Mesothelioma Surgery Overview

Mesothelioma Surgery Overview
Surgical Treatment Options
Category	Treatment / Medical
Preferred Pleural Surgery	Pleurectomy/Decortication (P/D)
P/D Operative Mortality	3%
EPP Operative Mortality	3.8-7%
CRS-HIPEC Median OS	53 months (peritoneal)
Best Candidate Subtype	Epithelioid histology
2025 NCCN Recommendation	P/D over EPP, stage I only
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Surgery remains a central but increasingly debated component in the treatment of malignant mesothelioma, with the surgical landscape undergoing profound transformation over the past five decades — from the high-mortality extrapleural pneumonectomies of the 1970s to the contemporary emphasis on lung-sparing procedures and multimodal protocols that combine surgery with chemotherapy, immunotherapy, and radiation. The two principal curative-intent surgical approaches for pleural mesothelioma are extrapleural pneumonectomy (EPP), which removes the affected lung along with the parietal and visceral pleura, pericardium, and diaphragm, and pleurectomy/decortication (P/D), which removes the pleural surfaces while preserving the underlying lung parenchyma. Current evidence and the 2025 NCCN guidelines strongly favor P/D over EPP due to comparable oncologic outcomes with significantly lower perioperative mortality (3% versus 3.8-7%) and improved quality of life.

For peritoneal mesothelioma, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) represents the established standard of care, achieving a median overall survival of 53 months in the landmark multicenter analysis and 5-year survival rates of 47% — outcomes dramatically superior to chemotherapy alone. Completeness of cytoreduction is the strongest predictor of survival, with CC-0 resections (no visible residual disease) achieving median survival exceeding 94 months.

The MARS 2 randomized controlled trial — the largest surgical trial in mesothelioma history with 335 patients — challenged the role of surgery by demonstrating that extended P/D combined with chemotherapy produced worse median overall survival than chemotherapy alone (19.3 versus 24.8 months), generating significant controversy and ongoing debate about optimal patient selection. Emerging technologies including fluorescence-guided surgery, intraoperative photodynamic therapy, VATS approaches, and integration with immunotherapy represent the evolving frontier of mesothelioma surgical management.

Mesothelioma surgery at a glance:

• P/D over EPP — the 2025 NCCN guidelines recommend pleurectomy/decortication with 3% operative mortality versus 3.8–7% for EPP
• MARS 2 controversy — 335-patient RCT found extended P/D plus chemotherapy yielded 19.3-month median survival versus 24.8 months for chemotherapy alone
• CRS-HIPEC landmark data — peritoneal mesothelioma patients achieved 53-month median survival and 47% 5-year survival across 405 patients at 8 centers
• Complete cytoreduction — CC-0 resection for peritoneal disease produces median survival exceeding 94 months versus 12 months for CC-3
• Surgical candidacy — epithelioid histology is required; sarcomatoid patients show no survival benefit from surgery (MARS 2 hazard ratio 2.66)
• Center volume impact — high-volume facilities achieve 10.0% 90-day mortality versus 14.6% at low-volume centers (p=0.029)
• Trimodal survival — Sugarbaker protocol (EPP + chemo + radiation) achieved 39% 5-year survival in selected epithelioid, node-negative patients
• Fluorescence-guided precision — TumorGlow technology detected 100% of mesothelioma deposits as small as 1 mm during clinical trials
• Photodynamic therapy — extended P/D combined with intraoperative PDT achieved near 3-year median survival in epithelioid patients
• Palliative options — indwelling pleural catheters reduce lifetime hospitalization days versus talc pleurodesis (median 10 versus 12 days) with fewer repeat procedures (4% versus 22.5%)

