Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study

Shanshan Wang; Yunchao Wang; Chengpei Zhu; Kai Liu; Jiashuo Chao; Nan Zhang; Mingjian Piao; Xu Yang; Longhao Zhang; Junyu Long; Ziyu Xun; Ting Zhang; Xinting Sang; Xiaobo Yang; Haitao Zhao

doi:10.1097/JS9.0000000000001540

Conversion surgery intervention versus continued systemic therapy in patients with a response after PD-1/PD-L1 inhibitor-based combination therapy for initially unresectable biliary tract cancer: a retrospective cohort study

Int J Surg. 2024 May 3. doi: 10.1097/JS9.0000000000001540. Online ahead of print.

Authors

Shanshan Wang¹, Yunchao Wang^{1

2}, Chengpei Zhu^{1

3}, Kai Liu^{1

4}, Jiashuo Chao¹, Nan Zhang¹, Mingjian Piao¹, Xu Yang¹, Longhao Zhang¹, Junyu Long¹, Ziyu Xun¹, Ting Zhang¹, Xinting Sang¹, Xiaobo Yang¹, Haitao Zhao¹

Affiliations

¹ Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
² Organ Transplantation Center, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
³ Department of General Surgery Center, Beijing Youan Hospital, Clinical Center for Liver Cancer, Capital Medical University, Beijing, China.
⁴ Digestive Disease Hospital Affiliated to Zunyi Medical University, Department of General Surgery, Affiliated Hospital of Zunyi Medical University Zunyi 563099, Guizhou, China.

PMID: 38704621
DOI: 10.1097/JS9.0000000000001540

Abstract

Background: The role of conversion surgery in patients with unresectable biliary tract cancer (BTC) who responded positively to PD-1/PD-L1 inhibitor-based therapy remains unclear. This study aimed to assess the outcomes in patients with or without conversion surgery.

Methods: In this cohort study, patients with advanced BTC who received combination therapy with PD-1/PD-L1 inhibitors from July 2019 to January 2023 were retrospectively. Patients who exhibited positive responses and met the criteria for conversion surgery were enrolled, and their surgical and oncological outcomes were analyzed.

Results: Out of 475 patients, 34 who met the conversion resection criteria were enrolled. The median follow-up was 40.5 months post-initiation of systemic therapy. Ultimately, 13 patients underwent conversion surgery, while 21 received continuation of systemic treatment alone (non-surgical group). The median interval from the initial antitumor therapy to surgery was 6.7 (interquartile range [IQR] 4.9-9.2) months. Survival with conversion surgery was significantly longer than the non-surgical cohort, with a median progression-free survival (PFS) (unreached vs. 12.4 mo; hazard ratio 0.17 [95% CI 0.06-0.48]; P=0.001) and overall survival (OS) (unreached vs. 22.4 mo; hazard ratio 0.28 [95% CI 0.09-0.84]; P=0.02), respectively. After a median postoperative follow-up of 32.2 months in the surgical cohort, 8 patients survived without recurrence. The estimated 3-year OS, PFS and recurrence-free survival rate in the surgical cohort were 59.9%, 59.2% and 60.6%, respectively. The R0 resection rate reached 92.3%, with 2 achieving a pathological complete response. One patient experienced a Clavien-Dindo grade 3 complication without surgery-related mortality. No serious adverse events or surgical delays were observed. Multivariate analysis indicated that conversion surgery was independently associated with OS (P=0.03) and PFS survival (P=0.003).

Conclusion: Conversion surgery appears safe and offers survival benefits to patients responding to immune checkpoint inhibitors (ICIs)-based combinations. However, further studies are required to validate this strategy in the era of immunotherapy.