Comparison of the efficacy of neoadjuvant chemotherapy with FLOT regimen and adjuvant chemotherapy with XELOX/FOLFOX regimen in patients with locally advanced gastric cancer: A retrospective study

Background. To date, there is no consensus on the preferred sequence of combined treatment in patients with locally advanced gastric cancer (perioperative chemotherapy – POCT or primary surgical treatment). No direct comparison of these approaches had been conducted before.

Aim. To compare, in retrospective analysis, 3-year relapse-free (RFS) and overall survival (OS) in patients receiving POCT FLOT or adjuvant chemotherapy XELOX/FOLFOX for locally advanced gastric cancer.

Materials and methods. The assessment included 153 patients who underwent POCT FLOT and 171 patients who underwent surgical treatment at the first stage. When evaluating the initial characteristics, it was shown that patients with ECOG (The Eastern Cooperative Oncology Group) stage 1-2, clinical stage cT4a-b, cN2-3 and Bormann type 4 to were significantly more common in the POCT group. Morphological characteristics: grade, presence of signet cell carcinoma, HER2/neu overexpression, microsatellite instability, sensitivity to immunotherapy (Combined Positive Score) didn't differ.

Results. With a median follow-up of 40 months, it was shown that the long-term results assessed in all included patients were better in the group with primary surgical treatment: 3-year RFS was 55 and 40% (risk ratio – RR 1.33, 95% confidence interval – CI 1.08–1.64; р=0.007). 3-year OS was 68 and 56% (RR 1.36, 95% CI 1.02–1.8; р=0.04), respectively. However, when evaluating patients who received surgical treatment in the POCT group (n=121, 79%), the results did not differ: 3-year RFS 55 and 50% (RR 0.9, 95% CI 0.71–1.16; р=0.97), 3-year OS 68 and 63% (RR 1.1, 95% CI 0.84–1.59; р=0.97). Insufficient volume of adjuvant chemotherapy (<75% of the dose) significantly worsened long-term results (3-year OS 43 and 71%; p=0.002).

Conclusion. The obtained data of a retrospective analysis did not reveal the advantages of any of the approaches provided that the surgical stage was performed in patients receiving POCT. To obtain more objective results, it is necessary to conduct randomized multicenter studies in the high volume centers, providing the necessary sample capacity, quality of diagnosis and treatment. Thus, the design of future studies should be based on the hypothesis of non-inferiority, which inevitably entails a significant increase in the required number of observations to obtain reliable sampling power.