Advances in Pleural Mesothelioma Treatment: ASCO Guideline Update

The lungs are covered by the pleura , a two-layered membrane  (see illustration below). A small amount of fluid lies between its layers, produced by mesothelial cells .

Similar linings occur elsewhere: the peritoneum around the abdomen and the pericardium around the heart. Malignant mesothelioma  is cancer arising from these membranes.

Among patients with malignant mesothelioma, 80% have pleural malignant mesothelioma .

Overview

The main cause is asbestos  exposure. Less common causes are described as genetic factors and a virus called Simian 40.

Pleural mesothelioma  symptoms  include breathlessness, chest pain, and cough. Early diagnosis may be difficult, and disease is generally detected at an advanced stage.

This rare cancer is more common in men in countries with occupational asbestos  exposure. In environmental settings such as Turkey, environmental asbestos  exposure produces equal rates in women and men.

Worldwide frequency is 1-2 per 1 million people; approximately 500 new cases are diagnosed annually in Turkey.

Current Progress in Pleural Mesothelioma Treatment

In 2020, nivolumab (Opdivo) plus ipilimumab (Yervoy), two immunotherapy  medicines, received FDA approval for adults with unresectable pleural mesothelioma  as first-line  treatment. This was the first immunotherapy approval for mesothelioma, providing an approved chemotherapy-free option  irrespective of subtype. Following this approval, there were 3 FDA-approved treatment options for pleural mesothelioma:

1. "Cisplatin + pemetrexed" chemotherapy;
2. Adding electrical field therapy (the NovoTTF-100L System) to that doublet; and
3. Nivolumab–ipilimumab.

The phase-III bevacizumab  (Altuzan, Avastin, Mvasi) evidence concerns adding this new-vessel-blocking antiangiogenic  medicine to cisplatin + pemetrexed, significantly improving survival. Results were reported in 2015 in the MAPS  trial. In practice, we seek off-label approval to add it to treatment.

Below is an indirect comparison of FDA-approved pleural mesothelioma treatments  for review:

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Current Treatment Guide: ASCO Update

This article discusses ASCO's 2025 “Treatment of Pleural Mesothelioma” guideline update, covering recent advances in surgery, immunotherapy, chemotherapy, pathology, and germline testing . These are among the important fields covered by recent developments. The guideline also emphasizes multidisciplinary approaches to managing patients with pleural mesothelioma.

Purpose and Scope

ASCO's first treatment guideline appeared in 2018. Rapid progress made an update necessary in four areas:

1. The Role of Surgery
2. New Systemic Treatments
3. Pathological Findings
4. Germline Testing

Surgery: Current Recommendations

Surgery has long been debated, with geographic differences in practice. New evidence, particularly MARS 2 , indicates that anatomical resectability alone should not make surgery routine. It should be considered only for patients meeting these criteria:

• Early-Stage Epithelioid Tumors: Operate on suitable early-stage patients after detailed staging.
• Centers of Excellence: Use expert centers with low morbidity and mortality, generally within multimodal treatment.
• Clinical Trials: Perform surgery within trials whenever possible.

NOTE: The terms epithelioid and nonepithelioid describe histological subtypes:

• Epithelioid Mesothelioma: The most common subtype, with a better prognosis. Cells resemble epithelial cells and are regular, round, or oval.

• Nonepithelioid Mesothelioma: Includes sarcomatoid and biphasic tumors, the latter containing both epithelioid and sarcomatoid components. Sarcomatoid disease is more aggressive and generally responds less well.

Classification matters for treatment planning and prognosis.

Immunotherapy: New Options

Progress includes FDA approval of ipilimumab–nivolumab in 2020 and chemotherapy plus immunotherapy in 2024.

• Dual Immunotherapy (Ipilimumab + Nivolumab): This treatment should be offered to all patients with mesothelioma as a first-line systemic option. The combination is particularly recommended for nonepithelioid histology.
• Chemotherapy + Immunotherapy (Pembrolizumab, Pemetrexed, Carboplatin): A 62% response rate makes this an option for newly diagnosed patients.
• Individualized Selection: Treatment selection should consider the patient's comorbidities, tolerance of toxicity, and individual treatment goals.

Chemotherapy: Current Recommendations

Pemetrexed with platinum-based chemotherapy remains a first-line treatment option for patients with epithelioid histology.

• Adding Bevacizumab: Recommended in suitable patients.
• Nonepithelioid Mesothelioma: Chemotherapy is not recommended unless immunotherapy is impossible.
• Pemetrexed Maintenance: Not recommended after platinum-based chemotherapy.

Pathology Updates

Important classification changes include:

• Disease Name: Use “mesothelioma” rather than “malignant mesothelioma.”
• Histological Subtypes: Report epithelioid, sarcomatoid, or biphasic disease; these carry prognostic and predictive significance.
• Mesothelioma In Situ: Defined as a precancerous condition in patients with longstanding pleural effusion.

Germline (Inherited) Testing: Universal Recommendations

All patients with mesothelioma should be offered germline genetic testing as recommended.

• BAP1 Mutations: These occur in 5-15% of patients and affect cancer risk for patients and relatives. Survival with platinum chemotherapy is also substantially longer in carriers (7.9 versus 2.4 years).

Conclusion and Future Research

The update comprehensively reviews major treatment advances and guides clinicians in integrating them into patient care.

Future research areas include:

• New immunotherapies, including bispecific antibodies and cell therapies.
• Early cancer detection and prevention.
• Prevention approaches for people with BAP1 and other germline mutations.