{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:19:59Z","timestamp":1788373199451,"version":"build-2803163510"},"reference-count":71,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Non-muscle-invasive bladder cancer (NMIBC) comprises approximately 75% of new bladder cancer cases and generally carries a favorable prognosis, yet high rates of recurrence and progression necessitate close surveillance with frequent cystoscopies and repeated transurethral resections. Upfront treatment for high-risk disease is typically Bacillus Calmette-Gu\u00e9rin (BCG), although combinations with immune checkpoint inhibitors have reported results. Patients with BCG-unresponsive, intolerant, or refractory disease represent a subset of patients with high risk of progression, with early radical cystectomy being the standard approach for this setting. Global BCG shortages and the substantial impact of cystectomy on quality of life underscore the need for therapeutic alternatives. Over the past decade, investigational trials in immunotherapy have expanded treatment options for BCG-unresponsive NMIBC with CIS, leading to FDA approval of intravesical nadofaragene firadenovec, nogapendekin alfa-inbakicept, and systemic pembrolizumab. This narrative review summarizes developments in intravesical and systemic immunotherapies for NMIBC, highlights ongoing trials, and addresses controversies in trial design, treatment sequencing, comparative efficacy, and safety.<\/jats:p>","DOI":"10.3390\/cancers18040623","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:09:54Z","timestamp":1771250994000},"page":"623","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Recent Advances in Immunotherapy for Non-Muscle-Invasive Bladder Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5199-8670","authenticated-orcid":false,"given":"Abby L.","family":"Grier","sequence":"first","affiliation":[{"name":"School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey Y.","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7458-4593","authenticated-orcid":false,"given":"Spyridon","family":"Basourakos","sequence":"additional","affiliation":[{"name":"Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Calaway","sequence":"additional","affiliation":[{"name":"Department of Urology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8548-6948","authenticated-orcid":false,"given":"Parminder","family":"Singh","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9480-2626","authenticated-orcid":false,"given":"Yousef","family":"Zakharia","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-345X","authenticated-orcid":false,"given":"Fabrice","family":"Lucien","sequence":"additional","affiliation":[{"name":"Department of Urology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Jeffrey","family":"Karnes","sequence":"additional","affiliation":[{"name":"Department of Urology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidit","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Urology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paras","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Urology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Costello","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance C.","family":"Pagliaro","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-0239","authenticated-orcid":false,"given":"Jacob J.","family":"Orme","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6225-7555","authenticated-orcid":false,"given":"Jason R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Solid Tumor Oncology, Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0461-6174","authenticated-orcid":false,"given":"Albert","family":"Jang","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Division of Solid Tumor Oncology, Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.eururo.2012.07.033","article-title":"Epidemiology and Risk Factors of Urothelial Bladder Cancer","volume":"63","author":"Burger","year":"2013","journal-title":"Eur. Urol."},{"key":"ref_2","first-page":"7","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.eururo.2021.08.010","article-title":"European Association of Urology Guidelines on Non\u2013muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ)","volume":"81","author":"Babjuk","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1097\/JU.0000000000003846","article-title":"Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA\/SUO Guideline: 2024 Amendment","volume":"211","author":"Holzbeierlein","year":"2024","journal-title":"J. Urol."},{"key":"ref_5","first-page":"642","article-title":"Non-muscle-invasive bladder cancer: An overview of potential new treatment options","volume":"39","author":"Shore","year":"2021","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1200\/JCO.2015.64.4070","article-title":"Definitions, End Points, and Clinical Trial Designs for Non\u2013Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group","volume":"34","author":"Kamat","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/bju.14995","article-title":"Risk-adapted management of low-grade bladder tumours: Recommendations from the International Bladder Cancer Group (IBCG)","volume":"125","author":"Matulay","year":"2020","journal-title":"BJU Int."