Palliative Care in Malignant Pleural Mesothelioma: A Comprehensive Clinical Review

 Palliative Care in Malignant Pleural Mesothelioma: A Comprehensive Clinical Review

Authors: Dr. Shekhar Ingle and Team, Doctor's Forum for All 🏥

Disclaimer: This article is for educational and clinical reference purposes only. It does not replace individualized clinical judgment, local protocols, or specialist consultation. Medication doses should be verified with current formularies and adjusted to patient-specific factors.

 Abstract

Background: Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related malignancy with a poor prognosis and a uniquely high symptom burden, including severe chest wall pain, dyspnoea, cough, fatigue, and profound psychosocial distress. Most patients present with advanced disease where curative intent is not feasible, making palliative care central to management.

Objective: This review provides a comprehensive, clinically verified framework for palliative care in MPM, covering symptom assessment and management, interventional palliative procedures, integration of disease-modifying therapies, psychological support, advance care planning, and end-of-life care.

Methods: A structured narrative review was conducted using evidence from peer-reviewed guidelines, systematic reviews, randomized controlled trials, and consensus statements published between 2000 and 2026. Key sources included the European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), National Comprehensive Cancer Network (NCCN), British Thoracic Society (BTS), and Cochrane systematic reviews.

Results: MPM requires early palliative care integration due to its aggressive trajectory and high symptom burden. Key interventions include opioids and adjuvants for chest wall pain, indwelling pleural catheters or pleurodesis for recurrent effusions, palliative radiotherapy for pain nodules, and comprehensive psychosocial support. Novel systemic therapies (immunotherapy, targeted agents) may provide symptom relief in selected patients. Advance care planning is essential given the predictable decline.

Conclusion: Palliative care is integral to MPM management from diagnosis. A multidisciplinary, patient-centred approach addressing physical symptoms, psychological distress, and existential concerns is essential. Early integration improves quality of life and supports goal-concordant care.

Keywords: Malignant pleural mesothelioma, palliative care, chest wall pain, dyspnoea, malignant pleural effusion, advance care planning, asbestos, immunotherapy.

1. Introduction

Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy arising from the mesothelial cells lining the pleura. It is almost exclusively linked to asbestos exposure, with a latency period of 20–50 years between exposure and disease onset [1]. Global incidence remains significant despite asbestos bans in many countries, with approximately 30,000 new cases annually worldwide [2].

MPM has a poor prognosis, with median overall survival of 8–14 months without treatment and 12–18 months with modern combination therapy [3]. The disease is characterised by diffuse pleural thickening, progressive encasement of the lung, chest wall invasion, and early metastatic spread.

The symptom burden in MPM is among the highest of all malignancies. Dyspnoea affects 90–100% of patients, chest wall pain affects 60–80%, cough affects 50–70%, fatigue affects 80–90%, anorexia and weight loss affect 50–70%, sweats and fever affect 30–50%, and psychological distress affects 40–60% [4]. Unlike many cancers where symptoms improve with treatment, MPM symptoms often progress relentlessly despite therapy. This makes early integration of palliative care essential.

2. Methods

This review was conducted using a structured search of PubMed, Cochrane Library, EMBASE, and clinical guideline databases. Search terms included "malignant pleural mesothelioma," "palliative care," "chest wall pain," "dyspnoea," "malignant pleural effusion," "pleurodesis," "indwelling pleural catheter," "advance care planning," "immunotherapy," and "end-of-life care."

Inclusion criteria encompassed systematic reviews and meta-analyses, randomized controlled trials, clinical practice guidelines, consensus statements, and large observational studies published in English between 2000 and 2026.

Key guidelines consulted included the ESMO Clinical Practice Guidelines for Malignant Pleural Mesothelioma (2021) [5], ASCO Guidelines on Treatment of Malignant Pleural Mesothelioma (2018) [6], NCCN Guidelines for Mesothelioma (2024) [7], BTS Guidelines for the Management of Malignant Pleural Effusions (2018) [8], and the European Respiratory Society Task Force on Malignant Pleural Effusion (2018) [9].

