Case report: Near-complete pathological response with Enfortumab vedotin plus toripalimab as neoadjuvant therapy for HER2-negative muscular-invasive bladder cancer

Case report: Near-complete pathological response with Enfortumab vedotin plus toripalimab as neoadjuvant therapy for HER2-negative muscular-invasive bladder cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Case report: Near-complete pathological response with Enfortumab vedotin plus toripalimab as neoadjuvant therapy for HER2-negative muscular-invasive bladder cancer Xi Zhang, Chao Cheng, ErChang Shen, Rui Meng, Chao Liu, Qiang Shao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8776083/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Purpose: To report the efficacy and safety of enfortumab vedotin combined with toripalimab as neoadjuvant therapy in an elderly patient with Muscular-invasive bladder cancer (MIBC) who sought bladder preservation. Methods: An 83-year-old male presented with painless gross hematuria. Imaging revealed a 44 mm×39 mm×60 mm bladder mass, and biopsy confirmed high-grade invasive papillary urothelial carcinoma (T2NxM0). After informed consent, the patient received three cycles of neoadjuvant therapy combining enfortumab vedotin (60 mg on days 1 and 8) with toripalimab (240 mg on days 1 and 8) in 21-day cycles. Results: Treatment-related adverse events included hyperglycemia and rash, both managed conservatively without treatment interruption. Post-treatment MRI demonstrated marked tumor reduction, showing only bladder wall thickening. Subsequent transurethral resection of bladder tumor (TURBT) revealed chronic mucosal inflammation with histiocyte aggregation and focal cystic cystitis, with no residual carcinoma identified, achieving near-complete pathological response. Conclusion: This case demonstrates that neoadjuvant enfortumab vedotin combined with toripalimab can achieve near-complete pathological response and successful bladder preservation in carefully selected elderly patients with MIBC, providing valuable real-world evidence for this perioperative treatment approach. muscle-invasive bladder cancer enfortumab vedotin toripalimab neoadjuvant therapy bladder preservation urothelial carcinoma antibody-drug conjugate Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Bladder cancer (BCA) is a common malignant tumor of the urinary system, ranking high in incidence and mortality among all malignancies [ 1 , 2 ] . Muscular-invasive bladder cancer (MIBC) refers to bladder cancer that invades the bladder muscle layer, characterized by high invasiveness, rapid progression, and poor prognosis. Currently, the majority of bladder cancers are urothelial carcinomas. Surgical treatments such as radical cystectomy are currently the primary therapeutic modalities for treating MIBC [ 3 ] . However, patients undergoing radical cystectomy experience decreased quality of life due to urinary diversion, leading a considerable proportion of patients to refuse surgical treatment. Therefore, bladder-sparing treatment regimens have become a current research hotspot [ 4 ] . This article reports a case of an elderly MIBC patient who underwent transurethral resection of bladder tumor (TURBT) after receiving neoadjuvant therapy with Enfortumab vedotin-ejfv (EV) combined with Toripalimab in real-world clinical practice, aiming to provide a reference for clinical practice. Case Presentation 1.1 Medical History, Past History, and Family History An 83-year-old male patient was admitted to the Department of Urology at Suzhou Municipal Hospital (Baita Campus) on November 4, 2025, due to “painless gross hematuria for more than one month.” One month prior, the patient experienced painless gross hematuria without obvious precipitating factors. The urine was dark red, resembling the color of black tea, accompanied by urinary frequency but no urgency, without lumbar soreness or pain, and without nausea or vomiting. At that time, no attention was paid to these symptoms, and there were no other accompanying symptoms. The hematuria persisted without improvement. The patient sought medical attention at an external hospital. On November 2, 2025, he underwent MRI of the urinary tract (kidneys, ureters, and bladder) with plain and enhanced imaging plus MRU at the external hospital. The examination showed: bladder mass, suggesting tumor (malignant possibility); bladder wall thickening and bladder diverticulum; recommendation: bladder MRI examination and biopsy. No special treatment was administered at that time. The patient came to the outpatient clinic of the Department of Urology at our hospital for surgical treatment. The outpatient diagnosis was “hematuria, bladder malignant tumor,” and the patient was admitted. During the course of the disease, the patient was conscious with fair mental status, had lost 3kg in weight recently, and had good appetite and sleep. The patient’s usual physical condition was fair, with a history of hypertension treated with losartan potassium tablets, with good blood pressure control. He denied diabetes but had a history of elevated blood glucose without medication. He denied history of cardiovascular and cerebrovascular diseases, pulmonary diseases, food or drug allergies, surgery, trauma, or blood transfusion. No similar symptoms were observed in the patient’s parents or children. 1.2 Physical Examination and Auxiliary Examination Results 1.2.1 Physical Examination Physical examination on November 4, 2025: The patient was conscious with fair mental status. The bilateral costovertebral angles were symmetrical, with no local tenderness or percussion pain, and bilateral kidneys were not palpable. There was no tenderness along the course of bilateral ureters, and no masses were palpable. The suprapubic bladder area was not distended and non-tender. Digital rectal examination: prostate two-finger width, non-tender, no blood on finger withdrawal. 1.2.2 Laboratory Examination On November 4, 2025, comprehensive biochemical panel, complete blood count, pre-transfusion screening panel, and coagulation function tests were completed, all within normal ranges. Urinalysis with urine sediment: red blood cell count 5560/µl↑, white blood cell count 237/µl↑, bacterial count 203.2/µl↑. 