Finding a predictive index for evaluating the efficacy of neoadjuvant therapy in locally advanced gastric cancer patients

BACKGROUND: Emerging evidence suggests that the addition of immunotherapy may improve tumor regression grade (TRG) in locally advanced gastric cancer (LAGC) patients. However, the clinical benefit of immunotherapy in patients with low PD-1 expression remains a subject of debate and requires further exploration. Importantly, a proportion of Neoadjuvant immuno-chemotherapy group (NICT) patients did not present significant benefits from neoadjuvant therapy. The aim and objectives of our study is to stratify LAGC patients who can benefit from neoadjuvant therapy based on TRG results. METHODS: We conducted a retrospective study (2020-2023) included 94 LAGC patients (cT3N + M0, 4a-bNanyM0) with gastric adenocarcinoma who receiving neoadjuvant therapy (57 patients in the neoadjuvant chemotherapy (NCT) group, and 37 in NICT group). All patients received ulterior radical surgery, and clinicopathological data were retrospectively reviewed and analyzed. We introduced multivariate analysis demonstrated significant associations between TRG and Tumor differentiation (OR, 7.985; 95% CI, 0.998-34.370; p = 0.007), N stage (OR, 13.286; 95% CI, 1.861-50.324; p = 0.013), tumor size (OR, 5.397; 95% CI, 1.174-24.818; p = 0.030), and immunotherapy (OR, 16.872; 95% CI, 2.889-75.563; p < 0.001). We developed the Clinical Predictive Pathological Remission Score (CPPRS) according to the four indicators mentioned above, assigning 0 points for immunotherapy, well-differentiated tumors, absence of lymph node metastasis, and tumor size < 3.55 cm, while 1 point was assigned for NCT, moderate/poor differentiation, tumor size > 3.55 cm, and lymph node metastasis. RESULTS: NICT group exhibited a significantly higher TRG0 rate compared to the NCT group, independent of PD-1 expression (9/37 vs. 2/57, p = 0.004). Tumor differentiation (OR, 7.985; 95% CI, 0.998-34.370; p = 0.007), N stage (OR, 13.286; 95% CI, 1.861-50.324; p = 0.013), tumor size (OR, 5.397; 95% CI, 1.174-24.818; p = 0.030), and immunotherapy (OR, 16.872; 95% CI, 2.889-75.563; p < 0.001) were significantly associated with TRG. CPPRS demonstrated a strong correlation with TRG (p < 0.001). CONCLUSIONS: The addition of immunotherapy improves TRG in LAGC patients without the need for PD-1 expression assessment. CPPRS serves as a valuable predictive tool for evaluating the efficacy of neoadjuvant therapy in LAGC patients.