Optimal Management of Clinical T2N0 Gastric Adenocarcinoma: Surgery or Chemotherapy First?

Randomized controlled trials have demonstrated substantial benefit of perioperative chemotherapy (PC) and surgery for locally advanced gastric adenocarcinoma. Patients with clinical T2N0 (cT2N0) gastric adenocarcinoma were included in these trials, but the benefit of PC remains unclear in this intermediate-stage disease due to the small number of patients included. The goal of this study was to determine the role and sequencing of chemotherapy for resected cT2N0 gastric adenocarcinoma.

The National Cancer Database from 2004 to 2020 was used to identify patients with cT2N0 gastric adenocarcinoma who underwent surgical resection. Patients were stratified by receipt of chemotherapy into three groups: (1) no chemotherapy, (2) perioperative chemotherapy (PC), and (3) adjuvant chemotherapy (AT). The primary outcome was overall survival.

Of 3676 patients with cT2N0 gastric adenocarcinoma, 61.3% received no chemotherapy, 19.4% received PC, and 19.2% received AT. Of the 2961 patients who underwent upfront surgical resection, 28.8% (854) were upstaged on final pathology. Multivariable survival analysis revealed that both PC and AT were associated with a decreased mortality compared to no chemotherapy (0.64 and 0.68, respectively, p < 0.001). AT was associated with a 21% decrease in mortality compared to PC (HR 0.79, p = 0.015).

Patients presenting with cT2N0 gastric adenocarcinoma benefit from chemotherapy in addition to surgery, although a minority of patients received guideline concordant care. Patients who received adjuvant chemotherapy had superior outcomes compared to those who received perioperative chemotherapy. The optimal treatment for cT2N0 gastric cancer should include surgery and chemotherapy, and consideration should be given to a strategy of upfront surgical resection and adjuvant therapy rather than perioperative chemotherapy.