1.2.3 Imaging Examination On November 2, 2025, MRI of the urinary tract (kidneys, ureters, and bladder) with plain and enhanced imaging plus MRU was performed at an external hospital. Imaging findings(as shown in Fig. 1 ): The bladder was poorly distended. A mass-like lesion was observed in the right lateral and posterior walls, appearing slightly hyperintense on T1WI, slightly hypointense on T2W-SPAIR, hyperintense on DWI, and hypointense on ADC, measuring approximately 44mm×39mm×60mm, connected to the wall by a broad base with heterogeneous signal intensity, and slight thickening of the adjacent bladder wall. Several round T2WI hyperintense lesions were also seen in the bladder wall. Diagnostic impression: bladder mass, suggestive of tumor (malignant possibility); bladder wall thickening, bladder diverticulum; recommendation: bladder MRI examination and biopsy 1.2.4 Cystoscopy and Biopsy Histopathology Report On November 6, 2025, cystoscopy was performed at our hospital. A cauliflower-like neoplasm with a broad base was observed on the right lateral wall of the bladder. Several biopsy specimens were taken with biopsy forceps. No obvious neoplasms were observed in the bladder trigone, bilateral ureteral orifices, left lateral wall, posterior wall, or dome of the bladder. Bladder biopsy pathology result: invasive high-grade papillary urothelial carcinoma. Microscopic findings (as shown in Fig. 2 ). Immunohistochemistry results: GATA-3(+), CK7(+), CK20(-), HER-2(0), P16(-), P53(wild-type), Ki-67(+, 40%). 1.3 Treatment Course After completing the examinations, following discussion by the treatment team and multidisciplinary consultation, and referring to the 2025 EAU Bladder Cancer Guidelines[4], combined with the patient’s imaging findings, the patient was highly suspected of having muscle-invasive bladder cancer, currently staged as T₂NₓM₀. Given the patient’s advanced age and strong desire for bladder preservation, combined with the biopsy pathology results, he met the indications for perioperative treatment with enfortumab vedotin combined with immune checkpoint inhibitor therapy. After full communication and informing the patient and family members about the expected treatment effects, treatment cycle, related risks, and costs of this drug therapy regimen, and signing the relevant informed consent forms, the patient began receiving enfortumab vedotin combined with toripalimab treatment on November 17, 2025. The treatment regimen followed the drug instructions and clinical guidelines: with a 21-day cycle, enfortumab vedotin 60mg and toripalimab injection (Tuoyi) 240mg were administered intravenously on days 1 and 8 (as shown in Fig. 3 ). A total of 3 cycles of treatment were administered, specifically on November 17, 2025, November 24, 2025, December 8, 2025, December 15, 2025, December 29, 2025, and January 5, 2026. Before each treatment, the patient’s complete blood count, thyroid function, comprehensive biochemical panel, and rash conditions were examined. After completion of the third cycle of treatment, MRU was repeated and transurethral resection of bladder tumor was scheduled. On day 1 of the first treatment cycle (November 17, 2025), dexamethasone sodium phosphate injection 5mg was administered as premedication before treatment. One week later, the patient developed hyperglycemia, with 2-hour postprandial blood glucose of 16 mmol/L after lunch and 20 mmol/L after dinner, and fasting blood glucose of 8.4 mmol/L the next day. Pancreatic islet function was fair, thyroid function was normal, and peripheral postprandial blood glucose fluctuated between 12–14 mmol/L. After consultation with the endocrinology department, the diagnosis was “type 2 diabetes,” and the patient was treated with metformin 0.5g bid and acarbose 50mg with lunch. After combined hypoglycemic treatment, the patient’s blood glucose returned to near-normal values. After day 8 of the second treatment cycle (December 15, 2025), the patient developed a rash on the shoulders, bilateral arms, back, and waist. Following dermatology consultation, the patient was treated with oral desloratadine tablets and topical fluticasone propionate cream. The rash improved after one week of treatment. Considering that the patient’s blood glucose was well controlled, dexamethasone sodium phosphate injection 5mg intravenous premedication was resumed starting from the third treatment cycle (December 29, 2025). After two treatments, the patient’s rash occasionally recurred but was less severe than before, with treatment continuing as before. Blood glucose control remained fair without significant fluctuations. On January 12, 2026, the patient completed the full course of treatment. Follow-up MRI of the urinary tract (kidneys, ureters, and bladder) with plain and enhanced imaging plus MRU showed(as shown in Fig. 4 ): The bladder was adequately distended with multiple diverticulum-like protrusions. Marked thickening of the anterior-superior bladder wall with heterogeneous signal intensity was observed. The mucosal surface of the right upper lateral wall showed focal enhancement greater than normal mucosa and local wall stiffness. Several round T2WI hyperintense lesions without enhancement were also seen in the bladder wall. Diagnosis: Post-treatment follow-up of bladder tumor, thickened mucosa of the right upper lateral bladder wall, please correlate with cystoscopy; glandular cystitis, multiple bladder diverticula. On January 13, 2026, the patient underwent transurethral resection of bladder tumor. Intraoperatively, severe trabeculation and cellules were observed in the bladder, with a small amount of neoplasm remaining on the right posterior wall. The bladder mass was completely resected down to the muscular layer, hemostasis was achieved, the bladder mass was removed, and the surgery was completed. Postoperative pathology results(as shown in Fig. 5 ): (bladder mass) chronic mucosal inflammation with histiocyte