DOI: https://doi.org/10.22263/2312-4156.2025.6.18
T.N. Nesterovich, V.V. Pohozhay
Prognostic factors in colorectal cancer
Gomel State Medical University, Gomel, Republic of Belarus
Vestnik VGMU. 2025;24(6):18-25.
Abstract.
Colorectal cancer (CRC) is the leading cause of malignant neoplasm morbidity and mortality worldwide and in the Republic of Belarus. 1926118 million new cases of CRC were registered in 2022, accounting for 9.6% of all malignant neoplasms worldwide. CRC is the second leading cause of cancer death worldwide (903,859 deaths were registered in 2022, accounting for 9.3%).
CRC is a heterogeneous group of tumors whose prognosis varies depending on factors related to the tumor’s biological, histological, and molecular genetic characteristics. TNM staging remains the most powerful prognostic factor in deciding on treatment strategies for patients with CRC. However, it does not provide sufficient prognostic information about the benefits of chemotherapy in patients with stage II/III CRC, given the tumor heterogeneity. Therefore, it is important to find a biomarker for assessing prognosis to individualize therapy in this patient group to improve long-term treatment outcomes. In this article, we describe criteria (tumor budding, tumor necrosis, neutrophil-lymphocyte ratio) that may serve as additional prognostic factors for deciding on the administration of adjuvant chemotherapy.
Keywords: colorectal cancer, prognostic factors, tumor budding, tumor necrosis, neutrophil-lymphocyte ratio.
References
1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a Cancer Journal for Clinicians. 2024 May-Jun;74(3):229-263. doi: http://dx.doi.org/10.3322/caac.21834
2. Kovtun DP, Anichkov NM, Polushin OG, Ponomareva EV, Khnykov GN. Features of pathological-anatomical diagnosis of colorectal cancer in oncosurgical clinic (literature review). Povolzhskii Onkologicheskii Vestnik. 2018;1(33):59-67. URL: https://cyberleninka.ru/article/n/osobennosti-patologo-anatomicheskoy-diagnostiki-kolorektalnogo-raka-v-onkohirurgicheskoy-klinike-obzor-literatury/viewer [Accessed 10th December 2025]. (In Russ.).
3. Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA: a Cancer Journal for Clinicians. 2023 May-Jun;73(3):233-254. doi: http://dx.doi.org/10.3322/caac.21772
4. Rusha KG, Kulesh ES, Trebukhovskiy AYu, Gromyko LYu, Kavenchuk AN, Davydov DA, i dr. Determination of metastatic potential and prediction of colorectal cancer flow using histological parameters of primary tumor. Zdravookhranenie. 2021;(3):61-69. (In Russ.).
5. Volchek VS, Sharshakova TM. Comprehensive evaluation of results of implementation of screening for colorectal cancer in the Gomel region. Voprosy Organizatsii i Informatizatsii Zdravookhraneniya. 2023;(2):70-75. (In Russ.).
6. Chen K, Collins G, Wang H, Toh JWT. Pathological features and prognostication in colorectal cancer. Current Oncology. 2021 Dec;28(6):5356-5383. doi: http://dx.doi.org/10.3390/curroncol28060447
7. Yokoyama S, Watanabe T, Fujita Y, Matsumura S, Ueda K, Nagano S, et al. Histology of metastatic colorectal cancer in a lymph node. PloS One. 2023 Apr;18(4):e0284536. doi: http://dx.doi.org/10.1371/journal.pone.0284536
8. Wei B, Li., Feng Y, Liu S, Fu P, Tian L. Exploring prognostic biomarkers in pathological images of colorectal cancer patients via deep learning. The Journal of Pathology Clinical Research. 2024 Nov;10(6):e70003. doi: http://dx.doi.org/10.1002/2056-4538.70003
9. Marks KM, West NP, Morris E, Quirke P. Clinicopathological, genomic and immunological factors in colorectal cancer prognosis. The British Journal of Surgery. 2018 Jan;105(2):e99-e109. doi: http://dx.doi.org/10.1002/bjs.10756
10. Luo X-J, Zhao Q, Liu J, Zheng J-B, Qiu M-Z, Ju H-Q, et al. Novel genetic and epigenetic biomarkers of prognostic and predictive significance in stage II/III colorectal cancer. Molecular Therapy. 2021 Feb;29(2):587-596. doi: http://dx.doi.org/10.1016/j.ymthe.2020.12.017
11. Konstantinov AS, Mitin NP, Shelekhova KV. Evaluation of the metastatic potential of localized forms of colorectal cancer. Arkhiv Patologii. 2021;83(5):5-12. (In Russ.). doi: http://dx.doi.org/10.17116/patol2021830515
