Research progress on pathological response after neoadjuvant chemoradiotherapy in locally advanced middle and low rectal cancer

doi:10.3760/cma.j.cn371439-20250727-00041

Abstract

Abstract:

Neoadjuvant chemoradiotherapy for locally advanced rectal cancer significantly downstages tumors， which can improve the rate of radical surgical resection and anal sphincter preservation， reduce the local recurrence rate， thereby improving patients' prognosis. However， there is currently a lack of effective methods to identify patients' response to neoadjuvant therapy. Studies have found that biological indicators such as hematological markers， tumor markers， nucleic acid markers， as well as tumor imaging characteristics， are associated with the sensitivity of neoadjuvant therapy for rectal cancer and can predict the sensitivity of preoperative concurrent chemoradiotherapy.

Key words: Rectal neoplasms, Neoadjuvant therapy, Pathological complete response

Li Zhilei, Fang Jinman, Wei Dandan, Sun Ruixia, Zhang Yuanwei. Research progress on pathological response after neoadjuvant chemoradiotherapy in locally advanced middle and low rectal cancer[J]. Journal of International Oncology, 2026, 53(4): 248-252.

References 36

[1]	Han BF, Zheng RS, Zeng HM, et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024, 4(1): 47-53. DOI: 10.1016/j.jncc.2024.01.006.
[2]	Gahagan JV, Whealon MD, Phelan MJ, et al. Improved survival with adjuvant chemotherapy in locally advanced rectal cancer patients treated with preoperative chemoradiation regardless of pathologic response[J]. Surg Oncol, 2020, 32: 35-40. DOI: 10.1016/j.suronc.2019.10.021. pmid: 31726418
[3]	Li JY, Huang XZ, Gao P, et al. Survival landscape of different tumor regression grades and pathologic complete response in rectal cancer after neoadjuvant therapy based on reconstructed individual patient data[J]. BMC Cancer, 2021, 21(1): 1214. DOI: 10.1186/s12885-021-08922-1.
[4]	Li S, Lu ZF, Wu SY, et al. The dynamic role of platelets in cancer progression and their therapeutic implications[J]. Nat Rev Cancer, 2024, 24(1): 72-87. DOI: 10.1038/s41568-023-00639-6. pmid: 38040850
[5]	Aires F, Rodrigues D, Lamas MP, et al. C-reactive protein as predictive biomarker for response to chemoradiotherapy in patients with locally advanced rectal cancer: a retrospective study[J]. Cancers (Basel), 2022, 14(3): 491. DOI: 10.3390/cancers14030491.
[6]	Belluco C, Forlin M, Delrio P, et al. Elevated platelet count is a negative predictive and prognostic marker in locally advanced rectal cancer undergoing neoadjuvant chemoradiation: a retrospective multi-institutional study on 965 patients[J]. BMC Cancer, 2018, 18(1): 1094. DOI: 10.1186/s12885-018-5022-1. pmid: 30419864
[7]	An SH, Kim IY. Can pretreatment platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios predict long-term oncologic outcomes after preoperative chemoradiation followed by surgery for locally advanced rectal cancer?[J]. Ann Coloproctol, 2022, 38(3): 253-261. DOI: 10.3393/ac.2021.00633.0090. pmid: 35249276
[8]	Rakotomalala A, Escande A, Furlan A, et al. Hypoxia in solid tumors: how low oxygenation impacts the “Six Rs” of radiotherapy[J]. Front Endocrinol (Lausanne), 2021, 12: 742215. DOI: 10.3389/fendo.2021.742215.