3. Results

3.1 Early Integration of Palliative Care

MPM is a paradigm disease for early palliative care integration. Unlike many cancers where prognosis is uncertain, MPM has a predictable and relatively short trajectory. The RESPECT-Meso trial (2019) was a landmark randomized controlled trial demonstrating that early specialist palliative care improved quality of life in patients with newly diagnosed MPM [10].

Key findings from RESPECT-Meso demonstrated that patients receiving early palliative care had better quality of life at 12 weeks, reduced symptom burden, improved mood, no difference in survival as expected, and earlier advance care planning discussions.

Current guidelines recommend palliative care referral at diagnosis, concurrent palliative care alongside systemic therapy, regular symptom screening, and early advance care planning [5,6,7].

3.2 Pain Management

Chest wall pain is the most challenging symptom in MPM, affecting 60–80% of patients. The pain is often multifactorial, comprising nociceptive pain from tumour invasion of chest wall, ribs, and intercostal nerves; neuropathic pain from intercostal nerve involvement or spinal cord compression; visceral pain from pleural irritation and lung encasement; and incident pain aggravated by breathing, coughing, and movement.

3.2.1 Pharmacological Management

The WHO Analgesic Ladder provides the framework for pharmacological management. Step 1 utilises paracetamol 1g every 6 hours regularly, with NSAIDs added cautiously due to renal impairment risk in older patients. Step 2 introduces weak opioids such as tramadol 50–100mg every 6 hours for moderate pain. Step 3 employs strong opioids including morphine, oxycodone, fentanyl, or hydromorphone for severe pain. Most MPM patients eventually require strong opioids.

Morphine remains the first-line strong opioid. Treatment should begin with immediate-release morphine 5–10mg every 4 hours as needed, converting to sustained-release formulations once stable. Oxycodone serves as an alternative if morphine causes intolerable side effects. Fentanyl patches are useful for stable chronic pain, especially in patients with dysphagia or compliance issues, but are not suitable for acute pain titration. Methadone may be useful for complex neuropathic pain but requires specialist supervision.

Adjuvants for neuropathic pain are essential in MPM. Gabapentin is started at 100–300mg at night and titrated to 900–3600mg daily in divided doses, with renal adjustment. Pregabalin is started at 25–75mg at night and titrated to 150–600mg daily. Amitriptyline 10–25mg at night helps neuropathic pain but requires caution with cardiac arrhythmias and glaucoma. Duloxetine 30–60mg daily is useful for neuropathic pain accompanied by depression.

Corticosteroids such as dexamethasone 4–8mg daily may reduce tumour-related oedema and pain, and are particularly useful for spinal cord compression, nerve root compression, or brain metastases. Low-dose ketamine at 0.1–0.5mg/kg intravenous or subcutaneous infusion may be considered for refractory neuropathic pain but requires specialist palliative care supervision [11]. Intravenous lidocaine infusion at 1–5mg/kg over 30–60 minutes may provide relief for refractory neuropathic pain and requires cardiac monitoring.

3.2.2 Non-Pharmacological Management

Transcutaneous electrical nerve stimulation may provide short-term relief for localised chest wall pain. Acupuncture has limited evidence but may help in selected patients. Cognitive behavioural therapy helps patients cope with chronic pain. Relaxation techniques including progressive muscle relaxation and guided imagery are beneficial. Heat and cold application may provide temporary comfort.

3.2.3 Interventional Pain Management

Intercostal nerve blocks are useful for localised chest wall pain and may be repeated. Paravertebral blocks provide more extensive coverage for unilateral chest pain. Epidural analgesia is reserved for severe refractory pain and may be used in hospital or hospice setting. Intrathecal drug delivery via implantable pump is indicated for severe refractory pain and requires a specialist centre.

Percutaneous cervical cordotomy is a neurosurgical procedure that interrupts the spinothalamic tract, providing contralateral pain relief below the level of C2. It is particularly effective for unilateral chest wall pain in MPM, with success rates of 80–90% [12]. The procedure is indicated for patients with life expectancy less than 12 months and refractory pain. Vertebroplasty or kyphoplasty may be considered for painful vertebral metastases.

