Extrapleural Pneumonectomy

Extrapleural Pneumonectomy
Radical Surgical Resection for Malignant Pleural Mesothelioma
Procedure Type	Radical Surgical Resection
Structures Removed	Lung, pleura, pericardium, diaphragm
First Described	1949 (Sarot)
First for Mesothelioma	1976 (Butchart)
Operative Mortality	3.8–7%
Median Survival	14–19 months (all comers)
Best Subgroup Survival	46% at 5 years (favorable triad)
Hospital Stay	10–11 days (median)
Current Status	Limited use; P/D preferred
Free Case Review →

Extrapleural Pneumonectomy: The Most Radical Surgical Treatment for Pleural Mesothelioma

Executive Summary

Extrapleural pneumonectomy (EPP) is the most radical surgical procedure used in the treatment of malignant pleural mesothelioma (MPM), involving the en bloc removal of the affected lung, visceral and parietal pleura, ipsilateral pericardium, and ipsilateral hemidiaphragm. First described by Sarot in 1949 for tuberculous empyema and later applied to mesothelioma by Butchart and colleagues in 1976, EPP was once the cornerstone of aggressive multimodal mesothelioma treatment.

The procedure gained prominence through the work of Dr. David Sugarbaker at Brigham and Women's Hospital, whose 1999 landmark series of 183 patients demonstrated 3.8% perioperative mortality and, in a carefully selected subgroup with epithelioid histology, negative nodes, and complete resection margins, a remarkable 46% five-year survival rate. However, the trajectory of EPP changed dramatically following the MARS trial in 2011, which found worse survival in the EPP group compared to no surgery, and the MARS 2 trial in 2024, which showed that even the less radical pleurectomy/decortication (P/D) did not improve survival over chemotherapy alone.

Current guidelines from the NCCN, BTS, and ASCO now recommend P/D over EPP, with EPP reserved for highly selected patients at specialized centers of excellence. For mesothelioma patients and their families evaluating surgical options, understanding the risks, benefits, and evolving evidence surrounding EPP is critical to making informed treatment decisions.

Extrapleural pneumonectomy at a glance:

• EPP removes the entire lung vs. P/D which preserves it — patients undergoing EPP lose all ipsilateral pulmonary function permanently, while P/D patients retain 65% of predicted FEV1 postoperatively
• Operative mortality is 2.5 times higher with EPP than P/D — 4.5% vs. 1.7% across 2,903 patients in the largest meta-analysis comparing the two procedures
• Overall morbidity after EPP is more than double that of P/D — 62% of EPP patients experience major complications vs. 27.9% for P/D
• Carefully selected EPP patients survive 3 times longer than unselected cases — the Sugarbaker favorable triad achieved 51 months median survival vs. 14–19 months for all-comers
• EPP achieves better local control but worse distant control than P/D — local recurrence is 33% after EPP vs. 65% after P/D, but distant recurrence is 66% vs. 35%
• SMART protocol EPP patients survived 4 times longer than standard EPP patients — 65.9 months median survival in the epithelioid node-negative SMART subgroup vs. 14–19 months in conventional series
• Post-EPP lung function drops nearly twice as much as after P/D — FEV1 declines from 76% to 48% predicted after EPP vs. 82% to 65% after P/D
• EPP costs 16% more than P/D per hospitalization — mean hospital cost of $62,408 for EPP vs. $53,993 for P/D based on national inpatient data
• Only 11% of mesothelioma surgery patients now receive EPP vs. 57% receiving P/D — reflecting a decisive shift toward lung-sparing approaches across major guidelines
• Patients treated at high-volume centers have 20–40% better survival than those at general hospitals — surgical volume is one of the strongest predictors of EPP outcomes

