Improved risk stratification scheme for mismatch repair proficient stage II colorectal cancers using the digital pathology biomarker QuantCRC.

PURPOSE:There is a need to improve current risk stratification of stage II colorectal cancer (CRC) to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines. EXPERIMENTAL DESIGN:ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch repair proficient (MMRP) stage II CRCs from three large academic medical centers. The ASCO stage II scheme was taken from recent guidelines. The QuantCRC-integrated scheme utilized pT3 vs. pT4 and a QuantCRC-derived risk classification. Evaluation of recurrence free survival (RFS) according to these risk schemes was compared using the log-rank test and hazard ratios. RESULTS:Integration of QuantCRC provides improved risk stratification compared to the ASCO scheme for stage II MMRP CRCs. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared to the ASCO scheme (62.5% vs. 42.2%) without compromising excellent 3-year RFS. The QuantCRC-integrated scheme provided larger hazard ratios (HR) for both intermediate-risk (2.27, 95%CI 1.32-3.91, P=0.003) and high-risk (3.27, 95%CI 1.42-7.55, P=0.006) groups compared to ASCO intermediate-risk (1.58, 95%CI 0.87-2.87, P=0.1) and high-risk (2.24, 95%CI 1.09-4.62, P=0.03) groups. The QuantCRC-integrated risk groups remained prognostic in the subgroup of patients that did not receive any adjuvant chemotherapy. CONCLUSIONS:Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance for stage II MMRP CRCs.