aggregation, focal cystic cystitis changes. Microscopic findings. Immunohistochemistry results: CK20 (umbrella cells +), P53 (wild-type), HER-2 (2+), Ki-67 (+, 5%), CD68 (histiocytes +). Discussion Radical cystectomy (RC) and pelvic lymphadenectomy (PLND) following neoadjuvant chemotherapy can reduce the risk of tumor recurrence and metastasis by maximally removing tumor tissue and surrounding high-risk lymph nodes, thereby improving patient survival, and have become the recognized gold standard for treating resectable muscle-invasive bladder cancer [ 5 ] . However, some patients undergoing radical cystectomy experience significantly decreased quality of life due to urinary diversion and ureterocutaneous stoma-related infections [ 6 ] . Therefore, exploring bladder preservation therapy (BPT) for MIBC patients has high clinical significance. Antibody-drug conjugates (ADCs) are currently a hot topic in novel drug therapy research for malignant tumors [ 7 ] . These drugs achieve their effects by targeting specific antigens to precisely deliver cytotoxic drugs to tumor tissues. Popular targets in bladder cancer include Nectin-4, human epidermal growth factor receptor-2 (HER2), and trophoblast cell-surface antigen-2 (TROP-2). Globally, three ADC drugs have been approved for the treatment of urothelial carcinoma, including enfortumab vedotin (Nectin-4 antibody-MMAE conjugate), disitamab vedotin (HER2 antibody-MMAE conjugate), and sacituzumab govitecan (Trop-2 antibody-SN-38 conjugate) [ 8 ] Enfortumab vedotin is a novel ADCs drug targeting Nectin-4. Nectin-4 is a cell adhesion molecule, and the EV101 trial demonstrated its high expression in the vast majority of urothelial carcinomas [ 9 , 10 ] . Therefore, no special target testing is required for treatment. Enfortumab vedotin destroys the cellular microtubule system through its cytotoxic effect targeting Nectin-4, leading to tumor cell death. Toripalimab is a programmed cell death protein 1 (PD-1) inhibitor. As an innovative drug developed domestically in China, research has shown significant efficacy and controllable safety in various malignant tumors. As neoadjuvant immunotherapy, it has been confirmed by multiple clinical studies to benefit clinical remission rates, and combination regimens are superior to monotherapy [ 11 , 12 ] . Studies have demonstrated that in muscle-invasive bladder cancer (MIBC), neoadjuvant combination therapy with tislelizumab plus GC resulted in superior pathological complete response (pCR) and pathological downstaging rates versus chemotherapy or immunotherapy monotherapy. Patients achieving pCR following maximal transurethral resection of bladder tumor (TURBT) may be eligible for bladder preservation, showing promising short-term follow-up results [ 13 ] . In this case, since the pre-treatment biopsy pathology immunohistochemistry indicated HER2(0), the conventionally used neoadjuvant treatment of disitamab vedotin combined with toripalimab (PD-1 class) or tislelizumab (programmed death ligand-1, PD-L1 class) would be difficult to be effective. Therefore, enfortumab vedotin combined with toripalimab was adopted instead. After the patient received three cycles of enfortumab vedotin combined with toripalimab treatment before surgery, MRU imaging indicated significant tumor reduction (from a 44mm×39mm×60mm mass with broad base to only bladder wall thickening on imaging), and symptoms such as hematuria no longer appeared. Overall, although this patient experienced adverse reactions such as rash and elevated blood glucose after medication, the established treatment plan was strictly followed without discontinuation, delay, or dose reduction. Instead, active supportive treatment was adopted to help the patient overcome problems arising during the treatment process. Overall, significant tumor shrinkage and downstaging were observed. After transurethral resection of bladder tumor, the patient’s bladder tumor showed near-complete remission, and quality of life was preserved. Currently, cases using enfortumab vedotin combined with toripalimab for perioperative treatment of locally advanced bladder cancer patients are relatively rare. This case provides valuable and authentic practical experience, and the author’s team will further track the patient’s usage and prognosis. Conclusion This case demonstrates that neoadjuvant therapy combining enfortumab vedotin with toripalimab represents a promising treatment approach for elderly patients with muscle-invasive bladder cancer who prioritize bladder preservation. The combination achieved near-complete pathological response following three treatment cycles, enabling successful bladder-sparing surgery while maintaining acceptable tolerability. Statements & Declarations Funding The author(s) declare that no financial support was received for the research and/or publication of this article. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Author contributions All authors contributed to the study conception and design. XI Zhang: Conceptualization, Methodology, Supervision, Validation, Writing – Original Draft, Writing – Review & Editing. RuiMeng: Visualization, Writing – Review & Editing. Chao Cheng and ErChang Shen: Writing – Review & Editing. Chao Liu and Qiang Shao: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Validation, Writing – Review & Editing. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript Ethics approval and consent to participate This manuscript is a single-patient case report. According to the policy of the Ethics Committee of Affiliated Suzhou Hospital of Nanjing Medical University, standalone case reports do not require formal ethical approval. The study was conducted in accordance with the Declaration of Helsinki and institutional ethical guidelines. The Ethics Committee of Affiliated Suzhou Hospital of Nanjing Medical University has confirmed exemption from full review for this type of study. Consent to participate and publish Written informed consent was obtained from the patient ‘s family for the publication of the case report and all accompanying images Data availability statement No datasets were generated or analysed during the current study. Generative AI statement The authors declare that no Gen AI was used in the creation of this manuscript References H S, J F, Rl S, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2021, 71(3). F B, M L, H S, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2024, 74(3). J D, M O. Bladder cancer: current challenges and future directions[J]. Medicina (Kaunas, Lithuania), 2021, 57(8). T L, S R, M G, et al. A narrative review of management of muscle-invasive bladder cancer perioperative period: will continuous and combined treatment be the new trend?