3.2.4 Palliative Radiotherapy

Palliative radiotherapy is effective for chest wall pain, with 20–30 Gy in 5–10 fractions providing pain relief in 50–70% of patients [13]. Single-fraction 8 Gy or short courses may be used for painful chest wall nodules. Urgent radiotherapy with corticosteroids is essential for spinal cord compression. Whole-brain or stereotactic radiotherapy addresses brain metastases. Urgent radiotherapy is indicated for superior vena cava obstruction.

The SMART trial (2016) demonstrated that prophylactic radiotherapy does not reduce procedure-tract metastases, but radiotherapy remains useful for established painful nodules [14]. Radiotherapy should be used selectively due to the risk of radiation pneumonitis and oesophagitis.

3.3 Dyspnoea Management

Dyspnoea affects virtually all MPM patients and is caused by malignant pleural effusion as the most common cause, pleural thickening and lung encasement producing trapped lung, chest wall restriction, respiratory muscle weakness, anaemia, pulmonary embolism, pneumonia, and comorbid COPD.

3.3.1 Malignant Pleural Effusion Management

Recurrent pleural effusion requires definitive palliation. Indwelling pleural catheters are recommended as first-line option for symptomatic recurrent effusion. The TIME2 trial demonstrated equivalent symptom relief to talc pleurodesis with fewer hospital days [15]. Indwelling catheters allow home drainage, patient autonomy, and remain effective even with trapped lung.

Talc pleurodesis is effective when lung re-expands after drainage, with success rates of 70–80%. The procedure requires hospital admission and chest drain insertion, and may cause pain and fever.

Thoracentesis provides immediate relief in acute dyspnoea and allows assessment of lung re-expansion. Repeated thoracentesis is not recommended as a long-term strategy. Pleuroperitoneal shunt is rarely used for refractory effusions when other options fail.

The choice between indwelling pleural catheter and talc pleurodesis depends on several factors. Indwelling pleural catheters offer outpatient or short hospital stay of 1–2 days, effectiveness of 90–95%, effectiveness even with trapped lung, high patient autonomy through home drainage, low infection risk of approximately 5%, minor procedure requirements, and higher initial costs. Talc pleurodesis requires hospital stay of 3–7 days, effectiveness of 70–80%, is not suitable for trapped lung, offers low patient autonomy, has low infection risk of approximately 3%, requires chest drain insertion, and has lower initial costs.

3.3.2 Pharmacological Management of Dyspnoea

Opioids remain the cornerstone of dyspnoea management. Low-dose morphine at 2.5–5mg every 4 hours as needed is effective for refractory dyspnoea [16]. Treatment should start low and titrate slowly. Continuous subcutaneous infusion may be needed for severe dyspnoea.

Benzodiazepines may be used for associated anxiety or panic, but evidence for direct dyspnoea relief is limited. They should be used cautiously due to respiratory depression risk [17]. Oxygen is only indicated if hypoxaemic with SpO₂ at or below 90%. The Abernethy trial demonstrated that oxygen is no better than room air for non-hypoxaemic patients [18]. Corticosteroids such as dexamethasone 4–8mg daily may reduce tumour-related inflammation and improve dyspnoea in selected patients.

3.3.3 Non-Pharmacological Management

Fan therapy with cool air directed at the face reduces dyspnoea. Positioning upright, leaning forward, or side-lying on the affected side provides relief. Pursed-lip breathing slows respiratory rate and improves oxygen saturation. Energy conservation through prioritising activities and using assistive devices is important. Pulmonary rehabilitation improves exercise capacity and quality of life [19]. Relaxation techniques reduce anxiety-related dyspnoea.

3.4 Cough Management

Cough affects 50–70% of MPM patients and is often persistent and distressing. Management begins with treating reversible causes including infection, gastro-oesophageal reflux, postnasal drip, or excessive secretions. Opioids such as codeine 30–60mg every 4–6 hours or morphine 2.5–5mg every 4 hours are effective antitussives. Corticosteroids may reduce tumour-related airway inflammation. Nebulised saline helps loosen secretions. Nebulised lidocaine may reduce cough reflex but requires monitoring. Benzonatate serves as a peripherally acting antitussive. Steam inhalation loosens secretions and soothes the airway.