},{"key":"ref_8","unstructured":"(2025, December 05). Bladder Cancer. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/bladder.pdf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1158\/0008-5472.CAN-16-0170","article-title":"Burden of non-synonymous mutations among TCGA cancers and candidate immune checkpoint inhibitor responses","volume":"76","author":"Colli","year":"2016","journal-title":"Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4537","DOI":"10.18632\/oncotarget.23344","article-title":"APOBEC-mediated mutagenesis in urothelial carcinoma is associated with improved survival, mutations in DNA damage response genes, and immune response","volume":"9","author":"Glaser","year":"2017","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0022-5347(17)58737-6","article-title":"Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors","volume":"116","author":"Morales","year":"1976","journal-title":"J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/oxfordjournals.aje.a121646","article-title":"CANCER AND TUBERCULOSIS*","volume":"9","author":"Pearl","year":"1929","journal-title":"Am. J. Epidemiol."},{"key":"ref_13","first-page":"47","article-title":"Intravesical administration of bacillus Calmette-Gu\u00e9rin in patients with recurrent superficial carcinoma of the urinary bladder: Report of a prospective, randomized trial","volume":"69","author":"Pinsky","year":"1985","journal-title":"Cancer Treat. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0022-5347(17)55282-9","article-title":"Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer","volume":"124","author":"Lamm","year":"1980","journal-title":"J. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1056\/NEJM199110243251703","article-title":"A Randomized Trial of Intravesical Doxorubicin and Immunotherapy with Bacille Calmette\u2013Gu\u00e9rin for Transitional-Cell Carcinoma of the Bladder","volume":"325","author":"Lamm","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_16","unstructured":"(2025, November 24). CJU-Article Abstract. Available online: https:\/\/www.canjurol.com\/abstract.php?ArticleID=&version=1.0&PMID=28646932."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1016\/S0022-5347(05)64273-5","article-title":"Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: A meta-analysis of the published results of randomized clinical trials","volume":"168","author":"Sylvester","year":"2002","journal-title":"J. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.eururo.2005.12.031","article-title":"Predicting Recurrence and Progression in Individual Patients with Stage Ta T1 Bladder Cancer Using EORTC Risk Tables: A Combined Analysis of 2596 Patients from Seven EORTC Trials","volume":"49","author":"Sylvester","year":"2006","journal-title":"Eur. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.eururo.2014.02.061","article-title":"Bacillus Calmette-Gu\u00e9rin Strain Differences Have an Impact on Clinical Outcome in Bladder Cancer Immunotherapy","volume":"66","author":"Rentsch","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.euf.2018.08.015","article-title":"Background and Update for S1602 \u201cA Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG Before Intravesical Therapy for BCG-na\u00efve High-grade Non-muscle-invasive Bladder Cancer\u201d","volume":"4","author":"Svatek","year":"2018","journal-title":"Eur. Urol. Focus"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"LBA4504","DOI":"10.1200\/JCO.2025.43.17_suppl.LBA4504","article-title":"Mitomycin plus BCG as adjuvant intravesical therapy for high-risk, non\u2013muscle-invasive bladder cancer: A randomized phase 3 trial (ANZUP 1301)","volume":"43","author":"Hayne","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.euf.2023.06.006","article-title":"Background and Update for ECOG-ACRIN EA8212: A Randomized Phase 3 Trial of Intravesical Bacillus Calmette-Gu\u00e9rin (BCG) Versus Intravesical Docetaxel and Gemcitabine Treatment in BCG-na\u00efve High-grade Non\u2013muscle-invasive Bladder Cancer (BRIDGE)","volume":"9","author":"Kates","year":"2023","journal-title":"Eur. Urol. Focus"},{"key":"ref_23","unstructured":"Protara Therapeutics (2025, November 24). A Phase 2, Open-Label Study to Evaluate the Safety and Anti-Tumor Activity of Intravesical Instillation of TARA-002 in Adults with High-Grade Non-Muscle Invasive Bladder Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05951179."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"TPS4620","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS4620","article-title":"Phase 1a\/b safety study of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer (ADVANCED-1)","volume":"40","author":"Bandari","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_25","unstructured":"(2025, November 24). Protara Therapeutics Announces Positive Three-Month Data from TARA-002 Clinical Program in NMIBC\u2013Protara Therapeutics, Inc.. Available online: https:\/\/ir.protaratx.com\/news-releases\/news-release-details\/protara-therapeutics-announces-positive-three-month-data-tara."