Efficacy of Gemcitabine Submucosal Injection for Preventing Recurrence in Intermediate- and High-Risk Non-Muscle-Invasive Bladder Cancer: A Randomized Trial

Summary

Bladder cancer is the most common malignant tumor of the urinary system in China, and its incidence has been increasing year by year. It is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). NMIBC accounts for 75% of newly diagnosed bladder cancer cases, and transurethral resection of bladder tumor (TURBT) followed by postoperative intravesical therapy is the standard treatment for NMIBC. However, the 5-year recurrence rate of NMIBC remains as high as 50%, with 20-30% of patients progressing to MIBC. MIBC is characterized by rapid progression and a high tendency for metastasis. The 5-year survival rate for patients with metastatic bladder cancer is only 5.4%. This study aims to investigate the efficacy of submucosal injection of the chemotherapeutic agent gemcitabine in preventing recurrence of intermediate- and high-risk NMIBC. Additionally, it seeks to develop software and devices related to submucosal injection to promote the clinical application of this new approach in the chemotherapeutic management of NMIBC. This research is expected to bring a revolutionary breakthrough in the standardisation of whole-process diagnosis and treatment of NMIBC, holding significant scientific value and major clinical translational importance for improving therapeutic outcomes and prognosis of bladder cancer.

Timeline

Start

2025-10

Primary completion

2028-05

Completion

2028-06

Publications

• Background Liu K, Peng J, Guo Y, Li Y, Qi X, Duan D, Li T, Li J, Niu Y, Han G, Zhao Y. Expanding the Potential of Neoantigen Vaccines: Harnessing Bacille Calmette-Guerin Cell-Wall-Based Nanoscale Adjuvants for Enhanced Cancer Immunotherapy. ACS Nano. 2024 May 7;18(18):11910-11920. doi: 10.1021/acsnano.4c01691. Epub 2024 Apr 29.
• Background Koya MP, Simon MA, Soloway MS. Complications of intravesical therapy for urothelial cancer of the bladder. J Urol. 2006 Jun;175(6):2004-10. doi: 10.1016/S0022-5347(06)00264-3.
• Background Gravestock P, Cullum D, Somani B, Veeratterapillay R. Diagnosing upper tract urothelial carcinoma: A review of the role of diagnostic ureteroscopy and novel developments over last two decades. Asian J Urol. 2024 Apr;11(2):242-252. doi: 10.1016/j.ajur.2022.08.003. Epub 2022 Sep 23.
• Background Morad G, Helmink BA, Sharma P, Wargo JA. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell. 2021 Oct 14;184(21):5309-5337. doi: 10.1016/j.cell.2021.09.020. Epub 2021 Oct 7.
• Background Kartolo A, Robinson A, Vera Badillo FE. Can Oncogenic Driver Alterations be Responsible for the Lack of Immunotherapy Efficacy in First-line Advanced Urothelial Carcinoma? Eur Urol. 2023 Jan;83(1):1-2. doi: 10.1016/j.eururo.2022.04.022. Epub 2022 May 20.
• Background Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.
• Background Advanced Bladder Cancer (ABC) Meta-analysis Collaborators Group. Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials. Eur Urol. 2022 Jan;81(1):50-61. doi: 10.1016/j.eururo.2021.09.028. Epub 2021 Nov 19.
• Background Cambier S, Sylvester RJ, Collette L, Gontero P, Brausi MA, van Andel G, Kirkels WJ, Silva FC, Oosterlinck W, Prescott S, Kirkali Z, Powell PH, de Reijke TM, Turkeri L, Collette S, Oddens J. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guerin. Eur Urol. 2016 Jan;69(1):60-9. doi: 10.1016/j.eururo.2015.06.045. Epub 2015 Jul 23.
• Background Comperat E, Amin MB, Cathomas R, Choudhury A, De Santis M, Kamat A, Stenzl A, Thoeny HC, Witjes JA. Current best practice for bladder cancer: a narrative review of diagnostics and treatments. Lancet. 2022 Nov 12;400(10364):1712-1721. doi: 10.1016/S0140-6736(22)01188-6. Epub 2022 Sep 26.
• Background Lopez-Beltran A, Cookson MS, Guercio BJ, Cheng L. Advances in diagnosis and treatment of bladder cancer. BMJ. 2024 Feb 12;384:e076743. doi: 10.1136/bmj-2023-076743.
• Background Qi J, Li M, Wang L, Hu Y, Liu W, Long Z, Zhou Z, Yin P, Zhou M. National and subnational trends in cancer burden in China, 2005-20: an analysis of national mortality surveillance data. Lancet Public Health. 2023 Dec;8(12):e943-e955. doi: 10.1016/S2468-2667(23)00211-6.
• Background Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

Drugs

Indications