Cytoreductive surgery and HIPEC improve survival compared to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups

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Abstract

Background

Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy.

Objective

To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC.

Material and methods

A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test.

Results

Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3–26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively.

Conclusion

Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.

Introduction

Biliary carcinoma represents 3% of digestive cancers, and 15% of primary hepatobiliary malignancy [1]. The only potentially curative treatment for biliary carcinoma is complete surgical resection. After curative surgery, 5-year overall survival (OS) is 30–45% [2], [3]. Peritoneal metastasis (PM) is the most frequent site of metastasis for biliary carcinoma, and is present at time of diagnosis in 10–20% of patients [4]. Metachronous PM is frequent in gallbladder carcinoma, occurrence is potentially increased when there is iatrogenic gallbladder perforation during surgery [5], [6], or after transparietal biopsy [7]. For patients with biliary carcinoma, PM is associated with limited survival despite modern chemotherapy. Median OS for unresectable biliary carcinoma treated with palliative chemotherapy is 15.2 months [8]. Based on international recommendations, biliary carcinoma with PM is not considered as a resectable disease, independently of the primary tumor resectability. Standard treatment for biliary carcinoma PM is palliative chemotherapy with combination of gemcitabin and cisplatin [9].

Since 1980's, the concept of complete cytoreductive surgery (CRS), to treat macroscopic disease, combined with intraperitoneal chemotherapy, to treat microscopic residual disease, was proposed as a potentially curative treatment for PM [10], [11].

This study aimed to assess OS in patients suffering from biliary carcinoma with peritoneal metastasis (PMC) treated by CRS and HIPEC. OS was compared to patients receiving palliative chemotherapy.

Section snippets

Patient population

From a multi-center international database (collaborative database of PSOGI and BIG-RENAPE working groups), two groups were identified. The “CRS/HIPEC group” represented patient with PMC treated with CRS and HIPEC. The “systemic chemotherapy group”, represented patients with PMC initially considered resectable (without PM identified on preoperative imaging), finally not resected due to incidental discovery of PM during surgical exploration. They were subsequently treated with palliative

Patients

Thirty-four patients in the CRS/HIPEC group were compared to 21 patients in the systemic chemotherapy group.

Table 1 describes the characteristics of theses 2 groups of patient. Significant differences were observed regarding location of the primary tumor, gallbladder tumors were significantly more frequent in the CRS/HIPEC group (35% vs 19%, p = 0.001). The median peritoneal cancer index (PCI) was 9 in the CRS/HIPEC group (ranged 3 to 26). PCI was unknown in the systemic chemotherapy group.

Discussion

Here we report the largest international multi-institutional series of patients with peritoneal metastases from biliary carcinoma treated with CRS and HIPEC. The major finding of this study was a statistically significant better OS for patients who underwent macroscopically complete CRS combined with HIPEC for biliary carcinoma with PM compared to palliative chemotherapy. To the best of our knowledge, such survival results have never been reported in the management of PM from biliary carcinoma.

Conclusion

CRS and HIPEC for biliary carcinoma with PM may provide promising survival when compared to palliative chemotherapy. This is the first study suggesting that improve survival for biliary carcinoma with PM can be obtained with CRS and HIPEC. This treatment should be considered only for selected patients with good general status, low burden of disease, and PM amenable to complete CRS.

Synopsis

Complete cytoreductive surgery and HIPEC may improve long-term survival in selected patients with peritoneal metastasis from biliary carcinoma.

Conflict of interest statement

The authors report no conflicts of interest that are relevant to this article.

Acknowledgments

The authors thank Peggy Jourdan-Enfer and Anaïs Poulet for their expert help with data collection. The authors thank and Christelle Maurice and Evelyne Decullier for help with the data analysis.

References (20)

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All authors reviewed and edited the manuscript. All were agree with the submission.

1

Collaborators (PSOGI and BIG-RENAPE Working Groups) are listed in Appendix section.

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