[9]	Huang CM, Huang CW, Ma CJ, et al. Predictive value of FOLFOX-based regimen, long interval, hemoglobin levels and clinical negative nodal status, and postchemoradiotherapy CEA levels for pathological complete response in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy[J]. J Oncol, 2020, 2020: 9437684. DOI: 10.1155/2020/9437684.
[10]	Rodrigues D, Simões J, Teixeira L, et al. Baseline anaemia increases locally advanced rectal cancer mortality in older patients undergoing preoperative chemoradiation[J]. Support Care Cancer, 2021, 29(3): 1403-1411. DOI: 10.1007/s00520-020-05618-3.
[11]	Damen PJJ, Peters M, Hobbs B, et al. Defining the optimal radiation-induced lymphopenia metric to discern its survival impact in esophageal cancer[J]. Int J Radiat Oncol Biol Phys, 2025, 122(1): 31-42. DOI: 10.1016/j.ijrobp.2024.12.014.
[12]	Liu H, Wang H, Wu JH, et al. Lymphocyte nadir predicts tumor response and survival in locally advanced rectal cancer after neoadjuvant chemoradiotherapy: immunologic relevance[J]. Radiother Oncol, 2019, 131: 52-59. DOI: 10.1016/j.radonc.2018.12.001. pmid: 30773187
[13]	Chen YF, Mi YL, Tan S, et al. CEA-induced PI3K/AKT pathway activation through the binding of CEA to KRT1 contributes to oxaliplatin resistance in gastric cancer[J]. Drug Resist Updat, 2025, 78: 101179. DOI: 10.1016/j.drup.2024.101179.
[14]	Engel RM, Oliva K, Koulis C, et al. Predictive factors of complete pathological response in patients with locally advanced rectal cancer[J]. Int J Colorectal Dis, 2020, 35(9): 1759-1767. DOI: 10.1007/s00384-020-03633-8. pmid: 32474708
[15]	Guo SP, Chen C, Zeng ZF, et al. Serum apolipoprotein A-I predicts response of rectal cancer to neoadjuvant chemoradiotherapy[J]. Cancer Manag Res, 2021, 13: 2623-2631. DOI: 10.2147/CMAR.S302677.
[16]	Cai ZR, Huang LY, Chen Y, et al. CEA decline predicts tumor regression and prognosis in locally advanced rectal cancer patients with elevated baseline CEA[J]. J Cancer, 2020, 11(22): 6565-6570. DOI: 10.7150/jca.49252. pmid: 33046977
[17]	Lee T, Teng TZJ, Shelat VG. Carbohydrate antigen 19-9-tumor marker: past, present, and future[J]. World J Gastrointest Surg, 2020, 12(12): 468-490. DOI: 10.4240/wjgs.v12.i12.468.
[18]	Song JY, Huang XY, Chen ZH, et al. Predictive value of carcino-embryonic antigen and carbohydrate antigen 19-9 related to down-staging to stage 0 -Ⅰ after neoadjuvant chemoradiotherapy in locally advanced rectal cancer[J]. Cancer Manag Res, 2018, 10: 3101-3108. DOI: 10.2147/CMAR.S166417.
[19]	刘启志, 张杭, 郝立强, 等. 中低位直肠癌新辅助放化疗后病理完全缓解的影响因素分析[J]. 中华胃肠外科杂志, 2020, 23(12): 1159-1163. DOI: 10.3760/cma.j.cn.441530-20200106-00009.
[20]	Udagawa S, Ooki A, Shinozaki E, et al. Circulating tumor DNA: the dawn of a new era in the optimization of chemotherapeutic strategies for metastatic colo-rectal cancer focusing on RAS mutation[J]. Cancers (Basel), 2023, 15(5): 1473. DOI: 10.3390/cancers15051473.
[21]	Molinari C, Marisi G, Laliotis G, et al. Assessment of circulating tumor DNA in patients with locally advanced rectal cancer treated with neoadjuvant therapy[J]. Sci Rep, 2024, 14(1): 29536. DOI: 10.1038/s41598-024-80855-8.
[22]	McDuff SGR, Hardiman KM, Ulintz PJ, et al. Circulating tumor DNA predicts pathologic and clinical outcomes following neoadjuvant chemoradiation and surgery for patients with locally advanced rectal cancer[J]. JCO Precis Oncol, 2021, 5: PO. 20.00220. DOI: 10.1200/PO.20.00220.
