{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:17:41Z","timestamp":1788499061669,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016545","name":"Roche Diagnostics","doi-asserted-by":"crossref","award":["KW\/1791\/ONC\/014\/013"],"award-info":[{"award-number":["KW\/1791\/ONC\/014\/013"]}],"id":[{"id":"10.13039\/100016545","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy has been the standard of care for muscle-invasive bladder cancer (MIBC) for two decades, yet a substantial proportion of patients derive no benefit. As antibody\u2013drug conjugates and immune checkpoint inhibitors reshape perioperative treatment, it is unclear which patients retain meaningful benefit from platinum. We describe long-term outcomes and exploratory paired immune and genomic analyses in a single-centre cohort treated with dose-dense MVAC (dd-MVAC). Methods: We retrospectively identified 54 consecutive patients with MIBC treated with neoadjuvant dd-MVAC between November 2013 and November 2019. Forty-two underwent radical cystectomy and are assessable for pathologic response. Immunohistochemistry for CD3, CD8, FOXP3, PD-1, PD-L1, PD-L2, and NY-ESO-1 was evaluable in 31 baseline specimens and 22 paired specimens; paired genomic profiling was evaluable in 12 cases, with paired tumour mutational burden (TMB) in 10 by whole-exome sequencing and 7 by TSO-500. Paired analyses necessarily exclude patients achieving a pathologic complete response (pCR), who have no residual tumour, and most early progressors. Results: pCR was achieved in 11\/42 operated patients (26%, 95% CI 15\u201341). Median follow-up was 87 months (IQR 24\u2013104). Hydronephrosis was the only baseline factor associated with absence of pCR (p = 0.016). Within the operated cohort, pCR was associated with longer recurrence-free survival (log-rank p = 0.017), but the difference in overall survival did not reach significance (p = 0.121). NAC reduced intratumoral FOXP3 (q = 0.001), NY-ESO-1 (q = 0.013), PD-L2 (q = 0.013), and CD3 (q = 0.043) after correction for multiple comparisons, whereas TMB showed no significant change (TSO-500 p = 0.67; WES p = 0.86). No statistically significant association was detected between any baseline immune marker, including PD-L1, and pCR. The mutational landscape was largely concordant before and after NAC. Conclusions: This study was exploratory and was not powered to validate predictive biomarkers. In this long-term cohort, dd-MVAC was associated with measurable depletion of intratumoral immune populations in chemoresistant tumours, while paired genomic profiles remained broadly concordant. No pre-treatment biomarker identified platinum-refractory patients, but the small evaluable subsets mean these are hypothesis-generating rather than negative findings, and prospective studies with pre-specified biomarker endpoints are required.<\/jats:p>","DOI":"10.3390\/cancers18172839","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:56:01Z","timestamp":1788339361000},"page":"2839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-Term Outcomes and Paired Immune and Genomic Exploratory Analyses After Neoadjuvant Dose-Dense MVAC in Muscle-Invasive Bladder Cancer: A Single-Centre Case Series"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-5621","authenticated-orcid":false,"given":"Daan","family":"De Maeseneer","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Medical Oncology, AZ Sint-Lucas, 8310 Brugge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6795-7606","authenticated-orcid":false,"given":"Alexander","family":"Decruyenaere","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joni","family":"Van der Meulen","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siebe","family":"Loontiens","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toon","family":"Rosseel","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2685-2637","authenticated-orcid":false,"given":"Pieter-Jan","family":"Volders","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Medicine, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Verbeke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Fonteyne","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy-Oncology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4467-0829","authenticated-orcid":false,"given":"Charles","family":"Van Praet","sequence":"additional","affiliation":[{"name":"Department of Urology, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8513-4985","authenticated-orcid":false,"given":"Camille","family":"Berquin","sequence":"additional","affiliation":[{"name":"Department of Urology, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Rottey","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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