12. Shi X, Lu L, Wang Z, Dai Y, Hu S, Wu Z, et al. The potential role of tumor deposits in the prognosis and TNM staging for colorectal cancer. Journal of Gastrointestinal Oncology. 2024 Dec;15(6):2473-2495. doi: http://dx.doi.org/10.21037/jgo-24-786
13. van den Berg I, van den Braak RRJC, van Vugt JLA, Ijzermans JNM, Buettner S. Actual survival after resection of primary colorectal cancer: results from a prospective multicenter study. World Journal of Surgical Oncology. 2021 Apr;19(1):96. doi: http://dx.doi.org/10.1186/s12957-021-02207-4
14. Tong S, Li M, Bao Y, Zhang L, Lu P, Tong T, et al. Size and number of lymph nodes were risk factors of recurrence in stage II colorectal cancer. BMC Cancer. 2023 Jun;23(1):518. doi: http://dx.doi.org/10.1186/s12885-023-10935-x
15. Lin B-Z, Lin C-L, Chiang F-F, Chen C-C, Chen M-C, Lin C-Y, et al. The clinical characteristics of a stage II colorectal cancer T4 tumor: a ten-year single-center research report. Current Oncology. 2024 Dec;31(12):7924-7935. doi: http://dx.doi.org/10.3390/curroncol31120584
16. Frei A, McGuigan A, Sinha RRAK, Jabbar F, Gneo L, Tomasevic T, et al. Multiplex analysis of intratumoural immune infiltrate and prognosis in patients with stage II–III colorectal cancer from the SCOT and QUASAR 2 trials: a retrospective analysis. The Lancet Oncology. 2024 Feb;25(2):198-211. doi: http://dx.doi.org/10.1016/S1470-2045(23)00560-0
17. Jiang W, Wang H, Dong X, Yu X, Zhao Y, Chen D, et al. Pathomics signature for prognosis and chemotherapy benefits in stage III colon cancer. JAMA Surgery. 2024 May;159(5):519-528. doi: http://dx.doi.org/10.1001/jamasurg.2023.8015
18. Jongeneel G, Greuter MJE, van Erning FN, Twisk JWR, Koopman M, Punt CJA, et al. Longitudinal effects of adjuvant chemotherapy and related neuropathy on health utility in stage II and III colon cancer patients: A prospective cohort study. International Journal of Cancer. 2021 Jun;148(11):2702-2711. doi: http://dx.doi.org/10.1002/ijc.33472
19. Maksimova PE, Golubinskaya EP, Seferov BD, Zyablitskaya EYu. Colorectal cancer: epidemiology, carcinogenesis, molecular-genetic and cellular mechanisms of resistance to therapy (analytical review). Koloproktologiya. 2023;22(2):160-171. (In Russ.). doi: http://dx.doi.org/10.33878/2073-7556-2023-22-2-160-171
20. Niezova ShKh. Modern possibilities for the correction of hepatotoxic syndrome in polychemotherapy of solid tumors (literature review). European science. 2019;47(5):73-79. (In Russ.). doi: http://dx.doi.org/10.24411/2410-2865-2019-10505
21. Chen G, Peng J, Xiao Q, Wu H-X, Wu X, Wang F, et al. Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer. Journal of Hematology and Oncology. 2021 May;14(1):80. doi: http://dx.doi.org/10.1186/s13045-021-01089-z
22. Eren T. Prognostic significance of the preoperative lymphocyte to C-reactive protein ratio in patients with stage III colorectal cancer. ANZ Journal of Surgery. 2022 Oct;92(10):2585-2594. doi: http://dx.doi.org/10.1111/ans.17896
23. Pavlic A, Boštjančič E, Kavalar R, Ilijevec B, Bonin S, Zanconati F, et al. Tumour budding and poorly differentiated clusters in colon cancer – different manifestations of partial epithelial–mesenchymal transition. The Journal of Pathology. 2022 Nov;258(3):278-288. doi: http://dx.doi.org/10.1002/path.5998
24. Xie H, Zeng Z, Hou Y, Ye F, Cai T, Cai Y, et al. Effects of tumour budding on adjuvant chemotherapy in colorectal cancer. British Journal of Surgery. 2024 Jan;8(1):zrad115. doi: http://dx.doi.org/10.1093/bjsopen/zrad115
25. Canguçu AL, Valério E, Peixoto RBP, Felismino TC, Lopes de Mello CA, Neotti T, et al. The prognostic influence of tumour budding in Western patients with stage II colorectal cancer. Ecancer Medical Science. 2020 Oct:14:1130. doi: http://dx.doi.org/10.3332/ecancer.2020.1130
26. NagiReddy TV, Gupta S, Bavikar R, A novel 4‐tier classification for tumor budding and the importance of tumor invasive patterns in the prognosis of colorectal cancer. World Journal of Surgery. 2025;49(4):830-839. doi: http://dx.doi.org/10.1002/wjs.12534
