Perioperative versus total neoadjuvant chemotherapy in gastric cancer

Background: Perioperative chemotherapy is standard of care management for locally advanced gastric cancer (GC), but a substantial proportion of patients do not complete adjuvant therapy due to postoperative complications and prolonged recovery. Administration of all chemotherapy prior to surgery in the form of total neoadjuvant therapy (TNT) may optimize complete delivery of systemic therapy. Methods: We performed a retrospective review of GC patients who had surgery at Memorial Sloan Kettering Cancer Center (MSKCC) from May 2014 to June 2020. Results: One hundred and forty-nine patients were identified; 121 patients received perioperative chemotherapy and 28 patients received TNT. TNT was chosen if patients had interim radiographic and/or clinical response to treatment. Baseline characteristics were well-balanced between the two group except for chemotherapy regimen; more TNT patients received FLOT compared to the perioperative group (79% vs. 31%). There was no difference in the proportion of patients who completed all planned cycles, but TNT patients received a higher proportion of cycles containing all chemotherapy drugs (93% vs. 74%, P<0.001). Twenty-nine patients (24%) in the perioperative group did not receive intended adjuvant therapy. There was no significant difference in hospital length of stay or surgical morbidity. The overall distribution of pathologic stage was similar between the two groups. Fourteen percent of TNT patients and 5.8% of perioperative patients achieved a pathologic complete response (P=0.6). There was no significant difference in recurrence free survival (RFS) or overall survival (OS) between the TNT and perioperative groups [24-month OS rate 77% vs. 85%, HR 1.69 (95% CI: 0.80-3.56)]. Conclusions: Our study was limited by a small TNT sample size and biases inherent to a retrospective analysis. TNT appears to be feasible in a select population, without any increase in surgical morbidity.