Does Preoperative Chemoradiotherapy Improve Survival in Resectable Gastric Cancer?

The role of radiation therapy in the preoperative management of esophagogastric adenocarcinoma is the subject of ongoing debate. In esophageal and gastroesophageal junction (GEJ) adenocarcinoma, the NEO-AEGIS trial indicated equipoise for preoperative chemotherapy with ECF (epirubicin, cisplatin, 5-FU) versus preoperative chemoradiotherapy with carboplatin/paclitaxel (NEJM JW Oncol Hematol October 20 2023 and Lancet Gastroenterol Hepatol 2023; 8:1015), and the recent ESOPEC trial indicated superiority of perioperative FLOT (5-FU, leucovorin, oxaliplatin, and docetaxel) over preoperative chemoradiotherapy with carboplatin/paclitaxel.

Investigators now report results of the open-label, randomized, phase 3 TOPGEAR trial in 574 patients with resectable gastric (65%) or GEJ (35%) adenocarcinoma, comparing preoperative chemotherapy to a sequence of preoperative chemotherapy followed by 4500 cGy of radiotherapy with concurrent capecitabine or fluorouracil, followed in all patients by surgery and adjuvant chemotherapy. Tumor stage was T3 or T4 in 88% of patients, and 62% had positive or unknown clinical node status. Two thirds were treated with ECF or ECX (epirubicin, cisplatin, capecitabine) and one third with FLOT.

At a median follow-up of 67 months, overall survival, the primary outcome, did not differ significantly between the preoperative chemotherapy/chemoradiotherapy and preoperative chemotherapy groups (median, 46 and 49 months; hazard ratio for death, 1.05). Progression-free survival also did not differ between groups (median, 31 and 32 months, respectively; HR for progression or death, 0.98). Curative resection rates with the two approaches were also similar (92% and 88%, respectively), as were rates of serious adverse events and surgical complications. Pathologic complete response was more frequent with chemotherapy/chemoradiotherapy (17%) than with chemotherapy (8%).