Super-selective bladder arterial chemotherapy for muscle invasive bladder cancer

Introduction

Bladder cancer represents the most prevalent malignancy of the urinary system, carrying substantial morbidity and mortality in China (1). Approximately 75% of cases are diagnosed as non-muscle invasive bladder cancer (NMIBC), while the remaining 25% present as muscle-invasive bladder cancer (MIBC) (2). Radical cystectomy (RC) is widely regarded as the optimal therapeutic option for MIBC (3). However, the associated high complication rates, surgical risks, and potential decline in postoperative quality of life often lead to reluctance among both clinicians and patients (4). Even with curative-intent radical surgery, the recurrence rate of MIBC remains substantial, ranging from 22% to 47% (5). Additionally, the typical advanced age and frequent comorbidities of bladder cancer patients further limit their eligibility for RC (6). Furthermore, recent studies have indicated that the efficacy of chemotherapy in treating MIBC remains suboptimal (7).

For patients ineligible for RC or systemic chemotherapy, bladder-preservation therapeutic options remain severely limited (8-10). Although contemporary bladder-preserving strategies have been developed, they are characterized by inconsistent efficacy and potential toxicities, highlighting an unmet clinical need for safer and more effective locoregional therapies. Intra-arterial chemotherapy (IAC) has been reported to decrease the recurrence and progression of bladder cancer. Most patients show good tolerance to this treatment method (11-13). Although there have been reports regarding the application of IAC in MIBC, its effectiveness remains uncertain, particularly for its role in downstaging and bladder preservation.

The aim of the present retrospective, single-arm study was to assess the efficacy and safety of super-selective bladder arterial chemotherapy in patients with MIBC, thereby addressing critical gaps in current evidence regarding its clinical utility. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0069/rc).

Methods

Study design and participants

To evaluate the efficacy and safety of super-selective bladder arterial chemotherapy in patients with MIBC, we conducted a retrospective analysis of all bladder cancer patients who were admitted to our department from January 2018 to September 2024 and received IAC. MIBC was diagnosed in accordance with the 8th edition (2017) of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, based on pathological evaluation of transurethral resection of bladder tumor (TURBT) or biopsy specimens, combined with contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis. All enrolled patients were histologically confirmed to have MIBC (stage II–IV). Prior to super-selective IAC, individualized therapeutic intent was determined based on patient clinical condition, tumor stage, comorbidities, and patient preference, including definitive treatment, bridge to surgery, palliative care, or tumor downstaging.

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No. 26/114-0440). A waiver of written informed consent was approved due to the retrospective and observational nature of this study, which only analyzed anonymized clinical data without additional intervention.

IAC treatment protocol

All patients underwent super-selective IAC under digital subtraction angiography (DSA) guidance using the Seldinger technique. After femoral artery puncture, a catheter was advanced to the bilateral internal iliac arteries and selectively positioned into the superior and inferior vesical arteries supplying the tumor. When angiography showed prominent tumor staining, two-thirds of the chemotherapeutic agents were infused into the tumor-feeding artery, and one-third into the contralateral side. In the absence of visible tumor staining, agents were evenly distributed, with half infused into each side.

The chemotherapy regimen consisted of gemcitabine and cisplatin. Cisplatin was administered at a dose of 70 mg/m² (maximum total dose: 180 mg), and gemcitabine at 1 g/m². Both drugs were infused into the bilateral bladder arteries over a period of 30 to 60 minutes, without subsequent embolization of the target arteries (14).

Outcomes and follow-up

Four weeks post-treatment, tumor response was evaluated using contrast-enhanced CT or MRI, in accordance with the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). While RECIST 1.1 is widely used in clinical practice to assess tumor shrinkage in MIBC, it has inherent limitations, as it primarily focuses on tumor size rather than invasive depth or pathological response—key determinants of treatment efficacy in this disease. To address this limitation, cystoscopic and pathological evaluations were integrated with imaging findings to comprehensively assess treatment response. Per RECIST 1.1 criteria, a complete response (CR) was defined as the absence of any residual tumor, along with no lymph node involvement or distant metastasis. For patients who did not achieve CR, RC was strongly recommended. Alternatively, other treatment options were considered, taking into account the patient’s age, preferences, and performance status.