Key Facts: Mesothelioma Surgery Overview

The 2025 NCCN guidelines recommend pleurectomy/decortication (P/D) over extrapleural pneumonectomy (EPP) and limit surgical consideration to patients with stage I disease confined to the pleura P/D achieves comparable oncologic outcomes to EPP with significantly lower operative mortality (3% versus 7%) and lower distant recurrence rates (35% versus 66%) The MARS 2 trial (335 patients, 26 UK hospitals) found that extended P/D plus chemotherapy produced worse median survival than chemotherapy alone (19.3 versus 24.8 months) Cytoreductive surgery with HIPEC for peritoneal mesothelioma achieves median survival of 53 months with 5-year survival of 47% in multicenter data Complete cytoreduction (CC-0) is the strongest predictor of peritoneal mesothelioma outcomes, with median survival exceeding 94 months Epithelioid histology is the primary requirement for surgical candidacy, while sarcomatoid mesothelioma patients generally receive no survival benefit from surgery High-volume surgical centers demonstrate significantly lower 90-day mortality (10.0% versus 14.6%) and lower readmission rates than low-volume facilities The Sugarbaker trimodal protocol (EPP + chemotherapy + radiation) achieved 5-year survival of 39% in selected patients with epithelioid histology and negative nodes Fluorescence-guided surgery identified residual mesothelioma deposits as small as 1 mm in 100% of lesions sampled during clinical trials Intraoperative photodynamic therapy combined with extended P/D achieved near 3-year median survival in epithelioid patients Indwelling pleural catheters significantly reduce lifetime hospitalization days compared to talc pleurodesis for managing recurrent pleural effusions

What Is Extrapleural Pneumonectomy and When Is It Used?

Extrapleural pneumonectomy is the most radical surgical procedure performed for malignant pleural mesothelioma, involving en bloc resection of the parietal and visceral pleura, the entire ipsilateral lung, the ipsilateral pericardium, and the ipsilateral hemidiaphragm. After removing these structures, the diaphragm and pericardium are reconstructed with synthetic mesh patches to restore thoracic anatomy. The fundamental rationale for EPP is achieving macroscopic complete resection (MCR) by removing all visible tumor in a single surgical specimen, thereby eliminating the diseased lung that serves as both a source of recurrence and a barrier to effective radiation delivery.

EPP is considered only for a highly selected subset of mesothelioma patients: those with epithelioid or biphasic histology, clinical stages T1 through T3 with N0 to N2 disease, ECOG performance status of 0 or 1, and adequate cardiopulmonary reserve to tolerate the loss of an entire lung. Patients with sarcomatoid mesothelioma are universally excluded from EPP protocols due to the aggressive biology of this subtype and consistent evidence demonstrating no surgical benefit. At high-volume centers with experienced surgical teams, perioperative mortality for EPP has been reported between 3.8% and 7%, a substantial improvement from the early surgical era when Butchart's pioneering 1976 series of 29 EPP patients documented a hospital mortality rate of 31%.

The landmark 1996 Sugarbaker series at Brigham and Women's Hospital/Dana-Farber Cancer Institute reported outcomes in 120 consecutive EPP patients, establishing the trimodal therapy paradigm that would influence mesothelioma management for decades. The series demonstrated an operative mortality rate of 5.0%, a major morbidity rate of 22%, and overall 2-year and 5-year survival rates of 45% and 22%, respectively. Critically, patients with epithelioid histology and negative resection nodes achieved dramatically better outcomes, with 2-year and 5-year survival rates of 74% and 39%. A subsequent Italian prospective replication of the Sugarbaker trimodal approach in 44 EPP patients confirmed the reproducibility of these results, reporting 30-day operative mortality of 4.5% and a projected 5-year survival of 50% for the subgroup with completely resected, node-negative epithelioid disease.

However, the original MARS trial (MARS 1), which randomized 50 patients to EPP versus no EPP after induction chemotherapy, found no overall survival advantage for EPP along with increased risk of death and significantly poorer quality of life. This pivotal trial effectively began the paradigm shift away from EPP toward lung-sparing alternatives, a trend reinforced by the 2025 meta-analysis of 24 retrospective studies confirming that EPP carried significantly higher 30-day postoperative mortality compared to P/D and that P/D was associated with a mean improvement in overall survival of approximately 7 months.

