Principle
Photodynamic therapy (PDT) is an ablation technique used to treat various forms of superficial cancer. A photosensitizer is used in conjunction with a light source with emission at a specific wavelength (e.g. 630 nm). The light activates photosensitizer accumulated in tumor tissue, which results in the death of tumor cells through the production of reactive oxygen species (ROS).

PDT therapy begins with the patient taking photosensitizer orally, intravenously, or topically. Photosensitizer tends to localize in tumor tissue at concentrations higher than those in normal tissue. A light source of a specific wavelength is then used to excite the photosensitizer to produce ROS, a toxic singlet oxygen and free radicals that are cytotoxic to cancer cells. Photodynamic therapy also induces capillary endothelial damage and blood clots which cause microcirculatory disorders and lead to further necrosis of tumor tissues. Recent studies have even shown that photodynamic therapy activates the immune system.

Photodynamic therapy has three key components: photosensitizer, oxygen, and laser light. The photosensitizer itself is non-toxic until excited by light of a specific wavelength. Photodynamic therapy selectively kills cancer cells with little damage to normal tissue. The reactive distance of singlet oxygen is short (only 20 nm) and the duration is short (40 nsec), which means that the cytotoxic effects are limited to the area in which the ROS is produced, i.e., in the photosensitizer-labeled cells.
 

Benefits of PDT
The PDT operation is brief, does not require hospitalization, and is minimally invasive, allowing patients to resume their normal lives shortly after treatment. The photosensitizer remains in the targeted tissue, such that PDT affects only the region exposed to light. PDT can be combined with surgical operations, radiotherapy, and chemotherapy. Furthermore, PDT can be administrated repeatedly without causing tolerance. Due to the limited depth of PDT treatment, it can be used as adjuvant therapy in combination with surgical procedures targeting small tumors at the surface without causing damage to normal tissue.
 

Limits of PDT
The major limitation of PDT is the depth of penetration. For example, light at a wavelength of 630 nm can penetrate only 0.2 to 2 centimeters into tissue. Blood clots, blood flow, and necrotic tissue within the tumors also tend to affect light penetration. Obviously, PDT is unsuitable for large tumors. Optical fibers have been inserted into tumors for the application of interstitial PDT or laser ablation; however, this approach is not always convenient or practical and the distribution of light is non-uniform.

Recent developments in photosensitizer technology have reduced the effects of photosensitivity; however, patients should avoid exposing their skin to strong sunlight for 4 to 6 weeks after PDT.
 

When to use

1. Cancerous and precancerous lesions, and a number of benign lesions, such as inflamed tissue, retain more photosensitizer. As long as these lesions can be exposed to light, they are candidates for PDT.
2. PDT is suitable for the treatment of superficial lesions as well as lesions that are reached by endoscopic illumination, such as the skin, mouth, lung, trachea, gastrointestinal tract, bladder, and other hollow organs.
3. PDT is suitable for non-metastatic cancers, such as brain glioma; however, it is generally inapplicable to metastatic cancers, such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant pleural mesothelioma (MPM), cholangiocarcinoma, precancerous changes such as actinic keratosis (AK), and in situ carcinoma (SCC in situ, Bowen's disease). PDT completely or partially reduces the bronchial obstruction in patients with non-small cell lung cancer and relieves the symptoms of obstruction.
4. PDT can also be used for other non-cancer diseases, such as age-related macular degeneration (AMD), coronary artery occlusion, rheumatoid arthritis, psoriasis, acne, solar keratosis, and warts.
5. Overseas, PDT has been used to treat bladder cancer, esophageal cancer, bronchial cancer, oral cancer, skin cancer, nasopharyngeal cancer, laryngeal cancer, cervical cancer, vaginal cancer, vulvar cancer, penile cancer, pleural mesothelioma, liver cancer, pancreatic cancer, bile duct cancer, brain tumors and other malignant tumors, and precancerous lesions such as esophageal squamous dysplasia, Barrett's esophagus, bronchial dysplasia, bladder transitional epithelium atypical hyperplasia, as well as age-related macular lesions, port wine stains and other benign skin lesions.
6. In Taiwan, PDT has been used for esophageal cancer patients who are failing as well as those for whom standard treatments are unsuitable (surgery, radiation, and chemotherapy). PDT has also been used to treat patients with non-small cell lung cancer who are not candidates for surgical or radiation therapies, for the complete or partial reduction of bronchial obstructions.
    

PDT: Two-step process
Step One: Treatment begins with an intravenous injection of photosensitive drugs to accumulate in tumor cells. These drugs are metabolized within 40-72 hours by normal tissue; however, tumors, skin cells, and the reticuloendothelial system retain them for much longer.
Step Two: Approximately 40-50 hours after the administration of photosensitizer, a laser fiber is used to guide an optical fiber to the lesion. The laser light activates a photochemical reaction that ultimately results in necrosis within the tumor. Necrotic and inflammatory responses may last for several days.
 

Preoperative considerations of PDT

1. Regular testing of blood, liver and kidney function, and coagulation.
2. Consent forms.
3. Patients receiving local anesthesia do not have to fast, but they must not eat excessively. Patients undergoing systemic anesthesia must observe fasting for no less than six hours.
4. Endoscopy, biliary photography, and other imaging tools can be used to determine the treatment path and plan the range of therapy.
5. Curtains and other shades must be used to block sunlight at home.
6. Patients need to wear sunglasses, a hat, gloves and a long-sleeved shirt following the administration of photosensitizer.
    

Intraoperative considerations of PDT

1. Patients should avoid light after being administered photosensitizer and before the laser treatment.
2. Use of local anesthesia, intravenous anesthesia, or general anesthesia as required.
3. Selection of percutaneous treatment, endoscopic therapy, or conventional surgical treatment.
4. Intraoperative conscious patients in any discomfort should contact healthcare providers.
    

Postoperative considerations of PDT

1. Patients that undergo percutaneous treatment should lie down or lie on one side for at least six hours to facilitate hemostasis. This is not necessary for patients that undergo endoscopic or conventional surgery.
2. For thirty days after treatment, patients should wear a long-sleeve shirt to cover skin, avoid exposure to direct sunlight, cover windows, avoid light sources of any sort, and wear dark sunglasses to protect the eyes.
3. Patients should not remain in a completely darkened room. Low wattage indoor lighting can help to decompose the photosensitizer in the skin and thereby reduce photosensitivity.
4. Sunscreen products do not provide sufficient protection, regardless of the protection factor.
5. After 30 days, patients may expose a small amount of skin to sunlight. Any photosensitive reaction, such as redness, swelling, or blistering within 24 hours, is an indication that light should be avoided for another two weeks. If no reaction is observed, exposure to sunlight may be gradually increased. Nonetheless, the time spent outdoors should be strictly curtailed and exposure to the sun completely avoided between 11 am and 2 pm.
6. CT or MRI could be used to track tumor progress. This is generally conducted at the first examination one month after treatment to ensure that any viable tumors are dealt with in a timely manner. Further regular examinations are then conducted every three to four months.
    

Risks and Complications
The laser used in PDT is a low-power light source that does not heat or burn. Most photosensitizers are low in toxicity. The most common side effects of PDT are swelling near the treatment site, inflammation, and physical discomfort, such as chest pain, back pain, abdominal pain, or difficulty breathing. Residual photosensitizer within the skin may also induce photosensitivity, leaving the skin and eyes sensitive to strong light for 30 days (varies by body metabolism) following the administration of photosensitizer.​