Overview

Did you know, sunlight¹ has been a therapeutic agent for centuries? This natural source has been the foundation for Photodynamic therapy (PDT). 

Recently, PDT has gained attention in the context of field cancerization (figure 1), especially in conditions such as oral potentially malignant disorders (OPMDs), actinic keratosis, and Barrett’s oesophagus.²

Photodynamic therapy is an innovative, minimally invasive technique used to target precancerous and cancerous lesions, particularly in the areas of the mouth, skin and oesophagus. This technique involves the use of photosensitising agents, a light source and oxygen to destroy abnormal tissue, leaving surrounding healthy tissue.³

Figure 1: (A) Illustration of cancer cell invasion into normal tissue. (B) Continuous exposure to cancer cells leads to adaptation of normal cells within the tumour microenvironment. (C) Surgical excision of cancerous tissue, along with surrounding normal tissue, is recommended to reduce the risk of secondary tumour recurrence.²

In this article, we will be looking at the mechanisms, applications, benefits, and limitations of Photodynamic therapy for managing precancerous lesions.

How does Photodynamic therapy work?³

Systemic application of highly localised photosensitizing agents 

Target precancerous / cancer cells, largely avoiding normal surrounding tissue

Following a predetermined Incubation period, the affected area is exposed to the light of a specific wavelength (red or blue spectrum)

Photosensitizers get activated and interact with molecular oxygen present in the affected tissue, releasing reactive oxygen species (ROS).

ROS causes oxidative damage to cellular components such as lipids, proteins and nucleic acids, resulting in cell death. Please refer to Figure 2  to understand the mechanism of Photodynamic therapy.

Figure 2: The image here illustrates the mechanism of Photodynamic therapy. (A) The image shows the pre-cancer cells invading the surrounding normal cells. (B) Upon the application of Photodynamic Therapy, the photosensitizer in the targeted area reacts with oxygen to generate reactive oxygen species (ROS), primarily singlet oxygen. (C) These ROS selectively destroy cancer cells while leaving the surrounding healthy tissue unaffected. Image created in BioRender.com.⁴ 

Clinical applications

Oral potentially malignant disorders (OPMD)                                               

PDT has shown promising results in the management of oral precancer lesions such as Leukoplakia, Erythroplakia, and Oral lichen planus.  OPMDs remain unaltered, grow, shrink, and sometimes disappear, or they might even develop further and underg malignant transformation. As these lesions are asymptomatic, long-standing and clinically similar to a majority of other oral infections, their clinical diagnosis does not clearly define the likelihood of progression. Predicting malignant transformation and linking it to risk factors is difficult because OPMDs do not always have a consistent course.⁵ Photodynamic therapy is a non-invasive method that could help destroy dysplastic cells, minimising the risk of malignant transformation. Studies have reported the method to be an alternative to conventional surgical excision of the lesion, which could benefit facial aesthetics.^5,6,7

Actinic keratosis (AK)

Actinic keratosis is a skin lesion believed to be the precursor of squamous cell carcinoma of the skin. AK has been treated in multiple ways previously, including surgical excision, cryotherapy, curettage and topical applications (5-fluorouracil, imiquimod, ingenol mebutate and diclofenac). Multiple AKs associated with field cancerization were treated successfully using PDT. Particularly, Daylight PDT has been convenient, attractive, tolerable, and valuable to treat AK.⁸

Barrett’s oesophagus

Barrett’s oesophagus is a chronic condition that typically develops from gastric-oesophageal reflux where acid, bile juice and other stomach contents flow back in a reverse direction to the gastro-oesophageal junction. This is due to prolonged exposure results in epithelial-metaplasia.⁹ PDT offers targeted therapy when combined with endoscopy, allowing effective penetration, thereby minimising the risk of esophageal perforation.¹⁰

Benefits of using PDT

Photodynamic therapy offers multiple advantages over conventional treatments in Precancerous lesions:

