Exploring the Efficacy of Immunotherapy in Combination with Surgical Resection in High-risk Muscle-invasive Bladder Cancer
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Abstract
Traditional radical cystectomy has a high recurrence rate, a high probability of metastasis, and a reduced quality of life for patients. This study aimed to explore the efficacy of combining immunotherapy and surgical resection for high-risk muscle-invasive bladder cancer.
In a retrospective study, 231 patients with high-risk muscle-invasive bladder cancer admitted to Yueyang People’s Hospital between January 2019 and May 2024 were selected. After exclusions, 200 cases were analyzed and divided into two groups according to the treatment modality: the control group (surgical resection alone, n=100) and the intervention group (combination of immunotherapy and surgical resection, n=100). The cellular immune function indexes (CD3+, CD4+/CD8+, and natural killer cell levels), tumor markers (carcinoembryonic antigen, carbohydrate antigen 125, cytokeratin 21-1, and neuron-specific enolase), serum cytokines (basic fibroblast growth factor, vascular endothelial growth factor, and tumor necrosis factor-α), pathological complete remission (pCR), 1-year survival, and Functional Assessment of Cancer Therapy-Bladder (FACT-BL) quality-of-life scores were assessed in the two groups.
After 1 year of treatment, the indicators of the two groups of patients were statistically significant in comparison with each other. Patients in the intervention group had substantial improvements in immune function indexes, pCR, 1-year survival rate, and FACT-BL scores in comparison with the control group. Tumor markers and serum cytokines were lower than those in the control group.
The combination of immunotherapy and surgical resection can enhance clinical efficacy, providing a scientific basis for optimizing the clinical treatment plan.
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26. Zhang M, Cheng S, Jin Y, Zhao Y, Wang Y. Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer. Biochim Biophys Acta Rev Cancer. 2021;1875(2):188503.
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28. Yuk HD, Han JH, Jeong SH, Jeong CW, Kwak C, Ku JH, et al. Beta-human chorionic gonadotropin, carbohydrate antigen 19-9, cancer antigen 125, and carcinoembryonic antigen as prognostic and predictive biological markers in bladder cancer. Front Oncol. 2024;14:1479988.
29. Duggan B, O’Rourke D, Anderson N, Browne S, Fitzgerald R, Thomas V, et al. Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific. Front Oncol. 2022;12:1009014.
30. Setianingsih YA, Djatisoesanto W, Laksita TB, Aryati A. Diagnostic accuracy of urinary cytokeratin fragment-19 (CYFRA21-1) for bladder cancer. Narra J. 2024;4(3):e1142.
31. Baessler A, Vignali D. T cell exhaustion. Annu Rev Immunol. 2024;42(1):179-206.
32. Siddhartha R, Goel A, Singhai A, Garg M. Matrix metalloproteinases -2 and -9, vascular endothelial growth factor, basic fibroblast growth factor and CD105-micro-vessel density are predictive markers of non-muscle invasive bladder cancer and muscle invasive bladder cancer subtypes. Biochem Genet. 2024.
33. Ott PA, Hu-Lieskovan S, Chmielowski B, Ribas A, Johnson DB, Daud A, et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. Cell. 2020;183(2):347-62.e24.
34. Nassif EF, Thibault C, Oudard S, Galon J. Precision immunity: immunoscore and neoadjuvant treatment in bladder cancer. Oncoimmunology. 2021;10(1):1888488.
35. Waqas A, Zaffar J, Jalil A, Butt S. Nivolumab-induced isolated neutropenia. Cureus. 2023;15(9):e45675.
36. Ren J. Advances in combination therapy for gastric cancer: integrating targeted agents and immunotherapy. Adv Clin Pharmacol Ther. 2024;1(1):1-15.
2. Viswambaram P, Hayne D. Gender discrepancies in bladder cancer: potential explanations. Expert Rev Anticancer Ther. 2020;20(10):841-9.
