Previstage™ GCC test for staging patients with colorectal cancer

Abstract

The presence of tumor cells in regional lymph nodes is the most important prognostic and predictive marker in staging patients with colorectal cancer. Cancer cells in lymph nodes are associated with a poorer prognosis and an increased risk of recurrent disease. Additionally, nodal metastases identify patients who derive maximum benefit from adjuvant therapy. However, traditional paradigms for staging patients with colorectal cancer underestimate the extent of metastases and patients whose lymph nodes are ostensibly free of tumor cells by histopathology (pN0) have a 25–30% risk of developing recurrent disease, reflected by the presence of occult nodal metastases. These observations underscore the unmet clinical need for molecular approaches to accurately detect metastatic disease and identify patients at risk for disease relapse that could benefit from adjuvant chemotherapy. Detection of disease-specific mRNA targets as prognostic and predictive markers employing quantitative reverse transcription (qRT)-PCR is an emerging technology that has become a benchmark for individualization of patient management. However, to date, applications of qRT-PCR to detecting occult nodal metastases in colorectal cancer have been equivocal, reflecting markers with suboptimal sensitivity and specificity; limitations of utilizing qualitative, rather than quantitative, RT-PCR; and underpowered study designs based on inadequate patient populations. In that context, guanylyl cyclase C (GCC) is the most sensitive and specific biomarker for metastatic colorectal cancer in extra-intestinal tissues. GCC qRT-PCR detects occult metastases in lymph nodes, providing the most powerful independent prognostic information for predicting disease recurrence in pN0 patients in prospective multicenter clinical trials. This technology forms the basis for the Previstage™ GCC Colorectal Cancer Staging Test encompassing a proprietary multiplex qRT-PCR assay compatible with formalin-fixed, paraffin-embedded lymph nodes for detecting occult metastases. Previstage GCC is a new diagnostic tool that may improve the accuracy of staging, prognosis of clinical outcomes and prediction of therapeutic responses to adjuvant therapy, representing a key advance in the management of patients with colorectal cancer.

Keywords::

• colorectal cancer
• guanylyl cyclase C
• lymph node
• metastatic disease
• predictive marker
• prognostic marker
• qRT-PCR
• quantitative reverse transcriptase-polymerase chain reaction
• staging

Financial & competing interests disclosure

This work was supported by funding from the National Institutes of Health (NIH; CA75123, CA95026) and Targeted Diagnostic & Therapeutics, Inc. (to Scott A Waldman). Alex Mejia was enrolled in the NIH-supported institutional K30 Training Program In Human Investigation (K30 HL004522) and was supported by NIH institutional award T32 GM08562 for Postdoctoral Training in Clinical Pharmacology. Scott A Waldman is the Samuel MV Hamilton Endowed Professor. Scott A Waldman is a paid consultant to Merck and is the Chair (uncompensated) of the Scientific Advisory Board of Targeted Diagnostic and Therapeutics, Inc.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.