},{"key":"ref_26","first-page":"EVIDoa2200167","article-title":"IL-15 Superagonist NAI in BCG-Unresponsive Non\u2013Muscle-Invasive Bladder Cancer","volume":"2","author":"Chamie","year":"2022","journal-title":"NEJM Evid."},{"key":"ref_27","unstructured":"(2026, January 24). AUA 2025: An Update on QUILT-3.032: Complete Responses to N-803 Plus BCG Therapy in BCG-Unresponsive Bladder Carcinoma In Situ (CIS) with or Without Ta\/T1 Papillary Disease. Available online: https:\/\/www.urotoday.com\/conference-highlights\/aua-2025\/aua-2025-bladder-cancer\/159988-aua-2025-an-update-on-quilt-3-032-complete-responses-to-n-803-plus-bcg-therapy-in-bcg-unresponsive-bladder-carcinoma-in-situ-cis-with-or-without-ta-t1-papillary-disease.html."},{"key":"ref_28","unstructured":"ImmunityBio, Inc. (2025, November 24). Phase 2 Clinical Trial of Ablation Therapy with Intravesical N-803 in Combination with BCG or Gemcitabine in Participants with Intermediate-Risk Non-Muscle Invasive Papillary Bladder Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06829823."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1470-2045(20)30540-4","article-title":"Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: A single-arm, open-label, repeat-dose clinical trial","volume":"22","author":"Boorjian","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"TPS4630","DOI":"10.1200\/JCO.2025.43.16_suppl.TPS4630","article-title":"ABLE-22: Safety and efficacy evaluation of nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy\u2014A randomized, open-label, phase 2 study","volume":"43","author":"Daneshmand","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"TPS888","DOI":"10.1200\/JCO.2025.43.16_suppl.TPS4632","article-title":"ABLE-32: A randomized, controlled, phase 3b clinical trial of nadofaragene firadenovec-vncg versus observation in patients with intermediate-risk non\u2013muscle-invasive bladder cancer","volume":"43","author":"Shore","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_32","unstructured":"Memorial Sloan Kettering Cancer Center (2025, November 24). COMparative Prospective Assessment Through Clinically Integrated Randomized Trials Evaluating Intravesical Treatments: The COMPARE IT Trial, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06929286."},{"key":"ref_33","first-page":"440","article-title":"An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non\u2013muscle-invasive bladder cancer: Interim results","volume":"36","author":"Packiam","year":"2018","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_34","unstructured":"(2025, November 24). AUA 2024: Pivotal Results from BOND-003: A Phase 3, Single-Arm Study of Intravesical Cretostimogene Grenadenorepvec for the Treatment of High Risk, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer. Available online: https:\/\/www.urotoday.com\/conference-highlights\/aua-2024\/aua-2024-bladder-cancer\/151709-aua-2024-pivotal-results-from-bond-003-a-phase-3-single-arm-study-of-intravesical-cretostimogene-grenadenorepvec-for-the-treatment-of-high-risk-bcg-unresponsive-non-mus."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2216","DOI":"10.1038\/s41591-024-03025-3","article-title":"Oncolytic adenoviral therapy plus pembrolizumab in BCG-unresponsive non-muscle-invasive bladder cancer: The phase 2 CORE-001 trial","volume":"30","author":"Li","year":"2024","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"TPS901","DOI":"10.1200\/JCO.2025.43.5_suppl.TPS901","article-title":"CORE-008: A phase 2, multi-arm, multi-cohort, open-label study to evaluate intravesical cretostimogene grenadenorepvec in participants with high-risk non-muscle invasive bladder cancer","volume":"43","author":"Bivalacqua","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_37","unstructured":"CG Oncology, Inc. (2025, November 24). A Phase 3, Randomized Study of Adjuvant Cretostimogene Grenadenorepvec Versus Observation for the Treatment of Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR-NMIBC) Following Transurethral Resection of Bladder Tumor (TURBT), Available online: https:\/\/clinicaltrials.gov\/study\/NCT06111235."},{"key":"ref_38","unstructured":"(2025, November 24). ASCO GU 2025: Preliminary Results from LEGEND: A Phase 2 Study of Detalimogene Voraplasmid (EG-70), a Novel, Non-Viral Intravesical Gene Therapy for Patients with BCG-Unresponsive NMIBC with CIS. Available online: https:\/\/www.urotoday.com\/conference-highlights\/asco-gu-2025\/asco-gu-2025-bladder-cancer\/158229-asco-gu-2025-preliminary-results-from-legend-a-phase-2-study-of-detalimogene-voraplasmid-eg-70-a-novel-non-viral-intravesical-gene-therapy-for-patients-with-bcg-unresponsive-nmibc-with-cis.html."