Impact of the 12-gene recurrence score assay on deciding adjuvant chemotherapy for stage II and IIIA/B colon cancer: the SUNRISE-DI study

Abstract

Background: Recent advances in adjuvant chemotherapy for early colon cancer have widened physicians' recommendations on the regimen and duration (3 or 6 months) of the treatment. We conducted this prospective study to evaluate whether the 12-gene recurrence score (12-RS) assay affected physicians' recommendations on adjuvant treatment selection. Patients and methods: Patients with stage IIIA/IIIB or stage II colon cancer were enrolled. After the patients discussed adjuvant treatment with their treating physicians, the physicians filled in the questionnaire before assay indicating the treatment recommendation. When the 12-RS assay results were available, the physicians again filled in the questionnaire after assay. The primary endpoint was the rate of change in treatment recommendations from before to after the assay, with a threshold rate of change being 20%. Patients with stage IIIA/B to II were enrolled in a ratio of 2 : 1. Results: Overall, the treatment recommendations changed in 40% of cases after obtaining 12-RS assay results. Recommendations were changed in 45% (80/178; 95% confidence interval, 37% to 53%; P < 0.001) and 30% (29/ 97; 95% confidence interval, 21% to 40%; P < 0.001) of patients with stage IIIA/B and II colon cancer, respectively. Patients with stage IIIA/B cancer had significantly more change than those with stage II cancer (P ¼ 0.0148). From before to after the 12-RS assay, the percentage of patients whose physicians reported being confident in their treatment recommendations significantly increased from 54% to 81% in stage IIIA/B (P < 0.001) and from 65% to 83% in stage II (P < 0.001). Conclusion:Our study confirmed the usefulness of the 12-RS assay in aiding the physicianepatient decision-making process for tailoring adjuvant chemotherapy for stage IIIA/B colon cancer.

Cost-effectiveness of precision molecular diagnostic tests for stage II colorectal cancer

“…Multiple genomic assays have been developed to identify high-risk subgroups in the heterogeneous population of stage II colorectal cancer patients that might benefit from adjuvant chemotherapy (5)(6)(7)(8)(9)(10). Currently, four genomic tests (the 12-gene assay, an 18-gene expression assay, a 482gene signature, and the Immunoscore assay) are available for clinical use in the US.…”

Cost-effectiveness of precision molecular diagnostic tests for stage II colorectal cancer

“…In each strategy, the patients were offered either the 12gene assay or the 18-gene expression assay, or the 482-gene signature or the Immunoscore assay and then distributed into two risk categories, either high risk or low risk. This stratification of patients into the two risk categories of high and low was based on the recurrence score of the marketed genomic tests (5)(6)(7)(8)(9)(10). Furthermore, the patients in the high-risk categories of the four genomic tests were assumed to be administered adjuvant chemotherapy, while the patients in the low-risk categories of the four genomic tests were assumed to be treated without adjuvant chemotherapy.…”

“…More recently, with advances in genomic medicine, precision molecular diagnostic tests have offered possibilities to predict disease relapse and guide adjuvant therapy decisions (5)(6)(7)(8)(9)(10). Currently, there are four tests being marketed for clinical use in the United States (US): a 12-gene assay; an 18-gene expression assay, a 482-gene signature, and the Immunoscore assay.…”

“…Currently, there are four tests being marketed for clinical use in the United States (US): a 12-gene assay; an 18-gene expression assay, a 482-gene signature, and the Immunoscore assay. The 12-gene assay provides an individual recurrence score for patients with stage II colon cancer (5,11). The 18-gene expression assay provides a relapse risk assessment using clinical and pathologic factors such as T4-stage and microsatellite instability status (8,12).…”

Recurrence monitoring using ctDNA in patients with metastasis of colorectal cancer: COSMOS- oligo study

“…12-Gene recurrence score assay is a test that evaluates the risk of recurrence of colon cancer using seven genes and ve reference genes and is used in medical practice in the United States and some European countries [1][2][3]. Attempts to evaluate this assay in Asia have also demonstrated that the 12-Gene recurrence score assay is a prognostic factor independent of pathologic stage classi cation and can change the actual chemotherapy prescription status after surgery [4,5]. Other assays that classify colon cancer into several subtypes based on RNA expression have shown that the mesenchymal subtype responds less effectively to adjuvant therapy, including oxaliplatin, whereas the microsatellite instability subtype responds more effectively [6].…”