How Does Pleurectomy/Decortication Compare to EPP?

Pleurectomy/decortication is a lung-sparing procedure that removes the parietal and visceral pleura to achieve macroscopic complete resection while preserving the underlying lung parenchyma. Three distinct variants are recognized with progressively increasing extent: partial pleurectomy (a cytoreductive/palliative procedure without the goal of MCR), standard P/D (complete resection of both parietal and visceral pleura), and extended P/D (pleurectomy with additional resection of the pericardium and/or diaphragm). The preservation of the ipsilateral lung in P/D offers several theoretical and practical advantages over EPP, including lower perioperative risk, preservation of pulmonary function, and improved postoperative quality of life.

The landmark 2008 Flores retrospective series of 663 patients at three major United States academic centers provided the first large-scale comparative analysis of P/D versus EPP outcomes. The study demonstrated improved median survival with P/D versus EPP (16 versus 12 months, p<0.001), lower operative mortality (3% versus 7%), and lower distant recurrence rates (35% versus 66%), though notably local recurrence was higher with P/D (65% versus 33%), reflecting the challenge of achieving complete macroscopic resection while preserving the lung. The International Association for the Study of Lung Cancer mesothelioma database, analyzing 3,101 patients from four continents, further confirmed that multimodality therapy was superior to surgery alone, regardless of the specific surgical approach.

The MARS 2 Trial: A Paradigm-Shifting Controversy

The MARS 2 trial represents the largest randomized surgical trial in mesothelioma history and has fundamentally challenged established assumptions about the role of surgery. This phase 3 randomized controlled trial enrolled 335 patients across 26 hospitals in the United Kingdom and compared extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. After two cycles of platinum-pemetrexed induction chemotherapy, patients were randomized 1:1 to surgery plus continued chemotherapy or chemotherapy alone. The results demonstrated that median overall survival was 19.3 months in the surgery group versus 24.8 months in the chemotherapy-alone group, with surgery associated with a 28% increase in the risk of death during the first 42 months of follow-up (hazard ratio 1.28, p=0.032). Serious adverse events (grade 3 or higher) were 3.6-fold higher in the surgery group, in-hospital and 30-day mortality were both 4%, and 90-day mortality reached 9%. Quality of life and quality-adjusted life years both favored chemotherapy alone.

The MARS 2 findings have generated substantial controversy within the thoracic surgical community. Critics argue that the trial's 9% 90-day mortality significantly exceeded rates reported at experienced high-volume centers, that staging relied predominantly on CT without mandatory PET-CT or invasive mediastinal staging, and that 34% of surgical patients had T3 disease with 8% having N2 disease — suggesting suboptimal patient selection that included patients unlikely to benefit from surgery. Additionally, the surgery group received significantly less subsequent immunotherapy (22% versus 39%) and fewer total chemotherapy cycles, potentially confounding the survival comparison. The effect of surgery on survival was dramatically worse for non-epithelioid subtypes (hazard ratio 2.66) compared to epithelioid disease (hazard ratio 1.12), supporting the principle that histological subtype should be a primary determinant of surgical candidacy.

Despite these criticisms, the MARS 2 results have clearly influenced current practice guidelines. The 2025 NCCN guidelines now recommend P/D over EPP and limit surgical consideration to patients with stage I disease confined to the pleura with no lymph node involvement — a significantly more restrictive recommendation than previous editions. The European Respiratory Society/European Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery/European Society for Radiotherapy and Oncology 2020 guidelines explicitly recommend that radical surgery should only be performed in high-volume centers, within clinical trials, and as part of a multimodal approach.

What Are the Surgical Options for Peritoneal Mesothelioma?