3. Xu N, Yao Z, Shang G, Chen J, Li Y, Wang Q, et al. Integrated proteogenomic characterization of urothelial carcinoma of the bladder. J Hematol Oncol. 2022;15(1):76.
4. Alouini S. Risk factors associated with urothelial bladder cancer. Int J Environ Res Public Health. 2024;21(7):954.
5. Santos LL, Santos J, Gouveia MJ, Vale N, Lopes C, Rinaldi G, et al. Urogenital schistosomiasis-history, pathogenesis, and bladder cancer. J Clin Med. 2021;10(2):205.
6. Wu J, Jin S, Gu C, Wang H, Zhou L, Xu W, et al. Inherited mutations in Chinese patients with upper tract urothelial carcinoma. Cell Rep Med. 2023;4(1):100883.
7. Gupta G, Gupta R, Pasricha S, Sharma A, Kumar V, Yadav R, et al. Molecular stratification of high-grade urothelial carcinoma by immunohistochemistry with its histomorphological and clinical correlation. Indian J Pathol Microbiol. 2022;65(4):832-8.
8. Dobruch J, Oszczudłowski M. Bladder cancer: current challenges and future directions. Medicina (Kaunas). 2021;57(8):749.
9. Hu J, Chen J, Ou Z, Wang Y, Zhang H, Liu P, et al. Neoadjuvant immunotherapy, chemotherapy, and combination therapy in muscle-invasive bladder cancer: a multi-center real-world retrospective study. Cell Rep Med. 2022;3(11):100785.
10. Dyrskjøt L, Hansel DE, Efstathiou JA, Knowles MA, Malats N, Hartmann A, et al. Bladder cancer. Nat Rev Dis Primers. 2023;9(1):58.
11. Ahmadieh N, Zeidan T, Chebel JA, Haddad FG, Nemr E. Neoadjuvant chemotherapy for muscle-invasive bladder cancer in a Lebanese experience: in all aspects. Gulf J Oncol. 2023;1(43):33-9.
12. Facchini G, Cavaliere C, Romis L, Veneziani M, Porricelli R, Iorio B, et al. Advanced/metastatic bladder cancer: current status and future directions. Eur Rev Med Pharmacol Sci. 2020;24(22):11536-52.
13. Flaig TW, Spiess PE, Abern M, Agarwal N, Bangs R, Boorjian SA, et al. NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024. J Natl Compr Canc Netw. 2024;22(4):216-25.
14. Ward Grados DF, Ahmadi H, Griffith TS, Warlick CA. Immunotherapy for bladder cancer: latest advances and ongoing clinical trials. Immunol Invest. 2022;51(8):2226-41.
15. Singh A, Osbourne AS, Koshkin VS. Perioperative immunotherapy in muscle-invasive bladder cancer. Curr Treat Options Oncol. 2023;24(9):1213-30.
16. Lopez-Beltran A, Cookson MS, Guercio BJ, Cheng L. Advances in diagnosis and treatment of bladder cancer. BMJ. 2024;384:e076743.
17. Powles T, Bellmunt J, Comperat E, Witjes JA, De Santis M, Necchi A, et al. ESMO clinical practice guideline interim update on first-line therapy in advanced urothelial carcinoma. Ann Oncol. 2024;35(6):485-90.
18. Basile G, Bandini M, Gibb EA, Gallina A, Fossati N, Gandaglia G, et al. Neoadjuvant pembrolizumab and radical cystectomy in patients with muscle-invasive urothelial bladder cancer: 3-year median follow-up update of PURE-01 trial. Clin Cancer Res. 2022;28(23):5107-14.
19. Galsky MD, Witjes JA, Gschwend JE, Bellmunt J, Merseburger AS, Huang Y, et al. Adjuvant nivolumab in high-risk muscle-invasive urothelial carcinoma: expanded efficacy from CheckMate 274. J Clin Oncol. 2025;43(1):15-21.
