What is palliative photodynamic therapy (PDT) plus stenting?

Palliative Photodynamic Therapy Plus Stenting

Palliative photodynamic therapy (PDT) plus stenting is a combination treatment for unresectable biliary tract cancers where a photosensitizing drug is administered intravenously, followed by endoscopic insertion of a biliary stent and laser light activation to destroy tumor tissue—however, this approach cannot be recommended for routine use as the most recent high-quality evidence demonstrates worse survival outcomes compared to stenting alone. 1

What the Procedure Involves

PDT combined with stenting is a two-component palliative intervention for malignant biliary obstruction:

• Photosensitizer administration: An intravenous photosensitizing agent (typically porfimer sodium/Photofrin) is injected 48 hours before the procedure 1
• Endoscopic stent placement: A biliary stent (plastic or self-expanding metal stent) is inserted via ERCP to relieve biliary obstruction 1
• Laser light activation: A laser fiber delivers red light at 630 nm wavelength (50-100 J/cm²) through an endoscope to the tumor site, activating the photosensitizer to generate reactive oxygen species that cause tumor cell death 1, 2
• Tissue penetration depth: The tumoricidal effect penetrates only 4-4.5 mm into tissue, which does not eradicate most tumors 3

Clinical Evidence and Outcomes

Early Promising Data (Now Superseded)

Initial small studies suggested benefit:

• An early trial of 39 patients with unresectable cholangiocarcinoma showed median survival of 493 days with PDT plus stenting versus 98 days with stenting alone 1
• These results led to initial enthusiasm for the technique 1

Definitive Evidence Against Routine Use

The UK Photostent-02 trial (2018)—the largest and most recent high-quality randomized controlled trial—definitively showed harm from PDT:

• 92 patients with biliary tract cancer were randomized to PDT plus stenting versus stenting alone 1, 4
• Overall survival was significantly worse with PDT: 5.6 months versus 8.5 months for stenting alone (HR 1.8, p=0.027) 1, 4
• Progression-free survival was also worse: 3.4 months versus 4.3 months (HR 1.43, p=0.10) 4
• Only 20% of PDT patients received subsequent chemotherapy compared to 41% in the stenting-alone group 1
• Even after adjusting for chemotherapy differences, the hazard ratio remained elevated at 1.6, indicating PDT itself contributed to worse outcomes 1

Current Guideline Recommendations

Based on the Photostent-02 trial results, major guidelines explicitly recommend against PDT:

• British Society of Gastroenterology (2012): "Photodynamic therapy cannot be recommended for routine use based on the most recent data (Grade A)" 1
• European Society for Medical Oncology (2011): PDT "has been proved to provide survival benefit in two small randomized trials" but notes this was before the definitive negative Photostent-02 data 1
• Asia-Pacific guidelines: Previously gave Grade A recommendation for PDT in inoperable perihilar cholangiocarcinoma, but this predates the Photostent-02 results 1

Adverse Effects and Complications

PDT carries specific risks beyond standard stenting complications:

• Prolonged skin photosensitivity: Lasts up to 3 months with Photofrin, requiring strict sun avoidance 5, 3
• Cholangitis: Most frequent adverse event (occurs in approximately 24% of patients) 6
• Mild dermatitis: Common but manageable 2
• No severe PDT-specific grade 3-4 adverse events were observed in the Photostent-02 trial 4
• Standard stenting complications include sepsis, biliary obstruction, stent occlusion, and acute cholecystitis from covered stents 1

Alternative Photosensitizers

Newer agents have been studied to reduce side effects:

• mTHPC (Foscan): Low-dose protocols (0.032-0.063 mg/kg) show median survival of 13 months with reduced skin photosensitivity risk 5
• Polyhematoporphyrin: Austrian nationwide study of 150 procedures showed median survival of 12.4 months from first PDT with acceptable safety profile 6

However, these alternatives lack randomized controlled trial evidence comparing them to stenting alone or standard chemotherapy 6, 5

Current Standard of Care

For malignant biliary obstruction, the evidence-based approach is:

• Initial biliary drainage: Plastic or covered self-expanding metal stents (SEMS) for biliary obstruction 1
• Systemic chemotherapy: Gemcitabine plus cisplatin for patients with ECOG performance status 0-2 provides survival benefit of approximately 4 months 7
• Optimal stenting remains the treatment of choice for malignant biliary obstruction 4

Critical Clinical Pitfalls

• Do not delay systemic chemotherapy in favor of PDT, as chemotherapy-eligible patients (ECOG 0-2) derive clear survival benefit from gemcitabine-cisplatin 7
• Do not use PDT outside clinical trials given the Grade A evidence against its routine use 1, 4
• Optimize biliary drainage first before considering any additional interventions 7
• PDT requires repeat treatments approximately every 6 months due to limited tissue penetration and tumor progression 3