Statistical analyses

Statistical analyses were performed using SPSS (version 19; SPSS, Chicago, IL, USA) and R (version 4.2.2). Owing to the small sample size, continuous variables are presented as median [interquartile range (IQR)], and paired comparisons were conducted using the Wilcoxon signed-rank test. Categorical variables were expressed as n (%). Survival analysis was performed using the Kaplan-Meier method. P<0.05 was considered statistically significant.

Results

Patient characteristics

A total of 25 patients with MIBC underwent 47 sessions of interventional therapy, among whom 8 patients received multiple treatment cycles, with the maximum number of interventions per patient reaching 7. All patients underwent super-selective transcatheter bladder arterial chemotherapy without embolization. All patients, comprising 20 males and 5 females, were diagnosed with MIBC. The mean age of the participants was 63.8±13.5 years, ranging from 34 to 87 years; the oldest patient was 87 years old. TNM staging distribution according to the 8th AJCC edition was as follows: stage II in 4 patients (16.0%), stage III in 17 patients (68.0%), and stage IV in 4 patients (16.0%). Notably, 60.0% of the patients had no prior treatment before the interventional therapy. Moreover, more than half of the patients (56.0%) underwent surgical resection of bladder tumors after the interventional treatment. CR was achieved in 52.0% of patients, while TURBT was carried out in 4.0%. A summary of patient demographics, tumor characteristics, and treatment details is provided (Table 1).

Follow‑up

During the follow-up period, 17 out of the 25 enrolled patients died. The median overall survival (OS) for the entire cohort was 34.4 months. The 1-, 2-, and 3-year survival rates were 75.4% [95% confidence interval (CI): 60.1–94.6%], 50.3% (95% CI: 33.8–74.8%) and 33.5% (95% CI: 19.1–58.9%), respectively (Figure 1).

Figure 1 Kaplan-Meier survival analysis of the overall survival rate for MIBC patients. MIBC, muscle-invasive bladder cancer.

Clinical outcomes

All patients underwent super-selective bladder arterial infusion chemotherapy successfully. Nevertheless, owing to the limited hemostatic effect of perfusion chemotherapy alone, there was a statistically significant difference in hemoglobin and hematocrit levels between the patients 4 weeks after the operation and their pre-operative levels (P<0.001). Both parameters showed a further decrease (Table 2).

Tumor response

Postoperative imaging data were not available for 3 patients, which precluded the evaluation of their therapeutic efficacy. Based on the RECIST 1.1, a partial response (PR) was noted in 11 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 2 patients. The overall response rate (ORR) and disease control rate (DCR) were 50.0% and 90.9%, respectively (Table 3). Angiography of the bladder artery showed thickening, twisting, disarray, and staining of the artery supplying the bladder tumor (Figures 2,3).

Figure 2 A 51-year-old male with bladder cancer treated with super-selective bladder arterial chemotherapy. (A,B) Preoperative enhanced MRI demonstrated a maximum tumor diameter of 4.9 cm × 2.7 cm on the left side of the bladder. (C,D) Postoperative MRI showing a significant size reduction of the tumor. (E,F) DSA image shows super-selective left bladder arteriography revealed staining of the bladder tumor. DSA, digital subtraction angiography; MRI, magnetic resonance imaging.

Figure 3 A 73-year-old male with bladder cancer who underwent super-selective bladder arterial chemotherapy. (A,B) Preoperative enhanced MRI reveals localized thickening of right bladder wall. (C,D) Postoperative MRI showing a significant size reduction of the tumor. (E,F) The bilateral angiographic revealed staining of the bladder tumor. MRI, magnetic resonance imaging.