Key Facts

Metric	Finding
Procedure scope	En bloc resection of lung, pleura, pericardium, and diaphragm
Operative mortality (Sugarbaker 1999, n=183)	3.8% (30-day); up to 7% in multi-institutional registries (Flores 2008, n=385)
Overall median survival	14–19 months (all comers); 18 months in 529-patient series (Sugarbaker 2014)
Favorable triad survival (Sugarbaker 1999, n=31)	Epithelioid + negative nodes + negative margins = 46% five-year survival (median 51 months)
MARS trial result (2011, n=50)	EPP 14.4 months vs. no surgery 19.5 months; HR 2.75 (95% CI 0.91–8.27; p=0.07)
EPP vs. P/D mortality (Taioli 2015, n=2,903)	30-day mortality: EPP 4.5% vs. P/D 1.7%
Major complication rate (Batirel systematic review)	EPP 62.0% overall morbidity vs. P/D 27.9%
Most common complication (Sugarbaker 2004, n=328)	Atrial fibrillation in 44.2% of EPP patients
Hospital cost (2014 NIS data)	Mean $62,408 (95% CI: $48,385–$76,431); median stay 10–11 days
SMART protocol result (de Perrot 2021, n=96)	30-day mortality 1%; epithelioid N0 subgroup median 65.9 months
Recurrence patterns (Baldini 2015, n=169)	75% overall recurrence at median 13.1 months; local 54%, abdominal 39%
Guideline consensus (NCCN 2025, BTS 2018, ASCO 2025)	P/D preferred over EPP; BTS explicitly recommends against EPP; EPP reserved for centers of excellence

What Is Extrapleural Pneumonectomy?

Extrapleural pneumonectomy is defined as the en bloc surgical removal of the ipsilateral lung together with the visceral and parietal pleura, ipsilateral pericardium, and ipsilateral hemidiaphragm for the treatment of malignant pleural mesothelioma. The procedure represents the most aggressive surgical approach to mesothelioma, designed to achieve macroscopic complete resection (MCR) of all visible tumor by removing every pleural surface and the organs they encase.

The term extrapleural refers to the surgical plane of dissection, which lies outside the parietal pleura. This distinguishes EPP from standard pneumonectomy (lung removal alone) and from pleurectomy/decortication (P/D), which removes the pleura but preserves the lung. Radical mediastinal lymph node dissection is performed concurrently to assess nodal disease, which is one of the strongest prognostic factors determining survival after EPP.

EPP is never performed in isolation. It is always part of a multimodal treatment strategy that typically combines surgery with chemotherapy (usually cisplatin and pemetrexed) and, in some protocols, hemithoracic radiation therapy. The rationale for combining these modalities is that surgery addresses local disease while chemotherapy and radiation target microscopic residual cancer cells that cannot be removed surgically.

How Is EPP Performed?

The EPP procedure is performed through an extended posterolateral thoracotomy, with the incision beginning midway between the posterior scapular tip and the spine and extending along the sixth rib to the costochondral junction. The latissimus dorsi and serratus anterior muscles are divided, and the sixth rib is typically resected to provide adequate surgical exposure. The posterior periosteum in the bed of the sixth rib is incised to expose the extrapleural plane.

The surgical sequence proceeds as follows:

1. Incision and exposure of the parietal pleura via posterolateral thoracotomy
2. Extrapleural dissection using combined sharp and blunt technique, separating tumor-bearing pleura from the chest wall, continuing to the apex, mediastinum, esophagus, and great vessels
3. En bloc resection of the lung, pleura, pericardium, and diaphragm with division of the hilar structures (pulmonary artery, pulmonary veins, and mainstem bronchus)
4. Radical lymph node dissection of mediastinal lymph node stations
5. Reconstruction of the diaphragm and pericardium with synthetic patches

The diaphragm and pericardium are reconstructed using Gore-Tex (PTFE) patches. Routine pericardial reconstruction has been shown to reduce the incidence of cardiac herniation, a potentially fatal complication. Published data on operative duration are limited, with informal estimates citing 6 to 10 hours for the complete procedure. The literature distinguishes standard EPP from extended EPP, which involves additional resection of chest wall structures, great vessels, or esophageal muscularis beyond the standard specimen.

Who Is a Candidate for EPP?

Patient selection is the single most important factor determining outcomes after EPP. Current practice restricts EPP candidacy to a narrow subset of mesothelioma patients meeting stringent clinical criteria.

Staging Requirements

EPP candidates must have clinical early-stage disease, typically T1 to T3, N0 (no lymph node involvement). N2 mediastinal nodal disease is a major adverse prognostic factor. In the Sugarbaker 529-patient series, patients with N2 disease had a median survival of only 13 months compared to 26 months for N0 patients, leading many centers to consider N2 involvement a contraindication to EPP. Preoperative mediastinal staging with mediastinoscopy or endobronchial ultrasound is recommended to exclude N2 disease before proceeding.

