The influence of intravesical photodynamic therapy on subsequent bladder irradiation tolerance

The aim of this project was to measure the irradiation tolerance of normal (non tumour bearing) mouse bladder after previous intravesical photodynamic therapy (PDT). Illumination with a range of light doses at 24 h after Photofrin was used as the initial PDT treatment and irradiation with a range of X-ray doses was given at 12 or 24 weeks after the initial therapy. Functional bladder damage was assessed from changes in micturition frequency (tested regularly for a follow-up period of 53 weeks after irradiation) and from cystometry measurements of the bladder at 53-56 weeks. PDT alone caused a marked increase in micturition frequency, with (partial) recovery by the time of irradiation. Irradiation alone caused a modest, transient acute response within 5 weeks and a progressive, permanent late response starting from about 25 weeks depending on X-ray dose. A reduced bladder capacity was also evident at 53-56 weeks after 20 Gy X-rays and after PDT alone. Irradiation after previous intravesical PDT caused an acute reaction similar to X-rays alone, but there was a much earlier expression of late functional bladder damage. The final level of damage prior to sacrifice at 53-56 weeks, was not significantly greater than after X-rays alone. These results suggest that irradiation after previous whole bladder PDT, for refractory bladder tumours, may lead to an increased risk of persistent increases in micturition frequency and reduced bladder capacity, beginning at very early times after irradiation.