Side effects

No significant complications were observed, such as necrosis affecting the bladder, genitals, perineal skin, or procedure-related mortality. The minor adverse reactions were mainly related to chemotherapy and included symptoms like fever, pain, and bone marrow suppression. All adverse reactions were relieved after symptomatic treatment (Table 4).

Discussion

In this study, we determined that the median OS for the entire cohort was 34.4 months, with 1-, 2- and 3-year survival rates of 75.4%, 50.3% and 33.5%, respectively. The ORR and DCR were found to be 50.0% and 90.9%, respectively. The mean age of the participants was 63.8±13.5 years, mostly consisting of elderly patients. Significantly, 56.0% of patients underwent surgical resection of bladder tumors after the interventional treatment. These results suggest favorable treatment outcomes for patients with MIBC. Additionally, no severe complications were noted. Collectively, our data suggest that super-selective bladder arterial chemotherapy is a safe and effective treatment option for MIBC.

The response of tumor cells to chemotherapeutic agents is profoundly influenced by the initial administered dosage. Repeatedly administering lower doses often leads to the development of drug resistance. In contrast, delivering a larger initial dose directly to the tumor site via IAC can significantly decrease the incidence of resistance (15,16). This approach enables higher local concentrations of chemotherapeutic agents, thus enhancing their therapeutic efficacy while minimizing systemic exposure and related adverse effects (17-19). Unlike previous IAC methods that targeted the internal iliac artery, this study utilized super-selective bladder arterial chemotherapy, which specifically targets the artery supplying the tumor. This technique increased the local concentration of the chemotherapeutic agent, demonstrating significant efficacy even without embolization. Most patients in this study had newly diagnosed large tumors that could not be completely resected surgically. Through the use of super-selective bladder arterial chemotherapy, substantial tumor shrinkage was achieved, facilitating total cystectomy. Two years later, the incidence of distant metastases and local recurrence remained low. However, bladder artery embolization was not performed, the rate of hematuria symptom relief at 1 month was limited.

Since 1976, when the foreign scholar Halt first recorded the use of transcatheter arterial embolization (TAE) for treating bladder hemorrhage, this technique has attracted significant attention and has been more frequently applied in the treatment of bladder cancer (20,21). Many studies have explored the effectiveness of IAC in NMIBC (22-24). Moreover, some research has evaluated the role of IAC as an adjuvant therapy in the treatment of bladder cancer (25,26). Generally, these studies report satisfactory results. However, MIBC is characterized by a high recurrence rate and poor prognosis (27), and currently, there is no agreement on the efficacy of IAC in MIBC. As far as we know, this study is the first to assess the therapeutic effect of super-selective bladder arterial chemotherapy in MIBC without embolization. Zhou et al. reported that, 1 month later, the frequencies of complete response, PR, SD, and PD were 5.0%, 55.0%, 25.0%, and 15.0%, respectively, resulting in an objective response rate of 60.0% and a DCR of 85.0% (28). Our findings are consistent with those of Zhou et al., indicating similar outcomes even though in the absence of bladder artery embolization in our approach.

This study has some limitations. First, there are certain limitations in the study design. This was a single-arm retrospective study without a concurrent control group, so a direct efficacy comparison between super-selective bladder arterial chemotherapy and standard treatments for MIBC could not be performed. Furthermore, the retrospective and non-controlled design indicates that the results of this study are only preliminary and exploratory, which can merely provide hypotheses for subsequent research but cannot clarify the superiority or inferiority of this therapy relative to standard treatments. Second, the limited sample size restricts the analysis and requires caution in extrapolation. Due to the small sample size, this study was unable to perform multivariate Cox regression analysis to adjust for confounding factors, including age, clinical TNM stage, lymph node status, previous treatment, and treatment intent, making it difficult to eliminate bias caused by heterogeneity among study participants. Therefore, the results should be interpreted with considerable caution.

