Extrapleural Pneumonectomy (EPP): 46% Five-Year Survival in Selected Mesothelioma Patients

Extrapleural pneumonectomy (EPP) remains one of the most aggressive surgical options for malignant pleural mesothelioma — and one of the most debated. The procedure removes the entire affected lung, pleura, hemidiaphragm, and pericardium. In carefully selected patients with epithelioid histology, negative resection margins, and no extrapleural lymph node metastases, EPP achieves 46% five-year survival and a median of 51 months [1]. Operative mortality at experienced centers ranges from 3% to 7% [12]. This article presents the verified surgical data, patient selection criteria, and the current evidence for and against EPP — information that mesothelioma patients and their families need when evaluating treatment options.

What Is Extrapleural Pneumonectomy?

Extrapleural pneumonectomy is a radical surgery that removes four structures in a single operation: the entire affected lung, the visceral and parietal pleura (the membrane lining the lung and chest wall), the ipsilateral hemidiaphragm, and the ipsilateral pericardium (the sac surrounding the heart). The diaphragm and pericardium are then reconstructed with synthetic patches, typically Gore-Tex [3].

The goal of EPP is macroscopic complete resection (MCR) — removing all visible tumor. Because pleural mesothelioma grows along surfaces rather than forming a discrete mass, achieving MCR requires removing the entire pleural envelope. EPP accomplishes this by removing the lung along with it. The alternative approach, pleurectomy/decortication, peels the tumor off the lung surface while preserving the underlying lung tissue.

EPP is performed as part of multimodality therapy — typically induction chemotherapy (pemetrexed plus cisplatin) followed by surgery, then hemithoracic radiation to the empty chest cavity. This trimodality approach, pioneered by Dr. David Sugarbaker at Brigham and Women's Hospital, remains the framework within which EPP outcomes are evaluated [1].

What Are the Sugarbaker Criteria for EPP Candidacy?

The most important contribution to EPP patient selection came from a 1999 study of 183 consecutive patients who underwent EPP with trimodality therapy at Brigham and Women's Hospital between 1980 and 1997. Sugarbaker et al. identified three independent prognostic factors that predict long-term survival after EPP [1]:

• Epithelioid cell type: 52% two-year survival, 21% five-year survival, median 26 months. Non-epithelioid histology carried a relative risk of 3.0 (95% CI: 2.0-4.5, p<0.0001)
• Negative resection margins: 44% two-year survival, 25% five-year survival, median 23 months. Positive margins carried a relative risk of 1.7 (95% CI: 1.2-2.6, p=0.008)
• No extrapleural lymph node metastases: 42% two-year survival, 17% five-year survival, median 21 months. Metastatic nodes carried a relative risk of 2.0 (95% CI: 1.3-3.2, p=0.003)

The 31 patients who met all three criteria — epithelioid histology, negative margins, and negative extrapleural nodes — achieved 68% two-year survival, 46% five-year survival, and a median of 51 months [1]. This best-subset result represents the strongest published evidence for EPP's curative potential and has driven patient selection ever since.

"The Sugarbaker criteria transformed EPP from a one-size-fits-all procedure into a precision surgical approach. The difference between 46% five-year survival in well-selected patients and 0% in sarcomatoid histology is not a marginal distinction — it is the difference between offering a meaningful chance at long-term survival and subjecting a patient to a major operation with no survival benefit."

— David Foster, Executive Director of Client Services, Danziger & De Llano

A subsequent analysis of 529 epithelioid-only patients at Brigham and Women's Hospital (1988-2011) further refined nodal staging. Overall median survival was 18 months, with dramatic differences by nodal status: N0 patients survived a median of 26 months, N1 patients 17 months, N2 patients 13 months, and N3 patients just 7 months [4].

What Are the Operative Risks of EPP?

