TEST:

Oncotype DX® Colon Recurrence Score test

Support: NSABP Foundation, ExactSciences. Clinical trial information: NCT05210283.

Using transcriptomic data of patients with stage III CC from 2 large-scale adjuvant trials, two predictive models based on signatures of the TME and the cell cycle, provide important information in addition to known prognostic factors for patient stratification on risk of recurrence. Beyond T and N stage, for the decision of adjuvant chemotherapy in stage III CC, the combination of these different variables could be exploited in the future for personalized care (de-escalation, intensification). >

This real-world analysis showed that the RS results provide independent prognostic information in stage II CC. Further studies are needed to investigate the potential role of the RS result as a predictor of CT benefit, but the data suggest that this benefit may be limited to pts with high RS results. >

The use of the 12-gene signature refutes the decision of tumour board in 25% of cases, with 75% of discordant decisions resulting in omission of adjuvant chemotherapy. Therefore, it is possible that a proportion of such patients are being overtreated when relying on tumour board decisions alone.

"Protocol#: NSABP C-14 / ES 16-002. Support: NSABP Foundation, ExactSciences Clinical trial information: 05210283."

Methods 3'RNAseq was performed in 1,734 FFPE samples from the PETACC8 trial including patients with stage III CC and treated with FOLFOX +/- cetuximab...Our study paves the way towards personalized care according to the estimation of this risk of recurrence, especially for the decision of adjuvant chemotherapy. Table: 321P The predictive model

The identified ERG signature is a promising and powerful biomarker predicting recurrence in CRC patients. Moreover, the presented ERG signature might help to stratify patients according to their tumor biology and contribute to personalized treatment.

CONCLUSION The results of the present study can easily be transferred to clinical practice. Thus, further studies are highly demanded evaluating the clinical feasibility of this innovative 7-ERG signature for recurrence and pave the way to improve personalized Medicine.

The effect of fluorouracil (5FU) was estimated with a meta-analysis of two studies. The PSMA integrates the 12-gene colon RS result with clinical and pathology factors to provide individualized recurrence risk estimates that reflect current medical practice. The risk estimates are in a range that may help inform treatment decisions for a substantial number of stage II and stage III patients.

RS was not associated with the decision to start adjuvant chemotherapy. Given its lack of association with clinical decision-making and inability to predict clinical outcome, our data suggest the RS should not be obtained in patients with stage IIa colon cancer.

"This work furthers our understanding of the underlying biology that propagates stage II/III CRC disease progression and provides scientific rationale for future high-risk stratification and targeted treatment evaluation in biomarker defined subpopulations of resectable high-risk CRC. Our results also shed light on an alternative GZMB source with context-specific implications on the disease's unique biology."

The new recurrence risk estimates provide more patient-specific information reflecting more current medical practice than previous reports using RS result, allowing better, more individualized treatment decisions.