Marlies S Reimers1, Peter J K Kuppen1, Mark Lee1, Margarita Lopatin1, Haluk Tezcan1, Hein Putter1, Kim Clark-Langone1, Gerrit Jan Liefers1, Steve Shak1, Cornelis J H van de Velde2. 1. Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS). 2. Department of Surgery (MSR, PJKK, GJL, CJHvdV) and Department of Medical Statistics (HP), Leiden University Medical Center, Leiden, the Netherlands; Genomic Health Inc., Redwood City, CA (MLe, MLo, HT, KCL, SS). c.j.h.van_de_Velde@lumc.nl.
Abstract
BACKGROUND: The 12-gene Recurrence Score assay is a validated predictor of recurrence risk in stage II and III colon cancer patients. We conducted a prospectively designed study to validate this assay for prediction of recurrence risk in stage II and III rectal cancer patients from the Dutch Total Mesorectal Excision (TME) trial. METHODS: RNA was extracted from fixed paraffin-embedded primary rectal tumor tissue from stage II and III patients randomized to TME surgery alone, without (neo)adjuvant treatment. Recurrence Score was assessed by quantitative real time-polymerase chain reaction using previously validated colon cancer genes and algorithm. Data were analysed by Cox proportional hazards regression, adjusting for stage and resection margin status. All statistical tests were two-sided. RESULTS:Recurrence Score predicted risk of recurrence (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.11 to 2.21, P = .01), risk of distant recurrence (HR = 1.50, 95% CI = 1.04 to 2.17, P = .03), and rectal cancer-specific survival (HR = 1.64, 95% CI = 1.15 to 2.34, P = .007). The effect of Recurrence Score was most prominent in stage II patients and attenuated with more advanced stage (P(interaction) ≤ .007 for each endpoint). In stage II, five-year cumulative incidence of recurrence ranged from 11.1% in the predefined low Recurrence Score group (48.5% of patients) to 43.3% in the high Recurrence Score group (23.1% of patients). CONCLUSION: The 12-gene Recurrence Score is a predictor of recurrence risk and cancer-specific survival in rectal cancer patients treated with surgery alone, suggesting a similar underlying biology in colon and rectal cancers.
RCT Entities:
BACKGROUND: The 12-gene Recurrence Score assay is a validated predictor of recurrence risk in stage II and III colon cancerpatients. We conducted a prospectively designed study to validate this assay for prediction of recurrence risk in stage II and III rectal cancerpatients from the Dutch Total Mesorectal Excision (TME) trial. METHODS: RNA was extracted from fixed paraffin-embedded primary rectal tumor tissue from stage II and III patients randomized to TME surgery alone, without (neo)adjuvant treatment. Recurrence Score was assessed by quantitative real time-polymerase chain reaction using previously validated colon cancer genes and algorithm. Data were analysed by Cox proportional hazards regression, adjusting for stage and resection margin status. All statistical tests were two-sided. RESULTS: Recurrence Score predicted risk of recurrence (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.11 to 2.21, P = .01), risk of distant recurrence (HR = 1.50, 95% CI = 1.04 to 2.17, P = .03), and rectal cancer-specific survival (HR = 1.64, 95% CI = 1.15 to 2.34, P = .007). The effect of Recurrence Score was most prominent in stage II patients and attenuated with more advanced stage (P(interaction) ≤ .007 for each endpoint). In stage II, five-year cumulative incidence of recurrence ranged from 11.1% in the predefined low Recurrence Score group (48.5% of patients) to 43.3% in the high Recurrence Score group (23.1% of patients). CONCLUSION: The 12-gene Recurrence Score is a predictor of recurrence risk and cancer-specific survival in rectal cancerpatients treated with surgery alone, suggesting a similar underlying biology in colon and rectal cancers.