Analytic lymph node number establishes staging accuracy by occult tumor burden in colorectal cancer

Background and Objectives: Recurrence in lymph node-negative (pN0) colorectal cancer suggests the presence of undetected occult metastases. Occult tumor burden in nodes estimated by GUCY2C RT-qPCR predicts risk of disease recurrence. This study explored the impact of the number of nodes analyzed by RT-qPCR (analytic) on the prognostic utility of occult tumor burden. Methods: Lymph nodes (range: 2-159) from 282 prospectively enrolled pN0 colorectal cancer patients, followed for a median of 24 months (range: 2-63), were analyzed by GUCY2C RT-qPCR. Prognostic risk categorization defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk category were defined by multivariable polytomous and semi-parametric polytomous logistic regression. Results: Occult tumor burden stratified this pN0 cohort into categories of low (60%; recurrence rate (RR) = 2.3% [95% CI 0.1-4.5%]), intermediate (31%; RR = 33.3% [23.7-44.1%]), and high (9%; RR = 68.0% [46.5-85.1%], P < 0.001) risk of recurrence. Beyond race and T stage, the number of analytic nodes was an independent marker of risk category (P < 0.001). When >12 nodes were analyzed, occult tumor burden almost completely resolved prognostic risk classification of pN0 patients. Conclusions: The prognostic utility of occult tumor burden assessed by GUCY2C RT-qPCR is dependent on the number of analytic lymph nodes.