Histopathology · 2025
Acellular mucin pools and neutrophil-to-lymphocyte ratio: unveiling hidden aggressiveness in pathological complete response after chemoradiotherapy for rectal cancer.
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Xu Zhenyu, Zhu Heyuan, Wang Xiaojie, Tang Yongqin, Huang Ying, Chi Pan, Sun Yanwu
Аннотация
BACKGROUND: Pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) does not eliminate tumor recurrence risk, with distant metastasis remaining a critical challenge. This study aimed to identify novel prognostic factors for risk stratification in pCR patients after nCRT.
METHODS: We enrolled 149 LARC patients who achieved pCR between 2016 and 2020. Acellular mucin pools (AMP) were classified by the deepest tissue layer of AMP (A0: absent; A1: within the muscularis propria; A2: exceeding the muscularis propria). The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and recurrence patterns.
RESULTS: After a median follow-up of 75.3 months, the 5-year OS and DFS rates were 95.3% and 89.9%, respectively. Among 15 recurrence events, all were distant metastases (80% pulmonary). AMP were present in 17.4% (26/149) of patients. Multivariate analysis identified AMP exceeding the muscularis propria (HR = 3.996, 95% CI: 1.073-14.660, P = 0.039), preoperative neutrophil-to-lymphocyte ratio (NLR) >4.4 (HR = 3.658, 95% CI: 1.304-10.263, P = 0.014) and tumour distance from the anal verge on pretreatment magnetic resonance imaging (MRI) (HR = 0.667, 95% CI: 0.481-0.925, P = 0.015) as independent predictors of distant metastasis-free survival (DMFS). A nomogram integrating these factors showed robust discriminative performance for 1-, 3-, and 5-year DMFS (AUC = 0.689, 0.815, 0.795). Meanwhile, AMP exceeding the muscularis propria (HR = 6.632, P = 0.010) and pretreatment MRI-assessed tumour distance from the anal margin (HR = 0.614, P = 0.018) were independent predictors for pulmonary metastasis.
CONCLUSIONS: AMP exceeding the muscularis propria and high pretreatment NLR are complementary prognostic markers that refine risk stratification in pCR patients, enabling personalized surveillance and treatment strategies to improve outcomes.
METHODS: We enrolled 149 LARC patients who achieved pCR between 2016 and 2020. Acellular mucin pools (AMP) were classified by the deepest tissue layer of AMP (A0: absent; A1: within the muscularis propria; A2: exceeding the muscularis propria). The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and recurrence patterns.
RESULTS: After a median follow-up of 75.3 months, the 5-year OS and DFS rates were 95.3% and 89.9%, respectively. Among 15 recurrence events, all were distant metastases (80% pulmonary). AMP were present in 17.4% (26/149) of patients. Multivariate analysis identified AMP exceeding the muscularis propria (HR = 3.996, 95% CI: 1.073-14.660, P = 0.039), preoperative neutrophil-to-lymphocyte ratio (NLR) >4.4 (HR = 3.658, 95% CI: 1.304-10.263, P = 0.014) and tumour distance from the anal verge on pretreatment magnetic resonance imaging (MRI) (HR = 0.667, 95% CI: 0.481-0.925, P = 0.015) as independent predictors of distant metastasis-free survival (DMFS). A nomogram integrating these factors showed robust discriminative performance for 1-, 3-, and 5-year DMFS (AUC = 0.689, 0.815, 0.795). Meanwhile, AMP exceeding the muscularis propria (HR = 6.632, P = 0.010) and pretreatment MRI-assessed tumour distance from the anal margin (HR = 0.614, P = 0.018) were independent predictors for pulmonary metastasis.
CONCLUSIONS: AMP exceeding the muscularis propria and high pretreatment NLR are complementary prognostic markers that refine risk stratification in pCR patients, enabling personalized surveillance and treatment strategies to improve outcomes.