all p < 0.001), but not multivisceral resection and number or type of metastases. Also the localization of the primary tumour, AEG vs GC did not influence overall survival (p = 0.48; Figure S2).

Of the 112

Discussion

Resection for Oesophago-gastric adenocarcinomas with cM1 metastatic disease is increasingly requested in multidisciplinary tumour boards. Heterogeneous studies indicate a potential role of surgery in patients with metastatic gastric cancer.1, 2, 6, 7, 10, 12, 13, 14, 15, 19, 20, 21, 22, 23, 24 Similar as other aggressive treatment strategies, i.e. salvage surgery for Oesophageal cancer after definitive radiotherapy,25 this aggressive surgical approach needs to be evaluated. Our data with a

Conflicts of interest

The authors declare no conflicts of interest.

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    ☆

    Presented in part at the ASCO GI 2014.

    1

    Contributed equally.

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