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e16613","DOI":"10.1200\/JCO.2025.43.16_suppl.e16613","article-title":"Comparative analysis of the anti-tumor activity and mechanism of action of TARA-002 and BCG in bladder cancer models","volume":"43","author":"Mauro","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_40","unstructured":"Food and Drug Administration (2026, January 23). FDA Approves Nogapendekin Alfa Inbakicept-Pmln for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s40364-022-00415-y","article-title":"Direct and indirect effects of IFN-\u03b12b in malignancy treatment: Not only an archer but also an arrow","volume":"10","author":"Xiong","year":"2022","journal-title":"Biomark. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"872","DOI":"10.4161\/cbt.6.6.4088","article-title":"Interferon-\u03b1 Induces TRAIL Expression and Cell Death Via an IRF-1-Dependent Mechanism in Human Bladder Cancer Cells","volume":"6","author":"Papageorgiou","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"ref_43","unstructured":"Food and Drug Administration (2026, January 23). FDA Approves First Adenoviral Vector-Based Gene Therapy for High-Risk Bacillus Calmette-Gu\u00e9rin Unresponsive Non-Muscle Invasive Bladder Cancer, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-first-adenoviral-vector-based-gene-therapy-high-risk-bacillus-calmette-guerin."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1158\/1078-0432.CCR-05-1059","article-title":"CG0070, a Conditionally Replicating Granulocyte Macrophage Colony-Stimulating Factor\u2013Armed Oncolytic Adenovirus for the Treatment of Bladder Cancer","volume":"12","author":"Ramesh","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_45","unstructured":"(2026, January 23). CG Oncology Receives Both FDA Fast Track and Breakthrough Therapy Designation for Cretostimogene Grenadenorepvec in High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer | CG Oncology. Available online: https:\/\/ir.cgoncology.com\/news-releases\/news-release-details\/cg-oncology-receives-both-fda-fast-track-and-breakthrough\/."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1245\/s10434-018-6498-2","article-title":"Clinical Role of Programmed Cell Death-1 Expression in Patients with Non-muscle-invasive Bladder Cancer Recurring After Initial Bacillus Calmette\u2013Gu\u00e9rin Therapy","volume":"25","author":"Fukumoto","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/S1470-2045(24)00178-5","article-title":"Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): A single-arm, multicentre, phase 2 trial","volume":"25","author":"Necchi","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1200\/JCO.2024.42.16_suppl.4597","article-title":"Outcomes of patients with bacillus Calmette-Gu\u00e9rin\u2013unresponsive high-risk non\u2013muscle-invasive bladder cancer who demonstrated nonresponse to pembrolizumab in KEYNOTE-057: A post hoc analysis","volume":"42","author":"Li","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.eururo.2023.08.004","article-title":"Phase 2 Trial of Atezolizumab in Bacillus Calmette-Gu\u00e9rin\u2013unresponsive High-risk Non\u2013muscle-invasive Bladder Cancer: SWOG S1605","volume":"84","author":"Black","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.eururo.2023.01.017","article-title":"A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin or External Beam Radiation Therapy in Patients with Bacillus Calmette-Guerin\u2013unresponsive Non\u2013muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16\u2013243 ADAPT-BLADDER Study","volume":"83","author":"Hahn","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S1509","DOI":"10.1016\/j.annonc.2024.10.293","article-title":"273MO DURANCE: A phase Ib\/II study to assess the safety and activity of durvalumab (MEDI4736) in combination with S-488210\/S-488211 vaccine in non-muscle invasive bladder cancer","volume":"35","author":"Leone","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/S0140-6736(25)01897-5","article-title":"Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): Final analysis of a randomised, open-label, phase 3 trial","volume":"406","author":"Santis","year":"2025","journal-title":"Lancet"},{"key":"ref_53","unstructured":"AstraZeneca (2026, January 21). A Phase IIIb Open-Label, Single-Arm, Multi-Center, US Study of Bacillus Calmette-Guerin (BCG) Administered in Combination with Durvalumab in Adult BCG-Na\u00efve, High-Risk Non-Muscle-Invasive Bladder Cancer Participants (PATAPSCO), Available online: https:\/\/clinicaltrials.gov\/study\/NCT05943106."