EPP carries higher operative risk than any other mesothelioma surgery. The most comprehensive complication data comes from 328 consecutive EPP procedures at Brigham and Women's Hospital, spanning 1980-2000 [3]:

• Operative mortality: 3.4% (improved over time from 5% in earlier series)
• Overall morbidity: 60.4% experienced at least one complication
• Atrial fibrillation: 44.2% — the most common complication
• Prolonged intubation: 7.9%
• Vocal cord paralysis: 6.7%
• Deep vein thrombosis: 6.4%
• Patch-related complications (dehiscence, hemorrhage): 6.1%
• Cardiac tamponade: 3.6%
• ARDS: 3.6%
• Median hospital stay: 10 days

A multi-institutional study of 251 EPP patients across three high-volume centers (Zurich, Vienna, Toronto) reported 5% thirty-day mortality, 8% ninety-day mortality, and 30% major morbidity. Right-sided EPP had significantly higher morbidity than left-sided (p=0.01), and elevated preoperative C-reactive protein predicted postoperative death (p=0.001) [10].

The National Cancer Database analysis of 438 EPP patients reported the lowest mortality figures: 3.0% at thirty days and 8.0% at ninety days. This study also confirmed that treatment at high-volume centers significantly reduces mortality risk (HR 0.834, p=0.032) [12].

"Volume matters enormously in mesothelioma surgery. A center performing two EPPs a year cannot match the outcomes of a center performing 30. Patients should ask not just whether surgery is recommended, but where it will be performed and how many mesothelioma operations that surgeon has completed."

— Dr. Raphael Bueno, Chief of Thoracic Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute

What Did the MARS Trials Find About Mesothelioma Surgery?

Two landmark randomized trials from the United Kingdom have challenged the role of surgery in mesothelioma treatment. Both require careful interpretation.

MARS trial (2011): EPP versus no EPP

The original MARS trial randomized 50 patients to EPP or no EPP after induction chemotherapy. EPP was completed in only 16 of 24 assigned patients. Median survival was 14.4 months with EPP versus 19.5 months without, with an adjusted hazard ratio of 2.75 (95% CI: 1.21-6.26, p=0.016) favoring no surgery [6].

The MARS trial was designed as a feasibility study, not a definitive survival trial. With only 50 patients, it lacked statistical power for survival endpoints. Its primary conclusion — that EPP within trimodality therapy "offers no benefit and possibly harms patients" — was influential but controversial.

MARS 2 trial (2024): Extended P/D versus chemotherapy alone

MARS 2 was a larger phase 3 trial (335 patients across 26 UK hospitals) that tested extended pleurectomy/decortication — not EPP — plus chemotherapy versus chemotherapy alone. Surgery plus chemotherapy produced worse two-year survival: 19.3 months versus 24.8 months (restricted mean survival difference: -1.9 months, p=0.019). Serious adverse events were 3.6 times more frequent in the surgery group [7].

A 2025 analysis by Waller et al. examined 79 of the 158 surgical patients from four of five MARS 2 surgical centers. The findings were striking: 52 of 79 patients (66%) would not have been offered surgery under contemporary selection criteria — they had non-epithelioid histology, advanced stage disease, or inadequate staging workup. The 27 patients (34%) who did meet current criteria had a median survival of 32 months, compared to 8.5 months for those who should not have been selected (p<0.0005) [8].

How Does EPP Compare to Pleurectomy/Decortication?

The EPP versus P/D debate has evolved significantly over two decades. The weight of evidence now favors P/D in most cases.

The largest direct comparison comes from Flores et al. (2008), analyzing 663 patients across three institutions (Memorial Sloan Kettering, NYU, University of Hawaii): 385 EPP and 278 P/D. EPP carried 7% operative mortality versus 4% for P/D. On multivariate analysis controlling for stage, histology, gender, and multimodality therapy, EPP carried a hazard ratio of 1.4 (p<0.001) [5].

