E455: Impact of Gastric Cancer Tumor Downstaging Following Neoadjuvant Therapy on Overall Survival: A National Cancer Database Analysis

Several clinical trials have shown the survival benefit of neoadjuvant systemic chemotherapy (NAC) for gastric adenocarcinoma. Moreover, pathologic response to NAC has been associated with increased survival. The aim of this study was to use the National Cancer Database (NCDB) to identify tumor and nodal downstaging following NAC and to evaluate if these were associated with overall survival (OS).   The hypothesis is that patients with post-NAC pathologic tumor downstaging have higher survival compared to those without tumor downstaging.

Methods: This retrospective cohort study utilized the NCDB gastric cancer participant user file spanning diagnosis years 2004-2020.  Resected patients with clinical T2-4 and/or N1-3B gastric adenocarcinoma treated with NAC were included. Patients with metastatic disease or treated with neoadjuvant radiation alone were excluded. Survival was compared stratified by response to NAC, which was defined as favorable when pathologic T or N stage improved from the clinical stage or unfavorable when pathologic T or N stage was either unchanged or increased. As a comparator, patients that received upfront surgery were evaluated separately.

Results:

Of 15,327 patients, 12,092 (78.9%) underwent NAC and 3,235 (21.1%) underwent upfront resection. The NAC group had 5,823 (48.2%) with favorable T stage response and 4,010 (33.2%) with favorable N stage response. Among the upfront resection group, 12.2% and 22.3% were inaccurately clinically T and N understaged. Adjusting for age, sex, race, Charlson-Deyo score, median income, facility type, adjuvant therapy, duration of NAC, tumor differentiation, and margin status, favorable response to NAC in T stage was significantly associated with OS (HR 0.64, 95% CI 0.60-0.68, p< 0.001). Favorable response to NAC in N stage was significantly associated with OS (HR 0.81, 95% CI 0.76-0.86, p< 0.001). Favorable T stage response alone was associated with longer OS compared to favorable N stage response alone (median OS 84.5 months, 95% CI 76.3-92.5 vs 57.3 months, 95% CI 51.7-66.2, p< 0.001). A response in the T stage was 43% sensitive and 76% specific in predicting a response to NAC in N stage.

Conclusions: Favorable response to NAC in both T stage and N stage are associated with increased OS in patients undergoing resection for gastric adenocarcinoma. Given the limited overlap between T and N stage response to NAC, further investigation into prognostic differences and recurrence patterns following primary tumor and/or nodal response are merited.