What Is Photodynamic Therapy

Introduction

Throughout history, the concept of light possessing healing properties has captivated human interest. Thanks to advancements in science and technology, we now have an innovative treatment called photodynamic therapy (PDT)—a promising method for addressing diverse diseases. This technique utilises the interaction of light, oxygen, and specialised molecules called photosensitisers. It is a gentle, non-invasive, and repeatable procedure effective in combating tumours, aiding in wound healing, and eliminating pathogens.¹ PDT, employing light to target abnormal cells in areas like the skin, eyes, mouth, oesophagus, and lungs, shows effectiveness in various conditions such as actinic keratoses, Bowen's disease, basal cell carcinoma, and more. The potential of PDT extends to treating different cancers, warts, acne, and a pre-cancerous condition known as extramammary Paget's disease, impacting the skin around the genital and anal areas.

In this article, we will delve deeper into how PDT works, the clinical applications of PDT, its advantages and challenges, current research initiatives, and potential future developments. By exploring case studies and examining the experiences of patients, we aim to provide a comprehensive overview of the current landscape and future prospects of photodynamic therapy.

How does it work?

Mechanism of action

PDT operates through three harmless elements: visible light, a photosensitiser, and oxygen. The photosensitiser is given, allowing it to selectively build up in the targeted tissue. When the area is exposed to light, the photosensitiser absorbs energy, transitioning to an excited state. This energy is then transferred to oxygen, generating reactive oxygen species, primarily singlet oxygen, causing damage to essential cell components and leading to cell death.² Since both light absorption and oxygen are crucial, PDT-induced cellular damage occurs only in areas both sensitised and exposed to light.

Administration of photosensitisers

First-generation photosensitisers like hematoporphyrin derivatives and porfimer sodium are already clinically approved, while second-generation ones like benzoporphyrin derivative monoacid ring are under evaluation. They can be given intravenously, orally, or topically. Intravenous administration ensures rapid circulation and generally even distribution. Oral administration is convenient, but absorption can be inconsistent. Topical and local delivery enables direct application to lesions, though penetration depth may be limited.³

Light delivery

PDT requires delivering visible light of the right wavelength to activate the photosensitiser. Light is typically delivered through laser fibres inserted interstitially into target tissues, using flexible fibre optics with diffusers emitting radially uniform light. Surface illumination can be applied for more superficial lesions. Appropriate light dosimetry considers both fluence rate and total fluence delivered. The light dose is planned based on tumour volume, photosensitiser properties, tissue optics, and the desired depth of necrosis.⁴

Current clinical applications

Photodynamic therapy (PDT) has emerged as a versatile and effective treatment with diverse clinical applications across various medical fields due to its non-invasive nature and targeted approach, making it particularly valuable in treating a spectrum of conditions.

Cancer treatment

PDT has shown remarkable success in treating certain cancers, both on the skin and internal organs. For skin cancers like basal cell carcinoma and Bowen's disease, PDT offers a highly effective and cosmetically favourable alternative. Internally, PDT has been used for early-stage esophageal and lung cancers, demonstrating its potential to cure these malignancies when applied in the initial phases. Additionally, PDT can provide relief from symptoms in more advanced cases, offering a palliative approach for patients with obstructive tumours.⁵ 

Skin problems

PDT finds extensive use in skin conditions, especially in managing actinic keratoses—precancerous skin lesions resulting from sun damage. Its ability to selectively target abnormal cells makes PDT a preferred option for treating these lesions⁶. Acne, a challenging condition to manage, has also been a focus of PDT applications, showcasing its efficacy in reducing inflammation and bacterial activity.⁷

Ophthalmology

In ophthalmology, PDT is employed to treat certain eye conditions, notably age-related macular degeneration (AMD). By selectively targeting abnormal blood vessels in the retina, PDT helps prevent further vision loss in patients with AMD.⁸