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) represents the established standard-of-care curative-intent treatment for malignant peritoneal mesothelioma. During cytoreductive surgery, the surgeon performs extensive peritonectomy procedures to remove all visible tumor deposits from the peritoneal surfaces, often involving resection of affected peritoneum, omentum, and portions of bowel or other abdominal organs as necessary to achieve complete macroscopic cytoreduction. Immediately following surgical debulking, the open abdomen is bathed in a heated chemotherapy solution — typically cisplatin-based or mitomycin C — at temperatures of 41 to 43 degrees Celsius for 60 to 120 minutes. The hyperthermia enhances chemotherapy drug penetration into residual microscopic disease and increases cytotoxic activity against malignant cells while the direct intraperitoneal delivery minimizes systemic absorption and toxicity.

PCI Scoring and Surgical Candidacy

The Peritoneal Cancer Index (PCI) quantifies intra-abdominal tumor burden by dividing the abdomen into 13 regions, with each region scored from 0 to 3 based on the largest tumor deposit size (0 indicating no tumor, 1 for deposits up to 0.5 cm, 2 for deposits between 0.5 and 5.0 cm, and 3 for deposits exceeding 5.0 cm or confluent disease), yielding a total score from 0 to 39. The PCI is determined preoperatively using cross-sectional imaging and reassessed intraoperatively for definitive scoring. For peritoneal mesothelioma, a PCI threshold of approximately 20 has been identified as the critical cutoff above which outcomes are significantly poorer and complete cytoreduction becomes technically challenging. Patients in the low-PCI group achieved median survival of 43 months versus substantially shorter survival for those in the high-PCI group.

The Completeness of Cytoreduction (CC) score assigned after surgery is the single strongest predictor of survival in peritoneal mesothelioma. CC-0 (no visible residual peritoneal disease) and CC-1 (residual tumor no larger than 2.5 mm) are both classified as complete cytoreductions, with the rationale that CC-1 residual disease is penetrable by the heated intraperitoneal chemotherapy delivered during HIPEC. The landmark multicenter analysis by Yan and colleagues, examining 405 patients from multiple institutions, demonstrated median overall survival of 53 months with 3-year and 5-year survival rates of 60% and 47%, respectively. Stratified by CC score, median survival was 94 months for CC-0, 67 months for CC-1, 40 months for CC-2, and only 12 months for CC-3 — illustrating the dramatically different outcomes based on completeness of tumor removal.

A large single-center study of 111 patients at the Washington Cancer Institute demonstrated that long-term survival improves significantly after patients pass early postoperative milestones: those surviving to the 1-year mark had a conditional median survival of 58.4 months, and those surviving to 3 years had conditional survival of 73.3 months. Performance of a second CRS-HIPEC procedure in selected patients with recurrent disease was associated with median survival of approximately 5.6 years versus 3.0 years for those undergoing only one procedure, suggesting that repeated cytoreduction may benefit carefully selected patients with favorable biology.

What Palliative Surgical Procedures Are Available?

Palliative surgical procedures play a critical role in mesothelioma management by controlling symptoms and maintaining quality of life, particularly for patients who are not candidates for curative-intent surgery due to advanced disease stage, poor performance status, or unfavorable histology. The most common palliative interventions target recurrent malignant pleural effusion, which affects the majority of pleural mesothelioma patients and causes progressive breathlessness, chest pain, and reduced functional capacity.

Pleurodesis

Pleurodesis obliterates the pleural space to prevent recurrent accumulation of malignant pleural effusion by instilling an irritant agent — most commonly sterile talc — into the pleural space to create inflammation and adhesion between the visceral and parietal pleural surfaces. Talc can be delivered as a slurry through an existing chest tube (talc slurry pleurodesis) or as a dry powder insufflated during thoracoscopy (talc poudrage), with poudrage generally achieving slightly higher success rates. Chemical pleurodesis may also use agents such as doxycycline or bleomycin, though talc remains the most widely used and studied agent. Pleurodesis failure, defined as clinically significant fluid reaccumulation, occurs in approximately 22.5% of cases and often requires subsequent intervention with an indwelling pleural catheter. The MesoVATS trial, which compared VATS partial pleurectomy to talc pleurodesis in 175 patients with malignant pleural mesothelioma, found no survival advantage for surgery along with increased respiratory complications and longer hospital stays, supporting talc pleurodesis as the preferred initial palliative approach for effusion management in most patients.

