Efficacy of concurrent intensity modulated chemoradiotherapy combined with induction chemotherapy or adjuvant chemotherapy in the treatment of locally advanced cervical cancer with 2018FIGO stage correction：a multicenter Retrospective Cohort Study

Background and purpose Concurrent chemoradiotherapy (CCRT) is currently the standard treatment for locally advanced cervical cancer (LACC), but there is a lot of room for treatment strategies improvement and the 5-year survival rate of patients is low, Comprehensive treatment is the treatment direction for LACC, The current comprehensive treatment models for LACC mainly include induction chemotherapy (IC) plus CCRT and CCRT plus adjuvant chemotherapy (AC),but it remains unclear which is optimal sequence of combined chemotherapy. The purpose of this study is to retrospectively report the outcome of long-term survival and related toxicity that IC plus CCRT versus CCRT plus AC in LACC. Materials/Methods: From December 2016 to December 2022, 525 patients of LACC with 2009FIGO(IB2, IIA2, and IIB-IVA)/2018FIGO staging༈IB3, IIA2, and IIB-IVA༉who initially underwent IC plus CCRT or CCRT plus AC from the Forth Affiliated Hospital of Guangxi Medical University, Yulin First People's Hospital and Liuzhou Hospital of Guangzhou Women and Children's Medical Center. All patients with 2009FIGO༈IB2, IIA2, and IIB-IVA༉were re-staged after 2018FIGO staging༈IB3, IIA2, and IIB-IVA༉correction. All patients were treated with IMRT to 50.4 Gy with concurrent weekly cisplatin 40 mg/m2 followed by intra-cavitary brachytherapy. The IC plus CCRT group received platinum-based combined chemotherapy with two or three cycles before CCRT. CCRT plus AC group received platinum-based combined chemotherapy with two cycles after CCRT. Propensity score matching (PSM) method was used to match the proportion of 1:1 between the neoadjuvant treatment group and the adjuvant treatment group,5-year overall survival (OS), 5-year progression free Survival survival(PFS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and treatment-related adverse reactions were evaluated and compared between the two groups.Cox proportional hazard regression model was used to analyze the effect of neoadjuvant or adjuvant therapy on the survival of patients with locally advanced cervical cancer. Results A total of 525 patients with complete follow-up data are available were included our study. Among these patients, 250 patients were treated with IC plus CCRT and 275 patients were treated with CCRT plus AC. IC/AC regimens included TP/DP(cisplatin + Paclitaxel/Docetaxel) and TC/DC(carboplatin་Paclitaxel/Docetaxel). The median follow-up of 56 months (range 20–80 ). Before propensity score matching(PSM), there were no significant differences in survival rates between the neoadjuvant treatment group and the adjuvant treatment group ( P  > 0.05). After propensity score matching(191 matched pairs), there were also no significant differences between the two group on the 5-year OS rates (83.9% vs. 84.7%), PFS rates (76.0% vs. 71.4%) or LRFS rates (79.3% vs 76.5%)and DMFS rates (88.7% vs 89.1%)) (all P  > 0.05).But Subgroup analysis revealed that CCRT plus AC showed a trend of improving OS (HR = 0.455, 95% CI (0.206–1.006), P  = 0.052) in 2018FIGO III-IVA stage and was associated with significantly improved OS(HR = 0.191,95%CI (0.057–0.641), P  = 0.007), PFS(HR = 0.288,95%CI(0.118–0.702), P  = 0.006) ,DMFS(HR = 0.211, 95% CI (0.068–0.654), P  = 0.007) in patients with positive pelvic lymph nodes. IC plus CCRT was associated with significantly improved PFS (HR = 2.276, 95% CI (1.187–4.363), P  = 0.013) in 2018FIGO IIB stage. There was no significant difference in adverse events between the two groups ( P  > 0.05). Multivariate Cox analysis identified Pathology, FIGO Stage, LNMS and Tumor diameter as independent prognostic factors for OS, PFS, LRFS and Pathology and LNMS were an independent risk factor for DMFS Conclusion There is no statistical difference between IC plus CCRT and CCRT plus AC in the outcome of long-term survival of LACC. However, for patients with stage III-IVA advanced cervical cancer, the CCRT plus AC shows a trend of improving survival benefits, especially for those with pelvic lymph node metastasis, where the benefit is more significant. For stage IIB patients, IC plus CCRT can reduce the risk of local progression. Lymph node status is a key decision factor: patients with positive pelvic lymph nodes should prioritize CCRT plus AC for enhanced treatment.