[J]. Translational Andrology and Urology, 2024, 13(2). Ag van der H, Hm B, A C, et al. European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2025 guidelines[J]. European Urology, 2025, 87(5). R Z, Cx K. Advances in bladder preservation therapy for muscle-invasive bladder cancer[J]. Frontiers in Oncology, 2025, 15. L M, A K, R J. Advancing bladder cancer management: the role of neoadjuvant and adjuvant therapies and biomarkers in muscle invasive bladder cancer[J]. Current Treatment Options in Oncology, 2025, 26(11). G D, Ml E, Mp D, et al. Spatial expression of HER2, NECTIN4, and TROP-2 in muscle-invasive bladder cancer and metastases: implications for pathological and clinical management[J]. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 2025, 38(7). M M, T O, K I, et al. Clinical relevance of nectin-4 downregulation and biological changes caused by cytotoxic chemotherapy in bladder cancer[J]. Cancer Chemotherapy and Pharmacology, 2025, 95(1). T P, Bp V, S G, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer[J]. New England Journal of Medicine, 2024, 390(10). L Z, D J, J Z, et al. Disitamab vedotin combined with toripalimab and radiotherapy for multimodal organ-sparing treatment of muscle invasive bladder cancer: a proof-of-concept study[J]. Neoplasia (New York, N.Y.), 2025, 68. Hq M, Qy C, D C, et al. Toripalimab plus chemotherapy for recurrent or metastatic nasopharyngeal carcinoma: the Jupiter-02 randomized clinical trial[J]. JAMA, 2023, 330(20). J H, J C, Z O, et al. Neoadjuvant immunotherapy, chemotherapy, and combination therapy in muscle-invasive bladder cancer: a multi-center real-world retrospective study[J]. Cell Reports. Medicine, 2022, 3(11). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Apr, 2026 Reviews received at journal 01 Apr, 2026 Reviewers agreed at journal 01 Apr, 2026 Reviewers invited by journal 30 Mar, 2026 Editor assigned by journal 30 Mar, 2026 Submission checks completed at journal 27 Mar, 2026 First submitted to journal 19 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8776083","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":614990314,"identity":"a1e720f2-6b24-4270-b787-449ba57773cb","order_by":0,"name":"Xi Zhang","email":"","orcid":"","institution":"Affiliated Suzhou Hospital of Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xi","middleName":"","lastName":"Zhang","suffix":""},{"id":614990315,"identity":"d423c03d-bbcc-43ce-88bb-1b56c714a27a","order_by":1,"name":"Chao Cheng","email":"","orcid":"","institution":"Affiliated Suzhou Hospital of Nanjing Medical 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1E).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8776083/v1/d411c8a610d73dbfa9389af4.png"},{"id":106093221,"identity":"714a025d-cf47-42bf-a12b-902f02aa793b","added_by":"auto","created_at":"2026-04-03 11:36:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":191977,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathology of biopsy specimens showing H\u0026amp;E staining (Fig. 2A) and CD7 staining (Fig. 2B).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8776083/v1/2771c75e6ab460dcbc25c8e0.png"},{"id":105983117,"identity":"e37db85c-3662-43b3-beab-2444dd203b92","added_by":"auto","created_at":"2026-04-02 07:07:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":25903,"visible":true,"origin":"","legend":"\u003cp\u003e21-day treatment protocol of enfortumab vedotin in combination with PD-1/PD-L1 inhibitors for locally advanced bladder cancer.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8776083/v1/036c3974df83bc502a7a0687.png"},{"id":106093696,"identity":"2e2d6021-cd75-4f64-a8e3-051ffb7b81ed","added_by":"auto","created_at":"2026-04-03 11:38:40","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":253246,"visible":true,"origin":"","legend":"\u003cp\u003eMRI of the urinary tract (kidneys, ureters, bladder) including unenhanced, contrast-enhanced, and MR urography sequences showed focal mucosal enhancement with slight wall rigidity in the right upper lateral bladder wall (arrows), more prominent than adjacent normal mucosa, on contrast-enhanced T2-weighted coronal (Fig. 4A), axial (Fig. 4B), and sagittal (Fig. 4C) images; the lesion demonstrated restricted diffusion with hypointense ADC (Fig. 4D) and hyperintense DWI (Fig. 4E) signals on axial images, with reduction in size compared to previous study.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8776083/v1/96da0a5e32b12e7562dd896a.png"},{"id":106093921,"identity":"df256ac4-d9c8-47ee-9fd6-b3d7a9397fb7","added_by":"auto","created_at":"2026-04-03 11:40:06","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":315758,"visible":true,"origin":"","legend":"\u003cp\u003eHistopathological examination of postoperative specimens with hematoxylin and eosin staining (Fig. 5A), CD68 immunohistochemical staining (Fig. 5B), and P53 immunohistochemical staining (Fig. 5C).