Peritoneal Metastasis in Non-Small Cell Lung Cancer: A Systematic Review of Clinical Features, Molecular Profiles, Diagnostic Approaches, and Outcomes.

Abstract

Introduction: Peritoneal metastasis is an uncommon but clinically significant manifestation of non-small cell lung cancer (NSCLC). While traditionally associated with gastrointestinal or ovarian malignancies, emerging reports suggest that NSCLC, particularly adenocarcinoma with driver mutations, can also exhibit peritoneal dissemination. This systematic review aims to synthesize current evidence on the clinical characteristics, diagnostic modalities, molecular profiles, treatment strategies, and outcomes of NSCLC patients with peritoneal metastasis.

Methods: A systematic literature search was conducted in PubMed, Embase, and Web of Science from inception through April 2025. Studies were eligible if they reported peritoneal metastasis in histologically confirmed NSCLC patients. Data on histopathology, molecular alterations, diagnosis, treatment, and survival were extracted. The review was conducted in accordance with PRISMA 2020 guidelines.

Results: Twenty-seven studies met inclusion criteria, comprising 19 case-based reports and seven retrospective cohort studies. Adenocarcinoma was the predominant histologic type (93%), and EGFR mutations were the most frequently reported molecular alteration. Diagnosis was primarily established via ascitic cytology, imaging, or intraoperative findings. Targeted therapy (eg, EGFR- or BRAF-directed TKIs) yielded temporary disease control in selected cases. However, median overall survival after peritoneal metastasis ranged from 2.0 to 5.2 months. Prognostic factors included poor performance status, absence of actionable mutations, and concurrent pleural metastasis.

Conclusion: Peritoneal metastasis in NSCLC is rare but associated with poor prognosis. Molecular-guided therapies offer transient benefit, underscoring the need for early recognition and individualized treatment approaches. Prospective studies are warranted to better define predictors and optimal management strategies for this atypical metastatic pattern.