27. Zhang H, Meng X, Gou D, Huang Y, Wang H, Li H. Tumour budding in gastric and colorectal cancers: a review. Medicine. 2025 Aug;104(31):e42215. doi: http://dx.doi.org/10.1097/MD.0000000000042215
28. Li J, Ma Y, Wen L, Zhang G, Huang C, Wang J, et al. Prognostic impact of tumor budding in rectal cancer after neoadjuvant therapy: a systematic review and meta-analysis. Systematic Reviews. 2024 Jan;13(1):22. doi: http://dx.doi.org/10.1186/s13643-023-02441-9
29. Kamall G, Ulusoy C, Nikolovski A, Kamall S. Tumour budding – an additional prognostic factor in colorectal cancer survival. Polish Journal of Pathology. 2023;74(1):36-41. doi: http://dx.doi.org/10.5114/pjp.2023.127040
30. Ueno H, Ishiguro M, Nakatani E, Ishikawa T, Uetake H, Matsuda C, et al. Prospective multicenter study on the prognostic and predictive impact of tumor budding in stage II colon cancer: results from the SACURA Trial. Journal of Clinical Oncology. 2019 Aug;37(22):1886-1894. doi: http://dx.doi.org/10.1200/JCO.18.02059
31. Nagata K, Shinto E, Yamadera M, Shiraishi T, Kajiwara Y, Okamoto K, et al. Prognostic and predictive values of tumour budding in stage IV colorectal cancer. British Journal of Surgery. 2020 Aug;4(4):693-703. doi: http://dx.doi.org/10.1002/bjs5.50300
32. Haddad TS, Lugli A, Aherne S, Barresi V, Terris B, Bokhorst J-M, et al. Improving tumor budding reporting in colorectal cancer: a Delphi consensus study. Virchows Archiv. 2021 Sep;479(3):459-469. doi: http://dx.doi.org/10.1007/s00428-021-03059-9
33. Kastinen M, Sirniö P, Elomaa H, Äijälä VK, Karjalainen H, Tapiainen VV, et al. Establishing criteria for tumor necrosis as prognostic indicator in colorectal cancer. The American Journal of Surgical Pathology. 2024 Oct;48(10):1284-1292. doi: http://dx.doi.org/10.1097/PAS.0000000000002286
34. Hausmann O, Schobert PP, Ose J, Associations of biomarkers of systemic inflammation, angiogenesis, and cell-to-cell adhesion with tumor budding among early-onset and later-onset colorectal cancer patients. Cancer Medicine. 2025 Sep;14(18):e71267. doi: http://dx.doi.org/10.1002/cam4.71267
35. Yamamoto T, Kawada K, Obama K. Inflammation-related biomarkers for the prediction of prognosis in colorectal cancer patients. International Journal of Molecular Sciences. 2021 Jul;22(15):8002. doi: http://dx.doi.org/10.3390/ijms22158002
36. Cho Y, Park SB, Yoon JY, Kwak MS, Cha JM. Neutrophil to lymphocyte ratio can predict overall survival in patients with stage II to III colorectal cancer. Medicine. 2023 Mar;102(11):e33279. doi: http://dx.doi.org/10.1097/MD.0000000000033279
37. Iaciu CI, Emilescu RA, Cotan H-T, Nitipir C. Systemic neutrophil-to-lymphocyte ratio as a prognostic biomarker for colon cancer. Chirurgia. 2023 Jun;118(3):260-271. doi: http://dx.doi.org/10.21614/chirurgia.2023.v.118.i.3.p.260
38. Turri G, Caligola S, Ugel S, Conti C, Zenuni S, Barresi V, et al. Pre-diagnostic prognostic value of leukocytes count and neutrophil-to-lymphocyte ratio in patients who develop colorectal cancer. Frontiers in Oncology. 2023 Jun:13:1148197. doi: http://dx.doi.org/10.3389/fonc.2023.1148197
39. López DO, Gómez JM, Nogués Ramia EM, Quesada YS, Pérez BA, Armas MA, et al. Prognostic value of neutrophil-to-lymphocyte ratio at diagnosis in colorectal cancer: propensity score analysis. Revista Española de Enfermedades Digestivas. 2024 Aug;116(8):408-415. doi: http://dx.doi.org/10.17235/reed.2024.10041/2023
40. Bogomolova IA, Dolgova DR, Kolodiy IO, Antoneeva II. Prediction of sensitivity of patients with colorectal cancer to chemotherapy according to the FOLFOX/XELOX scheme based on the index of neutrophil-lymphocyte ratio. Povolzhskii Onkologicheskii Vestnik. 2023;14(3). URL: https://oncovestnik.ru/archive/zhurnaly-za-2023-god/tom-14-nomer-3-2023-g/prognoz-chuvstvitelnosti-pacientov-s-kolorektalnym-rakom-k-himioterapii-po-sheme-folfox-xelox-na-osnovanii-indeksa-otnosheniya-nejtrofilov-k-limfocitam [Accessed 10th December 2025]. (In Russ.).