3.5 Fatigue, Anorexia, and Cachexia

Fatigue affects 80–90% of MPM patients. Management includes treating reversible causes such as anaemia requiring transfusion if symptomatic, infection, dehydration, hypothyroidism, depression, and medication side effects. Supervised physical activity improves fatigue [20]. Energy conservation through prioritising activities and planning rest periods is essential. Dexamethasone 4–8mg daily may improve energy and wellbeing in advanced disease. Methylphenidate may improve fatigue in selected patients.

Cancer cachexia is common in MPM and associated with poor prognosis. Dexamethasone 4–8mg daily improves appetite and wellbeing. Megestrol acetate at 160–480mg daily improves appetite but increases thromboembolic risk. Nutritional counselling with small frequent meals and oral nutritional supplements is beneficial. Exercise preserves muscle mass and function. Omega-3 fatty acids may have modest benefit.

3.6 Psychological and Existential Distress

MPM carries a unique psychological burden due to asbestos exposure producing anger, regret, and compensation-related stress. The occupational origin means many patients were industrial workers experiencing loss of identity. The poor prognosis brings short life expectancy and rapid decline. Physical disfigurement from chest wall nodules and cachexia adds distress. Medicolegal processes including workers' compensation claims and litigation create additional burden. Family concerns about asbestos exposure of family members compound the distress.

Management includes regular screening using PHQ-9, HADS, or Distress Thermometer. Pharmacotherapy with SSRIs such as sertraline, citalopram, or escitalopram addresses depression and anxiety. Psychotherapy including cognitive behavioural therapy, supportive counselling, and mindfulness is beneficial. Spiritual care through chaplaincy, meaning-making, and legacy work provides comfort. Mesothelioma-specific patient organisations offer peer support. Referral to legal services for compensation claims should be facilitated.

3.7 Sweats and Fever

Night sweats and fever occur in 30–50% of MPM patients, often due to tumour cytokine release. Dexamethasone 4–8mg daily reduces sweats and fever. NSAIDs may help but should be used cautiously. Paracetamol provides symptomatic fever control. A cool environment with fan and light bedding offers comfort. Adequate oral hydration should be encouraged.

4. Disease-Modifying Therapies in the Palliative Context

4.1 Chemotherapy

Platinum-based chemotherapy with cisplatin or carboplatin combined with pemetrexed has been standard first-line therapy, providing modest survival benefit with median survival of 12–14 months and symptom improvement [21]. In the palliative context, the decision to offer chemotherapy should balance potential benefits of symptom relief and modest survival prolongation against toxicity including nausea, fatigue, myelosuppression, and nephrotoxicity. Patient preference is paramount, as some patients prioritise quality of life over survival.

4.2 Immunotherapy

The CheckMate 743 trial (2021) demonstrated that first-line nivolumab plus ipilimumab improves survival compared to chemotherapy in unresectable MPM, with median survival of 18.1 months versus 14.1 months and hazard ratio of 0.74 [22]. Immunotherapy is now recommended as first-line treatment for most patients.

Palliative considerations include the potential for immunotherapy to improve symptoms without chemotherapy toxicity. Immune-related adverse events require monitoring. Response may be durable in a subset of patients. The decision should consider performance status and patient preference.

4.3 Targeted Therapy

Bevacizumab, an anti-VEGF agent, added to chemotherapy improves survival in selected patients [23]. Other targeted agents are under investigation.

4.4 Surgery

Extrapleural pneumonectomy and pleurectomy/decortication are radical surgeries with significant morbidity. In the palliative context, surgery is rarely indicated except for symptom relief in highly selected patients.

4.5 Palliative Radiotherapy

Radiotherapy is used for chest wall pain, painful nodules, spinal cord compression, brain metastases, and superior vena cava obstruction as described earlier.

5. Advance Care Planning

MPM has a predictable trajectory, making advance care planning essential. Discussions should be initiated at diagnosis when the patient is stable. Prognosis should be communicated honestly but compassionately, using phrases like "This is a serious diagnosis, and we will do everything we can to support you."

Goals should be explored with questions such as "What is most important to you now?" and "What are your hopes and worries for the future?" Preferences should be documented for preferred place of care and death, resuscitation status, and views on ventilation, intensive care, and artificial nutrition.

