The second independent validation study to test the prognostic value of the gene signature test ColoPrint has found that it can effectively identify patients with localized stage II colon cancer at high risk of recurrence. Researchers also found that ColoPrint was the only factor able to indicate the risk for development of distant metastasis with statistical significance. The German study of 135 patients with stage II colon cancer, who were followed for a median of 97 months, was presented at the 2011 Gastrointestinal Cancers Symposium in San Francisco.¹

ColoPrint is a microarray-based diagnostic test in which the genetic profiles of colorectal tumors are analyzed for expression of 18 colon cancer recurrence-specific genes. The expression profile of these recurrence-specific genes from a given tumor is compared to those from a reference population. Hundreds of "normal" genes are used to control the quality of each test. In this way, ColoPrint determines a score that indicates whether a patient's tumor is at high or low risk for recurrence.

Study Specifics

In the German study, investigators examined tumor tissue from patients who underwent surgical resection for stage II colorectal cancer from 1987 to 2003 at the University Hospital in Munich. ColoPrint effectively identified patients at higher risk of recurrence, according to senior author Robert Rosenberg, MD, an Assistant Professor at the University Hospital of the Technical University in Munich, Germany.

Among the 135 patients whose tumors were analyzed, 74% were characterized as low risk, and just 5% experienced a recurrence within 5 years or more. By contrast, 27% of patients in the study received a high-risk score, and 20% within this group experienced a recurrence after 5 years. The 5-year distant metastasis-free survival rate among patients characterized by ColoPrint as low risk was 94.9% and among those identified as high risk was 80.5%. The hazard ratio for distant metastases among high-risk patients was 4.1 when compared to low-risk patients (P = .009).

"Our results confirm previous validation studies on ColoPrint. The test was able to predict the development of distant metastasis in stage II colon cancer patients and those at low risk of recurrence, which facilitates the identification of patients who may not need chemotherapy," Dr. Rosenberg said.

'Compelling Results'

When the researchers compared the utility of ColoPrint to relevant clinical and histopathologic factors such as age, localization of tumor, grade, tumor stage, MSI status, and number of assessed lymph nodes (as used in the ASCO risk recommendations), the gene signature test was the only prognostic feature significantly associated with development of distant metastasis.

"We used the ASCO recommendations as our guideline, and while these factors indicate a difference in distant metastasis-free survival between patients assessed as having low vs high clinical risk, these parameters did not reach statistical significance," Dr. Rosenberg said.

When the ColoPrint test scores and assessments of ASCO predictive clinical parameters were compared in multivariate analysis, the results were discordant for 50% of patients in the study. "These are very compelling results," Dr. Rosenberg said. "There is certainly overlap between ColoPrint and ASCO results, but still there's a large discordance in identification of high-risk patients," he said.

International Research

ColoPrint was developed by researchers who searched the entire genome for genes that had the highest correlation to a relapse event. The training set was established by three Dutch institutes, led by the Netherlands Cancer Institute, who worked with Agendia, the company that developed ColoPrint and the FDA-approved MammaPrint test for breast cancer recurrence.

An initial clinical validation study on ColoPrint was conducted in Barcelona and recently published in the Journal of Clinical Oncology,² and a third validation study is currently underway in the United States. The Prospective Analysis of Risk Stratification by ColoPrint study, which will enroll 600 patients with stage II colon cancer from U.S., Asian, and European medical centers, will examine the accuracy of ColoPrint test results in predicting risk of relapse over 3 years compared to clinical prognostic factors. "It will be interesting to see how we might be able to combine ColoPrint results with clinical factors to identify high-risk patients," Dr. Rosenberg said.

"Our aim was to validate the genomic profile developed to identify high-risk patients with stage II colon cancer using ColoPrint, because we believe this group is not very precisely defined," he added. ■

Reference

1. Rosenberg R, Maak M, Simon I, et al: Independent validation of a prognostic genomic profile (ColoPrint) for stage II colon cancer patients. Gastrointestinal Cancers Symposium. Abstract 358. Presented January 22, 2011.

2. Salazar R, Roepman P, Capella G, et al: Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. J Clin Oncol 29(1):17-24, 2011.

Financial disclosure: No potential conflicts of interest were reported by Robert Rosenberg, MD, and Jennifer Obel, MD.