The clinicopathological and genetic differences among gastric cancer patients with no recurrence, early recurrence and late recurrence after curative surgery

Abstract

Background: To date, few reports have investigated the genetic alterations and clinicopathological features among gastric cancer (GC) patients with no tumor recurrence, early recurrence, and late recurrence following curative surgery. Methods: A total of 473 GC patients undergoing curative surgery were included. The clinicopathological characteristics, patient prognosis, recurrence patterns, and genetic alterations were compared between GC patients with early recurrence and late recurrence.Results: Among the 473 GC patients, 119 had early recurrence (<2 years) and 45 had late recurrence (≥2 years). Patients with early recurrence had tumor size larger than 5 cm, fewer superficial-type tumors, more lymphovascular invasion, more advanced pathological T and N categories and Tumor, Node, Metastasis (TNM) stages, and worse 5-year overall survival than patients with late recurrence and no recurrence. For intestinal-type GC, patients with no tumor recurrence had more Helicobacter pylori infection than patients with early recurrence and late recurrence; for diffuse-type GC patients, the frequency of PIK3CA amplification was the highest in early recurrence, followed by late recurrence and no recurrence. GC patients with single-site recurrence had more ARID1A mutations than those with multiple-site recurrence. Multivariate analysis demonstrated that age, tumor recurrence, and pathological N categories were independent prognostic factors. Conclusion: PIK3CA amplifications were more common in diffuse-type GC with early recurrence, whereas ARID1A mutations were more common in patients with single-site recurrence. Targeted therapy and immunotherapy might be helpful for these patients.

Molecular pathology-integrated clinicopathological prognostic factors

“…The article published in the January issue of the Journal of the Chinese Medical Association entitled "The clinicopathological and genetic differences among gastric cancer patients with no recurrence, early recurrence, and late recurrence after curative surgery" attempted to explore this topic, since the authors' enrolled subjects belonged to complete resection of tumors and all of them received the curable surgery claimed by authors. 12 The authors enrolled 473 patients with gastric cancer (GC) undergoing curative surgery to investigated the impact of genetic alterations and clinicopathological features on disease-free survival (DFS) and overall survival (OS) in these GC patients. 12 DFS was classified as no recurrence, early recurrence (defined by < 2 years) and late recurrence (defined by ≥ 2 years).…”

“…None of evaluated molecular pathological parameters, such as microsatellite instability (MSI), Helicobacter pylori (HP), Epstein-Bar virus (EBV), and genetical mutations (PI3K/AKT pathway, TP53, ARID1A, and B-Raf proto-oncogene [BRAF]) were useful in the prediction of DFS and OS, and by contrast, only conventional clinicopathological parameters, such as elder population (≥ 65 years), and pathological N (lymph node) category were involved in the OS. 12 Therefore, subgroup analysis was conducted and finally, the authors found the potential role of PIK3CA amplifications and ARID1A mutations may be related to the certain-type outcomes, such as early recurrence as well as single-site recurrence, respectively. 12 Recently, technological improvement, the better understanding of tumorigenesis, the continuous innovation of targeted therapy and chemotherapy regimens, the spread of advanced development of surgery and multidisciplinary decision-making have directed patient-tailored strategies, with the aim of improvement of DFS and OS.…”

“…12 Therefore, subgroup analysis was conducted and finally, the authors found the potential role of PIK3CA amplifications and ARID1A mutations may be related to the certain-type outcomes, such as early recurrence as well as single-site recurrence, respectively. 12 Recently, technological improvement, the better understanding of tumorigenesis, the continuous innovation of targeted therapy and chemotherapy regimens, the spread of advanced development of surgery and multidisciplinary decision-making have directed patient-tailored strategies, with the aim of improvement of DFS and OS. 9 Among them, a better understanding of tumorigenesis, genetic and epigenetic alternations may provide a brand-new therapeutic approach by developing many uniform and targeted or specific agents in the management of cancer patients when cancer treatment has reached to the plateau.…”

“…9 Among them, a better understanding of tumorigenesis, genetic and epigenetic alternations may provide a brand-new therapeutic approach by developing many uniform and targeted or specific agents in the management of cancer patients when cancer treatment has reached to the plateau. 2,[13][14][15] Dr Chen's suggestions 12 as targeted therapy and immunotherapy for specific subtypes of GC patients echoed Dr Grothey's mention 15 in 2020, who reported that nothing has changed cancer therapy more in the past 5 to 10 years than the application of immune checkpoint inhibitors, since MSI-H (high)-deficient mismatch repair (dMMR) cancers are sensitive to treatment with immune checkpoint inhibitors, such as programmed death 1 (PD-1) antibodies, with or without adding cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) antibodies with longer durability of response, better safety profile, and improved quality of life associated with immune checkpoint inhibitor treatment compared with chemotherapy making immune checkpoint inhibitors the preferred choice in these MSI-H-dMMR colorectal cancer patients. The aforementioned mention emphasized the importance in using biomarkers (molecular pathology) to identify the specific genetic/epigenetic alternations of cancers to give a uniform therapy, such as targeted therapy or immunotherapy to these cancer patients, which is also claimed by Dr Chen's group.…”

“…The aforementioned mention emphasized the importance in using biomarkers (molecular pathology) to identify the specific genetic/epigenetic alternations of cancers to give a uniform therapy, such as targeted therapy or immunotherapy to these cancer patients, which is also claimed by Dr Chen's group. 12 Furthermore, the benefits of targeted therapy and immunotherapy is limited to particular population with specific genetic/ epigenetic alternations, and by contrast, its value can be extended to the general population. A recent study 309-KEYNOTE-775 showed that even though proficient MMR (pMMR) endometrial cancer (EC) patients may have taken advantages of progression-free survival (PFS) and OS under the immune checkpoint inhibitors plus multikinase inhibitors (Lenvatinib as an example) treatment than with chemotherapy (6.6 vs 3.8 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.50-0.72 and 17.4 vs 12.0 months; HR, 0.68; 95% CI, 0.56-0.84, respectively).…”