[23]	Wang YQ, Yang LF, Bao H, et al. Utility of ctDNA in predicting response to neoadjuvant chemoradiotherapy and prognosis assessment in locally advanced rectal cancer: a prospective cohort study[J]. PLoS Med, 2021, 18(8): e1003741. DOI: 10.1371/journal.pmed.1003741.
[24]	André T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer[J]. N Engl J Med, 2020, 383(23): 2207-2218. DOI: 10.1056/NEJMoa2017699.
[25]	Kim JK, Qu X, Chen CT, et al. Identifying diagnostic microRNAs and investigating their biological implications in rectal cancer[J]. JAMA Netw Open, 2021, 4(12): e2136913. DOI: 10.1001/jamanetworkopen.2021.36913.
[26]	Baek DW, Kim G, Kang BW, et al. High expression of microRNA-199a-5p is associated with superior clinical outcomes in patients with locally advanced rectal cancer[J]. J Cancer Res Clin Oncol, 2020, 146(1): 105-115. DOI: 10.1007/s00432-019-03099-4. pmid: 31781865
[27]	Santos A, Cristóbal I, Rubio J, et al. MicroRNA-199b deregulation shows oncogenic properties and promising clinical value as circulating marker in locally advanced rectal cancer patients[J]. Int J Mol Sci, 2022, 23(4): 2203. DOI: 10.3390/ijms23042203.
[28]	Rubio J, Cristóbal I, Santos A, et al. Low microRNA-19b expression shows a promising clinical impact in locally advanced rectal cancer[J]. Cancers (Basel), 2021, 13(6): 1456. DOI: 10.3390/cancers13061456.
[29]	Machackova T, Trachtova K, Prochazka V, et al. Tumor microRNAs identified by small RNA sequencing as potential response predictors in locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy[J]. Cancer Genomics Proteomics, 2020, 17(3): 249-257. DOI: 10.21873/cgp.20185.
[30]	Wada Y, Shimada M, Morine YJ, et al. Circulating miRNA signature predicts response to preoperative chemoradiotherapy in locally advanced rectal cancer[J]. JCO Precis Oncol, 2021, 5: PO.21. 00015. DOI: 10.1200/PO.21.00015.
[31]	Shin J, Seo N, Baek SE, et al. MRI radiomics model predicts pathologic complete response of rectal cancer following chemoradiotherapy[J]. Radiology, 2022, 303(2): 351-358. DOI: 10.1148/radiol.211986. pmid: 35133200
[32]	Chiloiro G, Cusumano D, Romano A, et al. Delta radiomic analysis of mesorectum to predict treatment response and prognosis in locally advanced rectal cancer[J]. Cancers (Basel), 2023, 15(12): 3082. DOI: 10.3390/cancers15123082.
[33]	Feng LL, Liu ZY, Li CF, et al. Development and validation of a radiopathomics model to predict pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a multicentre observational study[J]. Lancet Digit Health, 2022, 4(1): e8-e17. DOI: 10.1016/S2589-7500(21)00215-6.
[34]	Xu K, Motiwala Z, Corona-Avila I, et al. The gut microbiome and its multifaceted role in cancer metabolism, initiation, and progression: insights and therapeutic implications[J]. Technol Cancer Res Treat, 2025, 24: 15330338251331960. DOI: 10.1177/15330338251331960.
[35]	Shi W, Shen LJ, Zou W, et al. The gut microbiome is associated with therapeutic responses and toxicities of neoadjuvant chemoradiotherapy in rectal cancer patients-a pilot study[J]. Front Cell Infect Microbiol, 2020, 10: 562463. DOI: 10.3389/fcimb.2020.562463.
[36]	Jang BS, Chang JH, Chie EK, et al. Gut microbiome composition is associated with a pathologic response after preoperative chemo-radiation in patients with rectal cancer[J]. Int J Radiat Oncol Biol Phys, 2020, 107(4): 736-746. DOI: 10.1016/j.ijrobp.2020.04.015.