Legal aspects include appointing a healthcare proxy or lasting power of attorney. Preferences should be reviewed regularly and updated with clinical changes. Medicolegal considerations ensure compensation claims are filed early.

6. End-of-Life Care

Recognising the terminal phase is crucial. Features suggesting imminent death include progressive decline despite optimal therapy, refractory dyspnoea at rest, worsening cachexia and fatigue, delirium or reduced consciousness, and patient expressing desire for comfort-focused care.

Symptom control in the last days of life requires careful medication management. Morphine 2.5–5mg subcutaneously every 4 hours as needed or continuous subcutaneous infusion addresses dyspnoea. Midazolam 2.5–5mg subcutaneously treats associated anxiety and agitation. Glycopyrronium 0.2–0.4mg subcutaneously every 6 hours as needed manages respiratory secretions. Haloperidol 0.5–1.5mg subcutaneously every 8 hours as needed controls nausea and vomiting. Paracetamol or NSAIDs as needed address sweats and fever.

Non-essential medications should be discontinued, including chemotherapy, immunotherapy, and routine medications that do not provide immediate symptom benefit [24]. Fluid management should avoid intravenous fluids unless for comfort. Oxygen should be continued if it provides comfort.

Family care includes providing emotional support, information, and bereavement follow-up.

7. Discussion

7.1 The Unique Challenges of MPM

MPM presents unique palliative care challenges compared to other thoracic malignancies. The diffuse pleural involvement means that unlike lung cancer which may be localised, MPM diffusely infiltrates the pleura, causing widespread chest wall pain and lung encasement. The severity and refractoriness of chest wall pain in MPM is distinctive, with many patients requiring high-dose opioids and adjuvants, and some benefiting from interventional procedures such as cordotomy.

Rapid progression means MPM often advances quickly despite treatment, making timely advance care planning essential. Medicolegal considerations including compensation claims and litigation add psychological burden and may influence treatment decisions. Occupational exposure means many patients have a history of industrial work, which may affect their identity and coping mechanisms.

7.2 The Role of Specialist Palliative Care

The RESPECT-Meso trial demonstrated that early specialist palliative care improves quality of life in MPM [10]. Specialist palliative care teams provide expert symptom management, psychological and spiritual support, advance care planning, coordination of community services, and bereavement support.

7.3 Integration with Oncology

Palliative care should be integrated with oncology from diagnosis. This includes joint clinics with oncology and palliative care, regular symptom screening, shared decision-making about disease-modifying therapies, and early discussion of goals of care.

7.4 The Importance of the Interdisciplinary Team

MPM management requires an interdisciplinary team including medical oncologist, palliative care physician, thoracic surgeon, interventional radiologist, pain specialist, clinical nurse specialist, physiotherapist, dietitian, psychologist, social worker, chaplain, and legal advisor.

7.5 Gaps in Evidence and Future Directions

Despite advances, several gaps remain. Optimal management of refractory chest wall pain requires further study. The role of cordotomy in MPM pain needs more evidence. The effectiveness of immunotherapy in symptom control requires investigation. Integration of palliative care in low-resource settings needs attention. Use of telehealth for palliative care delivery should be explored. Biomarkers for prognostication and treatment selection are needed.

Future research should focus on these areas, as well as on implementation science to ensure evidence-based palliative care reaches all patients who need it.

8. Conclusion

Malignant pleural mesothelioma is a devastating asbestos-related malignancy with a uniquely high symptom burden and poor prognosis. Palliative care is integral to management from diagnosis and should be delivered alongside disease-modifying therapies. Key interventions include opioids and adjuvants for chest wall pain, indwelling pleural catheters or pleurodesis for recurrent effusions, palliative radiotherapy for pain and spinal cord compression, and comprehensive psychosocial support. Early specialist palliative care improves quality of life and should be standard practice. A multidisciplinary, patient-centred approach addressing physical symptoms, psychological distress, and existential concerns is essential.

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Prepared By: Dr. Shekhar Ingle and Team, Doctor's Forum for All 🏥

Copyright: © 2026 Dr. Shekhar Ingle and Team, Doctor's Forum for All. All rights reserved.

Date: 2026