HPB SO47 - Adjuvant chemotherapy for early pancreatic cancer: Meta-analysis of survival benefit and the need for a national study of UK practice

Abstract Background Stage I pancreatic cancer is defined as disease localised to the pancreas (T1-T2, N0, M0). Whilst landmark trials have demonstrated adjuvant chemotherapy (AC) improves survival in resectable disease, early stages comprise only 3-8% of cases. The benefit of AC in stage 1 pancreatic cancer is yet to be defined and there currently exists no data outlining the use of AC for early disease in the United Kingdom (UK). We aimed to perform a meta-analysis evaluating comparative outcomes of pancreatic cancer resection with or without AC in patients with stage I pancreatic cancer and outline plans for a national collaborative study. Method A systematic search of MEDLINE, CENTRAL and Web of Science and bibliographic reference lists were conducted. All comparative studies reporting outcomes of pancreatic cancer resection for stage I cancer with or without AC were included and their risk of bias were assessed using ROBINS-I tool. Survival outcomes were analysed using hazard ratio (HR) and odds ratio (OR) for the time-to-event and dichotomous outcomes, respectively. Results We included six studies reporting 6,874 patients with resected stage 1 pancreatic cancer of whom 3,951 patients had no AC and the remaining 2,923 patients received AC. The use of AC was associated with significantly higher overall survival (HR 0.71, P<0.00001) and 2-year survival (65.1% versus 57.4%, OR 1.99, P=0.04) compared to no use of AC. There was no statistically significant difference in 1-year (86.8% versus 78.4%, OR 1.60, P =0.25), 3-year (46.0% versus 44.0%, OR 1.07; P =0.43), or 5-year survival (24.8% versus 23.3%, OR 1.03; P =0.81) between the two groups. Conclusion Meta-analysis of best available evidence (level 2a with low to moderate certainty) demonstrates that AC may confer survival benefits for stage I pancreatic cancer when compared to the use of surgery alone. National evaluation of the use of AC within the UK is currently lacking but is necessary. Randomized control trials are required to escalate the level of evidence and confirm these findings with consideration of contemporary chemotherapy agents and regimens.