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
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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Cited by (26)
Tumor biology reflected by histological growth pattern is more important than surgical margin for the prognosis of patients undergoing resection of colorectal liver metastases
2023, European Journal of Surgical OncologyCitation Excerpt :The obvious objective of surgery for CRLMs is to be radical, meaning achieving a margin-free resection of all resected lesions. However, despite improvements in liver imaging and operative techniques, the rate of positive margins remains relatively high in these patients, ranging from 10% to 32% [22–26], reflecting the importance of this problem and the limited accuracy of preoperative and intraoperative methods to determine the limits of surgical resection. This is confirmed in the present study, in which we observed 16% positive margins among the patients who underwent curative-intent resection.
Local tumour control after radiofrequency or microwave ablation for colorectal liver metastases in relation to histopathological growth patterns
2022, HPBCitation Excerpt :Local regrowth occurs in 10%–40% of patients after ablation and in 4%–17% of patients after resection of CRLM.9,10,14–19 It must be noted, however, that there is a substantial risk of selection bias as most of these studies compare hepatectomy for resectable CRLM with ablation for unresectable CRLM.9,10,14–19 Several studies indicate that local tumour control is similar between ablation and resection when sufficient resection and ablation margins are reached.20,21
Liver Resection and role of Extended Histology (LiREcH study) in patients with multifocal colorectal cancer liver metastases
2021, HPBCitation Excerpt :Hence it is essential to strike a balance between adequate excision of a metastatic lesion and obtaining a negative margin status. The reported liver recurrence rate with margin positivity is 24.5–33%, and NAR-site-specific recurrence was reported in 8% of patients.5,9 The studies mentioned above have not evaluated the histological status at the tumour base.
MULTIMODAL THERAPY FOR METASTATIC COLORECTAL CANCER: A CASE OF COMPLETE CLINICAL AND RADIOLOGICAL RESPONSE OF LIVER METASTASES
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