PD-012 - Validation study of the 12-gene Recurrence Score (RS) in patients (pts) with stage II and III colon cancer (CC) without adjuvant chemotherapy; SUNRI...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Colon and Rectal Cancer
Pathology/Molecular Biology
Basic Scientific Principles
Presenter M. Ikeda
Citation Annals of Oncology (2015) 26 (suppl_4): 101-107. 10.1093/annonc/mdv234
Authors M. Ikeda1, A. Ohtsu2, T. Nishina3, T. Kato4, K. Muro5, E. Oki6, K. Yamaguchi7, T. Yamanaka8, K. Yamazaki9, T. Kusumoto10, H. Uetake11, T. Sato12, A. Kanazawa13, C. Chao14, T. Maddala14, J. Krishnakumar14, K. Akagi15, A. Ochiai16, Y. Ohashi17, T. Yoshino18
  • 1Osaka National Hospital, Osaka/JP
  • 2National Cancer Center, Kashiwashi/JP
  • 3National Shikoku Cancer Center, Matsuyama/JP
  • 4Dept of Surgery, Amagasaki/JP
  • 5Aichi Cancer Center Hospital, Nagoya/JP
  • 6Kyushu University, Fukuoka/JP
  • 7Saitama Cancer Center, Kita-adachi-gun/JP
  • 8Yokohama City University School of Medicine, Yokohama/JP
  • 9Shizuoka Cancer Center, Sunto-gun/JP
  • 10National Kyushu Medical Center, Fukuoka/JP
  • 11Tokyo Medical and Dental University, Tokyo/JP
  • 12Kitasato University School of Medicine, Sagamihara/JP
  • 13The Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka/JP
  • 14Genomic Health Inc., Redwood City/US
  • 15Saitama Cancer Center, Kitaadachi-Gun/JP
  • 16National Cancer Center, Tokyo/JP
  • 17Chuo University, Tokyo/JP
  • 18National Cancer Center Hospital East, Kashiwa-city/JP



The 12-gene RS is validated for stage II surgery alone and stage II & III chemotherapy-treated CC pts as a predictor of recurrence. We conducted a prospective analysis to perform a confirmatory study of RS to predict recurrence in stage II & III CC pts treated with surgery alone. This is the first validation study of RS in Asian pts and in stage III CC pts treated with surgery alone.


We identified consecutive stage II & III CC pts with complete resection without adjuvant chemotherapy at 12 hospitals from 2000-05. A cohort sampling design was used with a recurrence and non-recurrence sampling of 1:2. Gene expression was analyzed by RT-PCR using fixed primary tumor tissue. Mismatch repair (MMR) status was assessed by IHC for MLH1 and MSH2. Primary aims: prognostic value of continuous RS alone and in presence of conventional clinical/pathologic variables. Weighted Cox regression models were used.


630 pts (210 recurrences) were sampled from 1,487 eligible pts. Of 624 with available samples, RT-PCR succeeded in 597 (96%): stage II/III, 41/59%; male, 53%; age > 70 years, 33%; MMR-deficient, 5%; nodes examined < 12, 20%. Continuous RS was associated with recurrence-free interval after adjustment for stage (HR/25 units, 2.05; 95%CI, 1.47–2.86; p < 0.001) and in a pre-specified analysis with stage, T-stage, and MMR (HR, 1.92; 95%CI, 1.35–2.72; p < 0.001). 5-year recurrence risk estimates from the primary analysis model are shown below. Continuous RS was associated (all p < 0.001) with recurrence-free, disease-free, and overall survival: (HR/25 units) 1.77, 1.90 and 2.02, respectively.


RS predicts recurrence risk in stage II and III CC pts with surgery alone, providing information beyond conventional factors. Results reconfirm RS as a prognostic marker in resectable colon cancer and establish clinical validity of RS in Asian pts. Study ID: UMIN000009395.

Table: PD-012