Effect of postsurgical adjuvant chemotherapy timing on outcomes in patients with pancreatic cancer – a systematic review and meta-analysis

To assess the association between the timing of postsurgical adjuvant chemotherapy and overall survival (OS) and disease-free survival (DFS) in patients with pancreatic cancer (PC). Literature search of PubMed, EMBASE, and Scopus databases was done for randomized controlled trials (RCTs) or observational studies (cohort studies, case-control studies), reporting outcomes of adult PC patients (aged 18 and above) who underwent surgery and received adjuvant chemotherapy at different time points after the operation. Pooled effect sizes were quantified and reported as hazard ratio (HR). The primary outcomes were OS and DFS. A random effects model to was used account for potential variability across studies. Sixteen studies were included. There was no significant difference between early and delayed initiation of adjuvant chemotherapy in terms of OS (HR 1.03, 95% CI: 0.98, 1.08) and DFS (HR 1.09, 95% CI: 0.91, 1.31). Subgroup analyses based on tumour stage, sample size, and the number of chemotherapeutic agents used did not reveal significant associations. Delayed initiation was associated with reduced OS in patients with well- to moderately differentiated tumours, with the confidence intervals approaching statistical significance (HR 1.12, 95% CI: 1.00,1.25). There was no significant association between the timing of postoperative adjuvant chemotherapy initiation and OS and DFS in patients with pancreatic cancer. These findings underscore the importance of optimizing treatment strategies and suggest that clinicians need to focus on other critical aspects such as drug selection, dosage, and patient-specific factors that might substantially impact treatment efficacy.