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

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 9; pp. 6601 - 6611
• Main Authors: Nappo, Floriana, Fornaro, Lorenzo, Pompella, Luca, Catanese, Silvia, Lavacchi, Daniele, Spallanzani, Andrea, Cappetta, Alessandro, Puzzoni, Marco, Murgioni, Sabina, Barsotti, Giulia, Tirino, Giuseppe, Pellino, Antonio, Vivaldi, Caterina, Strippoli, Antonia, Aprile, Giuseppe, Di Donato, Samantha, Mazza, Elena, Prisciandaro, Michele, Antonuzzo, Lorenzo, Zagonel, Vittorina, Cascinu, Stefano, De Vita, Ferdinando, Lonardi, Sara
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2023; Springer Nature B.V
• Subjects: 5-Fluorouracil; Adenocarcinoma - pathology; Cancer Research; Cancer therapies; Chemotherapy; Clinical outcomes; DNA Mismatch Repair; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Female; Gastric cancer; Hematology; Humans; Internal Medicine; Lymph nodes; Lymphatic system; Medical prognosis; Medical research; Medicine; Medicine & Public Health; Microsatellite Instability; Mismatch repair; Mortality; Observational studies; Oncology; Phenotypes; Population studies; Retrospective Studies; Statistical analysis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Surgery; Tumors; Perioperative chemotherapy; FLOT; Gastro-esophageal junction adenocarcinoma; Gastric cancer; Microsatellite instability status
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-023-04636-y

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.