Two meta-analyses have synthesized the broader evidence:

• Taioli et al. (2015): 24 datasets, 2,903 patients. Short-term mortality was 4.5% for EPP versus 1.7% for P/D (p<0.05) — a 2.5-fold difference. No significant difference in two-year mortality, though with substantial heterogeneity [11]
• Magouliotis et al. (2022): 18 studies, 4,852 patients. Thirty-day mortality was significantly higher with EPP (OR: 2.79, 95% CI: 1.30-6.01, p=0.009). Median overall survival favored P/D by 4.55 months (p<0.001). EPP also had higher rates of atrial fibrillation, hemorrhage, pulmonary embolism, and reoperation [15]

A 2018 systematic review of quality of life after mesothelioma surgery found that only P/D patients returned to baseline quality of life scores at 12 months. EPP patients experienced permanent reductions in lung function (FEV1 and FVC typically drop 30-40% after losing an entire lung) and significantly reduced exercise tolerance [14].

When Is EPP Still Considered Appropriate?

The 2024 NCCN guidelines list both EPP and P/D as surgical options for selected patients at experienced centers, but note the clear trend toward lung-sparing approaches [13]. Current indications where EPP may still be considered include:

• Extensive chest wall or diaphragmatic invasion where P/D cannot achieve macroscopic complete resection
• Fissure involvement that prevents adequate lung-sparing decortication
• Planned hemithoracic radiation — the empty hemithorax after EPP allows higher radiation doses with less risk to remaining lung tissue
• Epithelioid histology confirmed by preoperative biopsy — sarcomatoid or biphasic tumors should not undergo EPP

The critical requirement is a multidisciplinary tumor board at a high-volume center making the surgical decision. This team should include a thoracic surgeon with mesothelioma experience, a medical oncologist, a radiation oncologist, a pulmonologist, and a pathologist [13].

What Results Does Trimodality Therapy Achieve?

The strongest EPP outcomes come from trimodality therapy: induction chemotherapy followed by EPP followed by hemithoracic radiation. A multicenter phase II trial (Krug et al., 2009) enrolled 77 patients who received neoadjuvant pemetrexed plus cisplatin. Of those, 54 completed EPP and 40 completed radiation [9].

• Entire cohort median survival: 16.8 months
• Patients completing all three modalities: 29.1 months median survival, 61.2% two-year survival
• Radiologic response to chemotherapy predicted improved survival (26.0 vs 13.9 months, p=0.05)
• Pathologic complete response rate: 5%

These results demonstrate a fundamental challenge in interpreting EPP data: patients who complete all therapy do well, but many cannot tolerate the full regimen. Of 77 enrolled patients, only 40 (52%) completed all three modalities. The intention-to-treat survival of 16.8 months is arguably more representative of the real-world EPP experience than the 29.1 months achieved by those who tolerated the full protocol.

What Should Mesothelioma Patients Consider Before EPP?

Patients considering EPP should discuss several factors with their treatment team:

• Histology confirmation: Epithelioid histology is essential. Sarcomatoid or biphasic tumors do not benefit from EPP [1]
• Complete staging: Mediastinoscopy or endobronchial ultrasound to assess nodal status. Extrapleural node metastases eliminate the survival benefit [1]
• Cardiopulmonary reserve: The patient must have sufficient heart and lung function to survive with one lung. Preoperative pulmonary function tests and cardiac evaluation are mandatory
• Center experience: Ask how many EPP or P/D procedures the surgeon and institution perform annually. Volume directly correlates with outcomes [12]
• P/D as an alternative: In most cases, lung-sparing P/D achieves comparable survival with lower mortality and better quality of life [11][14]
• Clinical trial access: Emerging treatments including immunotherapy combinations and targeted therapies may offer additional options [13]

Regardless of which treatment approach a patient pursues, mesothelioma caused by asbestos exposure may qualify for compensation through asbestos trust fund claims, personal injury lawsuits, or VA benefits for veterans. Filing early ensures financial resources are available during treatment. For a free case evaluation, call (855) 699-5441.