Gastrointestinal disorders

PDT is utilised in treating gastrointestinal disorders, including Barrett's esophagus—a condition characterised by changes in the lining of the lower esophagus that may lead to cancer if left untreated. By selectively destroying abnormal cells, PDT can mitigate the risk of cancer development.⁹

Infectious diseases

Beyond oncology and dermatology, PDT has shown promise in treating infectious diseases by targeting and destroying pathogens. PDT offers a potential alternative or adjunct to conventional antimicrobial therapies, extending to conditions like periodontal diseases, effectively combating bacteria associated with gum infections. This holds significant potential, especially considering the rising occurrence of drug-resistant pathogens.¹⁰

Case studies and success stories

In a poignant success story, a 51-year-old man diagnosed with early-stage small cell lung cancer (LS-SCLC) underwent a triumphant journey to full recovery. A strategic combination of chemotherapy, radiotherapy, and photodynamic therapy (PDT) proved instrumental. Despite multiple rounds of chemotherapy, a lingering lung mass persisted, and its complete removal was successfully achieved through the application of PDT. Astonishingly, both clinical and histological data reveal the patient's sustained freedom from cancer for an impressive two years without requiring further intervention.¹²

Shifting the focus to vascular lesions, a promising breakthrough emerged for a 21-year-old individual who had endured severe issues from previous treatments. Photodynamic Therapy (PDT) administered at London's National Medical Laser Centre ushered in swift and positive changes. The tumour vanished entirely after just one treatment, as confirmed by subsequent scans eight weeks later, rendering the individual pain-free. Optimism resonates among doctors regarding the chances of recurrence.¹³

Amidst these success stories, the Scottish Photodynamic Therapy Centre shines as a beacon of progress. Having conducted over 11,500 treatments, the centre extends its reach to patients from across Scotland and beyond the UK. Specializing in skin malignancies and pre-malignancies, the centre capitalises on significant advancements in dermatological PDT. The Center has also concluded successful studies on PDT for bile duct and brain tumours, with ongoing investigations into photo diagnostic techniques for the bladder and urinary tract.¹⁴

Advantages of PDT

Photodynamic Therapy (PDT) offers distinct advantages in cancer treatment. Firstly, it enables selective destruction of targeted tumour cells while sparing normal tissues, a notable departure from conventional methods like chemotherapy and radiotherapy.¹³ Another key advantage lies in its minimal invasiveness, making it applicable to tumours inaccessible to surgery through the use of interstitial fibres and endoscopic light delivery techniques.² Unlike cumulative chemotherapy or radiotherapy, PDT allows for repeated treatments without encountering dose limits, and it avoids cross-resistance issues.³ Additionally, the adoption of newer LED light sources at a comparatively lower cost makes PDT an economically viable option for treating larger areas.⁴ Furthermore, PDT showcases synergy with other therapies, providing the opportunity to combat tumours through multiple mechanisms simultaneously, including combinations with chemotherapy, anti-angiogenics, and immunotherapy.¹³

Limitations of PDT

Despite its advantages, PDT does have limitations. Tumor destruction is confined to the depth of adequate light penetration, limiting its effectiveness in deeper tissues.¹⁴ Patients undergoing PDT need to exercise caution and avoid bright light for weeks after treatment due to sustained skin photosensitization.⁶ The significant upfront and maintenance costs associated with lasers and fibre optic delivery systems pose financial challenges.⁴ Moreover, reimbursement issues, including a lack of insurance coverage policies, hinder widespread adoption, as PDT is not reimbursed at the same level as traditional treatments like surgery and chemotherapy.¹⁴ 

Future perspectives

The future of Photodynamic Therapy (PDT) holds exciting prospects in the realm of cancer treatment and beyond. Researchers are actively exploring novel photosensitisers to enhance the efficacy of PDT and broaden its applicability to various types of cancers. Advances in nanotechnology are facilitating the development of targeted drug delivery systems, allowing for more precise localization of photosensitisers within tumours. This targeted approach aims to improve the selectivity of PDT, minimizing damage to healthy tissues. Additionally, ongoing investigations focus on overcoming one of PDT's limitations—the depth of light penetration—by exploring innovative light sources and delivery techniques.¹⁵