Indwelling Pleural Catheter

Indwelling pleural catheters provide a patient-centered approach to managing recurrent malignant pleural effusions through a tunneled catheter inserted into the pleural space that allows patients to drain fluid at home on a scheduled basis without repeated hospital visits. A randomized trial of 146 patients demonstrated that indwelling pleural catheters significantly reduced lifetime hospitalization days compared to talc pleurodesis (median 10 versus 12 days), with substantially fewer patients requiring further ipsilateral pleural procedures (4% versus 22.5%). An additional benefit is that indwelling pleural catheters can induce spontaneous pleurodesis over time through the chronic inflammatory response generated by catheter presence, potentially allowing catheter removal once fluid production ceases.

Pericardial Window and Peritoneal Port

Pericardial effusion can complicate mesothelioma, particularly in cases with pericardial involvement or following extended P/D with pericardial resection. A pericardial window involves creating a surgical opening in the pericardium to drain accumulated fluid and prevent cardiac tamponade, most commonly through a subxiphoid approach though thoracoscopic and thoracotomic techniques are also used. Surgical pericardial window has a significantly lower recurrence rate compared to pericardiocentesis alone (0% versus 34% in comparative studies), though at the cost of slightly longer hospital stays. Pericardio-peritoneal windows, which allow pericardial fluid to drain into the abdominal cavity where it is reabsorbed, have demonstrated 80.8% overall survival at 34 months of follow-up. For peritoneal mesothelioma patients who are not candidates for CRS-HIPEC, peritoneal port systems can be implanted to facilitate repeated intraperitoneal chemotherapy administration or home drainage of ascites.

What Emerging Surgical Techniques Show Promise?

Several innovative surgical technologies are under active investigation for their potential to improve outcomes in mesothelioma surgery by enhancing the completeness of tumor removal, targeting residual microscopic disease, and reducing surgical invasiveness.

Fluorescence-Guided Surgery

Fluorescence-guided surgery uses systemically administered optical contrast agents that preferentially accumulate in cancerous tissues, enabling real-time intraoperative identification of residual disease using near-infrared imaging systems. A clinical trial of TumorGlow technology at the University of Pennsylvania demonstrated fluorescent signal in 100% of malignant pleural mesothelioma lesions sampled during surgery, with deposits as small as 1 millimeter identifiable under near-infrared illumination. Results were reproducible even following neoadjuvant chemotherapy, likely because the superficial growth pattern of mesothelioma along pleural surfaces is favorable for near-infrared imaging approaches that penetrate tissue to a depth of several millimeters. This technology has significant potential to improve macroscopic complete resection rates and reduce local recurrence by identifying tumor deposits invisible to the naked eye during surgery.

Intraoperative Photodynamic Therapy

Photodynamic therapy involves administering a photosensitizing agent (such as porfimer sodium) that is preferentially taken up by tumor cells, followed by intraoperative activation with specific wavelengths of light to destroy residual microscopic disease remaining after surgical debulking. The photochemical reaction generates reactive oxygen species that directly kill cancer cells and damage tumor vasculature while sparing adjacent normal tissue. Friedberg and colleagues at the University of Pennsylvania reported that extended P/D combined with intraoperative photodynamic therapy and adjuvant chemotherapy in patients with epithelial-subtype mesothelioma yielded a median survival of nearly three years, with particularly impressive outcomes in patients with node-negative disease. Multiple phase I/II trials are currently evaluating photodynamic therapy in combination with immune checkpoint inhibitors for pleural malignancies, based on evidence that PDT can stimulate antitumor immune responses that synergize with immunotherapy.