Conclusions

In summary, this study proves super-selective IAC is feasible and well-tolerated for MIBC, with a favorable tumor response, especially in downstaging unresectable tumors. Given the lack of a control group, small sample, significant heterogeneity and unadjusted confounders, our findings are preliminary. Large-scale prospective controlled trials are needed to verify its clinical value in MIBC comprehensive treatment.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0069/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0069/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0069/prf

Funding: This study was supported by the National Natural Science Foundation of China (No. 82330061), the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2024-I2M-C&T-B-073), and the Science and Education Cultivation Fund of the National Cancer and Regional Medical Center of Shanxi Provincial Cancer Hospital (No. TD2023003).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-1-0069/coif). All authors report the funding from the National Natural Science Foundation of China (No. 82330061), the CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2024-I2M-C&T-B-073), and the Science and Education Cultivation Fund of the National Cancer and Regional Medical Center of Shanxi Provincial Cancer Hospital (No. TD2023003). The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (No. 26/114-0440). A waiver of written informed consent was approved due to the retrospective and observational nature of this study, which only analyzed anonymized clinical data without additional intervention.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Tian Z, Meng L, Wang X, et al. Young age increases the risk of lymph-node metastasis in patients with muscle-invasive bladder urothelial carcinoma. BMC Cancer 2020;20:851. [Crossref] [PubMed]
2. Wang R, Zheng Z, Mao S, et al. Construction and Validation of a Novel Eight-Gene Risk Signature to Predict the Progression and Prognosis of Bladder Cancer. Front Oncol 2021;11:632459. [Crossref] [PubMed]
3. van der Heijden AG, Bruins HM, Carrion A, et al. European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Summary of the 2025 Guidelines. Eur Urol 2025;87:582-600. [Crossref] [PubMed]
4. Kim KS, Kim SH, Cho HJ, et al. Holmium laser-assisted laparoscopic partial cystectomy for bladder cancer: a single-institutional pilot study with technical feasibility and short-term oncological outcome. BMC Cancer 2022;22:195. [Crossref] [PubMed]
5. Yoo SH, Jeong CW, Kwak C, et al. Intravesical Chemotherapy after Radical Nephroureterectomy for Primary Upper Tract Urothelial Carcinoma: A Systematic Review and Network Meta-Analysis. J Clin Med 2019;8:1059. [Crossref] [PubMed]
6. Schmidt B, Velaer KN, Thomas IC, et al. Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer. Eur Urol Open Sci 2022;35:29-36. [Crossref] [PubMed]
7. Kong C, Zhang S, Lei Q, et al. State-of-the-Art Advances of Nanomedicine for Diagnosis and Treatment of Bladder Cancer. Biosensors (Basel) 2022;12:796. [Crossref] [PubMed]
8. Gupta S, Hensley PJ, Li R, et al. Bladder Preservation Strategies in Muscle-invasive Bladder Cancer: Recommendations from the International Bladder Cancer Group. Eur Urol 2026;89:18-28. [Crossref] [PubMed]
9. Kimura T, Inoue S, Sano T, et al. Recent Advances and Future Directions in Bladder Preservation Therapy for Muscle-Invasive Bladder Cancer. Int J Urol 2025;32:1334-41. [Crossref] [PubMed]
10. Popli S, Durant AM, Tyson M, et al. Current State of Bladder Preservation in High Grade Non-Muscle Invasive Bladder Cancer and Localized Muscle Invasive Bladder Cancer. Curr Oncol Rep 2025;27:761-73. [Crossref] [PubMed]
