Complications of Whole Bladder Dihematoporphyrin Ether Photodynamic Therapy

Abstract

Photodynamic therapy with dihematoporphyrin ether was used to treat superficial bladder tumors in 7 patients with a followup of at least 1 year. Each patient received treatment to the whole bladder and those with papillary lesions received additional focal treatment. At 3 months 4 of the 5 patients with papillary tumors (stages Ta and T1) and 1 of the 2 with diffuse carcinoma in situ (Tis) were free of disease. However, at 1 year only 3 patients remained free of disease. Of 5 patients with an increase in irritative bladder symptoms 4 had a contracted bladder, hydroureteronephrosis and vesicoureteral reflux. Deep bladder biopsies showed replacement of smooth muscle by fibrous tissue. Six patients had mild to moderate skin phototoxicity. We conclude that although photodynamic therapy is an attractive and exciting method to treat cancer, its use with dihematoporphyrin ether in cases of bladder carcinoma can be associated with significant complications. The correct treatment parameters for safe, effective therapy are not known to date.

Functional and histological bladder damage in mice after photodynamic therapy: the influence of sensitiser dose and time of administration

“…The bladders of these animals always showed an acute inflammatory and/or epithelial denudation response ( Figure Sd to moderately severe acute reactions with haematuria, dysuria and urination frequency lasting for up to 3 months Time after treatment (weeks) (Benson, 1985;Nseyo et al, 1987;Naito et al, 1991;Prout et neoplastic lesions, are probably required for effective tumour control. Permanent reductions in bladder capacity necessitating cystectomy are rare but can occur, particularly if PDT is given within 4 weeks of TUR, or if high total light doses are given (Harty et al, 1989;D'Hallewin et al, 1992). The biological effect of PDT is determined by the energy absorbed by the photosensitiser.…”

“…Individual papillary lesions may be given additional focal PDT (Prout et al, 1987). Preliminary results from clinical studies using integral PDT for superficial bladder cancer are promising (Naito et al, 1901;Prout et al, 1987;Nseyo et al, 1987;Shumaker & Hetzel, 1987;Harty et al, 1989;D'Hallewin et al, 1992;Jocham, 1987) but follow up of the patients is still fairly short (less than 1 year in many cases). Many aspects of PDT, such as the optimal timing of light delivery and optimal light and sensitiser doses still have to be defined to achieve effective tumour response without loss of bladder function.…”

“…Many aspects of PDT, such as the optimal timing of light delivery and optimal light and sensitiser doses still have to be defined to achieve effective tumour response without loss of bladder function. Nearly all clinical studies in which the whole bladder is treated with PDT report a high incidence of bladder irritability, increased urination frequency and haematuria during the first few weeks after treatment (Naito et al, 1991;Prout et al, 1987;Nseyo et al, 1987;Harty et al, 1989;D'Hallewin et al, 1992;Benson, 1985;Hisazumi et al, 1983;Jocham, 1987). This may be an unavoidable consequence of treatment, since successful therapy involves urothelial sloughing and exposure of the submucosa as the malignant (and premalignant) areas are shed.…”

“…Both experiment and clinical studies, however, indicate a remarkable degree of recovery from the acute damage (Naito et al, 1991;Prout et al, 1987;Nseyo et al, 1987;Sindelar et al, 1991;Stewart et al, 1992;Pope & Bown, 1991), within certain tolerance limits. The consequence of exceeding these tolerance limits may be a permanently shrunken bladder requiring cystectomy, as evidenced by several clinical studies in which the non-scattered light dose to the whole bladder exceeded 15 to 20 J cm-2 (D'Hallewin et al, 1992;Harty et al, 1989).…”

The detection of phthalocyanine fluorescence in normal rat bladder wall using sensitive digital imaging microscopy

“…Clinical series of bladder PDT using HpD have shown some significant complications including bladder irritability and a greatly reduced bladder capacity, which are probably the result of unwanted photosensitiser activation and subsequent fibrosis in the deep muscle layers of the bladder wall (Nseyo et al, 1987;Harty et al, 1989). Many photosensitising agents are relatively poor localisers, achieving only a 2 or 3:1 ratio in tumour vs normal tissue.…”