Does Timing Matter? Impact of Time to Surgery on Pathologic Response in Gastric Cancer Patients Treated with...

Background and Objectives: The optimal timing of surgery after preoperative fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) chemotherapy (ChT) in gastric cancer (GC) remains unclear. We aimed to evaluate the association between time to surgery (TTS) and pathological as well as survival outcomes in patients treated with perioperative FLOT. Materials and Methods: This retrospective cohort study included 76 patients with locally advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who underwent curative-intent surgery after preoperative FLOT at a single tertiary center. TTS was defined as the interval between completion of preoperative FLOT and surgery. Patients were categorized into two groups according to TTS: ≤4 weeks and >4 weeks. Pathological response (PR) was assessed using the Becker tumor regression grading system. The primary endpoint was PR, including tumor regression grade and pathological complete response (pCR). Secondary endpoint was overall survival (OS). Results: The median TTS was 31 days (IQR, 21-47). Forty-five (59.2%) patients underwent surgery within 4 weeks. Favorable PR was more frequently observed in the ≤4-week group. Becker TRG 0-1 was significantly more common among patients undergoing surgery within 4 weeks compared with those undergoing surgery after more than 4 weeks (26.2% vs. 6.5%, p = 0.03). Similarly, pCR was observed exclusively in the ≤4-week group (14.3% vs. 0%, p = 0.02). ypN0 status was numerically higher in the ≤4-week group (54.7% vs. 32.2%, p = 0.05). Postoperative complication rates did not differ significantly between groups (4.8% vs. 12.9%, p = 0.17). In multivariable Cox regression analysis, TTS was not independently associated with OS, whereas poor tumor differentiation remained an independent predictor of worse survival (HR 2.57, 95% CI 1.17-5.63, p = 0.01). Conclusions: Among patients treated with preoperative FLOT, surgery within 4 weeks was associated with improved PR without an apparent increase in postoperative morbidity. However, earlier surgery was not independently associated with improved OS. These findings suggest that prolonged delay after preoperative FLOT may not be necessary in clinically recovered patients and support the need for prospective multicenter studies to define the optimal surgical interval in FLOT-treated GC.