20. Wu Z, Zheng Y, Sheng J, Zhang W, Chen X, Li Q, et al. CD3(+)CD4(-)CD8(-) (double-negative) T cells in inflammation, immune disorders, and cancer. Front Immunol. 2022;13:816005.
21. Wu SY, Fu T, Jiang YZ, Shao ZM. Natural killer cells in cancer biology and therapy. Mol Cancer. 2020;19(1):120.
22. Schmit T, Klomp M, Khan MN. An overview of flow cytometry: its principles and applications in allergic disease research. Methods Mol Biol. 2021;2223:169-82.
23. Tabatabaei MS, Ahmed M. Enzyme-linked immunosorbent assay (ELISA). Methods Mol Biol. 2022;2508:115-34.
24. Saltalamacchia G, Bernardo A, Quaquarini E. Prognostic role of pathological complete response in early stage epithelial solid tumors. Cancer Control. 2023;30:10732748231161466.
25. Pazeto CL, Baccaglini W, Tourinho-Barbosa RR, Glina S, Cathelineau X, Sanchez-Salas R, et al. HRQOL related to urinary diversion in radical cystectomy: a systematic review of recent literature. Int Braz J Urol. 2019;45(6):1094-104.
26. Zhang M, Cheng S, Jin Y, Zhao Y, Wang Y. Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer. Biochim Biophys Acta Rev Cancer. 2021;1875(2):188503.
27. Xiang W, Lv Q, Shi H, Xie B, Gao L. Aptamer-based biosensor for detecting carcinoembryonic antigen. Talanta. 2020;214(6):120716.
28. Yuk HD, Han JH, Jeong SH, Jeong CW, Kwak C, Ku JH, et al. Beta-human chorionic gonadotropin, carbohydrate antigen 19-9, cancer antigen 125, and carcinoembryonic antigen as prognostic and predictive biological markers in bladder cancer. Front Oncol. 2024;14:1479988.
29. Duggan B, O’Rourke D, Anderson N, Browne S, Fitzgerald R, Thomas V, et al. Biomarkers to assess the risk of bladder cancer in patients presenting with haematuria are gender-specific. Front Oncol. 2022;12:1009014.
30. Setianingsih YA, Djatisoesanto W, Laksita TB, Aryati A. Diagnostic accuracy of urinary cytokeratin fragment-19 (CYFRA21-1) for bladder cancer. Narra J. 2024;4(3):e1142.
31. Baessler A, Vignali D. T cell exhaustion. Annu Rev Immunol. 2024;42(1):179-206.
32. Siddhartha R, Goel A, Singhai A, Garg M. Matrix metalloproteinases -2 and -9, vascular endothelial growth factor, basic fibroblast growth factor and CD105-micro-vessel density are predictive markers of non-muscle invasive bladder cancer and muscle invasive bladder cancer subtypes. Biochem Genet. 2024.
33. Ott PA, Hu-Lieskovan S, Chmielowski B, Ribas A, Johnson DB, Daud A, et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. Cell. 2020;183(2):347-62.e24.
34. Nassif EF, Thibault C, Oudard S, Galon J. Precision immunity: immunoscore and neoadjuvant treatment in bladder cancer. Oncoimmunology. 2021;10(1):1888488.
35. Waqas A, Zaffar J, Jalil A, Butt S. Nivolumab-induced isolated neutropenia. Cureus. 2023;15(9):e45675.
36. Ren J. Advances in combination therapy for gastric cancer: integrating targeted agents and immunotherapy. Adv Clin Pharmacol Ther. 2024;1(1):1-15.
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| Issue | Articles in Press | |
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| Keywords | ||
| High‐risk Immunotherapy Muscle invasive bladder neoplasms Surgical margins | ||
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How to Cite
1.
Li Z, Liu C, Wang H. Exploring the Efficacy of Immunotherapy in Combination with Surgical Resection in High-risk Muscle-invasive Bladder Cancer. Iran J Allergy Asthma Immunol. 2025;:1-13.
