Anatomical precision in the omics era: a proposed framework for selective para-aortic lymphadenectomy in epithelial...

The LION and CARACO trials demonstrated that routine systematic pelvic and para-aortic lymphadenectomy (LAD) confers no survival benefit in clinically node-negative advanced epithelial ovarian cancer (EOC), while significantly increasing perioperative morbidity. However, these trials evaluated unselected populations without molecular stratification. This review proposes an omics-guided, anatomically precise surgical paradigm to identify patients who may benefit from selective retroperitoneal clearance.

A synthesis of recent landmark clinical trials, international surgical guidelines, and emerging multi-omics datasets was conducted to evaluate retroperitoneal lymph nodes as complex architectural niches characterized by passive drug diffusion limits and chemotherapy-induced structural remodelling.

Approximately 30-50% of advanced high-grade serous EOC cases exhibit primary or acquired resistance to standard platinum/taxane chemotherapy. Biological and spatial transcriptomic data indicate that retroperitoneal nodes can act as sanctuaries where resistant clones persist despite systemic therapy, driving later recurrence. Validated preoperative biomarkers; including homologous recombination proficiency (HRD-negative status), investigational markers such as enhancer-associated MSH6 downregulation and specific proteomic panels under investigation (e.g., PRKAR2B/SKP2) show strong predictive potential for primary chemoresistance within exploratory validation cohorts.

A one-size-fits-all approach to surgical de-escalation tends to overlook a critical, molecularly defined minority. Shifting the surgical paradigm toward biomarker-guided anatomical precision offers a conceptual, hypothesis-generating blueprint for future clinical trials, testing whether restricting systematic para-aortic lymphadenectomy to preoperatively identified chemoresistant subsets provides true therapeutic utility.