• Minimally Invasive: PDT eliminates the need for incisions, which minimises the risk of infection, scarring, and complications post-surgery
• Selective Targeting: One of the treatment's strongest points is its ability to target abnormal cells only, leaving healthy tissue unaffected. The function and appearance of the treated area are maintained while collateral damage is reduced due to this selectivity (Figure 2)
• Repeatability: One of the main benefits of PDT in cases with numerous or recurring lesions is its ability to be safely repeated if needed. It is a versatile alternative for patients who need continuous treatment since, in contrast to radiation therapy, it does not produce long-term adverse effects.  
• Cosmetic Outcomes: PDT is a recommended treatment for visible regions like the face and neck because it produces significant cosmetic results with less scarring, especially in skin lesions
• Minimal adverse effects: Most patients only experience minor, temporary side effects, such as swelling and redness at the treatment region¹¹

Limitations of PDT

Despite various benefits, Photodynamic therapy does have limitations that need to be taken into consideration.

• Restricted Penetration Depth: The light used to activate the photosensitizers has a limited penetration depth, which is one of PDT's major drawbacks. As a result, the treatment works effectively for superficial lesions. Unless advanced techniques, such as endoscopic light delivery, are employed, different treatment approaches could be required for deeper tissues, such as massive or invasive tumours
• Photosensitivity: Although the photosensitizers remain in the body for a few days following treatment, patients undergoing PDT may have temporary sensitivity to sunlight.   To avoid skin reactions, patients are recommended to stay out of direct sunlight and other bright light sources during this period
• Limited Availability: PDT may only be available at specific medical facilities or centres, and it requires specialised equipment and trained staff. For patients in isolated or underprivileged areas, this may limit their access to the treatment¹²

Future

To improve the therapeutic benefit of Photodynamic therapy, research is currently ongoing on novel photosensitizers, improved light delivery systems, and combination therapies.   The use of PDT in addressing more advanced lesions and tumours can be explored because of developments in immunomodulatory techniques and nanoparticle-based photosensitisers.¹³ Furthermore, PDT's function in conjunction with other medicines, such as immunotherapy, which may have synergistic benefits in the treatment of cancer, is being investigated in clinical trials.¹⁴

FAQs

What is photodynamic therapy (PDT)?

Photodynamic Therapy (PDT) is a medical procedure that uses a photosensitising drug plus a specific sort of light to destroy abnormal or precancerous cells. When exposed to light, the drug induces reactive oxygen species, which target and destroy these cells while causing minimal impact on adjacent healthy tissue.

How is PDT used to treat precancerous lesions?

Precancerous lesions can be treated by applying a photosensitising agent to the affected area. Following a period, the area is exposed to a particular wavelength of light, which causes the agent to eliminate aberrant cells. This selective technique helps prevent the development of cancerous cells.

Is PDT a painful procedure?

PDT may cause discomfort, particularly during the light exposure phase, where patients may experience tingling or burning sensations. This normally resolves following therapy. If needed, your healthcare practitioner can advise you on pain management options.

Are there any adverse effects to PDT?

Common adverse effects include redness, swelling, and light sensitivity in the treated area. Patients are frequently advised to avoid direct sunlight exposure for a while after treatment since their skin may still be sensitive to sunlight.

How long does a PDT therapy session last?

A PDT session can last anywhere from a few minutes to an hour, depending on the area that needs to be treated and the amount of light exposure necessary. Additional preparation time may be needed for the photosensitising agent to absorb into the targeted cells.

How many sessions of PDT are required?

The number of PDT treatments required varies depending on the nature and severity of the lesion or malignancy. Some people may just require a single session, whilst others may require numerous sessions for the best outcomes.

Who is a suitable candidate for PDT?

PDT is often suitable for patients with localised precancerous lesions, early-stage malignancies, or some forms of skin cancer. It is important to discuss with a healthcare professional to establish whether PDT is a suitable treatment, depending on the individual's conditions and overall health.

Summary

Photodynamic therapy is a vital tool in the treatment of precancerous lesions, providing a targeted, minimally invasive, and repeatable therapeutic option with great aesthetic results. While it has limits, notably in terms of tissue penetration depth and temporary photosensitivity, the advantages outnumber the drawbacks in many therapeutic instances.   As research advances, PDT's significance in combating the progression of precancerous lesions to cancer will continue to increase, offering the possibility for early cancer prevention and treatment.