MSI and gastric cancer. MSI와 위암. EndoTODAY 이준행

[MSI and gastric cancer. MSI와 위암] - 終

1. 2022 KSGA guideline에 언급되었던 내용

Microsatellite instability (MSI) is assessed by polymerase chain reaction (PCR)-based tests, which can be replaced by IHC tests for the 4 MMR proteins (MMR deficient [dMMR]). Instability is examined by PCR of a representative panel of microsatellites. The grade of the instability is determined by the numbers of unstable microsatellites: MSI-H, MSI-low (MSI-L), or microsatellite stable (MSS). MSI-H is considered MSI-positive. In the IHC method, the IHC staining is done for the 4 MMR proteins: MLH1, MSH2, PMS2, and MSH6. When the expression of any one of the MMR proteins is lost, the case is considered to be dMMR. MSI positivity is the criteria for MSI-subtype gastric cancer.
MSI-positive gastric cancer is classified as a separate subtype in the molecular classifications of gastric cancer and shows elevated mutation rates and distinctive patterns of methylation. This subtype has unique clinical characteristics, including distal location, high frequency of intestinal-type histology, lower stage, and good prognosis. In the palliative setting, MSI positivity is an indication for immune checkpoint inhibitor therapy (pembrolizumab).

2. dMMR/MSI-H GC에서 adjuvant chemotherapy가 필요한가에 대한 논란 (2024)

dMMR/MSI-H GC는 상대적으로 예후가 좋고 adjuvant chemotherapy의 효과가 낮고 immune checkpoint inhibitor의 효과가 크기 때문에 adjuvant setting에서 (1) chemotherapy로 adjuvant를 할지, (2) immune checkpoint inhibitor로 adjuvant를 할 지, (3) 아무 것도 하지 않을지 논란이 있습니다.

JGC 2024의 첫 문제제기 (J Gastric Cancer 2024) The Necessity of Guidance: Optimizing Adjuvant Therapy for Stage II/III MSI-H Gastric Cancer Through the Interplay of Evidence, Clinical Judgment, and Patient Preferences

Recent ESMO guideline (Ann Oncol 2022) recommends “Adjuvant (postoperative) chemotherapy should be avoided in resected MSI-H GC". While evidence (J Clin Oncol 2019) suggests that adjuvant chemotherapy may not be beneficial, the clinical dilemma persists owing to the potential for recurrence prevention. Although administering chemotherapy can reduce the risk of recurrence, subjecting patients to ineffective adjuvant chemotherapy may expose them to unnecessary risks and adverse effects. This dilemma lies between the academic and practical decisions for this patient subset. Thus, guidelines must address this issue...

KGCA 가이드라인 팀의 답변 (https://doi.org/10.5230/jgc.2024.24.e40)

In the most recent large-scale meta-analysis including 23 studies (n=22,011; 9.8% MSI-H), (neo)adjuvant chemotherapy did not significantly reduce the risk of death or relapse in patients with MSI-H GC (Ther Adv Med Oncol 2024). Conversely, another recent meta-analysis (Ann Surg Oncol 2022)and retrospective study (Cancer Res Treat 2020) focusing solely on adjuvant chemotherapy for locally advanced dMMR/MSI-H GC suggested that adjuvant chemotherapy is beneficial in terms of OS. Furthermore, more recent evidence supports the use of (neo)adjuvant ICIs, including in patients with dMMR/MSI-H GC, although data on dMMR/MSI-H subgroups in randomized phase 3 trials have not been reported.

[References]

1) EndoTODAY EBV-associated gastric cancer
2) EndoTODAY Gastric carcinoma with lymphoid stroma (GCLS) Lymphoepithelioma-like carcinoma (LELC). 림프양상피종양 암종.