Minimally Invasive VATS Pleurectomy/Decortication

Video-assisted thoracoscopic pleurectomy/decortication is emerging as a feasible alternative to open thoracotomy for selected patients, particularly those at higher perioperative risk. An analysis of the New York SPARCS database comparing 115 VATS-P/D patients to 269 open P/D patients demonstrated improved short-term outcomes with the minimally invasive approach, including shorter hospital stays and fewer immediate complications. While the optimal surgical technique for mesothelioma P/D remains a subject of debate, VATS approaches have historically been underutilized in mesothelioma management despite their established role in other thoracic malignancies.

Hyperthermic Intrathoracic Chemotherapy (HITHOC)

Analogous to HIPEC for peritoneal disease, hyperthermic intrathoracic chemotherapy (HITHOC) involves perfusing the thoracic cavity with heated chemotherapy — typically cisplatin and doxorubicin — after pleurectomy/decortication. A 20-year single-institution study demonstrated that extended P/D combined with HITHOC and adjuvant chemotherapy yielded a median overall survival of 38.1 months, significantly longer than chemotherapy alone. The principle relies on heated chemotherapeutic drugs achieving enhanced cytotoxic activity and deeper tissue penetration against residual malignant cells while the heated perfusion technique minimizes systemic absorption and toxicity.

How Does Multimodal Therapy Combine Surgery with Other Treatments?

Multimodal therapy — the combination of surgery with systemic chemotherapy, radiation therapy, or both — represents the dominant treatment philosophy for operable mesothelioma, based on the recognition that surgery alone is insufficient to control a disease characterized by microscopic invasion beyond visible tumor boundaries. The concept was pioneered by Sugarbaker in the 1990s with the trimodal protocol of EPP followed by combination chemotherapy and adjuvant hemithoracic radiation therapy, establishing a framework that has been refined and adapted over subsequent decades.

Trimodal Therapy

De Perrot and colleagues reported a large single-center trimodal experience using induction cisplatin-based chemotherapy followed by EPP and adjuvant high-dose hemithoracic radiation (50 to 60 Gray). Patients who completed the full trimodal protocol with N0 disease achieved remarkable outcomes, with a median survival of 59 months and 5-year disease-free survival of 53%. However, only approximately half of enrolled patients were able to complete the full three-modality protocol due to disease progression during induction therapy, complications precluding surgery, or inability to tolerate postoperative radiation — highlighting the challenge of delivering intensive multimodal treatment to a patient population that is often elderly with comorbidities from decades of occupational exposure.

Neoadjuvant Versus Adjuvant Sequencing

The optimal sequencing of chemotherapy relative to surgery remains an active area of investigation. The EORTC 1205 randomized phase II trial compared immediate surgery followed by chemotherapy versus neoadjuvant chemotherapy followed by surgery and found that the rate of treatment success at 20 weeks was 70% in the immediate-surgery arm versus 50% in the deferred-surgery arm, suggesting that a surgery-first approach may facilitate completion of both treatment modalities. Multiple Japanese and European feasibility studies have confirmed the safety of induction pemetrexed-cisplatin followed by P/D, with the Japanese JMIG 1101 trial achieving a macroscopic complete resection rate of 90% with no treatment-related 30-day or 90-day mortality.

The Surgery for Mesothelioma After Radiation Therapy (SMART) protocol pioneered a novel approach of neoadjuvant intensity-modulated radiation therapy followed by EPP within one week. The rationale is that delivering radiation before lung removal may provide superior tumor control and avoid the technical challenges of post-pneumonectomy radiation fields. The 2025 NCCN guidelines state that pleural intensity-modulated radiation therapy is preferred after surgery only in select cases, is no longer advised for patients receiving EPP, and should only be delivered at highly experienced cancer centers with demonstrated expertise in mesothelioma radiation planning.

Ongoing clinical trials represent the next frontier in multimodal mesothelioma management by integrating immunotherapy into the surgical treatment paradigm. The AtezoMeso trial is investigating atezolizumab after P/D, and the CHIMERA study is evaluating pembrolizumab combined with perioperative chemotherapy and surgery, reflecting the growing recognition that immune checkpoint inhibitors may synergize with surgical debulking to achieve durable disease control.