Histological Requirements

Epithelioid histology is the only subtype routinely considered for EPP. Biphasic mesothelioma carries a significantly worse prognosis and is approached with caution at most centers. Sarcomatoid histology is generally excluded from curative-intent surgery, including EPP, due to its aggressive biology and uniformly poor surgical outcomes.

Cardiopulmonary and Performance Requirements

EPP requires sufficient cardiopulmonary reserve to tolerate permanent single-lung physiology. Specific thresholds vary by institution but generally include adequate predicted postoperative FEV1, acceptable DLCO, and satisfactory cardiac function assessed by echocardiography. Performance status must be ECOG 0 to 1. There is no formal age cutoff, though outcomes deteriorate with advancing age, and most contemporary protocols exercise caution with patients over 70 years.

What Are the Survival Outcomes After EPP?

Survival after EPP varies dramatically depending on patient selection, histology, nodal status, and completeness of resection. The following data represent the largest published series.

Overall EPP Survival

Series	Patients	30-Day Mortality	Median OS	5-Year Survival
Sugarbaker 1999	183	3.8%	19 months	15%
Sugarbaker 2014	529	5.0%	18 months	14%
Flores 2008	385 (EPP arm)	7.0%	12 months	—
MARS Trial 2011	24 (16 completed)	12.5%	14.4 months	—

Survival by Nodal Status

Lymph node involvement is the strongest independent prognostic variable after EPP. The Sugarbaker 529-patient series demonstrated a clear survival gradient:

Node Status	Patients	Median OS
N0 (negative)	224	26 months
N1	118	17 months
N2	181	13 months
N3	5	7 months

The Favorable Triad

The most cited finding in EPP outcomes research is the favorable triad identified by Sugarbaker in 1999: patients with epithelioid histology, negative resection margins, and negative extrapleural lymph nodes achieved 68% two-year survival, 46% five-year survival, and a median of 51 months. This subgroup comprised only 31 of 183 patients (17%). This result has not been consistently replicated at other centers but remains the benchmark cited by EPP advocates.

What Complications Can Occur After EPP?

EPP carries substantially higher morbidity and mortality than P/D. The overall major complication rate after EPP is approximately 62% compared to 27.9% for P/D, and 30-day operative mortality is 6.8% versus 2.9% for P/D.

Major Complications

Complication	EPP Rate	P/D Rate
Overall morbidity	62.0%	27.9%
30-day mortality	6.8%	2.9%
Atrial fibrillation	17.6–44.2%	7.4%
Bronchopleural fistula	2.3%	0.4%
DVT/PE	3.3%	1.4%
Serious respiratory complications	10.0%	6.4%

Atrial fibrillation is the most common complication, occurring in 44.2% of patients in the Sugarbaker 328-patient series (2004). Other significant complications include vocal cord paralysis (6.7%), prolonged intubation (7.9%), bronchopleural fistula, cardiac herniation if pericardial reconstruction fails, empyema, and pulmonary embolism. A 2022 meta-analysis confirmed that atrial fibrillation, hemorrhage, pulmonary embolism, air leak, and reoperation were all significantly increased after EPP compared to P/D (p < 0.05). Pulmonary embolism has been identified as the most common cause of perioperative mortality following EPP.

Median postoperative hospital stay is approximately 10 to 11 days, with national database analysis reporting a mean length of stay of 11.2 days.

How Does EPP Affect Quality of Life?

EPP results in substantially greater pulmonary function loss than P/D. A 2021 study from Zurich documented FEV1 declining from 76% predicted to 48% predicted after EPP, compared with 82% to 65% after P/D.

A 2018 systematic review encompassing 659 patients (102 EPP, 432 P/D) across 14 datasets found that quality of life remained compromised at 6 months following both procedures, but P/D patients had better scores across all measures including physical function, social function, and global health status. Critically, only P/D patients demonstrated return to baseline quality of life at 12 months; EPP patients did not reach pre-surgical quality of life levels within the study follow-up periods.

