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Lymph node response ratio complements tumor regression grade in prognostic stratification after neoadjuvant therapy
Mengya Zhou1, Jiajun Ying2, Mengxuan Cao3
1Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China; Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, China; Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, Zhejiang, China; Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
Background:
Tumor regression grade (TRG) is widely used to evaluate pathological response after neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC), but it may not adequately reflect nodal response. We investigated the prognostic value of the lymph node response ratio (LNRR), a novel indicator of nodal response, and its complementary role to TRG.
Methods:
We retrospectively analyzed 505 patients with clinically node-positive LAGC who underwent NAC followed by curative gastrectomy. LNRR was defined as the relative change between pretreatment clinically positive lymph node burden and postoperative pathological metastatic lymph node burden. Associations between LNRR, pathological response, and overall survival (OS) were evaluated using logistic regression, Kaplan-Meier analysis, Cox regression, and comparative prognostic performance analyses.
Results:
LNRR was significantly associated with pathological response, with progressively higher values observed across worsening TRG categories (P < 0.001). In multivariable logistic regression, poor pathological response remained independently associated with high LNRR (TRG 2: OR 2.77, 95% CI 1.68-4.57; TRG 3: OR 3.19, 95% CI 1.88-5.39; both P < 0.001). Patients with high LNRR had significantly worse OS than those with low LNRR. On multivariable Cox analysis, high LNRR remained independently associated with inferior OS (HR 2.01, 95% CI 1.44-2.79; P < 0 0.001). Combined LNRR-TRG classification provided better prognostic discrimination than either parameter alone. Patients with high LNRR and poor TRG had the worst survival outcomes, whereas persistently high LNRR identified patients with unfavorable prognosis even among those with favorable TRG.
Conclusions:
LNRR reflects treatment-induced nodal response and provides prognostic information complementary to conventional TRG assessment. Combined evaluation of LNRR and TRG may improve postoperative risk stratification in patients with LAGC after NAC. Further validation in independent multicenter cohorts is warranted before routine clinical application.