The evolving concept of conversion surgery for upfront unresectable upper gastrointestinal and hepato-pancreato-biliary cancers: comprehensive review

Abstract

Background: In the absence of a commonly accepted definition, conversion surgery is generally considered as surgical resection with the intent of prolonging survival after non-surgical induction therapy in patients with upfront unresectable disease at diagnosis. Despite the heterogeneity of possible targets, conversion surgery is a quickly evolving concept, with commonalities for upper gastrointestinal (UGI) and hepato-pancreato-biliary (HPB) malignancies.

Methods: A comprehensive narrative review of the most recent and relevant literature was conducted by experts in the field of different UGI and HPB tumours.

Results: The increased interest of the surgical scientific community in the concept of conversion surgery can be explained by the continuous improvements in non-surgical therapies aimed at controlling the systemic tumour burden and the local extension of cancer, supported by improvements in surgical outcomes for advanced resections in expert centres. The toolbox of the surgical oncologist seeking conversion in the case of unresectable UGI and HBP tumours is large and includes (but is not limited to) systemic chemotherapy, (chemo)radiation, targeted therapy/immunotherapy, locoregional ablation techniques, intra-arterial therapies, liver hypertrophy induction techniques, treatments of underlying medical conditions, and prehabilitation.

Conclusions: Conversion surgery represents a powerful instrument to prolong the survival of patients with unresectable UGI and HPB malignancies. However, most of the available evidence is of a low level and at very high risk of selection bias. Alongside a profound understanding of (and respect for) the biology of cancer, which remains key to selecting appropriate patients and avoiding non-therapeutic surgeries, a commonly accepted definition is urgently needed to standardize practice, monitor outcomes, and improve the quality of research.

Fig. 1

Specific targets of conversion surgery and the surgeon oncologist's toolbox, among different UGI and HPB malignancies AJCC, American Joint Committee on Cancer; LAPC, locally advanced pancreatic cancer; NCCN, National Comprehensive Cancer Network; HIPEC, hyperthermic intraperitoneal chemotherapy; IPC, intraperitoneal catheter-based chemotherapy; PIPAC, pressurized intraperitoneal aerosol chemotherapy; MWA, microwave ablation; RFA, radiofrequency ablation; TACE, transarterial chemoembolization; TARE, transarterial radioembolization; PVE, portal vein embolization; HVE, hepatic vein embolization; ALPPS, associating liver partition and portal vein ligation for staged hepatectomy; HAI, hepatic arterial infusion chemotherapy. (Created with BioRender.com.)

Fig. 2

Definitions of oligometastatic disease in oesophagogastric and pancreatic cancers OMD, oligometastatic disease; OMEC, OligoMetastatic Esophagogastric Cancer project. (Created with BioRender.com.)

Fig. 3

Overview of different types of oesophageal oligometastatic disease Patients have induced OMD in case of a history of polymetastatic disease before diagnosis of OMD. Patients with genuine OMD have no history of polymetastatic disease before diagnosis of OMD. In the OMEC project, only patients with genuine OMD were included. OMD, oligometastatic disease; OMEC, OligoMetastatic Esophagogastric Cancer project.

Fig. 4

Multiparametric and converse therapeutic hierarchy for hepatocellular carcinoma This figure is derived from Altmayer et al. and Napoli et al.. *PS is an indicator of tumour-related symptoms, and therefore tumour aggressiveness. #Includes extrahepatic metastases and invasion of the main trunk of the portal vein or inferior vena cava. The arrow on the right indicates the converse therapeutic hierarchy (conversion or adjuvant approach); note that the evidence supporting this concept is still weak. PS, performance status; AFP, α-fetoprotein; PIVKA-II, protein induced by vitamin K absence II; LDLT, living donor liver transplantation; DCD, donor after circulatory death; DBD, donor after brain death; MELD, model for end-stage liver disease; CRPH, clinically relevant portal hypertension; TACE, transarterial chemoembolization; PVT, portal vein thrombosis.