What are the recommendations for a patient considered a candidate for Extrapleural Pneumonectomy (EPP) surgery?

Extrapleural Pneumonectomy (EPP) Candidate Recommendations

EPP should only be offered to highly selected patients with clinical early-stage (T1-3N0) epithelioid mesothelioma, good performance status, no comorbidities, and the ability to receive multimodality therapy at a high-volume center of excellence. 1

Patient Selection Criteria

Mandatory Inclusion Criteria

• Disease stage: Early-stage disease confined to the pleural envelope (Stage I), with no N2 lymph node involvement 1
• Histology: Epithelioid subtype only—sarcomatoid histology is an absolute contraindication to EPP 1
• Performance status: Good functional status with absence of significant comorbidities 1
• Cardiopulmonary function: Must meet specific preoperative criteria including adequate spirometry (FEV1 and FVC are critical predictors of mortality) 1, 2
• Disease extent: No evidence of extrathoracic disease on comprehensive staging 1
• Multimodality treatment capability: Patient must be able to receive adjuvant or neoadjuvant chemotherapy and/or radiation therapy 1

Absolute Contraindications

• Sarcomatoid or mixed (biphasic) histology 1
• Stage IV disease 1
• N2 lymph node involvement 1
• Multiple sites of chest wall invasion 1
• Poor performance status (PS ≥2) 1
• Significant comorbidities 1
• Inability to tolerate multimodality therapy 1

Critical Preoperative Evaluation

Required Staging Procedures

• Single-port thoracoscopy on the line of potential incision to assess resectability 1
• Mediastinoscopy or EBUS-FNA of mediastinal lymph nodes to rule out N2 disease 1
• Pulmonary function tests with perfusion scanning if FEV1 <80% 1
• Cardiac stress testing 1
• Laparoscopy if imaging suggests transdiaphragmatic extension (peritoneal involvement indicates unresectable Stage IV disease) 1

High-Risk Preoperative Markers

• Elevated C-reactive protein is significantly associated with 30-day and 90-day mortality (p<0.001) 2
• Reduced FEV1 and FVC predict perioperative mortality 2

Multimodality Treatment Framework

Chemotherapy Integration

• Four to six cycles of pemetrexed/platinum-based chemotherapy should be administered either pre- or postoperatively 1
• Standard regimen: Pemetrexed 500 mg/m² day 1 + Cisplatin 75 mg/m² day 1 every 3 weeks 1
• Neoadjuvant immunotherapy-based treatment may be offered as an emerging option 1
• EPP as single modality treatment is insufficient and should never be performed without additional systemic therapy 1

Adjuvant Radiation Therapy

• 50-60 Gy in 1.8-2.0 Gy fractions to the hemithorax for patients with good performance status to improve local control 1
• Radiation should cover the surgical bed, surgical scars, and biopsy tracks 1
• Treatment is complex and should only be delivered at experienced centers 1

Surgical Considerations

Important Caveats

• Lung-sparing options (P/D, extended P/D) should be the first choice over EPP due to decreased operative and long-term risk 1
• EPP may only be offered when performed at centers of excellence with documented low morbidity and mortality 1
• The procedure should be performed by board-certified thoracic surgeons with mesothelioma experience 1
• Mediastinal lymph node sampling or dissection is mandatory during EPP 1

Expected Outcomes at High-Volume Centers

• 30-day mortality: 5% 2
• 90-day mortality: 8% 2
• Major morbidity: 30% (higher with right-sided EPP and longer operative times) 2
• Median overall survival: 20.7-27.6 months in selected patients 3, 4

Common Pitfalls to Avoid

• Never proceed without comprehensive preoperative mediastinal staging—understaging is common and N2 disease fundamentally changes management 1, 5
• Do not offer EPP to patients with advanced disease (high nodal disease, areas of local invasion) as P/D is superior in this population 1
• Abort surgery if complete gross cytoreduction is not achievable (e.g., multiple chest wall invasion sites)—incomplete resection has poor outcomes 1, 5
• Avoid tunneled pleural catheters in EPP candidates due to risk of tumor implantation into the chest wall 1
• Do not recommend EPP based solely on anatomic resectability—favorable prognostic characteristics are essential 1

Evolving Evidence

The 2025 ASCO guidelines 1 represent a significant shift from earlier 2012 NCCN recommendations 1, emphasizing that surgical cytoreduction should not be routinely offered to all anatomically resectable patients. The MARS trial demonstrated that EPP is not beneficial compared to chemotherapy alone in unselected patients 1. However, retrospective data suggests survival benefit in highly selected patients at experienced centers with multimodality therapy 1, 3.