Photodynamic therapy (PDT) in the treatment of patients with resistant superficial bladder cancer: a long-term experience.

INTRODUCTION AND OBJECTIVE: Photodynamic therapy (PDT) combines a photosensitizer such as Photofrin with red laser light (630 nm) to destroy cancer cells. Investigators have reported effectiveness of PDT in the management of patients with recurrent superficial bladder cancer. We retrospectively reviewed our experience in 58 patients to assess the long-term role of PDT in the management of resistant superficial transitional cell carcinoma (TCC) including Ta, T1, and refractory carcinoma in situ (CIS) of the urinary bladder. MATERIALS AND METHODS: All 58 patients had failed at least one course of standard intravesical therapy or had contraindication for intravesical chemo- or immunotherapy. Patients with malignancy present (Ta-T1/Grade I-III, CIS) were accepted for ablative PDT. Patients undergoing prophylactic PDT after complete resection were confirmed to be tumor-free by cystoscopy and bladder was cytology before PDT. Post-PDT evaluations included weekly telephone contact to assess acute adverse reactions and assessment of efficacy and bladder toxicity at three months and quarterly thereafter. RESULTS: These 58 patients underwent a single PDT treatment with 2.0 or 1.5 mg/kg of Photofrin and 10-60 J/cm2 light (630 nm). At three months, complete response rates were 84% and 75% for residual resistant papillary TCC and refractory CIS respectively; and 90% of patients treated prophylactically had not had recurrences. At a median followup of 50 months (range 9-110), 59% (34/58) of the responders are alive, with 31/34 still disease-free. CONCLUSION: PDT using 1.5 mg/kg of Photofrin and 15 J/cm2 of light (630 nm) should be considered a safe and effective treatment for refractory CIS or recurrent papillary TCC.

Three-dimensional characterization of the light distribution from diffusing cylindrical optical-fiber tips.

A rapid and sensitive technique for quantitatively examining the three-dimensional light distribution from optical-fiber diffusers for photodynamic therapy applications was developed. We have used this system to evaluate the longitudinal and azimuthal uniformity of the light output from cylindrical diffusing tips and have determined a standard detector configuration for assessing the optical quality of these diffusers. As an example of the sensitivity and the accuracy of this method, the effect of microbending of the fiber on the output intensity distribution, as well as the effect of the choice of laser used, was investigated and was seen to have a significant impact on the uniformity of these diffusers.

Green light photodynamic therapy in the human bladder.

We conducted this pilot clinical study to investigate the safety, primarily acute toxicity, of green light (514.5 nm) whole bladder photodynamic therapy (PDT) in human bladders with transitional cell carcinoma. We enrolled five patients who were scheduled to undergo radical cystectomy and urinary diversion for locally muscle invasive bladder cancer. Four patients received intravenous injection of Photofrin at 1 mg/kg, while one patient received no drug, 48 hr before undergoing green light whole bladder photoactivation with light doses of 20-60 J/cm 2. Each patient underwent radical cystectomy on day 7 following light treatment. Post-PDT evaluation included daily monitoring of voiding symptoms, cystometric measurements of bladder capacity, and gross and histopathologic examination of the excised bladders. Our results show that the intensity of acute bladder irritation and acute post-PDT loss in bladder volume depended on the light dose and extent of bladder tumor with the associated inflammation. There was no transmural bladder injury and no treatment related morbidity. These data on acute toxicity suggest that green light whole bladder PDT treatment with 1 mg/kg of Photofrin and 20-40 J/cm 2 of laser power is safe.

Canine bladder response to red and green light whole bladder photodynamic therapy.

A normal canine bladder model was used to compare the effects of red and green light whole bladder photodynamic therapy (PDT). Eighteen dogs were treated with Photofrin 1 mg/kg and whole bladder irradiation with red or green light at doses ranging from 20 to 60 J/cm2. Toxicity was assessed using cystometry, cystoscopy, and histopathology. Green light produced more significant vesical toxicity than red light, and this toxicity tended to vary with the light dose administered. Whole bladder PDT with green light at doses greater than 20 J/cm2 resulted in permanent reductions in bladder capacity. Conversely, a green light dose of 20 J/cm2 and red light doses ranging from 20 to 60 J/cm2 did not produce any significant permanent reductions in bladder capacity. Thus, while green light may be more toxic to the bladder than red light, there are distinct combinations of red or green light and Photofrin which can be used in the canine bladder to achieve mucosal degradation without causing permanent vesical dysfunction.

Whole bladder photodynamic therapy: critical review of present-day technology and rationale for development of intravesical laser catheter and monitoring system.

Present-day whole bladder photodynamic therapy (WBPDT) is cumbersome and time consuming because cystoscopic and ultrasonic manipulations are necessary to position the light emitter within the bladder. More important, WBPDT is inherently unsafe and often ineffective since neither uniform photoirradiation nor accurate light dosimetry can be achieved with the techniques employed to photoirradiate the bladder wall. The intravesical laser catheter (IVLC) eliminates the need for cystoscopy and ultrasonography because passage of the treatment fiber into the catheter's central lumen automatically positions its light-diffusing tip within the center of the bladder. Use of the IVLC delivery system also assures accurate photoirradiation of the bladder wall since inflation of the catheter's balloon transforms the asymmetric bladder into a sphere of known diameter. The light sensor incorporated in the balloon wall provides a method to monitor light fluence and measure total light dose. When provided the parameters of bladder volume, laser energy output, and desired light dose, the computerized control system calculates treatment time and automatically adjusts the period of photoirradiation to compensate for variations in laser light production, energy losses during transmission, and for variations in light intensity resulting from the integrating sphere effect of the bladder wall. This delivery system also increases the safety of WBPDT since the monitor automatically discontinues treatment if any unsafe situation, with respect to light fluence, develops during photoirradiation.

Urinary cytokines following photodynamic therapy for bladder cancer. A preliminary report.

This preliminary study was undertaken to test for the presence of urinary cytokines whose detection would provide evidence in support of the theory that photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2, and tumor necrosis factor-alpha were assayed for in the urine of 4 patients treated with photodynamic therapy for bladder cancer, in 7 control patients undergoing transurethral surgical procedures, and in 5 healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy nor in any of the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer.

Development and evaluation of a community cancer resource directory.

The Frederick Cancer-Related Resource Directory was developed in response to the community's need to be informed about available services for cancer patients. A 1-year followup and evaluation was conducted to determine what changes or corrections were needed in the text of the directory and if the objectives of the project had been met. The evaluation survey of the listed resources revealed that a large number of changes in the directory were required. Seventy-eight percent of the respondents replied that at least one change was required in their entry. The followup also revealed that 16 percent of the listed resources knew of at least one referral that they received as a result of the directory listing. The survey of directory recipients indicated that 27 percent of the private practice physicians and 61 percent of the other health-related service providers who have a directory have used it or read through it. Approximately 64 percent of the users have provided clients or patients with information from the directory. Almost half of all respondents replied that, as a result of the directory listing, they had developed closer working relationships with at least one other cancer-related service organization, although the percentage was considerably higher for health-related service providers (51.2 percent) than for private physicians (27.3 percent). More than half of the respondents (58 percent) believed that a simpler directory should be made available to patients instead of or in addition to the providers' directory. Members of the project's multi agency committee became much more aware of the wide variety of cancer patients' needs and available resources. The most beneficial aspect of the project for them was the opportunity to work with persons from other agencies and to develop closer, long-term relationships.