Pattern of recurrence and overall survival in esophagogastric cancer after perioperative FLOT and clinical outcomes in MSI-H population: the PROSECCO Study

Abstract

Background FLOT regimen is the standard perioperative treatment in Western countries for patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC). High microsatellite instability (MSI-H) and Mismatch Repair deficient (dMMR) demonstrated a favorable prognostic role and a concomitant negative predictive impact on the benefit of perioperative 5-fluorouracil-based doublets; however, its role in pts receiving FLOT chemotherapy is still unclear. Methods This is a retrospective, multicenter observational study of 265 pts with GC/GEJC treated with perioperative FLOT regimen in 11 Italian oncology centers between January 2017 to December 2021 and analyzed for microsatellite status. Results The MSI-H phenotype was found in 27 (10.2%) of 265 analyzed tumors. Compared to microsatellite stable (MSS) and Mismatch Repair proficient (pMMR) cases, MSI-H/dMMR were more frequently female (48.1% vs. 27.3%, p = 0.0424), elderly pts (age > 70 years, 44.4% vs. 13.4%, p = 0.0003), Laurens’s intestinal type (62.5% vs. 36.1%, p = 0.02) and pts with a primary location tumor in the antrum (37 vs. 14.3%, p = 0.0004). A statistically significant difference in the rate of pathologically negative lymph node emerged (63% vs 30.7%, p = 0.0018). Compared to the MSS/pMMR tumor population, the MSI-H/dMMR subgroup had a better DFS (median not reached [NR] vs. 19.5 [15.59–23.59] mos, p = 0.031) and OS (median NR vs. 34.84 [26.68–47.60] mos, p = 0.0316). Conclusions These real-world data confirm that FLOT treatment is effective in daily clinical practice for locally advanced GC/GEJC, also in the MSI-H/dMMR subgroup. It also showed a higher rate of nodal status downstaging and a better outcome of MSI-H/dMMR pts in comparison to MSS/pMMR.

Microsatellite instability and sex-specific differences of survival in gastric cancer after neoadjuvant chemotherapy without and with taxane: An observational study in real world patients

“…Similar to our results, an Italian group demonstrated that MSI-H was a positive prognostic marker in perioperatively FLOT-treated patients (Giommoni et al 2021). In addition, in the multicenter, retrospective PRO-SECCO study, the outcome of patients with MSI-H was remarkably better than that of patients with MSS after treatment according to the FLOT protocol (Nappo et al 2023). Furthermore, preliminary results of the DANTE study analyzing FLOT in comparison with FLOT and atezolizumab showed high rates of pathological tumor regression in MSI patients, with the current restriction that survival data are not yet available, and translation of pathological complete response into improved survival of the patients has to be shown (Al-Batran et al 2022).…”

Case Report: The molecular fingerprint and the clinical implication of an exceptional response to neoadjuvant therapy in a metastatic cardia adenocarcinoma

“…The FLOT or FOLFOX scheme is currently the recommended first-line therapy to improve the OS in cases of locally advanced HER2-negative CA ( 6 , 15 ). In addition, high microsatellite instability (MSI-H) and Mismatch Repair deficient (dMMR) tumors appear to be favorable prognostic factors ( 16 ), both in terms of nodal status and downstaging ( 17 , 18 ).…”

Use of Chemoimmunotherapy for Locally Advanced Deficient Mismatch Repair (dMMR) Gastric Adenocarcinoma With Curative Intent: A Case Report

“…Furthermore, individual patient data meta-analysis focused on the value of MSI-H as a biomarker in gastric cancer, not using taxanes, and did not show a benefit of perioperative chemotherapy for patients with MSI-H gastric cancer [ 9 ]. On the contrary, the PROSECCO study based on real-world data suggests that the perioperative FLOT regimen is effective in both MSI-H and microsatellite stability (MSS) localized gastric adenocarcinoma being progression-free and overall survival longer in the MSI-H subgroup [ 10 ].…”