Occult tumor burden contributes to racial disparities in stage‐specific colorectal cancer outcomes

Abstract

Background There are differences in outcomes in blacks, compared to whites, with lymph node-negative (pN0) colorectal cancer. Recurrence in pN0 patients suggests the presence of occult metastases undetected by conventional approaches. This study explores the association of racial differences in outcomes with occult tumor burden in regional lymph nodes. 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 subjected to molecular analysis. Occult tumor burden was estimated by quantifying the expression of the biomarker GUCY2C, a biomarker for metastatic colorectal cancer cells. Risk categories defined using occult tumor burden was the primary outcome measure. Association of prognostic variables and risk were defined by multivariate polytomous logistic regression. Results Occult tumor burden stratified this cohort of 259 whites and 23 blacks into categories with 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. Blacks, compared to whites, exhibited 4-fold greater occult metastases in individual nodes (p<0.001). Multivariate analysis revealed that race (p=0.02), T stage (p=0.02), and number of nodes collected (p=0.003) were independent prognostic markers of risk category. Blacks, compared to whites, were more likely to harbor levels of occult tumor burden, associated with the highest recurrence risk (adjusted odds ratio=5.08 [1.69-21.39]; p=0.007). Conclusions Racial disparities in stage-specific outcomes in colorectal cancer are associated with differences in occult tumor burden in regional lymph nodes.

Lymph Node Yield in Colon Cancer: Individuals Can Make the Difference

“…Studies have identified multiple factors associated with higher LNY such as patient characteristics (age, sex, ethnicity), macroscopic characteristics (tumour size and location) and microscopic traits (differentiation grade, tumour invasion) [9,11]. …”

GUCY2C Molecular Staging Personalizes Colorectal Cancer Patient Management

“…In that context, prospective evaluation of the utility of GUCY2C to detect occult metastases in lymph provided a unique opportunity to explore the racial distribution of occult tumor burden and its association with prognostic risk in colorectal cancer [42,101]. Analysis of GUCY2C expression in this cohort revealed a fourfold greater level of categorical occult metastases in individual nodes in 23 black patients compared with 259 white patients (p < 0.001; 95% CI: 3.3–6.7).…”

“…Black patients, compared with white patients, were more likely to harbor levels of occult tumor burden associated with the highest risk (adjusted odds ratio = 5.08 [95% CI: 1.55–16.65]; p = 0.007). These analyses highlight the utility of occult tumor burden quantified by GUCY2C RT-qPCR as a marker of tumor metastases that estimates prognostic risk contributing to racial disparities in stage-specific outcomes in colorectal cancer [101]. Beyond prognostic risk, they suggest that if occult tumor burden predicts therapeutic benefit, it represents a detect–treat paradigm that could reduce racial disparities in mortality in colon cancer.…”

“…Furthermore, occult tumor burden across the regional lymph node network stratified pN0 patients into cohorts with low, intermediate and high risk [90]. Moreover, differences in occult tumor burden contribute to racial disparities in stage-specific outcomes in colon cancer [101]. This prospective clinical trial represents the first level I evidence supporting the importance of occult metastases in regional lymph nodes in defining prognostic risk in patients with colon cancer.…”

“…This heterogeneity of therapeutic benefit in node-negative patients may in part reflect the inherent inaccuracy of staging by histopathology [1,4,20,23,40–42]. By contrast, molecular staging has identified node-negative patients with a prognostic risk profile that closely matched stage III patients, a cohort that derives benefit from adjuvant chemotherapy [42,90,101]. These observations suggest that pN0 patients who harbor occult metastases detected by molecular staging could also benefit from adjuvant chemotherapy.…”