Background: Neoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has recently been proposed as an alternative to adjuvant chemotherapy, with potential increase in resectability rate and overall survival.
Aim: To undertake a systematic review and critical appraisal of available literature on the use of neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of advanced GBC.
Methods: Systematic review carried out in line with the Meta-analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of complete response, partial response and stable disease, resectability rate and R0 resection. Secondary outcomes were overall and disease-free survival.
Results: 8 studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who responded to chemotherapy did not proceed to surgery. 50.4% of the patients were considered suitable for surgical resection, of which 191 (40.3%) underwent curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival ranged from 18.5 to 50.1 months for those who underwent curative resection versus 5.0-10.8 months for non-resected group.
Conclusions: There is insufficient data to support the routine use of NACT or NACRT in advanced GBC, as this has only benefited a third of whole cohort, who eventually achieved a R0 resection. Future studies should be in the form of randomized controlled trials to investigate the role of neoadjuvant therapy in advanced GBC.
Keywords: Advanced; Chemotherapy; Down-staging; Gallbladder cancer; Neoadjuvant; Preoperative; Survival.
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