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A combination of minimally-invasive photodynamic therapy (PDT) with ionizing radiation (IR) could be beneficial for bladder tumor regression. Here, we tested the hypothesis that PDT with the near-infrared photosensitizer tetrahydroporphyrin-tetratosylate (THPTS) could treat bladder tumors safely and effectively in an orthotopic rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Response additivity analysis of cytotoxicity was investigated in cultured tumor cells (AY-27) and spheroids consisting of AY-27 and bladder fibroblasts of F344 Fischer rats. For in vivo evaluation, tumors were induced in female Fischer rats by intravesical instillation of AY-27 cells. Triple-time treatments were performed, with ten rats each in four treatment groups: untreated controls (UTC), PDT, IR, PDT with prior IR (IR\u2009+\u2009PDT). Animals were euthanized when reaching the termination criteria, and bladders were evaluated by macroscopy, histology and CD45 immunohistology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Synergism of combined treatment was demonstrated for all tested THPTS concentrations in AY-27\/fibroblast spheroids but not in 2D cultured AY-27 cells. Tumor cell inoculation resulted in massive growth of solid bladder tumors (pT3a\/b) in UTC. Triple-time treatment led to doubling of survival in the PDT group (mOS: 70 d) compared to UTC group (mOS: 36.5 d). IR monotherapy and IR\u2009+\u2009PDT resulted in complete survival without reaching the termination criteria. Histology revealed advantage of combination therapy vs. IR monotherapy by demonstrating treatment responses in all tumors of the IR\u2009+\u2009PDT group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first in vivo study reporting doubling of survival time after PDT with a new near-infrared photosensitizer, and nearly complete tumor remission by neoadjuvant IR. This multimodal approach possibly allows minmally-invasive, organ-preserving BCa treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12935-026-04465-2","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:05:15Z","timestamp":1789646715000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced survival through repeated photodynamic therapy and almost complete tumor regression by prior radiation therapy in an orthotopic rat bladder cancer model"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2212-2693","authenticated-orcid":false,"given":"Mandy","family":"Berndt-Paetz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"N\u00fcrnberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susann","family":"Gonsior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"P\u0105czek-Hippe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Patties","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"Weimann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy","family":"Michalik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Neuhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annegret","family":"Glasow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"4465_CR1","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/ijc.33588","volume":"149","author":"J Ferlay","year":"2021","unstructured":"Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Pi\u00f1eros M, Znaor A, et al. 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