Colorectal cancer staging and adjuvant chemotherapy

Abstract

Colorectal cancer is a significant cause of morbidity and mortality in Western populations. The standard of care for staging patients with colorectal cancer to determine prognosis and identify patients who will receive adjuvant therapy continues to be histopathology of regional lymph nodes. However, the significant variability in survival within each staging category likely reflects the heterogeneity of detecting micrometastatic disease employing this technique. Novel molecular markers of micrometastases currently in development will permit more accurate staging of patients with colorectal cancer. These advances in staging will distinguish patients who will maximally benefit from adjuvant therapy from those who have an especially good prognosis in whom chemotherapy can be avoided. In addition, new adjuvant chemotherapeutic agents, novel combinations of those agents and creative dosing schedules currently being investigated will offer considerable advantages with respect to ease of administration, safety and tolerability, quality of life and efficacy. Ultimately, it is anticipated that advances in molecular diagnostics will define unique biochemical characteristics of patients' tumours, permitting individualization of chemotherapeutic regimens employing novel agents that specifically exploit those characteristics.

Guanylyl cyclase C is a marker of intestinal metaplasia, dysplasia, and adenocarcinoma of the gastrointestinal tract

“…The most important determinant for predicting survival in patients with colorectal cancer is the presence of tumor cells in regional lymph nodes and evaluation of those nodes for metastatic disease is a central component of all colorectal cancer staging schema [2]. Cancer stage at diagnosis not only determines prognosis, but also guides selection of patients to receive adjuvant chemotherapy [2].…”

“…Cancer stage at diagnosis not only determines prognosis, but also guides selection of patients to receive adjuvant chemotherapy [2]. Despite the critical importance of lymph node involvement, sensitive and specific techniques to assess regional lymph node micrometastases are lacking.…”

“…Gastrointestinal (GI) cancers, including adenocarcinomas of the esophagus, stomach, colon, and rectum, continue to be major causes of cancer-related mortality worldwide [1,2]. In part, mortality reflects unrecognized advanced disease at the time of staging, associated with occult metastases that escape detection by routine histopathology [3].…”

Molecular Staging Estimates Occult Tumor Burden in Colorectal Cancer

“…Indeed, the heterogeneity of therapeutic benefit in pN0 patients may reflect a contribution of inaccurate staging [4,5,21,24,[43][44][45]. In our prospective trial [45], GUCY2C qRT-PCR identified a subset of pN0 patients whose clinical outcomes matched that of stage III patients, staged by established criteria.…”

“…This uncertainty of therapeutic 8 benefit is reflected in the evolution of treatment guidelines, in which adjuvant therapy is optional in pN0 patients with clinicopathologic characteristics suggesting poor prognostic risk [9,[40][41][42]. Heterogeneous responses to therapy in pN0 patients reflect, in part, the variability of occult lymph node metastases [4,5,21,24,[43][44][45]. Consequently, there is an unmet clinical need for better methods that detect prognostic occult nodal metastases, to identify pN0 patients who could benefit from adjuvant therapy [6,38] and who are candidates for pharmacogenomic testing to identify critical mutations defining responses to molecular targeted agents [46].…”