\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8776083/v1/d39b54e8b3179ddf0df02cf3.png"},{"id":106401763,"identity":"783623a4-32e9-4a7c-b447-fda1d095fac2","added_by":"auto","created_at":"2026-04-08 09:09:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1712770,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8776083/v1/159e201c-edfa-463e-856f-92a225cd1ad7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eCase report: Near-complete pathological response with Enfortumab vedotin plus toripalimab as neoadjuvant therapy for HER2-negative muscular-invasive bladder cancer\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBladder cancer (BCA) is a common malignant tumor of the urinary system, ranking high in incidence and mortality among all malignancies\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Muscular-invasive bladder cancer (MIBC) refers to bladder cancer that invades the bladder muscle layer, characterized by high invasiveness, rapid progression, and poor prognosis. Currently, the majority of bladder cancers are urothelial carcinomas. Surgical treatments such as radical cystectomy are currently the primary therapeutic modalities for treating MIBC\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. However, patients undergoing radical cystectomy experience decreased quality of life due to urinary diversion, leading a considerable proportion of patients to refuse surgical treatment. Therefore, bladder-sparing treatment regimens have become a current research hotspot\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis article reports a case of an elderly MIBC patient who underwent transurethral resection of bladder tumor (TURBT) after receiving neoadjuvant therapy with Enfortumab vedotin-ejfv (EV) combined with Toripalimab in real-world clinical practice, aiming to provide a reference for clinical practice.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.1 Medical History, Past History, and Family History\u003c/h2\u003e \u003cp\u003eAn 83-year-old male patient was admitted to the Department of Urology at Suzhou Municipal Hospital (Baita Campus) on November 4, 2025, due to \u0026ldquo;painless gross hematuria for more than one month.\u0026rdquo;\u003c/p\u003e \u003cp\u003eOne month prior, the patient experienced painless gross hematuria without obvious precipitating factors. The urine was dark red, resembling the color of black tea, accompanied by urinary frequency but no urgency, without lumbar soreness or pain, and without nausea or vomiting. At that time, no attention was paid to these symptoms, and there were no other accompanying symptoms. The hematuria persisted without improvement. The patient sought medical attention at an external hospital. On November 2, 2025, he underwent MRI of the urinary tract (kidneys, ureters, and bladder) with plain and enhanced imaging plus MRU at the external hospital. The examination showed: bladder mass, suggesting tumor (malignant possibility); bladder wall thickening and bladder diverticulum; recommendation: bladder MRI examination and biopsy. No special treatment was administered at that time. The patient came to the outpatient clinic of the Department of Urology at our hospital for surgical treatment. The outpatient diagnosis was \u0026ldquo;hematuria, bladder malignant tumor,\u0026rdquo; and the patient was admitted. During the course of the disease, the patient was conscious with fair mental status, had lost 3kg in weight recently, and had good appetite and sleep.\u003c/p\u003e \u003cp\u003eThe patient\u0026rsquo;s usual physical condition was fair, with a history of hypertension treated with losartan potassium tablets, with good blood pressure control. He denied diabetes but had a history of elevated blood glucose without medication. He denied history of cardiovascular and cerebrovascular diseases, pulmonary diseases, food or drug allergies, surgery, trauma, or blood transfusion. No similar symptoms were observed in the patient\u0026rsquo;s parents or children.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e1.2 Physical Examination and Auxiliary Examination Results\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e1.2.1 Physical Examination\u003c/h2\u003e \u003cp\u003ePhysical examination on November 4, 2025: The patient was conscious with fair mental status. The bilateral costovertebral angles were symmetrical, with no local tenderness or percussion pain, and bilateral kidneys were not palpable. There was no tenderness along the course of bilateral ureters, and no masses were palpable. The suprapubic bladder area was not distended and non-tender. Digital rectal examination: prostate two-finger width, non-tender, no blood on finger withdrawal.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e1.2.2 Laboratory Examination\u003c/h2\u003e \u003cp\u003eOn November 4, 2025, comprehensive biochemical panel, complete blood count, pre-transfusion screening panel, and coagulation function tests were completed, all within normal ranges. Urinalysis with urine sediment: red blood cell count 5560/\u0026micro;l\u0026uarr;, white blood cell count 237/\u0026micro;l\u0026uarr;, bacterial count 203.2/\u0026micro;l\u0026uarr;.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e1.2.3 Imaging Examination\u003c/h2\u003e \u003cp\u003eOn November 2, 2025, MRI of the urinary tract (kidneys, ureters, and bladder) with plain and enhanced imaging plus MRU was performed at an external hospital. Imaging findings(as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e): The bladder was poorly distended. A mass-like lesion was observed in the right lateral and posterior walls, appearing slightly hyperintense on T1WI, slightly hypointense on T2W-SPAIR, hyperintense on DWI, and hypointense on ADC, measuring approximately 44mm\u0026times;39mm\u0026times;60mm, connected to the wall by a broad base with heterogeneous signal intensity, and slight thickening of the adjacent bladder wall. Several round T2WI hyperintense lesions were also seen in the bladder wall. Diagnostic impression: bladder mass, suggestive of tumor (malignant possibility); bladder wall thickening, bladder diverticulum; recommendation: bladder MRI examination and biopsy\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003e1.2.4 Cystoscopy and Biopsy Histopathology Report\u003c/h2\u003e \u003cp\u003eOn November 6, 2025, cystoscopy was performed at our hospital. A cauliflower-like neoplasm with a broad base was observed on the right lateral wall of the bladder. Several biopsy specimens were taken with biopsy forceps. No obvious neoplasms were observed in the bladder trigone, bilateral ureteral orifices, left lateral wall, posterior wall, or dome of the bladder. Bladder biopsy pathology result: invasive high-grade papillary urothelial carcinoma. Microscopic findings (as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Immunohistochemistry results: GATA-3(+), CK7(+), CK20(-), HER-2(0), P16(-), P53(wild-type), Ki-67(+, 40%).