What is the Oncotype DX® Colon Recurrence Score?

Addressing an Unmet Need in the Treatment of Colon Cancer

Colon cancer is the fourth* most prevalent cancer in both men and women in the USA, and the third most common cause of cancer-related deaths. Approximately 28% of patients with colon cancer present with Stage II disease, while 38% present with Stage III disease.

The 12-gene Oncotype DX Colon Recurrence Score is a validated predictor of recurrence risk in both Stage II and Stage III. The Colon Recurrence Score result predicts recurrence risk in stage II and III colon cancer, capturing underlying biology and providing risk information beyond conventional factors

Incorporating the Colon Recurrence Score result into the clinical context may better inform adjuvant therapy decisions for patients with stage II and stage III colon cancer

  • In stage II patients with T3 MMR-P tumors, the Colon Recurrence Score result informs whether additional therapy should be considered beyond surgery
  • In Stage III A/B patients, the Colon Recurrence Score result informs whether the absolute benefit of oxalipatin out weighs the risk of toxicities including, the potential for long term neuropathy

Current NCCN Guidelines™ do not recommend the routine use of adjuvant chemotherapy for all patients with Stage II colon cancer but recommend consideration of adjuvant treatment in the setting of high recurrence risk as determined by clinical and pathologic features. The five-year survival rate for the overall Stage II patient population has been estimated to be 75-80%. Despite these relatively high cure rates with surgery alone, a significant proportion of Stage II patients will recur. Considerable effort has been made to identify markers of risk to distinguish lower risk patients from those at higher risk of colon cancer recurrence who would be candidates for adjuvant chemotherapy for colon cancer.

Unlike in breast cancer, where molecular markers such as ER, PR, and HER2 have been in long-standing clinical use, markers in Stage II colon cancer have been limited to clinical and pathologic parameters. The presence of any of the following features places a patient into a “high risk” category while a patient without these features would be considered “standard risk”:

  • T4 lesions
  • Fewer than 12 lymph nodes examined
  • Presence of bowel perforation or obstruction
  • Poorly differentiated tumors
  • Lymphatic or venous invasion

These parameters are generally qualitative and are not informative for further differentiating risk in standard risk colon cancer patients, who constitute the majority of Stage II colon cancer. In patients with Stage III disease, the NCCN Guidelines™ recommend 6 months of adjuvant chemotherapy following primary surgical treatment

*Jemal A, Center MM, DeSantis C, et al. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 2010; 19: 1893-1907

The Oncotype DX Colon Recurrence Score

The availability of the Oncotype DX Colon Recurrence Score represents another successful application of a unique technology developed by Genomic Health, Inc. that provides an individualized score reflective of the risk of colon cancer recurrence for individual patients with either Stage II or Stage III colon cancer. This quantitative information about recurrence risk, based on the biology of a patient’s specific colon cancer tumor, may help to inform adjuvant treatment decisions.

The Oncotype DX Colon Recurrence Score is a standardized multi-gene reverse transcriptase-polymerase chain reaction (RT-PCR) assay conducted on paraffin-embedded primary colon tumor tissue. This test is performed by Genomic Health in its CLIA-certified, CAP-accredited reference laboratory.

The Oncotype DX Colon Recurrence Score was developed by evaluating 761 colon cancer-related genes in 1,851 patients with resected colon cancer in four large development studies. These development studies led to the definition of the 12-gene panel, including 7 cancer-related genes and 5 reference genes, as well as the Colon Recurrence Score algorithm, which was then prospectively validated in the QUASAR validation study.

Development and Validation

The Oncotype DX Colon Recurrence Score uses Genomic Health’s well-established RT-PCR platform to quantitate the level of expression of all 12 genes in the panel for each patient’s colon cancer tumor sample. For the patient, the test produces a Recurrence Score result, which predicts the risk of recurrence for individuals with Stage II or Stage III colon cancer.

Stage II: The QUASAR validation study results demonstrated that the Colon Recurrence Score result will have the greatest clinical utility when used as a complement to T stage and MMR status, specifically for patients who have T3, MMR-proficient Stage II disease. These patients comprise the majority (approximately 70%) of those with Stage II colon cancer. The QUASAR results have been subsequently confirmed in the CALGB 9581 and NSABP C-07 studies.

Stage II and III: The NSABP C-07 validation study results indicate that the absolute benefit from the addition of oxaliplatin was greater in the high Colon Recurrence Score group than in the low Colon Recurrence Score group.

Colon Cancer Treatment

Through the development of the Oncotype DX Colon Recurrence Score, Genomic Health, as a leader in the field of genomics in cancer, provides a much-needed resource for patients with colon cancer and the physicians who care for them. The results from this test support physicians and patients in their colon cancer treatment decisions. Furthermore, they allow for improved confidence during the decision making process.

“Oncologists have struggled for a long time with the standard risk Stage II patients in large part because the existing markers suffer from lack of reproducibility and supporting evidence. The Oncotype DX Colon Recurrence Score, a rigorously and well validated test, thus represents a significant advance, providing individual recurrence risk information that has not been possible until now. An informed patient is a happy patient and the Colon Recurrence Score result now enables patients to have a more complete picture when deciding on a treatment plan.”

          -Professor David Kerr, MD, University of Oxford

References: 1. Gray R, Quirke P, Handley K, et al. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol.2011; 29 (35):4611-9.
2. Abstract # 3518- Venook A, Niedzwiecki D, Lopatin M, et al. Validation of a 12-gene colon cancer recurrence score in stage II colon cancer patients from CALGB 9581. Presented at the American Society of Clinical Oncology annyal meeting; June 2011; Chicago, IL.
3. O’Connell M, Lavery I, Yother G, et al. Relationship between tumor gene expression and recurrence in four independent studies of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin. J Clin Oncol. 2010;28 (25) :3937-44.
NCCN Guidelines is a trademark of the National Comprehensive Cancer Network. NCCN does not endorse any product or therapy.
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