Clinical trial · Observational
Predicting Response to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Cancer
The Impact of Tumor Microenvironment and Clinicopathological Features in Predicting Response to Neoadjuvant Chemotherapy in Muscle Invasive Bladder Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
Bladder cancer (BC) is the 10th most commonly diagnosed cancer worldwide and the second most common cancer among Egyptian males. The mainstay of treatment of muscle-invasive BC( MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) or bladder preservation(BP) using maximal transurethral resection of the bladder tumor followed by chemoradiation. The rationale to use NAC before RC or BP is to eradicate micro-metastasis and to downstage the primary tumor. The 5-year cancer-specific survival for responders to NAC is 90%, in contrast to 30-40% for those not obtaining an objective response. Drawbacks of NAC are disappointing delay of surgery in non-responders and the potential toxicity. So, predictors of response to NAC are necessary to identify patients who may achieve pathologic complete response and will benefit from BP, and the others who may not respond to NAC and spare them NAC toxicity and RC delay. Tumor microenvironment (TME), including neutrophil extracellular traps (NETs), and CD8+ T lymphocytes is a promising predictor of response to NAC in MIBC. NETs are reticulated DNA structures decorated with various protein substances (e.g., histones, myeloperoxidase, neutrophil elastase).NETs are involved in tumor growth, metastasis, and treatment resistance. Moreover, NETs can inhibit T cell responses, thereby promoting tumor growth. On the other hand, immune cells that are present in the TME play a major role in slowing down tumor progression. CD8+T lymphocytes play a central role in immune-mediated control of cancer . Also, they have been found to be a prognostic tool for advanced BC.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Muscle-Invasive Bladder Carcinoma | Muscle Invasive Bladder Carcinoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| neoadjuvant chemotherapy | Combination Product | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- label
- MIBC patients who received NAC
- description
- Patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy before radical cystectomy or bladder preservation
- interventionNames
- Combination Product: neoadjuvant chemotherapy
Primary outcomes (2)
- measure
- Evaluation of the expression of NETs and CD8 in paraffin-embedded TUR biopsies
- timeFrame
- 6 months
- description
- evaluation of the density of Citrullinated Histone H3 as a hallmark of NETs and the density of CD8 in the baseline FFPE TUR specimens
- measure
- - Response to platinum-based chemotherapy in localized MIBC in relation to: NETs expression, CD8 expression, NET/CD8 ratio and baseline clinicopathological features
- timeFrame
- 6 months
- description
- Correlation between NETs expression, CD8 expression, NETs/CD8 ratio and the baseline clinicopathological features of MIBC and the response to neoadjuvant chemotherapy
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 19 Years
Show eligibility criteria text
Inclusion Criteria: * Pathologically proven pure urothelial carcinoma, or morphologic variant of urothelial carcinoma. * Patients with ≥T2, N0-1, M0, according to American Joint Committee on Cancer (AJCC) TNM Staging System for Bladder Cancer 8th ed., 2017. * Patients who received platinum-based neoadjuvant chemotherapy before RC or BP. * Available paraffin-embedded TUR specimens for Immunohistochemistry (IHC). Exclusion Criteria: * Non urothelial carcinoma. * Not muscle invasive \< T2. * Metastatic bladder cancer. * No available paraffin-embedded TUR specimens for IHC.
References
Publications (12)
- RESULTSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
- RESULTSkinner DG, Lieskovsky G. Contemporary cystectomy with pelvic node dissection compared to preoperative radiation therapy plus cystectomy in management of invasive bladder cancer. J Urol. 1984 Jun;131(6):1069-72. doi: 10.1016/s0022-5347(17)50809-5. PMID 6726903
- RESULTRosenblatt R, Sherif A, Rintala E, Wahlqvist R, Ullen A, Nilsson S, Malmstrom PU; Nordic Urothelial Cancer Group. Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol. 2012 Jun;61(6):1229-38. doi: 10.1016/j.eururo.2011.12.010. Epub 2011 Dec 13. PMID 22189383
- RESULTJiang DM, Jiang H, Chung PWM, Zlotta AR, Fleshner NE, Bristow RG, Berlin A, Kulkarni GS, Alimohamed NS, Lo G, Sridhar SS. Neoadjuvant Chemotherapy Before Bladder-Sparing Chemoradiotherapy in Patients With Nonmetastatic Muscle-Invasive Bladder Cancer. Clin Genitourin Cancer. 2019 Feb;17(1):38-45. doi: 10.1016/j.clgc.2018.09.021. Epub 2018 Oct 4. PMID 30686350
- RESULTWitjes JA, Comperat E, Cowan NC, De Santis M, Gakis G, Lebret T, Ribal MJ, Van der Heijden AG, Sherif A; European Association of Urology. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol. 2014 Apr;65(4):778-92. doi: 10.1016/j.eururo.2013.11.046. Epub 2013 Dec 12. PMID 24373477
- RESULTIkarashi D, Kitano S, Tsuyukubo T, Takenouchi K, Nakayama T, Onagi H, Sakaguchi A, Yamashita M, Mizugaki H, Maekawa S, Kato R, Kato Y, Sugai T, Nakatsura T, Obara W. Pretreatment tumour immune microenvironment predicts clinical response and prognosis of muscle-invasive bladder cancer in the neoadjuvant chemotherapy setting. Br J Cancer. 2022 Mar;126(4):606-614. doi: 10.1038/s41416-021-01628-y. Epub 2021 Nov 15.