Beyond oncology, PDT is showing promise in addressing antimicrobial resistance. Researchers are exploring its potential in treating infections, particularly in cases where traditional antibiotics may falter.¹⁰ Moreover, PDT's application in neurological disorders, cardiovascular diseases, and dermatological conditions is under scrutiny, signalling its versatility as a therapeutic modality.¹⁵

As technological advancements continue, the integration of PDT with other treatment modalities, such as immunotherapy and targeted therapies, is being explored to capitalise on synergistic effects.¹⁶ The future landscape of PDT envisions a more personalised and effective approach to disease management, harnessing the power of light for precise and tailored therapeutic interventions.

FAQs

What is the success rate of PDT in treating various conditions?

PDT has demonstrated notable success rates across different conditions. In lung cancer, a 72% complete response rate was achieved, indicating a complete cure.¹⁷ For oral cancer, an overall response rate of 86.2% was observed, with 55.2% achieving complete remission.¹⁸ In skin conditions like Acne and Basal cell carcinoma, full clinical remission was observed in 84.7% and 75.7% of lesions, respectively.¹⁹ Overall, the success rate of PDT has been promising in effectively treating a range of medical conditions.

How long does a Photodynamic Therapy (PDT) session last, and how many sessions are typically required?

The duration of a PDT session varies depending on the treated condition and the specific protocol, averaging between 30 minutes to a few hours. The number of sessions required is determined by the medical condition's severity, with healthcare providers customizing the treatment plan for each patient.

Can PDT be used for all types of cancers?

PDT has shown effectiveness in treating certain types of cancers, particularly skin, lung, and oesophagal cancers. However, its applicability depends on the specific diagnosis and the recommendation of healthcare professionals.

What precautions should be taken after Photodynamic Therapy (PDT)?

Due to sustained photosensitivity, it is crucial to avoid exposure to bright light for several weeks. Wearing protective clothing and sunglasses becomes essential during this period to prevent potential skin burn reactions. Additionally, individuals should follow any specific post-treatment instructions provided by their healthcare professionals to optimise recovery and minimise side effects.

Are there any side effects of Photodynamic Therapy (PDT)?

While PDT is generally well-tolerated, some individuals may experience temporary side effects. These can include redness, swelling, and mild discomfort at the treatment site. In addition to this, some patients may experience mild discomfort during and after PDT.²⁰ It's essential to note that these side effects are usually short-lived, and the benefits of PDT in targeted cell destruction often outweigh these temporary inconveniences. Patients should communicate any concerns with their healthcare providers for personalised guidance.

What is the typical recovery period after PDT?

Generally, recovery after PDT is brief. Patients may encounter mild side effects for a few days, and complete recovery is typically attained within one week. Clear post-treatment instructions will direct the recovery journey.

Are there insurance challenges for PDT? 

Yes, insurance issues exist as PDT may not be covered at the same level as traditional treatments like surgery and chemotherapy, impacting its widespread adoption. It is advisable for patients to check with their insurance providers to determine coverage levels and potential out-of-pocket expenses.

Summary

In conclusion, Photodynamic Therapy (PDT) utilises the healing power of light to selectively destroy targeted cells in conditions like cancer, wounds, and infections. Its clinical applications, notably in cancer treatment, have produced noteworthy success stories, highlighting PDT's efficacy and safety. The therapy boasts advantages such as minimal invasiveness, lack of resistance, and potential synergy with other treatments. Nevertheless, PDT faces limitations, including restricted tumour depth penetration and the necessity for patients to avoid bright light post-treatment due to sustained photosensitivity. Looking ahead, ongoing research into novel photosensitisers and innovative delivery systems promises to enhance PDT's role in personalised and effective medical interventions, marking a transformative future for this light-driven therapeutic approach.