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.1038\/s41591-025-03738-z","article-title":"Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer: The randomized phase 3 CREST trial","volume":"31","author":"Shore","year":"2025","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.annonc.2025.09.017","article-title":"ALBAN (GETUG-AFU 37): A phase III, randomized, open-label international trial of intravenous atezolizumab and intravesical Bacillus Calmette\u2013Gu\u00e9rin (BCG) versus BCG alone in BCG-naive high-risk, non-muscle-invasive bladder cancer (NMIBC)","volume":"37","author":"Roupret","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"TPS722","DOI":"10.1200\/JCO.2024.42.4_suppl.TPS722","article-title":"Phase 3 KEYNOTE-676 cohort A: Bacillus Calmette-Gu\u00e9rin (BCG) with or without pembrolizumab for high-risk (HR) non\u2013muscle-invasive bladder cancer (NMIBC) that persists\/recurs after BCG induction","volume":"42","author":"Shore","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1200\/JCO-25-01651","article-title":"TAR-200 for Bacillus Calmette-Gu\u00e9rin\u2013Unresponsive High-Risk Non\u2013Muscle-Invasive Bladder Cancer: Results From the Phase IIb SunRISe-1 Study","volume":"43","author":"Daneshmand","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_58","unstructured":"Janssen Research & Development, LLC. (2025, November 24). A Phase 3, Open-Label, Multi-Center, Randomized Study Evaluating the Efficacy and Safety of TAR-200 in Combination with Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Gu\u00e9rin (BCG) in Participants with BCG-Na\u00efve High-Risk Non-Muscle Invasive Bladder Cancer, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05714202."},{"key":"ref_59","unstructured":"Food and Drug Administration (2026, January 23). FDA Approves Pembrolizumab for BCG-Unresponsive, High-Risk Non-Muscle Invasive Bladder Cancer, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-pembrolizumab-bcg-unresponsive-high-risk-non-muscle-invasive-bladder-cancer."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"S1224","DOI":"10.1016\/j.annonc.2023.09.2825","article-title":"2407TiP SunRISe-3: TAR-200 plus cetrelimab (CET) or TAR-200 versus intravesical bacillus Calmette-Gu\u00e9rin (BCG) in patients (pts) with BCG-naive high-risk non-muscle-invasive bladder cancer (HR NMIBC)","volume":"34","author":"Necchi","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41586-021-03642-9","article-title":"ctDNA guiding adjuvant immunotherapy in urothelial carcinoma","volume":"595","author":"Powles","year":"2021","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1056\/NEJMoa2511885","article-title":"ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer","volume":"393","author":"Powles","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.euo.2025.05.019","article-title":"Real-World Experience with a Commercial Circulating Tumor DNA Assay in Non-muscle-invasive Bladder Cancer","volume":"8","author":"Wang","year":"2025","journal-title":"Eur. Urol. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Zhang, J., Dai, D., Tian, J., Li, L., Bai, J., Xu, Y., Wang, Z., and Tang, A. (2021). Circulating Tumor DNA Analyses Predict Disease Recurrence in Non-Muscle-Invasive Bladder Cancer. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.657483"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.eururo.2016.01.007","article-title":"Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer","volume":"70","author":"Nordentoft","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.eururo.2025.03.023","article-title":"Urine Tumor DNA to Stratify the Risk of Recurrence in Patients Treated with Atezolizumab for Bacillus Calmette-Gu\u00e9rin-unresponsive Non-muscle-invasive Bladder Cancer","volume":"88","author":"Singh","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/S0140-6736(99)04265-8","article-title":"Immunoassay for urothelial cancers that detects DNA replication protein Mcm5 in urine","volume":"354","author":"Stoeber","year":"1999","journal-title":"Lancet"},{"key":"ref_68","first-page":"161","article-title":"Novel urinary biomarkers ADXBLADDER and bladder EpiCheck for diagnostics of bladder cancer: A review","volume":"39","author":"Wolfs","year":"2021","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/cncy.22152","article-title":"Diagnostic predictive value of the Bladder EpiCheck test in the follow-up of patients with non\u2013muscle-invasive bladder cancer","volume":"127","author":"Trenti","year":"2019","journal-title":"Cancer Cytopathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102333","DOI":"10.1016\/j.clgc.2025.102333","article-title":"mRNA-Based Urine Test Performance in High and Very-High Risk Non\u2013Muscle-Invasive Bladder Cancer Patients Undergoing Contextual Endoscopic Follow-up (VERNAL: Vesical Tumor Early Monitoring: mRNA-Based Follow-up)","volume":"23","author":"Macchi","year":"2025","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Bizzarri, F.P., Campetella, M., Russo, P., Palermo, G., Moosavi, S.K., Rossi, F., D\u2019Amico, L., Cret\u00ec, A., Gavi, F., and Panio, E. (2025). Prognostic Value of PLR, SIRI, PIV, SII, and NLR in Non-Muscle Invasive Bladder Cancer: Can Inflammatory Factors Influence Pathogenesis and Outcomes?. Cancers, 17.","DOI":"10.3390\/cancers17132189"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/4\/623\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T14:17:31Z","timestamp":1771251451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/4\/623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,14]]},"references-count":71,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cancers18040623"],"URL":"https:\/\/doi.org\/10.3390\/cancers18040623","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,14]]}}}