Elsevier

Surgery

Volume 165, Issue 4, April 2019, Pages 712-720
Surgery

The impact of R1 resection for colorectal liver metastases on local recurrence and overall survival in the era of modern chemotherapy: An analysis of 1,428 resection areas

https://doi.org/10.1016/j.surg.2018.09.005Get rights and content

Abstract

Background

It is still unclear whether a positive surgical margin after resection of colorectal liver metastases remains a poor prognostic factor in the era of modern perioperative chemotherapy. The aim of this study was to evaluate whether preoperative chemotherapy has an impact on reducing local recurrence after R1 resection, and the impact of local recurrence on overall survival.

Methods

Between 2000 and 2014, a total of 421 patients underwent resection for colorectal liver metastases at our unit after preoperative chemotherapy. The overall number of analyzed resection areas was 1,428.

Results

The local recurrence rate was 12.8%, significantly higher after R1 resection than after R0 (24.5% vs 8.7%; P < .001). These results were also confirmed in patients with response to preoperative chemotherapy (23.1% after R1 vs 11.2% after R0; P < .001). At multivariate analysis, R1 resection was the only independent risk factor for local recurrence (P < .001). At the analysis of the 1,428 resection areas, local recurrence significantly decreased according to the increase of the surgical margin width (from 19.1% in 0 mm margin to 2.4% in ≥10 mm). At multivariable logistic regression analysis for overall survival, the presence of local recurrence showed a significant negative impact on 5-year overall survival (P < .001).

Conclusion

Surgical margin recurrence after modern preoperative chemotherapy for colorectal liver metastases was still significantly higher after R1 resection than it was after R0 resection. Local recurrence showed a negative prognostic impact on overall survival. R0 resection should be recommended whenever technically achievable, as well as in patients treated by modern preoperative chemotherapy.

Introduction

Hepatic resection together with perioperative chemotherapy is currently the only treatment option that can offer a chance of long-term outcome in patients with colorectal liver metastases (CRLM), resulting in 5-year survival rates of 40%,1, 2, 3 and exceeding 50% in selected patients.4, 5, 6

The surgical margin status has been considered to be one of the most powerful prognostic factors for overall survival (OS). Historically, the anticipated inability to achieve a 1-cm margin was considered to be a contraindication to liver resection for CRLM in many centers.7, 8, 9 A resection margin greater than 10 mm was initially defined as the ideal distance owing to the observation that, in the absence of preoperative chemotherapy, microsatellite lesions were located within 1 cm of the tumor border.10 Over the years, the definition of the recommended safe width of the surgical margin associated with improved survival has evolved, decreasing from 5 mm11 to 2 mm,12 and then to 1 mm.13, 14 Recent advances in hepatobiliary surgical techniques, together with the use of more effective perioperative chemotherapy, have increased the indications for liver resection for CRLM,15, 16 including patients with more advanced disease, those with multiple and bilobar CRLM, and those with CLRM close to the major vascular structures. For these reasons, the reported rates of liver resection with positive margins have progressively increased in surgical series,17 showing that potential cure can be achieved in approximately 4% to 18% of R1 selected patients treated by aggressive modern perioperative chemotherapy.18, 19 The dogma that the anticipated inability to resect all disease with negative margins should be considered a contraindication to liver resection for CRLM has been challenged in the era of modern chemotherapy. Furthermore, some recent studies showed that R1 resection in patients treated with perioperative modern chemotherapy was associated with similar long-term survival to that after R0 resection.20, 21 However, these results are controversial and not confirmed in other large series with perioperative chemotherapy in which the positive resection margin remained a strong poor prognostic factor of OS.22, 23, 24 The crucial issue related to the margin status is the surgical margin recurrence rate, which has rarely been reported in these studies. Whether modern preoperative chemotherapy has an impact on reducing local recurrence rate after R1 resection has not been documented, and the clinical impact of local recurrence on overall survival remains controversial.

The aim of our study was to evaluate the impact of surgical margin width on the risk of local recurrence in patients treated with modern preoperative chemotherapy and the influence of local recurrence on OS.

Section snippets

Inclusion criteria

This study included patients who underwent primary hepatectomy (first liver resection) for CRLM in our unit between January 2000 and December 2014. The inclusion criteria were as follows: administration of preoperative chemotherapy, a minimum follow-up ≥2 years, complete resection of all CRLM, and the absence of unresectable extrahepatic disease. The exclusion criteria were as follows: patients treated with concomitant radiofrequency ablation, and incomplete liver resection (R2 resections).

Preoperative assessment

All

Results

Between January 2000 and December 2014, a total of 630 patients underwent curative liver resection for CRLM in our unit. A total of 2 patients (0.3%) died during the postoperative course and were excluded from the study. Another 207 patients did not fulfill the inclusion criteria: 185 patients (29.4%) did not undergo preoperative chemotherapy; 13 (2.1%) underwent R2 resection, and 9 (1.4%) were treated with concomitant radiofrequency ablation. The remaining 421 patients underwent preoperative

Discussion

This is the first large series showing that the risk of local recurrence after liver resection for CRLM was significantly higher after R1 resection than after R0 resection in patients treated with modern preoperative chemotherapy. From the analysis of 421 patients resected after chemotherapy, the overall local recurrence rate was 12.8%; but, it was significantly higher after R1 resection than after R0 resection (24.5% vs 8.7%; P < .001).

Among all prognostic factors after liver resection for

Conclusion

Our study showed that local recurrence in patients treated by modern preoperative chemotherapy for CRLM was still significantly higher after R1 resection than it was after R0 resection. Local recurrence showed a negative prognostic impact on OS. R0 resection should be recommended, whenever technically achievable, in patients also treated by preoperative chemotherapy in the modern era. However, a 5-year OS similar to that observed in our study after R1 resection cannot be reached by other types

Conflicts of interest

The authors have indicated that they have no conflicts of interest regarding the content of this article.

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