In the MARS trial, quality of life scores were lower in the EPP group at all time points, with particularly striking differences at 6 weeks post-surgery (global health: 33.3 versus 75.0), though the small sample size limited statistical significance. Despite these findings, the 2021 Zurich study argued that quality of life alone should not be used as an argument against EPP, noting that both procedures ultimately achieved similar long-term functional outcomes in survivors. This remains a minority view in the mesothelioma surgical community.

How Does EPP Compare to Pleurectomy/Decortication?

The EPP versus P/D debate is the central controversy in mesothelioma surgery, with accumulating evidence favoring the less radical lung-sparing approach.

Arguments for EPP

Proponents of EPP argue that complete removal of the lung allows for more thorough macroscopic complete resection in certain anatomic configurations where tumor extensively involves the visceral pleura. EPP also enables full-dose hemithoracic radiation therapy without the risk of radiation pneumonitis, since no lung tissue remains to be damaged. The Sugarbaker favorable triad data, showing 46% five-year survival in selected patients, remains the strongest argument for EPP in appropriate candidates. Additionally, local recurrence rates are lower after EPP (33%) compared to P/D (65%) in registry data.

Arguments Against EPP

The evidence against EPP has grown substantially. The MARS trial (2011) randomized 50 patients and found median survival of only 14.4 months for EPP versus 19.5 months without EPP (HR 2.75). While designed as a feasibility study, the results were striking. The MARS 2 trial (2024) showed that even the less morbid P/D did not improve survival over chemotherapy alone (19.3 versus 24.8 months), further undermining the rationale for the more radical EPP.

Meta-analyses consistently show EPP carries 2.5-fold higher short-term mortality than P/D (4.5% vs. 1.7%, Taioli 2015, 2,903 patients) and significantly higher overall morbidity (62% vs. 27.9%). While EPP achieves better local control (33% local recurrence vs. 65% for P/D), it is associated with higher distant recurrence (66% vs. 35%), possibly due to immunosuppression from losing the lung and its lymphatic tissue. Modern radiation techniques including intensity-modulated radiation therapy (IMRT) and proton therapy can now deliver targeted pleural radiation with the lung in situ, weakening one of the historical advantages of EPP.

Metric	EPP	P/D	Source
30-day mortality	4.5%	1.7%	Taioli 2015 (n=2,903)
Overall morbidity	62.0%	27.9%	Batirel systematic review
Local recurrence	33%	65%	Flores 2008
Distant recurrence	66%	35%	Flores 2008

What Role Does EPP Play in Multimodal Treatment?

EPP is never performed as a standalone treatment. It is always integrated into a multimodal strategy combining surgery with systemic chemotherapy and, in many protocols, radiation therapy.

The Sugarbaker Trimodal Protocol

The classic Brigham and Women's protocol follows the sequence: EPP followed by adjuvant chemotherapy (cisplatin and pemetrexed) followed by hemithoracic radiation therapy. A multicenter phase II trial of neoadjuvant pemetrexed/cisplatin followed by EPP and radiation achieved median overall survival of 16.8 months for intention-to-treat patients and 29.1 months for patients completing all three modalities, with surgical mortality of 3.7%.

The SMART Protocol

The Surgery for Mesothelioma After Radiation Therapy (SMART) protocol, developed by de Perrot and colleagues at Princess Margaret Cancer Centre in Toronto, reverses the traditional treatment sequence: accelerated hemithoracic IMRT (25 Gy in 5 fractions) followed by EPP within approximately one week. The published phase II results from 96 treated patients demonstrated 30-day mortality of only 1% (one patient) and grade 3-4 complications in 49%. For the epithelioid, node-negative subgroup (19 patients), the SMART protocol achieved a remarkable median survival of 65.9 months.

EPP and Immunotherapy

Several phase I and II clinical trials are investigating the combination of immune checkpoint inhibitors with surgical resection for mesothelioma. Perioperative pembrolizumab, nivolumab, and nivolumab plus ipilimumab are all under active study. However, most contemporary surgical immunotherapy trials use P/D rather than EPP as the surgical modality, reflecting the broader shift away from EPP.

What Are the Recurrence Patterns After EPP?

Understanding where mesothelioma recurs after EPP is essential for planning adjuvant treatment and surveillance. The foundational study by Baldini and colleagues (1997) characterized recurrence patterns in 49 patients undergoing EPP with adjuvant chemotherapy and hemithoracic radiation, finding an overall recurrence rate of 54% at a median of 19 months.

