Prognostic and predictive value of Immunoscore and its correlation with ctDNA in stage II colorectal cancer

Abstract

This study aimed to validate the prognostic value of Immunoscore (IS) in stage II colorectal cancer (CRC), and explore the roles of IS and circulating tumor DNA (ctDNA) in the adjuvant treatment for early-stage CRC. Resected tumor samples from stage II CRC patients were collected from the Sun Yat-sen University Cancer Center. The densities of CD3+ and CD8+ lymphocytes were quantified and converted to IS and classified into Low, Intermediate (Int), and High groups according to predefined cutoffs. A total of 113 patients were included in the study. Patients with IS-High, Int, and Low were 43 (38%), 62 (55%), and 8 (7%), respectively. Patients with IS-High had an excellent clinical outcome, with none recurring during a median follow-up of 3 years, including 15 (35%) clinical high-risk patients. The 3-year disease-free survival (DFS) was 100% for IS-High, 76% for IS-Int, and 47% for IS-Low ( P < .001). In the multivariate Cox analysis, IS was the only significant parameter associated with DFS. IS-Int and IS-Low patients with adjuvant chemotherapy had improved DFS compared to those who did not receive adjuvant chemotherapy (HR = 0.3; 95% CI 0.1–0.92; P = .026). Among the 49 patients with postoperative ctDNA data, IS-High patients had the lowest ctDNA positivity rate, suggesting that they were most eligible for chemotherapy-free treatment. IS had a strong prognostic value in Chinese patients with stage II CRC and demonstrates its clinical utility. IS and ctDNA will jointly optimize the adjuvant treatment strategies for early-stage CRC.

Principles of risk assessment in colon cancer: immunity is key

“…To investigate this, we examined the roles of IS and ctDNA in guiding adjuvant treatment in Chinese early-stage colorectal cancer (CRC). 50 Our recent study demonstrated that IS-High patients, including clinically high-risk individuals, exhibited excellent clinical outcomes with no recurrences observed over a three-year follow-up period. Additionally, the 3-year DFS rates were 100% for IS-High, 76% for IS-Intermediate (IS-Int), and 47% for IS-Low ( p < 0.001).…”

“…While post-operative ctDNA assay effectively identified patients at heightened risk of recurrence, it was IS that reliably determined patients at low risk of recurrence. 50 This underscores the complementary roles of ctDNA and IS assessment in guiding treatment decisions and prognostication in early-stage CRC.…”

“…Multivariate Cox analysis underscored IS as the sole significant parameter associated with DFS, thus proving its clinical utility in prognostication and treatment decision-making. 50 …”

“…Based on these results combining IS with ctDNA assessment, a decision algorithm has been formulated for guiding adjuvant treatment strategies in stage II CC. 50 Firstly, patients with IS-High had the lowest risk of recurrence and may be spared from ACT. Secondly, patients with negative postoperative ctDNA and an intermediate or low IS demonstrated an intermediate risk of recurrence and therefore could be considered for ACT.…”

“…Notably, the quantitative evaluation of immune response was not considered a powerful biomarker in clinical pathology until the introduction of IS. This AI-assisted DP-immune assay has revealed the prognostic impact of the immune response in CC patients to improve treatment decision-making in early stages, 32–34 , 50–52 In a study comparing immune response assessment in CC using IS (automated DP) and pathologist visual scoring (T-score), four pathologists evaluated tumor specimens from 50 early-stage CC patients and classified CD3+ and CD8+ stained slides. 51 While digital pathology IS proved highly reproducible, 34 agreement among pathologists was minimal to weak.…”