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Life sciences · Journal article
Cancer Cell International · September 17, 2026
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Abstract Introduction The development of new organ-preserving treatment alternatives is still an important issue in bladder cancer (BCa) research. 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. Materials and methods 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 + PDT). Animals were euthanized when reaching the termination criteria, and bladders were evaluated by macroscopy, histology and CD45 immunohistology. Results 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 + PDT 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 + PDT group. Conclusion 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.