An updated 2015 analysis of 169 patients treated from 2001 to 2010 with modern adjuvant regimens found a higher overall recurrence rate of 75% at a median of 13.1 months. The distribution of recurrence sites remained strikingly similar to the 1997 report despite advances in radiation technique:

Recurrence Site	1997 (n=49)	2015 (n=169)
Ipsilateral hemithorax (local)	35%	54%
Abdomen	26%	39%
Contralateral hemithorax	17%	28%
Other distant sites	8%	5%

When comparing recurrence patterns between EPP and P/D, EPP achieves better local control (33% local recurrence vs. 65% for P/D) but is associated with significantly higher distant recurrence (66% vs. 35%). This paradox may result from the immunosuppressive effect of removing the lung and its lymphatic tissue, which may compromise the body's ability to contain distant spread.

How Much Does EPP Cost?

EPP is among the most expensive surgical procedures for mesothelioma. Based on 2014 National Inpatient Sample (NIS) data, the mean hospital cost for pneumonectomy in mesothelioma patients was $62,408 (95% CI: $48,385 to $76,431), compared to $53,993 for P/D and $24,901 for the average mesothelioma hospitalization.

These figures represent hospital charges only and do not include surgeon and anesthesia fees, the cost of neoadjuvant or adjuvant chemotherapy, radiation therapy, rehabilitation, or long-term follow-up care. A comprehensive cost-effectiveness analysis comparing the full EPP multimodal pathway to the P/D pathway or to chemotherapy alone has not been published. For more detailed information on treatment costs, see our comprehensive guide. Mesothelioma patients may offset these expenses through asbestos trust fund claims and legal compensation.

What Do Current Medical Guidelines Say About EPP?

The consensus of major medical guidelines has shifted decisively away from EPP and toward lung-sparing approaches.

Organization	Year	Position on EPP
NCCN	2025	P/D recommended over EPP; surgery limited to stage I disease
ASCO	2025	Hemithoracic adjuvant RT may be offered post-EPP at centers of excellence; neoadjuvant RT + EPP only in clinical trials
ERS/ESTS/EACTS/ESTRO	2020	Radical surgery candidates should be treated in clinical trials at dedicated centers
British Thoracic Society	2018	"Do not offer Extra-Pleural Pneumonectomy in MPM" (Grade B recommendation)

The BTS recommendation against EPP is the most explicit, while the ASCO guidelines maintain a narrow window for EPP at centers of excellence with hemithoracic radiation capability. The European joint guidelines emphasize that both EPP and extended P/D remain options in principle but should be performed within clinical trials at specialized mesothelioma centers.

Where Is EPP Performed?

Surgical volume and institutional expertise are strongly correlated with EPP outcomes. Patients treated at specialized mesothelioma centers have been reported to have 20 to 40% better survival than those at general hospitals, with surgical mortality two to three times lower at high-volume centers.

Center	Key Surgeons	Notable Contribution
Brigham and Women's / Dana-Farber	David Sugarbaker (d. 2018), Raphael Bueno	Largest single-institution EPP series (529+ patients)
Memorial Sloan Kettering	Valerie Rusch, Raja Flores	663-patient international registry
MD Anderson Cancer Center	David Rice	Pioneering lung-sparing techniques
Princess Margaret, Toronto	Marc de Perrot	SMART protocol innovator
University Hospital Zurich	Walter Weder, Isabelle Opitz	EPP mortality 2.2% in Swiss multimodality trial

A retrospective single-institution study spanning 18 years confirmed that higher patient volumes were associated with lower perioperative morbidity and better overall survival, with mortality rates of 6% or less documented only at high-volume centers performing EPP as part of multimodality treatment.

Frequently Asked Questions

Is EPP still performed for mesothelioma?

Yes, but in very limited circumstances. EPP is still performed at a small number of high-volume mesothelioma centers for highly selected patients with early-stage (T1-3, N0), epithelioid mesothelioma and excellent performance status. However, its use has declined significantly following the MARS trial results, and current guidelines from the NCCN and BTS recommend P/D over EPP.

What is the difference between EPP and P/D?

