Evolving approaches in advanced gallbladder cancer with complete pathological response using chemo‑immunotherapy: A case report

Abstract

The combination of chemotherapy and immunotherapy for metastatic cholangiocarcinoma (CCA) offers promising improvements in survival and response rates beyond traditional treatments. TOPAZ-1 and KEYNOTE-966 have demonstrated the efficacy of combining immunotherapy (durvalumab and pembrolizumab) with chemotherapy, even in gallbladder cancer (GBC), with a complete response rate of 2.7% in the TOPAZ-1 trial. Advanced CCA treated with immunotherapy combinations has shown complete responses influenced by high programmed death-ligand 1 (PD-L1) or Epstein-Barr virus expression. These responses were enhanced by combining radiotherapy with programmed cell death protein 1 (PD-1) blockade. A 62-year-old man was diagnosed with unresectable GBC, distant lymphatic metastases, and local invasion of liver segments 4i and 5, the colonic hepatic flexure, the duodenal bulb, and the pancreatic head. Immunohistochemical examination revealed poorly differentiated squamous cell carcinoma, without expression of PD-L1. Next generation sequencing revealed the mutation of ERBB2 R678Q and a microsatellite stable tumour. The patient started chemo-immunotherapy with cisplatin-gemcitabine plus durvalumab in June 2022. After eight cycles, a significant reduction in tumour volume and markers was reported, and therapy with durvalumab was maintained through November 2023. The subsequent computed tomography scans showed further reduction in the tumour volume, and surgical resection was performed. Histological examinations confirmed the absence of residual tumour or lymph node metastases. As of June 2024, the patient has shown no signs of disease recurrence. Several reports of conversion surgery in GBC exist, but data on pre-surgical chemo-immunotherapy are limited. Furthermore, a complete response without pathological confirmation in CCA and GBC raises several questions regarding the need for surgery after immunotherapy. Although effective disease control and tumour regression have been reported in advanced GBC with combined anti-cytotoxic T-lymphocyte associated protein 4 and anti-PD-1 agents and chemotherapy, further studies are needed to identify reliable predictive biomarkers due to unclear associations with PD-L1 expression or tumour mutational burden. Overall, chemo-immunotherapy has been effective in treating metastatic CCA, especially when tailored to specific molecular profiles. These treatments may lead to complete responses and novel strategies.

Keywords: GBC; chemo-immunotherapy; conversion therapy; pathological complete response.

Figure 1.

Timeline of patient treatment. 1,8 q3w, days 1 and 8 every 3 weeks; q3w, every 3 weeks; q4w, every 4 weeks.

Figure 2.

CT scan evolution over the course of 17 months of treatment. Enhanced CT scans showing a gallbladder lesion infiltrating the hepatic pedicle, the head of the pancreas, colonic hepatic flexure and liver lesions during the course of treatment, with a progressive reduction in the size of the lesion and the infiltrative component. (A) First three images: Axial CT scans showing the initial size of the lesion, infiltration of the hepatic pedicle, and impact on the head of the pancreas. Fourth image: Coronal CT scan highlighting the colonic hepatic flexure and liver lesions. (B) First three images: Axial CT scans showing a slight reduction in the lesion size, decreased infiltration of the hepatic pedicle and reduced impact on the head of the pancreas. Fourth image: Coronal CT scan showing less pronounced lesions in the liver. (C) First three images: Axial CT scans showing a marked reduction in lesion size, further decreased infiltration of the hepatic pedicle and minimal impact on the head of the pancreas. Fourth image: Coronal CT scan showing smaller liver lesions. (D) First three images: Axial CT scans showing the lesion was almost completely reduced, minimal to no infiltration of the hepatic pedicle and negligible impact on the head of the pancreas. Fourth image: Coronal CT scan showing near resolution of liver lesions. (E) First three images: Axial CT scans showing the lesion was almost completely reduced, minimal to no infiltration of the hepatic pedicle and negligible impact on the head of the pancreas. Fourth image: Coronal CT scan showing near resolution of liver lesions.

Figure 3.

MRI before and after 12 months of chemo-immunotherapy. At the initial diagnosis, the three images in the left column are axial MRI scans. The first image shows the initial size of the lesion and its infiltration into the liver. The second image illustrates the lack of a clear cleavage plane with the duodenum. The third image highlights the involvement of the hepatic flexure. After 12 months of chemo-immunotherapy, the three images in the right column show marked changes. The first image demonstrates a marked reduction in the lesion size and a notable decrease in the infiltrative component in the liver. The second image highlights the re-establishment of a clear cleavage plane with the duodenum. The third image depicts reduced involvement of the hepatic flexure.