Pattern of recurrence and overall survival in esophagogastric cancer after perioperative FLOT and clinical outcomes in MSI-H population: the PROSECCO Study
Floriana Nappo, Lorenzo Fornaro, Luca Pompella, Silvia Catanese, Daniele Lavacchi, Andrea Spallanzani, Alessandro Cappetta, Marco Puzzoni, Sabina Murgioni, Giulia Barsotti, Giuseppe Tirino, Antonio Pellino, Caterina Vivaldi, Antonia Strippoli, Giuseppe Aprile, Samantha Di Donato, Elena Mazza, Michele Prisciandaro, Lorenzo Antonuzzo, Vittorina Zagonel, Stefano Cascinu, Ferdinando De Vita, Sara Lonardi
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.