EPP removes the entire affected lung along with the pleura, pericardium, and diaphragm. P/D removes only the pleura (and sometimes the pericardium and diaphragm in extended P/D) while preserving the lung. P/D has lower operative mortality (1.7% vs. 4.5%), lower morbidity (27.9% vs. 62%), and is now the preferred surgical approach for mesothelioma.

What is the Sugarbaker favorable triad?

The favorable triad refers to the combination of epithelioid histology, negative surgical margins, and negative extrapleural lymph nodes. In the Sugarbaker 1999 study, 31 patients with all three favorable factors achieved 46% five-year survival and median survival of 51 months, the best outcomes ever reported for EPP.

What is the SMART protocol?

SMART (Surgery for Mesothelioma After Radiation Therapy) is an experimental protocol developed at Princess Margaret Cancer Centre in Toronto that reverses the traditional treatment sequence by delivering accelerated hemithoracic radiation (25 Gy in 5 fractions) before EPP. In the epithelioid, node-negative subgroup, the SMART protocol achieved median survival of 65.9 months with only 1% 30-day mortality.

Can I receive compensation for mesothelioma treatment costs?

Yes. Mesothelioma patients may be eligible for compensation through multiple pathways, including asbestos trust fund claims, personal injury lawsuits, VA benefits for veterans, and workers' compensation. Over $30 billion remains available in active asbestos trust funds. An experienced mesothelioma attorney can help evaluate which compensation options apply to your specific situation.

What are the contraindications for EPP?

Absolute contraindications include sarcomatoid histology, N3 nodal disease, distant metastatic disease, contralateral pleural involvement, poor performance status (ECOG 2 or higher), and insufficient cardiopulmonary reserve for single-lung physiology. Relative contraindications include N2 mediastinal nodal disease, biphasic histology, advanced age over 70 to 75 years, T4 disease with chest wall invasion, and significant cardiac comorbidity.

Get Help

Mesothelioma patients and families can connect with experienced legal and medical advocates:

• Danziger & De Llano provides free case evaluations and can connect families with specialized treatment centers — call (866) 222-9990
• Mesothelioma Lawyer Center offers resources on treatment options and legal rights
• Mesothelioma.net provides comprehensive information on surgical options

Quick Statistics

• EPP use declined from majority-share to only 11% of mesothelioma surgical cases between 2005 and 2025, while P/D rose to 57%
• The Sugarbaker 529-patient series found node-negative patients survived twice as long as N2-positive patients — 26 months vs. 13 months median
• Recurrence after EPP increased from 54% in 1997 data to 75% in 2015 data despite improved adjuvant regimens
• Abdominal recurrence after EPP rose from 26% to 39% between the 1997 and 2015 Baldini analyses, suggesting transdiaphragmatic tumor spread during reconstruction
• The SMART protocol achieved only 1% 30-day mortality across 96 patients, well below the 3.8–7% range in conventional EPP series
• A 2022 meta-analysis confirmed EPP carries significantly higher rates of atrial fibrillation, hemorrhage, pulmonary embolism, air leak, and reoperation compared to P/D
• EPP hospital costs exceed the average mesothelioma hospitalization by 2.5 times — $62,408 vs. $24,901 mean charges
• Over $30 billion remains available in asbestos trust funds to help offset surgical and multimodal treatment costs
• Quality of life after EPP remains below baseline at 12 months, while P/D patients typically return to pre-surgical function within the same timeframe
• The European joint guidelines (ERS/ESTS/EACTS/ESTRO 2020) recommend that all radical mesothelioma surgery, including EPP, be performed exclusively within clinical trials at dedicated centers

Related Pages

• Mesothelioma Surgery Overview — comprehensive guide to all surgical options
• Pleurectomy and Decortication (P/D) — the preferred lung-sparing alternative
• Mesothelioma Treatment Costs — financial analysis of treatment options
• Understanding Your Diagnosis — diagnosis types, staging, and prognosis
• Mesothelioma Diagnosis and Staging
• Mesothelioma Settlements and Verdicts
• Asbestos Trust Funds — $30+ billion available for mesothelioma victims

⚠ Statute of Limitations Warning: Filing deadlines vary by state from 1-6 years from diagnosis. Texas allows 2 years from diagnosis or discovery. Contact an attorney immediately to preserve your rights.

Free, Confidential Case Evaluation Call (866) 222-9990 or visit dandell.com/contact-us No upfront fees • Experienced representation • National practice