Photodynamic Therapy for Bladder Cancers, A Focused Review^†

Abstract

Bladder cancer is the first cancer for which PDT was clinically approved in 1993. Unfortunately, it was unsuccessful due to side effects like bladder contraction. Here, we summarized the recent progress of PDT for bladder cancers, focusing on photosensitizers and formulations. General strategies to minimize side effects are intravesical administration of photosensitizers, use of targeting strategies for photosensitizers and better control of light. Non-muscle invasive bladder cancers are more suitable for PDT than muscle invasive and metastatic bladder cancers. In 2010, the FDA approved blue light cystoscopy, using PpIX fluorescence, for photodynamic diagnosis of nonmuscle invasive bladder cancer. PpIX produced from HAL was also used in PDT but was not successful due to low therapeutic efficacy. To enhance the efficacy of PpIX-PDT, we have been working on combining it with singlet oxygen-activatable prodrugs. The use of these prodrugs increases the therapeutic efficacy of the PpIX-PDT. It also improves tumor selectivity of the prodrugs due to the preferential formation of PpIX in cancer cells resulting in decreased off-target toxicity. Future challenges include improving prodrugs and light delivery across the bladder barrier to deeper tumor tissue and generating an effective therapeutic response in an In vivo setting without causing collateral damage to bladder function.

Ruthenium-Based Photoactivated Chemotherapy

“…Such effects have been observed in red-light PDT treatment of the bladder using Photofrin in the 1990s, which destroyed part of the healthy muscle tissues underlying the tumor, which stopped clinical trials. 141 Photoactivated technologies that trigger other forms of cell death, such as apoptosis, ferroptosis, or immunologic cell death, may lead to tumor eradication without pain and without tissue necrosis, which could benefit the development of Ru-based PACT. Apoptosis may not necessarily generate as much immune response as that generated by PDT, which some see as detrimental to the development of PACT.…”

“…Pain can be managed by lowering the light intensity (in mW/cm 2 ) while increasing irradiation time to keep the light dose (in J/cm 2 ) constant. − However, if necrosis reaches essential tissues, clinical success of a PDT treatment may be an issue for the patient, notably if PDT is performed on tissues that should be conserved. Such effects have been observed in red-light PDT treatment of the bladder using Photofrin in the 1990s, which destroyed part of the healthy muscle tissues underlying the tumor, which stopped clinical trials . Photoactivated technologies that trigger other forms of cell death, such as apoptosis, ferroptosis, or immunologic cell death, may lead to tumor eradication without pain and without tissue necrosis, which could benefit the development of Ru-based PACT.…”

Photodynamic Therapy: Current Trends and Potential Future Role in the Treatment of Bladder Cancer

“…Recent advances in molecular technologies have led to the development of new emerging therapies in the oncological field, such as sonodynamic and chemodynamic therapy, also leading to the generation of ROS [66][67][68][69][70]. The available data also show the insufficient ability of the above-mentioned therapies to cure the tumor if used as a monotherapy.…”

Evolving Role of Lasers in Endourology: Past, Present and Future of Lasers

“…Historically, diode lasers were used as an alternative to the 120 W lithium triborate (LBO) lasers, due to their higher haemostatic ability [56]. Diode lasers have been used for direct tumour ablation or as a "photosensitizer" in the contest of photodynamic therapy (PDT), due to their ability to match the desired wavelengths of many photosensitizer drugs (630-760 nm) and increase their penetration in the tumoral tissue [51,57]. Recently, Wu et al conducted a noninferiority study to assess the efficacy and safety of the newer 450 nm wavelength blue diode laser compared to the conventional electrocautery performed with the plasmakinetic loop for non-muscular invasive bladder cancer [58].…”