Why Does Surgeon and Center Volume Matter?

The relationship between institutional surgical volume and outcomes in mesothelioma is well documented and has direct implications for patient referral patterns and treatment decisions. A study of 1,307 patients from the National Cancer Database demonstrated that high-volume facilities achieved shorter postoperative hospitalization (p=0.035), lower 30-day readmission rates (4.6% versus 6.1%, p=0.021), and significantly lower 90-day mortality rates (10.0% versus 14.6%, p=0.029) compared to lower-volume centers. The median overall survival was 18 months at high-volume facilities versus 15 months at lower-volume centers (p=0.010), though this difference did not remain independently significant after propensity score matching.

The European guidelines explicitly recommend that radical mesothelioma surgery should only be performed in high-volume centers, within the context of clinical trials, and as part of a multimodal treatment approach. The International Association for the Study of Lung Cancer defines low volume as fewer than five radical mesothelioma procedures per year. Within the MARS 2 trial, the average annual case volumes for radical mesothelioma surgery at the four expert centers ranged from 8.6 to 36.5 cases per year, compared with only 3.4 at the non-expert center, though no statistically significant survival difference was found between expert and non-expert surgical sites within the trial itself. Given the highly specialized nature of mesothelioma surgery, patients are strongly advised to seek treatment at specialized academic institutions with dedicated mesothelioma multidisciplinary teams that include thoracic surgeons, medical oncologists, radiation oncologists, pulmonologists, and mesothelioma-experienced pathologists.

Who Is a Candidate for Mesothelioma Surgery?

Surgical candidacy for mesothelioma is determined by the intersection of several clinical factors, each of which independently influences the likelihood of deriving meaningful survival benefit from operative intervention. Histological subtype is the single most important predictor of surgical outcome: epithelioid mesothelioma patients are the primary surgical candidates with median post-surgical survival of approximately 19 months in population data, biphasic cases are considered on an individual basis with median survival of approximately 12 months, while sarcomatoid mesothelioma patients (median survival approximately 4 months) are generally excluded from curative-intent surgical protocols because the MARS 2 trial confirmed a dramatically worse impact of surgery in non-epithelioid patients (hazard ratio 2.66 versus 1.12 for epithelioid).

Performance status is equally critical, with ECOG performance status of 0 or 1 required for consideration of curative-intent surgery. In peritoneal mesothelioma, ECOG 3 status was independently associated with dramatically higher postoperative mortality (hazard ratio 13.3, p<0.001). Staging requirements have become increasingly restrictive: the 2025 NCCN guidelines now recommend curative-intent surgery only for patients with stage I disease limited to the pleura with no lymph node involvement, a significant tightening from previous recommendations that included stages I through IIIA. Preoperative evaluation should include contrast-enhanced CT, PET-CT imaging, and consideration of mediastinal staging to assess nodal disease status. Adequate cardiopulmonary function is essential, particularly for EPP which removes an entire lung — in the MARS 2 cohort, mean FEV1 was approximately 75% predicted, mean FVC approximately 78% predicted, and mean transfer factor approximately 74-78% predicted.

Patients diagnosed with mesothelioma should be evaluated at specialized treatment centers where multidisciplinary teams can assess surgical candidacy alongside molecular and genetic testing results and all available treatment modalities. Those with confirmed mesothelioma related to occupational or environmental asbestos exposure may also be eligible for compensation through mesothelioma lawsuits, asbestos trust funds, and the legal claims process that can help cover substantial treatment costs and provide financial security for affected families.

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See Also

• Pleurectomy and Decortication
• Heated Chemotherapy (HITHOC and HIPEC)
• Mesothelioma Surgery Recovery
• Mesothelioma Biopsy Procedures
• Mesothelioma Diagnosis and Staging
• Immunotherapy for Mesothelioma
• Mesothelioma Molecular and Genetic Testing
• Mesothelioma Treatment Centers
• Treatment Options
• Clinical Trials