Clinical significance of microsatellite instability for stage II or III colorectal cancer following adjuvant therapy with doxifluridine.
Microsatellite instability (MSI) is a molecular marker that can provide valuable prognostic information for colorectal cancer (CRC). However, the predictive role of the MSI status remains less clear than its role in prognostication due to mixed results from previous studies. Therefore, this study investigated the usefulness of the MSI status as a predictive factor for stage II or III CRC patients who received adjuvant doxifluridine therapy. Among 3030 patients with CRC who underwent surgical resection between 1997 and 2006, 564 patients were diagnosed with stage II or III, and adjuvant doxifluridine therapy was administered to 394 patients (70.0%). The MSI status was assessed using the markers BAT25 and BAT26, and samples with instability at both markers were scored as exhibiting high-frequency MSI (MSI-H). Among the 564 patients, 290 patients (51.4%) had stage II, and MSI-H was found in 41 patients (7.3%). With a median follow-up duration of 35.1 months (range, 0.5-135.2), the 5-year overall survival (OS) rate and relapse-free survival (RFS) rate were 87.5 and 76.2%, respectively. MSI-H showed a favorable survival trend for OS (P = 0.098) and significant survival benefit for RFS (P = 0.037) in all patients. In a univariate analysis, the doxifluridine-treated patients with MSI-H showed improved RFS compared to those with low or stable MSI (MSI-L/S) (P = 0.036), while the MSI status was not significantly associated with OS (P = 0.107). In a multivariate analysis, MSI-H was not significantly associated with RFS (Hazard ratio = 2.467, P = 0.125). In conclusion, this study confirmed the positive prognostic role of MSI-H. However, MSI-H patients with stage II or III CRC did not seem to benefit from doxifluridine adjuvant therapy.
Kang
Byung Woog
BW
Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 200 Dongduk-Ro, Daegu, Jung-Gu 700-712, South Korea.
Kim
Jong Gwang
JG
Lee
Soo Jung
SJ
Chae
Yee Soo
YS
Moon
Joon Ho
JH
Sohn
Sang Kyun
SK
Jeon
Seong Woo
SW
Jung
Min Kyu
MK
Lim
Kyoung-Hoon
KH
Jang
You Seok
YS
Park
Jun Seok
JS
Jun
Soo Han
SH
Choi
Gyu-Seog
GS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D053842:Microsatellite Instability / Q000187:drug effects; D008875:Middle Aged; D009367:Neoplasm Staging; D055815:Young Adult
D005467:Floxuridine; C025034:doxifluridine