Evidence It Works

The Colon Recurrence Score test uses Exact Sciences' well-established RT-PCR (reverse transcriptase-polymerase chain reaction) platform to offer individualized, quantifiable risk of recurrence for patients with colon cancer (anatomic stages II, MMR-P or III A/B).^4-7 With this information, you and your patient can more confidently plan a course of treatment based on clinically validated results.

Developing the 12-gene score

The Colon Recurrence Score test was developed in four steps^1-3:

These development studies resulted in a 12-gene panel (seven cancer-related genes and five reference genes)—as well as the Colon Recurrence Score algorithm, which is validated in several studies.^4-7

The Oncotype DX Colon Recurence Score 12-Gene Panel

About the studies

The Recurrence Score result showed a consistent and significant relationship to colon cancer risk of recurrence in four clinical validation studies with approximately 3,000 patients:

• The first validation study, QUASAR was prospectively designed and included archived tissue from 711 stage II colon cancer patients randomized to surgery. The study found that the Colon Recurrence Score test is strongly associated with the risk of recurrence and provides information beyond clinical and pathologic factors, such as grade, lymphovascular invasion, patient age, and number of lymph nodes examined.⁴
• The CALGB 9581 prospectively-designed study included archived tissue from 690 stage II colon cancer patients and confirmed the ability to stratify patients by risk.⁵
• The NSABP C-07 prospectively-designed study included archived tissue from 892 stage II and stage III patients treated with either 5-FU/LV or 5-FU/LV + oxaliplatin. The study further confirmed the use of the Colon Recurrence Score to stratify patients in stage II, and validated the test as prognostic of risk of recurrence in stage III colon cancer patients.⁶
• The SUNRISE retrospective-cohort study included archived tissue from 597 stage II and stage III patients treated with surgery alone. The study confirmed the prognostic capabilities of the test, beyond clinical and pathologic factors, in both stage II and stage III colon cancer.⁷

QUASAR study findings

The first validation study, QUASAR was prospectively-designed and included archived tissue from 1,436 stage II colon cancer patients randomized to surgery or surgery + 5-FU/LV. The landmark QUASAR study showed⁴:

• A significant association between the continuous Recurrence Score result and the risk of recurrence (p=0.004).
• In the multivariate analysis of patients randomized to surgery alone (n=605), the most significant independent predictors of risk of recurrence were:
• Recurrence Score result
• Mismatch Repair (MMR) status
• T-stage
• T3, MMR-P patients with Recurrence Score result ≥41 have similar risk to T4, MMR-P patients and may have a higher absolute benefit from adjuvant chemotherapy.

In Stage II patients following surgery, Recurrence Score values predict individual recurrence risk

Validated as an independent, quantitative assessment of recurrence risk in Stage II colon cancer—QUASAR Study²

• Patients with RS ≥ 41 had recurrence risk > 18%, similar to some T2, MMR-P patients
• Therefore, these patients are expected to have higher absolute benefit from 5-FU/LV compared to those with low RS results

CALGB 9581 study findings

Consistent with QUASAR, the CALGB 9581 study, the Recurrence Score result was shown to be prognostic for recurrence risk, supporting the results of the first validation study. This study featured 690 stage II colon cancer patients perceived to be low risk (based on the clinical and pathologic characteristics), with an average five-year risk of recurrence of approximately 15%.⁵

According to the study, the Recurrence Score result⁵:

• Is a significant predictor of risk of recurrence (p = .004) in multivariable analysis, providing independent value beyond conventional clinical/pathologic factors.
• Identified 22% of the patients in the high Recurrence Score group, with an average five-year recurrence risk of 21%.
• Therefore, the test can discriminate a higher-risk patient population beyond conventional measures—even in a cohort of perceived low-risk patients.

NSABP C-07 trial findings

This independent, prospectively-designed, validation study of the Colon Recurrence Score test includes 892 stage II and stage III patients randomized to 5-FU/LV or 5-FU/LV plus oxaliplatin. The NSABP C-07 trial⁶:

• Validated the test as prognostic of recurrence risk in patients with stage III colon cancer.
• Confirmed the ability of the Recurrence Score result to quantify the risk of recurrence in stage II and III patients treated with either 5-FU/LV or 5-FU/LV + oxaliplatin.
• Predicted risk of recurrence beyond conventional measures, including T and N stage, and MMR status.

SUNRISE trial findings

The SUNRISE retrospective-cohort study included archived tissue from 597 stage II and stage III Japanese patients treated with surgery alone. The SUNRISE study⁷:

• Confirmed the prognostic capabilities of the Colon Recurrence Score test in stage II colon cancer.
• Was the first clinical validation of the test as a prognostic marker of recurrence risk in patients with stage III colon cancer treated without adjuvant chemotherapy.
• Provided new insight into the natural history of stage III colon cancer treated without chemotherapy and showed the heterogeneity in risk of recurrence.

Recurrence Risk Estimated by Oncotype DX Risk Group and Disease Stage

Stage II Disease

Risk Group	% of patients	5-year recurrence % (95% CI)
All	100	11 (9 to 14)
Low	60	8 (6 to 11)
Intermediate	26	13 (8 to 19)
High	14	24 (17 to 34)

Stage III A/B Disease

Risk Group	% of patients	5-year recurrence % (95% CI)
All	100	27 (22 to 32)
Low	46	22 (16 to 30)
Intermediate	31	25 (17 to 35)
High	23	39 (28 to 51)

 

Clinical validation references

Validation of the 12-gene colon cancer Recurrence Score in NSABP C-07 as a predictor of recurrence in stage II and III colon cancer patients treated with 5-FU/LV and 5-FU/LV+ oxaliplatin.
Yothers et al. J Clin Oncol. 2013

Biologic determinants of tumor recurrence in stage II colon cancer: validation study of the 12-gene recurrence score in cancer and leukemia group B (CALGB) 9581.
Venook et al. J Clin Oncol. 2013

Validation study of a quantitative multigene reverse transcriptase–polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer.
Gray et al. J Clin Oncol. 2011.

12-gene Recurrence Score assay stratifies the recurrence risk in stage II/III colon cancer with surgery alone: The SUNRISE study.
Yamanaka et al. J Clin Oncol. 2016