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e1.3 Treatment Course\u003c/h2\u003e \u003cp\u003eAfter completing the examinations, following discussion by the treatment team and multidisciplinary consultation, and referring to the 2025 EAU Bladder Cancer Guidelines[4], combined with the patient\u0026rsquo;s imaging findings, the patient was highly suspected of having muscle-invasive bladder cancer, currently staged as T₂NₓM₀. Given the patient\u0026rsquo;s advanced age and strong desire for bladder preservation, combined with the biopsy pathology results, he met the indications for perioperative treatment with enfortumab vedotin combined with immune checkpoint inhibitor therapy. After full communication and informing the patient and family members about the expected treatment effects, treatment cycle, related risks, and costs of this drug therapy regimen, and signing the relevant informed consent forms, the patient began receiving enfortumab vedotin combined with toripalimab treatment on November 17, 2025. The treatment regimen followed the drug instructions and clinical guidelines: with a 21-day cycle, enfortumab vedotin 60mg and toripalimab injection (Tuoyi) 240mg were administered intravenously on days 1 and 8 (as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). A total of 3 cycles of treatment were administered, specifically on November 17, 2025, November 24, 2025, December 8, 2025, December 15, 2025, December 29, 2025, and January 5, 2026. Before each treatment, the patient\u0026rsquo;s complete blood count, thyroid function, comprehensive biochemical panel, and rash conditions were examined. After completion of the third cycle of treatment, MRU was repeated and transurethral resection of bladder tumor was scheduled.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOn day 1 of the first treatment cycle (November 17, 2025), dexamethasone sodium phosphate injection 5mg was administered as premedication before treatment. One week later, the patient developed hyperglycemia, with 2-hour postprandial blood glucose of 16 mmol/L after lunch and 20 mmol/L after dinner, and fasting blood glucose of 8.4 mmol/L the next day. Pancreatic islet function was fair, thyroid function was normal, and peripheral postprandial blood glucose fluctuated between 12\u0026ndash;14 mmol/L. After consultation with the endocrinology department, the diagnosis was \u0026ldquo;type 2 diabetes,\u0026rdquo; and the patient was treated with metformin 0.5g bid and acarbose 50mg with lunch. After combined hypoglycemic treatment, the patient\u0026rsquo;s blood glucose returned to near-normal values.\u003c/p\u003e \u003cp\u003eAfter day 8 of the second treatment cycle (December 15, 2025), the patient developed a rash on the shoulders, bilateral arms, back, and waist. Following dermatology consultation, the patient was treated with oral desloratadine tablets and topical fluticasone propionate cream. The rash improved after one week of treatment.\u003c/p\u003e \u003cp\u003eConsidering that the patient\u0026rsquo;s blood glucose was well controlled, dexamethasone sodium phosphate injection 5mg intravenous premedication was resumed starting from the third treatment cycle (December 29, 2025). After two treatments, the patient\u0026rsquo;s rash occasionally recurred but was less severe than before, with treatment continuing as before. Blood glucose control remained fair without significant fluctuations.\u003c/p\u003e \u003cp\u003eOn January 12, 2026, the patient completed the full course of treatment. Follow-up MRI of the urinary tract (kidneys, ureters, and bladder) with plain and enhanced imaging plus MRU showed(as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e): The bladder was adequately distended with multiple diverticulum-like protrusions. Marked thickening of the anterior-superior bladder wall with heterogeneous signal intensity was observed. The mucosal surface of the right upper lateral wall showed focal enhancement greater than normal mucosa and local wall stiffness. Several round T2WI hyperintense lesions without enhancement were also seen in the bladder wall. Diagnosis: Post-treatment follow-up of bladder tumor, thickened mucosa of the right upper lateral bladder wall, please correlate with cystoscopy; glandular cystitis, multiple bladder diverticula.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOn January 13, 2026, the patient underwent transurethral resection of bladder tumor. Intraoperatively, severe trabeculation and cellules were observed in the bladder, with a small amount of neoplasm remaining on the right posterior wall. The bladder mass was completely resected down to the muscular layer, hemostasis was achieved, the bladder mass was removed, and the surgery was completed. Postoperative pathology results(as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e): (bladder mass) chronic mucosal inflammation with histiocyte aggregation, focal cystic cystitis changes. Microscopic findings. Immunohistochemistry results: CK20 (umbrella cells +), P53 (wild-type), HER-2 (2+), Ki-67 (+, 5%), CD68 (histiocytes +).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eRadical cystectomy (RC) and pelvic lymphadenectomy (PLND) following neoadjuvant chemotherapy can reduce the risk of tumor recurrence and metastasis by maximally removing tumor tissue and surrounding high-risk lymph nodes, thereby improving patient survival, and have become the recognized gold standard for treating resectable muscle-invasive bladder cancer\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. However, some patients undergoing radical cystectomy experience significantly decreased quality of life due to urinary diversion and ureterocutaneous stoma-related infections\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Therefore, exploring bladder preservation therapy (BPT) for MIBC patients has high clinical significance.