What is the role of extended pleurectomy and decortication (PD) in treating malignant pleural mesothelioma?

Extended Pleurectomy/Decortication in Malignant Pleural Mesothelioma

Extended pleurectomy/decortication (EPD) is the preferred surgical approach for carefully selected patients with resectable malignant pleural mesothelioma, offering superior perioperative safety compared to extrapleural pneumonectomy while achieving comparable long-term survival, and should be performed as part of multimodality therapy in specialized centers. 1

Definition and Surgical Technique

Extended pleurectomy/decortication involves parietal and visceral pleurectomy with complete macroscopic tumor resection, including resection of the diaphragm and/or pericardium as required, while preserving the lung 1. This distinguishes it from standard P/D (which does not include diaphragm/pericardium resection) and from extrapleural pneumonectomy (which removes the lung en bloc) 1.

Mediastinal nodal dissection is mandatory during EPD to ensure accurate staging and guide adjuvant therapy 1.

Patient Selection Criteria

EPD is appropriate for patients with:

• Clinical stage I-III disease who are medically operable 1
• Good performance status (ECOG 0-1) 1, 2
• Absence of significant comorbidities that would preclude major thoracic surgery 1
• Epithelioid or biphasic histology (sarcomatoid histology is a contraindication to surgery) 1
• No N2 lymph node involvement on preoperative staging 1, 3
• No stage IV disease (distant metastases or transdiaphragmatic extension) 1

EPD may be particularly appropriate for patients with advanced local disease (stages II-III), mixed histology, or high-risk factors where extrapleural pneumonectomy would carry excessive risk 1.

Survival and Oncologic Outcomes

Long-term survival after EPD is superior to or equivalent to extrapleural pneumonectomy with significantly lower mortality:

• A 2022 meta-analysis demonstrated lower hazard for death with P/D compared to EPP (HR 0.76,95% CI 0.62-0.94, p<0.001), with survival advantage increasing from 0.54 months at one year to 4.23 months at five years 4
• Propensity-matched analysis showed median overall survival of 22 months for P/D versus 15 months for EPP when adjusted for perioperative mortality 5
• The EORTC 1205 trial demonstrated median overall survival of 27-34 months with EPD as part of multimodality therapy 2

Macroscopic complete resection is the critical determinant of survival (HR 0.41, p=0.004), not the specific surgical technique 5. The goal should be achieving complete cytoreduction by the safest operation the patient can tolerate 5.

Perioperative Safety Profile

EPD has dramatically lower perioperative mortality compared to extrapleural pneumonectomy:

• 30-day mortality: 0-1.7% for EPD versus 10-11% for EPP 4, 2, 5
• 90-day mortality shows similar trends favoring EPD 4
• Perioperative morbidity ranges from 13-43%, but is consistently lower than EPP 1

Common complications specific to EPD include:

• Prolonged air leak (characteristic of lung-sparing surgery) 4
• Lower rates of empyema, atrial fibrillation, bleeding, and bronchopleural fistula compared to EPP 4

Quality of Life Considerations

The impact of EPD on quality of life is highly dependent on baseline performance status:

• Minimally symptomatic patients (PS 0) experience no improvement in global health or symptoms, with significant decreases in pulmonary function (FVC, FEV1, TLC, DLCO all decline, p<0.01) 6
• Symptomatic patients (PS 1-2) demonstrate significant improvements in global health, function, and symptom scores at 4-5 months with continued improvement at 7-8 months, without decline in pulmonary function 6, 7
• Patients with non-epithelioid histology and large tumor volume show the greatest improvement in quality of life following EPD 7

This creates a clinical paradox: EPD provides the most quality-of-life benefit to patients who are already symptomatic, while potentially harming minimally symptomatic patients 6.

Multimodality Treatment Integration

EPD must be performed as part of trimodality therapy (chemotherapy, surgery, radiotherapy) for optimal outcomes 1:

• Chemotherapy sequence: Either neoadjuvant or adjuvant chemotherapy with pemetrexed/platinum is appropriate, as the EORTC 1205 trial found no superior sequence (70% success rate with immediate surgery vs 50% with deferred surgery) 2
• Standard regimen: Pemetrexed 500 mg/m² plus cisplatin 75 mg/m² every 3 weeks 1, 3
• Adjuvant radiotherapy: 50-60 Gy in 1.8-2.0 Gy fractions to the hemithorax for local control 1

Center Experience and Quality Metrics

EPD should only be performed at specialized centers with demonstrated expertise:

• Macroscopic complete resection should be achieved in >80% of cases 2
• 30-day mortality should not exceed 2-3% 3
• Surgeon experience is an independent predictor of survival 1
• The decision between EPD and EPP may not be made until surgical exploration 1

Critical Contraindications

Do not perform EPD in patients with:

• Stage IV disease or sarcomatoid histology (chemotherapy alone is indicated) 1
• N2 mediastinal lymph node involvement on preoperative staging 1, 3
• Multiple sites of chest wall invasion where complete resection is not achievable 1, 3
• Poor performance status (ECOG ≥2) or significant comorbidities 1

Common Pitfalls to Avoid

Never proceed with EPD without:

• Thorough preoperative mediastinal staging including PET-CT and invasive nodal assessment if indicated 3
• Confirmation that complete macroscopic resection is technically achievable 1, 3
• Careful patient counseling about the high morbidity (despite low mortality) and uncertain quality-of-life impact in minimally symptomatic patients 6, 2

If complete resection is not possible intraoperatively, abort the procedure and proceed with definitive chemoradiotherapy rather than accepting incomplete resection 3.

The controversy surrounding EPP versus EPD has largely been resolved by recent evidence favoring lung-sparing surgery, though the overall role of any surgical cytoreduction in mesothelioma remains debated given the lack of randomized trials demonstrating survival benefit over chemotherapy alone 1.