Molecular testing for lymph node metastases as a determinant of colon cancer recurrence: results from a retrospective multicenter study
Menée sur 366 patients atteints d'un cancer du côlon de stade T3N0, cette étude évalue l'intérêt de mesurer les niveaux d'ARN messager de guanylate cyclase C dans les ganglions lymphatiques pour prédire le risque de récidive
Background: Recurrence risk assessment to make treatment decisions for early stage colon cancer patients is a major unmet medical need. The aim of this retrospective multicenter study was to evaluate the clinical utility of guanylyl cyclase C (GCC) mRNA levels in lymph nodes on colon cancer recurrence.
Methods: The proportion of lymph nodes (LN) with GCC positive mRNA (LNR) was evaluated in 463 untreated T3N0 patients, blinded to clinical outcomes. One site's (n=97) tissue grossing method precluded appropriate LN assessment resulting in post hoc exclusion. Cox regression models tested the relationship between GCC and the primary endpoint of time to recurrence (TTR). Assay methods, primary analyses, and cut-points were all pre-specified.
Findings: Final data set contained 366 patients, 38 (10%) of whom had recurrence. Presence of 4 or more GCC-positive LNs was significantly associated with risk of recurrence (HR=2.46, 95% CI: 1.07-5.69, p=0.035), while binary GCC LNR risk class (HR=1.87, 95% CI: 0.99-3.54, p=0.054) and MMR status (HR=0.77, 95% CI: 0.36-1.62, p=0.49) were not. In a secondary analysis using a 3-level GCC LNR risk group classification of high (LNR>0.20), intermediate (0.10<LNR≤0.20) and low (LNR≤0.10), high risk patients had a 2.5 times higher recurrence risk compared to low risk patients (HR=2.53, 95% CI: 1.24-5.17, p=0.011).
Interpretation: GCC status is a promising prognostic factor independent of traditional histopathology risk factors in a contemporary population of stage IIa colon cancer patients not treated with adjuvant therapy, but GCC determination must be performed with methodology adapted to the tissue procurement and fixation technique.
Clinical Cancer Research , résumé, 2014