Abstract:Background and Aims Early postoperative recurrence is a significant risk factor for poor prognosis of gallbladder cancer, and growing evidence suggests that adjuvant chemotherapy can improve the outcomes of patients. However, there have been no reports on early postoperative recurrence after the second surgery and the impact of adjuvant chemotherapy on patients with incidental gallbladder cancer (IGBC). Therefore, this study explored the risk factors for early postoperative recurrence after the second surgery in IGBC patients and analyzed the efficacy of adjuvant chemotherapy in early and non-early recurrence patients to provide clinical decision support.Methods The clinicopathologic data of 170 patients who underwent curative-intent resection for IGBC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2021 were retrospectively collected. The factors influencing early postoperative recurrence (defined as recurrence within 12 months after the second radical surgery), as well as recurrence-free survival (RFS) and overall survival (OS) after surgery of patients, were analyzed.Results Among the 170 patients who underwent curative-intent resection for IGBC, 73 (42.94%) experienced recurrence during the follow-up period, with 41 (24.12%) experiencing early postoperative recurrence. The median OS in patients with early postoperative recurrence was significantly shorter than those without early recurrence (χ2=192.910, P<0.001). The degree of pathological differentiation (OR=20.758, 95% CI=5.557-80.239), CA19-9 level (OR=7.920, 95% CI=1.557-39.771), and residual lesions (OR=8.050, 95% CI=3.06-21.160) were independent risk factors for early postoperative recurrence of IGBC (all P<0.05). The degree of pathological differentiation (HR=6.160, 95% CI=2.877-13.193), CA19-9 level (HR=2.538, 95% CI=1.297-4.965), surgical resection scope (HR=2.111, 95% CI=1.154-3.860), and residual lesions (HR=2.571, 95% CI=1.547-4.273) were independent risk factors for RFS in IGBC patients after surgery (all P<0.05). The degree of pathological differentiation (HR=3.225, 95% CI=1.461-7.121), early recurrence (HR=29.558, 95% CI=14.250-61.311), and residual lesions (HR=2.416, 95% CI=1.361-4.287) were independent risk factors for OS in IGBC patients after surgery (all P<0.05). Adjuvant chemotherapy was an independent protective factor for OS (HR=0.260, 95% CI=0.123-0.551, P<0.05). Stratified analysis based on residual lesions and early recurrence showed that adjuvant chemotherapy prolonged RFS and OS in patients with residual lesions and extended OS in early recurrence patients (all P<0.05).Conclusion Residual lesions are independent risk factors for early postoperative recurrence and prognosis in IGBC patients after the second surgery. Adjuvant chemotherapy after surgery can effectively improve the prognosis of patients with residual lesions and early recurrence.