41. Nogueira-Costa G, Fernandes I, Gameiro R, Gramaça J, Xavier AT, Pina I. Prognostic utility of neutrophil-to-lymphocyte ratio in patients with metastatic colorectal cancer treated using different modalities. Current Oncology. 2020 Oct;27(5):237-243. doi: http://dx.doi.org/10.3747/co.27.6573
42. Naszai M, Kurjan A, Maughan TS. The prognostic utility of pre‐treatment neutrophil‐to‐lymphocyte‐ratio (NLR) in colorectal cancer: A systematic review and meta‐analysis. Cancer Medicine. 2021 Sep;10(17):5983-5997. doi: http://dx.doi.org/10.1002/cam4.4143
43. Ming-Sheng F, Mei-Ling D, Xun-Quan C, Yuan-Xin H, Wei-Jie Z, Qin-Cong P. Preoperative neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and CEA as the potential prognostic biomarkers for colorectal cancer. Canadian Journal of Gastroenterology and Hepatology. 2022 Jan:2022:3109165. doi: http://dx.doi.org/10.1155/2022/3109165
44. Wang CY, Li X-L, Ma X-L, Yang X-F, Liu Y-Y, Yu Y-J. Preoperative neutrophil-to-lymphocyte ratio predicts symptomatic anastomotic leakage in elderly colon cancer patients: multicenter propensity score-matched analysis. World Journal of Gastrointestinal Surgery. 2024;16(2):438-450. doi: http://dx.doi.org/10.4240/wjgs.v16.i2.438
45. Ye H, Wang Y, Yao, Liu Z, Liang C, Zhu Y, et al. Necrosis score as a prognostic factor in stage I–III colorectal cancer: a retrospective multicenter study. Discover Oncology. 2023 May;14(1):61. doi: http://dx.doi.org/10.1007/s12672-023-00655-w
46. Jakubowska K, Koda M, Grudzińska M, Kisielewski W, Lomperta K, Famulski W. Neutrophil infiltration combined with necrosis in the primary tumor is a useful prognostic indicator for three year disease free survival time in patients with colorectal cancer. Oncology Letters. 2022 Jun;23(6):199. doi: http://dx.doi.org/10.3892/ol.2022.13320
47. Kastinen M, Sirniö P, Elomaa H, Ahtiainen M, Väyrynen SA, Herzig K-H, et al. Immunological and prognostic significance of tumour necrosis in colorectal cancer. British Journal of Cancer. 2023 Jun;128(12):2218-2226. doi: http://dx.doi.org/10.1038/s41416-023-02258-2
48. Dong Sh, Xu J, Li M, Tumor necrosis serves as an important pathological characteristic of stage I–II colon cancer. Indian Journal of Pathology & Microbiology. 2024 Oct;67(4):794-800. doi: http://dx.doi.org/10.4103/ijpm.ijpm_483_23
49. Shevchenko TI, Shvorob DS. Clinical and morphological factors for the prediction of metastatic potential of colorectal cancer. Klinicheskaya i Eksperimental'naya Morfologiya. 2020;9(2):26-32. (In Russ.). doi: http://dx.doi.org/10.31088/CEM2020.9.2.26-32
50. Kit OI, Gevorkyan YuA, Soldatkina NV, Timoshkina NN, Kharagezov DA, Kaymakchi DO, i dr. Modern prognostic factors in colorectal cancer. Koloproktologiya. 2021;20(2):42-49. (In Russ.). doi: http://dx.doi.org/10.33878/2073-7556-2021-20-2-42-49
Submitted 28.10.2025
Accepted 10.12.2025
Information about authors:
Tatyana N. Nesterovich – lecturer of the Chair of Oncology, Gomel State Medical University, https://orcid.org/0000-0001-5692-1042, e-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра.;
V.V. Pohozhay – Candidate of Medical Sciences, associate professor, vice-rector for Clinical Work, Gomel State Medical University, https://orcid.org/0000-0001-6866-547X