\u003c/p\u003e \u003cp\u003eAntibody-drug conjugates (ADCs) are currently a hot topic in novel drug therapy research for malignant tumors\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. These drugs achieve their effects by targeting specific antigens to precisely deliver cytotoxic drugs to tumor tissues. Popular targets in bladder cancer include Nectin-4, human epidermal growth factor receptor-2 (HER2), and trophoblast cell-surface antigen-2 (TROP-2). Globally, three ADC drugs have been approved for the treatment of urothelial carcinoma, including enfortumab vedotin (Nectin-4 antibody-MMAE conjugate), disitamab vedotin (HER2 antibody-MMAE conjugate), and sacituzumab govitecan (Trop-2 antibody-SN-38 conjugate)\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eEnfortumab vedotin is a novel ADCs drug targeting Nectin-4. Nectin-4 is a cell adhesion molecule, and the EV101 trial demonstrated its high expression in the vast majority of urothelial carcinomas\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Therefore, no special target testing is required for treatment. Enfortumab vedotin destroys the cellular microtubule system through its cytotoxic effect targeting Nectin-4, leading to tumor cell death. Toripalimab is a programmed cell death protein 1 (PD-1) inhibitor. As an innovative drug developed domestically in China, research has shown significant efficacy and controllable safety in various malignant tumors. As neoadjuvant immunotherapy, it has been confirmed by multiple clinical studies to benefit clinical remission rates, and combination regimens are superior to monotherapy\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. Studies have demonstrated that in muscle-invasive bladder cancer (MIBC), neoadjuvant combination therapy with tislelizumab plus GC resulted in superior pathological complete response (pCR) and pathological downstaging rates versus chemotherapy or immunotherapy monotherapy. Patients achieving pCR following maximal transurethral resection of bladder tumor (TURBT) may be eligible for bladder preservation, showing promising short-term follow-up results\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn this case, since the pre-treatment biopsy pathology immunohistochemistry indicated HER2(0), the conventionally used neoadjuvant treatment of disitamab vedotin combined with toripalimab (PD-1 class) or tislelizumab (programmed death ligand-1, PD-L1 class) would be difficult to be effective. Therefore, enfortumab vedotin combined with toripalimab was adopted instead. After the patient received three cycles of enfortumab vedotin combined with toripalimab treatment before surgery, MRU imaging indicated significant tumor reduction (from a 44mm\u0026times;39mm\u0026times;60mm mass with broad base to only bladder wall thickening on imaging), and symptoms such as hematuria no longer appeared.\u003c/p\u003e \u003cp\u003eOverall, although this patient experienced adverse reactions such as rash and elevated blood glucose after medication, the established treatment plan was strictly followed without discontinuation, delay, or dose reduction. Instead, active supportive treatment was adopted to help the patient overcome problems arising during the treatment process. Overall, significant tumor shrinkage and downstaging were observed. After transurethral resection of bladder tumor, the patient\u0026rsquo;s bladder tumor showed near-complete remission, and quality of life was preserved. Currently, cases using enfortumab vedotin combined with toripalimab for perioperative treatment of locally advanced bladder cancer patients are relatively rare. This case provides valuable and authentic practical experience, and the author\u0026rsquo;s team will further track the patient\u0026rsquo;s usage and prognosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case demonstrates that neoadjuvant therapy combining enfortumab vedotin with toripalimab represents a promising treatment approach for elderly patients with muscle-invasive bladder cancer who prioritize bladder preservation. The combination achieved near-complete pathological response following three treatment cycles, enabling successful bladder-sparing surgery while maintaining acceptable tolerability.\u003c/p\u003e"},{"header":"Statements \u0026 Declarations ","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author(s) declare that no financial support was received for the research and/or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eXI Zhang: Conceptualization, Methodology, Supervision, Validation, Writing – Original Draft, Writing – Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eRuiMeng: Visualization, Writing – Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eChao Cheng and ErChang Shen: Writing – Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eChao Liu and Qiang Shao: Conceptualization, Funding Acquisition, Methodology, Project Administration, Supervision, Validation, Writing – Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003eAll authors commented on previous versions of the manuscript. All authors read and approved the final manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript is a single-patient case report. According to the policy of the Ethics Committee of Affiliated Suzhou Hospital of Nanjing Medical University, standalone case reports do not require formal ethical approval. The study was conducted in accordance with the Declaration of Helsinki and institutional ethical guidelines. The Ethics Committee of Affiliated Suzhou Hospital of Nanjing Medical University has confirmed exemption from full review for this type of study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate and publish\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient ‘s family for the publication of the case report and all accompanying images\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenerative AI statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no Gen AI was used in the creation of this manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eH S, J F, Rl S, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2021, 71(3).