Optimal Pathological Response in LACC After Neoadjuvant Chemoimmunotherapy Shows Promising Short-Term Survival

This real-world study evaluated short-term survival outcomes and potential risk factors in patients with locally advanced cervical cancer (LACC) who achieved optimal pathological response (OPR) following neoadjuvant chemoimmunotherapy and radical surgery. A retrospective analysis was conducted on LACC patients treated at a high-volume tertiary medical system between 2022 and 2025. All eligible patients received neoadjuvant chemoimmunotherapy followed by radical hysterectomy. Pathological response was categorized as pathological complete response (pCR; no residual tumor) or major pathological response (MPR; ≤10% residual tumor). Clinical data, treatment details, and follow-up information were systematically collected. Additionally, transcriptomic profiling and multi-algorithm immune infiltration consensus analyses were performed on matched pre- and post-treatment tumor specimens to uncover treatment-induced microenvironmental remodeling. Among 89 eligible patients who underwent surgery, 32 (35.9%) achieved an OPR, comprising 18 (20.2%) with pCR and 14 (15.7%) with MPR. Over a median follow-up of 13 months, the estimated 2-year disease-free survival was 90.7% with an estimated overall survival of 100%. No specific baseline clinicopathological factor emerged as a significant predictor of recurrence in univariable analysis. The regimen was well-tolerated, with grade 3 treatment-related adverse events occurring in 21.9% and no grade 4–5 events reported. Transcriptomic profiling of 10 paired pCR specimens revealed preliminary microenvironmental remodeling post-treatment, characterized by the activation of the NFAT signaling pathway and extracellular matrix reorganization. LACC patients attaining pCR or MPR after neoadjuvant chemoimmunotherapy and surgery demonstrated excellent short-term survival outcomes. These findings provide a rationale for considering de-escalated adjuvant therapy in this highly responsive subgroup. Validation through larger prospective cohorts with extended follow-up is warranted.