11. Cambier S, Sylvester RJ, Collette L, et al. 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-Guérin. Eur Urol 2016;69:60-9. [Crossref] [PubMed]
12. Chen MK, Qin ZK, Zhou FJ, et al. Intra-arterial chemotherapy is reliable in preventing high-risk superficial bladder cancer from recurrence and progression. J Chemother 2009;21:681-6. [Crossref] [PubMed]
13. Eapen L, Stewart D, Collins J, et al. Effective bladder sparing therapy with intra-arterial cisplatin and radiotherapy for localized bladder cancer. J Urol 2004;172:1276-80. [Crossref] [PubMed]
14. Kusano S, Tobu S, Yukimoto M, et al. Palliative Intra-Arterial Chemotherapy Without Radiotherapy for Elderly Patients With Muscle-Invasive Bladder Cancer: A Single-Center Retrospective Comparison With Radical Cystectomy and Best Supportive Care. Int J Urol 2026;33:e70386. [Crossref] [PubMed]
15. Laface C, Laforgia M, Molinari P, et al. Intra-Arterial Infusion Chemotherapy in Advanced Pancreatic Cancer: A Comprehensive Review. Cancers (Basel) 2022;14:450. [Crossref] [PubMed]
16. Bahl A, Bakhshi S. Metronomic chemotherapy in progressive pediatric malignancies: old drugs in new package. Indian J Pediatr 2012;79:1617-22. [Crossref] [PubMed]
17. Schäfer T, Sperling J, Kollmar O, et al. Early effect of hepatic artery TNF-alpha infusion on systemic hemodynamics and inflammation: a dose-response study in pigs. Int J Colorectal Dis 2010;25:523-32. [Crossref] [PubMed]
18. Dong Z, Zhang Q, Wang C, et al. Combined Thermosensitive Gel Co-Loaded with Dermaseptin-PP and PTX Liposomes for Effective Local Chemotherapy. Int J Nanomedicine 2023;18:413-24. [Crossref] [PubMed]
19. Wu C, Yi X, Xu R, et al. Biodistribution of etoposide via intratumoral chemotherapy with etoposide-loaded implants. Drug Deliv 2020;27:974-82. [Crossref] [PubMed]
20. Hald T, Mygind T. Control of life-threatening vesical hemorrhage by unilateral hypogastric artery muscle embolization. J Urol 1974;112:60-3. [Crossref] [PubMed]
21. Korkmaz M, Şanal B, Aras B, et al. The short- and long-term effectiveness of transcatheter arterial embolization in patients with intractable hematuria. Diagn Interv Imaging 2016;97:197-201. [Crossref] [PubMed]
22. Lian F, Chen W, Liu Y, et al. Intra-arterial chemotherapy combined with intravesical chemotherapy is effective in preventing recurrence in non-muscle invasive bladder cancer. J Cancer Res Clin Oncol 2019;145:1625-33. [Crossref] [PubMed]
23. Arends TJ, Nativ O, Maffezzini M, et al. Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer. Eur Urol 2016;69:1046-52. [Crossref] [PubMed]
24. Zhang Y, Xie L, Chen T, et al. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study. Onco Targets Ther 2016;9:605-11. [Crossref] [PubMed]
25. Chen J, Yao Z, Qiu S, et al. Comparing intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone: a randomised prospective pilot study for T1G3 bladder transitional cell carcinoma after bladder-preserving surgery. Cardiovasc Intervent Radiol 2013;36:1521-6. [Crossref] [PubMed]
26. Sun F, Zhao R, Zhu Y, et al. A prospective comparison of intra-arterial chemotherapy combined with intravesical chemotherapy and intravesical chemotherapy alone after transurethral resection with a thulium laser in high-risk non-muscle invasive bladder cancer. Cancer Chemother Pharmacol 2017;79:1099-107. [Crossref] [PubMed]
27. Zhou X, Qiu S, Nie L, et al. Classification of Muscle-Invasive Bladder Cancer Based on Immunogenomic Profiling. Front Oncol 2020;10:1429. [Crossref] [PubMed]
28. Zhou Y, Chen J, Chen P, et al. Super-selective transcatheter vesical arterial chemoembolization with drug-loaded beads for muscle-invasive bladder cancer with hematuria. Abdom Radiol (NY) 2023;48:780-6. [Crossref] [PubMed]