\u003c/li\u003e\n\u003cli\u003eF B, M L, H S, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2024, 74(3).\u003c/li\u003e\n\u003cli\u003eJ D, M O. Bladder cancer: current challenges and future directions[J]. Medicina (Kaunas, Lithuania), 2021, 57(8).\u003c/li\u003e\n\u003cli\u003eT L, S R, M G, et al. A narrative review of management of muscle-invasive bladder cancer perioperative period: will continuous and combined treatment be the new trend?[J]. Translational Andrology and Urology, 2024, 13(2).\u003c/li\u003e\n\u003cli\u003eAg van der H, Hm B, A C, et al. European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2025 guidelines[J]. European Urology, 2025, 87(5).\u003c/li\u003e\n\u003cli\u003eR Z, Cx K. Advances in bladder preservation therapy for muscle-invasive bladder cancer[J]. Frontiers in Oncology, 2025, 15.\u003c/li\u003e\n\u003cli\u003eL M, A K, R J. Advancing bladder cancer management: the role of neoadjuvant and adjuvant therapies and biomarkers in muscle invasive bladder cancer[J]. Current Treatment Options in Oncology, 2025, 26(11).\u003c/li\u003e\n\u003cli\u003eG D, Ml E, Mp D, et al. Spatial expression of HER2, NECTIN4, and TROP-2 in muscle-invasive bladder cancer and metastases: implications for pathological and clinical management[J]. Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc, 2025, 38(7).\u003c/li\u003e\n\u003cli\u003eM M, T O, K I, et al. Clinical relevance of nectin-4 downregulation and biological changes caused by cytotoxic chemotherapy in bladder cancer[J]. Cancer Chemotherapy and Pharmacology, 2025, 95(1).\u003c/li\u003e\n\u003cli\u003eT P, Bp V, S G, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer[J]. New England Journal of Medicine, 2024, 390(10).\u003c/li\u003e\n\u003cli\u003eL Z, D J, J Z, et al. Disitamab vedotin combined with toripalimab and radiotherapy for multimodal organ-sparing treatment of muscle invasive bladder cancer: a proof-of-concept study[J]. Neoplasia (New York, N.Y.), 2025, 68.\u003c/li\u003e\n\u003cli\u003eHq M, Qy C, D C, et al. Toripalimab plus chemotherapy for recurrent or metastatic nasopharyngeal carcinoma: the Jupiter-02 randomized clinical trial[J]. JAMA, 2023, 330(20).\u003c/li\u003e\n\u003cli\u003eJ H, J C, Z O, et al. Neoadjuvant immunotherapy, chemotherapy, and combination therapy in muscle-invasive bladder cancer: a multi-center real-world retrospective study[J]. Cell Reports. Medicine, 2022, 3(11).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"muscle-invasive bladder cancer, enfortumab vedotin, toripalimab, neoadjuvant therapy, bladder preservation, urothelial carcinoma, antibody-drug conjugate","lastPublishedDoi":"10.21203/rs.3.rs-8776083/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8776083/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003ePurpose:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo report the efficacy and safety of enfortumab vedotin combined with toripalimab as neoadjuvant therapy in an elderly patient with Muscular-invasive bladder cancer (MIBC) who sought bladder preservation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAn 83-year-old male presented with painless gross hematuria. Imaging revealed a 44 mm\u0026times;39 mm\u0026times;60 mm bladder mass, and biopsy confirmed high-grade invasive papillary urothelial carcinoma (T2NxM0). After informed consent, the patient received three cycles of neoadjuvant therapy combining enfortumab vedotin (60 mg on days 1 and 8) with toripalimab (240 mg on days 1 and 8) in 21-day cycles.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTreatment-related adverse events included hyperglycemia and rash, both managed conservatively without treatment interruption. Post-treatment MRI demonstrated marked tumor reduction, showing only bladder wall thickening. Subsequent transurethral resection of bladder tumor (TURBT) revealed chronic mucosal inflammation with histiocyte aggregation and focal cystic cystitis, with no residual carcinoma identified, achieving near-complete pathological response.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis case demonstrates that neoadjuvant enfortumab vedotin combined with toripalimab can achieve near-complete pathological response and successful bladder preservation in carefully selected elderly patients with MIBC, providing valuable real-world evidence for this perioperative treatment approach.\u003c/p\u003e","manuscriptTitle":"Case report: Near-complete pathological response with Enfortumab vedotin plus toripalimab as neoadjuvant therapy for HER2-negative muscular-invasive bladder cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-02 07:07:14","doi":"10.21203/rs.3.rs-8776083/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-09T11:46:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-01T18:56:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"209139521768616337637272126302356507209","date":"2026-04-01T18:34:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-30T07:50:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-30T07:25:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-27T14:04:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cancer Research and Clinical Oncology","date":"2026-03-19T16:17:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cancer-research-and-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jocr","sideBox":"Learn more about [Journal of Cancer Research and Clinical Oncology](https://www.springer.com/journal/432)","snPcode":"432","submissionUrl":"https://submission.nature.com/new-submission/432/3","title":"Journal of Cancer Research and Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9d2414b0-fbb9-4f4a-9bd7-2f38c9291e46","owner":[],"postedDate":"April 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T06:39:59+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-02 07:07:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8776083","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8776083","identity":"rs-8776083","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}