Surgery with adjuvant or neoadjuvant treatment vs surgery alone for resectable pancreatic cancer: A network meta-analysis

BACKGROUND Pancreatic cancer is one of the most common and lethal malignancies worldwide. The common treatment options for resectable pancreatic cancer include surgery alone, neoadjuvant chemotherapy (CT), neoadjuvant chemoradiotherapy (CRT), adjuvant CT, and adjuvant CRT. However, the optimal treatment is still controversial. AIM To identify the most effective approach for pancreatic cancer using network meta-analysis. METHODS Eligible studies were searched from PubMed, MEDLINE, EMBASE, Cochrane database, and Google scholar. We searched and included randomized controlled trials reporting on neoadjuvant and adjuvant therapies. For direct comparisons, standard pairwise meta-analysis was performed using the inverse variance DerSimonian-Laird random-effects model. For indirect comparisons, Bayesian network meta-analysis was used to combine direct and indirect evidence. We used relative hazard ratios (HRs) to estimate death difference of different treatments, and relative odds ratios (ORs) for toxic effects. Treatment effects were ranked based on their efficacy for improving survival or reducing toxicity using rankogram. The quality of evidence of estimates from direct comparison and network meta-analysis was evaluated following the GRADE approach. RESULTS We included 13 high quality trials with 1591 participants in this network metaanalysis. Compared with surgery alone [pooled HR = 0.7, 95% confidence interval (CI): 0.62-0.79] and surgery with adjuvant CRT (pooled HR = 0.6, 95%CI: 0.54-0.72), surgery with adjuvant CT had a higher rate of overall survival. In contrast, standard pairwise meta-analysis showed a statistically significant survival advantage of surgery with adjuvant CT compared with surgery alone (pooled HR = 0.75, 95%CI: 0.63-0.89;P < 0.001). Rankogram showed that surgery with adjuvant CT was most likely to rank the best in terms of overall survival (probability: 94.2%), followed by surgery alone (probability: 5.8%). No significant differences in overall toxicity or haematological toxicity were found between all the therapies. High quality evidence supported surgery with adjuvant CT over surgery alone for increasing overall survival. Moderate quality evidence supported surgery with adjuvant CT over surgery with adjuvant CRT for increasing overall survival. CONCLUSION Surgery with adjuvant CT prolongs overall survival compared with surgery alone and surgery with adjuvant CRT, suggesting surgery with adjuvant CT is the optimal treatment for resectable pancreatic cancer.