Introduction: in need of an accurate chemoradiotherapy response assessment
The strategies for rectal preservation
The selective strategy
The opportunistic strategy
Assessing the response
Defining clinical complete response
Improving good responder selection by imaging
Near-future solutions to improve response assessment
Biomarkers
Responses assessment method (reference) | Main performances for nCRT tumor response prediction | Limits and needed developments for clinical use | ||
---|---|---|---|---|
Tumor biomarkers | Wild-type P53 status [42] | Good pathological response; RR = 1.20, 95% CI = 1.01–1.43, p = 0.043 | Lack of harmonized detection methods (immunohistochemistry or gene analysis) | |
Complete pathological response; RR = 1.92, 95% CI = 1.26–2.91, p = 0.002 | ||||
Poor pathological response; RR = 0.91, 95% CI = 0.68–1.12, p = 0.284 | ||||
Positive MSI status [47] | Reduced pCR rate; OR = 0.65, 95% CI 0.43–0.96 | Lack of harmonized detection methods (immunohistochemistry or molecular analysis) | ||
Negative MSI status [46] | Association with pCR: p = 0.048 | |||
Circulating biomarkers | Pre-nCRT elevated CEA plasma concentration[63] | Inverse correlation with pathologic complete response rate; OR = 2 | Recommendations for a pre-nCRT CEA threshold | |
Blood inflammation-based index | Elevated pre-nCRT platelets rate [63] | Association with lower pathologic complete response and good pathological response rate; p = 0.001 | Conflicting studies Lack of homogenous cut-offs Need for larger prospective validation studies | |
Elevated post-nCRT NLR [64] | Independent negative predictive factor for pathologic complete response; OR = 0.365, 95% CI 0.145–0.918 | |||
ctDNA | Post-nCRT ctDNA drop [65] | Positive association between MAF decrease after nCRT and pCR; p = 0.015 | Need for larger prospective validation studies Lack of ctDNA detection assays harmonization | |
Post-nCRT ctDNA positive detection [66••] | Positive ctDNA status after nCRT was associated with mrTRG primary tumor response; p = 0.03 | |||
CTC | Low pre-nCRT CK20 + circulating cells count [67] | Positive association with response to nCRT; p = 0.03 | Need for larger prospective validation studies Increasing CTC detection by enhancing technologies and technical tests | |
Low post-nCRT CTC count [68] | Positive association with response to nCRT; p < 0.001 |