Frequently Asked Questions About Extrapleural Pneumonectomy

References

1. [1] Sugarbaker DJ, et al. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg. 1999;117(1):54-65. Best subset: 46% 5-year, 51-month median. PMID 9869758
2. [2] Sugarbaker DJ, et al. Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma: results in 120 consecutive patients. Ann Surg. 1996;224(3):288-296. 5% mortality; epithelioid 27% 5-year. PMID 8813257
3. [3] Sugarbaker DJ, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg. 2004;128(1):138-146. 3.4% mortality; 60% morbidity. PMID 15224033
4. [4] Sugarbaker DJ, et al. Extrapleural pneumonectomy in the treatment of epithelioid malignant pleural mesothelioma: N1 and N2 nodal involvement in 529 patients. Ann Surg. 2014;260(4):577-582. N0=26 mo; N2=13 mo. PMID 25203873
5. [5] Flores RM, et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008;135(3):620-626. EPP 7% vs P/D 4% mortality; EPP HR 1.4. PMID 18329481
6. [6] Treasure T, et al. Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma: MARS randomised feasibility study. Lancet Oncol. 2011;12(8):763-772. 14.4 vs 19.5 mo; adjusted HR 2.75. PMID 21723781
7. [7] Lim E, et al. Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2). Lancet Respir Med. 2024;12(6):457-466. 19.3 vs 24.8 mo; p=0.019. PMID 38740044
8. [8] Waller D, et al. Why the MARS2 Trial Does Not Mean the End of All Mesothelioma Surgery. Cancers. 2025;17(5):724. 66% of surgical patients outside contemporary criteria. PMID 40075572
9. [9] Krug LM, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by EPP and radiation for MPM. J Clin Oncol. 2009;27(18):3007-3013. All-therapy completers: 29.1 mo. PMID 19364962
10. [10] Lauk O, et al. Extrapleural pneumonectomy after induction chemotherapy: perioperative outcome in 251 patients from three high-volume institutions. Ann Thorac Surg. 2014;98(5):1748-1754. 5%/8% 30/90-day mortality. PMID 25110339
11. [11] Taioli E, et al. Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma. Ann Thorac Surg. 2015;99(2):472-480. EPP 4.5% vs P/D 1.7% mortality. PMID 25534527
12. [12] Wright C, et al. Quantitation and predictors of short-term mortality following EPP, P/D, and nonoperative management for MPM. J Thorac Dis. 2020;12(11):6476-6493. NCDB: 3.0%/8.0% 30/90-day. PMID 33282350
13. [13] Stevenson J, et al. NCCN Guidelines Insights: Mesothelioma: Pleural, Version 1.2024. JNCCN. 2024;22(2):72-81. Both EPP and P/D listed; P/D preferred. PMID 38503043
14. [14] Schwartz RM, et al. Systematic review of quality of life following P/D and EPP for malignant pleural mesothelioma. BMC Cancer. 2018;18(1):1188. Only P/D returns to baseline QoL at 12 mo. PMID 30497433
15. [15] Magouliotis DE, et al. Meta-analysis of survival after EPP versus P/D for MPM in the context of macroscopic complete resection. Updates Surg. 2022;74(6):1827-1837. EPP 30-day OR 2.79 vs P/D. PMID 36057027

Related Articles

• Pleurectomy vs. Extrapleural Pneumonectomy: 5-Year Survival Rates and Recovery Timelines — Side-by-side comparison of P/D and EPP outcomes for mesothelioma
• Mesothelioma Staging Explained: How 4 Stages Determine Treatment Options — How staging affects surgical candidacy and treatment planning
• Brigham and Women's Hospital: 40+ Years Pioneering Mesothelioma Surgery — Profile of the institution where the largest EPP series was developed
• Mesothelioma Treatment Comparison 2026: 3 Options That Change Your Odds — How surgery, chemotherapy, and immunotherapy compare
• Mesothelioma Clinical Trial Pipeline 2026 — Emerging treatments that may complement or replace surgical approaches