非转移性腹主动脉旁淋巴结重塑作为局部晚期宫颈癌结局的预测因子

Purpose: Treatment of locally advanced cervical cancer (LACC) is guided notably by the European Society of Gynaecological Oncology guidelines; unfortunately, relapse remains frequent despite standard chemoradiotherapy and brachytherapy. We evaluated whether histologic assessment of nonmetastatic para-aortic lymph nodes (PAoLN) provides prognostic value in LACC. Experimental design: Primary tumor and PAoLNs from 137 patients with nonmetastatic LACC were stratified by pretherapeutic 18F-2'-deoxy-2'-fluorodeoxyglucose PET/CT into pelvic PET-positive (pPET+, n = 72) and pelvic PET-negative (pPET-, n = 65) groups. Immunohistochemistry on whole sections assessed germinal centers, CD4+, CD8+, FOXP3+ cells, neutrophils [CD66b+, neutrophil extracellular traps (NET)], and high-endothelial venules (HEV). Associations with progression-free survival (PFS) were examined via uni- and multivariate analyses after a median follow-up of 55.4 months. Results: The primary tumor profile was not associated with outcome, whereas PAoLN features were strongly predictive. In pPET- patients, higher NETs were associated with shorter PFS [P = 0.015; hazard ratio (HR) = 2.768], whereas an elevated CD4/CD8 ratio improved outcomes (P = 0.047, HR = 0.497). In pPET+ patients, shorter PFS was linked to FOXP3+ (P = 0.04, HR = 1.918) and proliferating FOXP3+ cell (P = 0.018, HR = 1.668) density. Across the full cohort, abundant germinal centers (P = 0.0355, HR = 0.273) and an elevated CD4/CD8 ratio (P = 0.001, HR = 0.490) independently correlated with lower recurrence risk. Internal validation was conducted through a bootstrap resampling method. Combinatorial analyses revealed distinct predictive signatures according to pPET status: higher NETs, fewer germinal centers, and International Federation of Gynaecology and Obstetrics IIA1 to IIIB status predicted relapse in pPET- patients. Conclusions: Integrating pPET status with PAoLN histologic analyses improves recurrence risk stratification in LACC. PAoLN evaluation may serve as a complementary tool to guide treatment intensification and surveillance strategies.