Photodynamics can be used for diagnosis and treatment in bladder cancer. This involves administration of 5-aminolevulinic acid (5-ALA) either intravenously or intravesically, which accrues preferentially in neoplastic tissue and fluoresces when exposed to photodynamic light in specific wavelengths. If the blue light is used (wavelength 375-445 nm) it can be used for diagnosis, and if the green light is used (wavelength 480-580 nm), it is used for treatment, figure 1.
Figure 1 – Photodynamic Diagnosis vs. Therapy:
There have been several photodynamic therapy (PDT) trials demonstrating promising results in bladder cancer patients, ranging from an early response rate of 45% to 90.9%. 1 The problem with PDT is the “collateral damage” that is caused to the surrounding areas. There are several ways to attempt to remedy or ameliorate this collateral damage:
1. Active measurement of light delivery
2. Account for the reflected light
3. Increased cancer cell specificity
The compound used for this phase 1 trial was the TLD-1433, which is completely soluble and stable in water. It has a preferential bladder tumor accumulation with exceptional ability to ablate in-vivo tumors across multiple animal models. It has been proven to be safe in pharmacologically and toxicology studies. The procedure itself is quite simple and is depicted in figure 2. After intravesical instillation of the compound, the compound accumulates in tumor regions only (Figure 3). A flexible cystoscope is inserted into the bladder with a flexible light fiber running through it. The bladder is then illuminated with green laser light and treatment is stopped when there is confirmation that there has been a delivery of approximately 90J/cm2.
Figure 2 – PDT Procedure:
Figure 3 – Preoperative Intravesical Instillation:
In this phase 1b study design, six patients with BCG unresponsive disease were assessed. In phase 1 of the study, three patients received PDT at 0.35mg/cm2 of the compound and then 90J/cm2 green laser light. In the second phase of the site six patients received PDT 0.7 mg/cm2, and 90J/cm2 green laser light. The overall operating time was quite long for these patients, ranging from 160 to 181 minutes. All patients were discharged the same day. The most common adverse events included mild fatigue, mild penile discomfort, urinary frequency, and nocturia. The pathology demonstrated that two patients were not with any sign of disease at last follow-up, two patients had Carcinoma in situ, and two patients had T1 HG disease with CIS.
The phase 2 study will start to accrue soon, with a goal to include 100 CIS+, BCG-unresponsive patients at multiple centers.
Presented by: Girish Kulkarni, MD, Ph.D., FRCSC, Medical Advisory, and Research Board, University of Toronto, Toronto, ON
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter: @GoldbergHanan at the CUOS – Canadian Uro-Oncology Summit 2019, #CUOS19 January 10-12, 2019 Westin Harbour Castle, Toronto, Ontario, Canada
References:
1. Lee et al. J Urol 2013