Unmet Needs and Practice Gaps in Malignant Pleural and Peritoneal Mesothelioma Management: A Narrative Review Across China, the United States, and Europe

Introduction

Malignant mesothelioma—both pleural (PM) and peritoneal (PeM)—remains one of oncology's most diagnostically and therapeutically demanding diseases. Despite meaningful advances in immunotherapy, cytoreductive surgery, and multimodal treatment, the gap between guideline-recommended care and real-world clinical practice remains wide and demonstrably harmful to patient outcomes. China faces a potentially increasing or unevenly characterized disease burden, with mesothelioma incidence possibly rising in some regions due to historical asbestos exposure during rapid industrialization in the 1980s–2000s, while rates have declined in countries that banned asbestos decades earlier15. Against this epidemiological backdrop, this review examines four intersecting domains of unmet need—diagnostic delays, undertreatment of older adults, surveillance deficiencies, and disparate access to specialized care—and their downstream impact on outcomes across these three geographic regions.

1. Diagnostic Delays and Pathway Fragmentation

Mesothelioma's insidious onset is perhaps the most fundamental contributor to late-stage presentation. Both PM and PeM present with nonspecific symptoms—dyspnea (reported in 82% of patients in the ASSESS-meso UK cohort), chest pain, cough, fatigue, and weight loss—that closely mimic common cardiopulmonary and abdominal conditions1. In the ASSESS-meso prospective cohort of 244 UK patients, 43.9% reported symptoms for at least one month before diagnosis, and 35.6% for more than three months1. Pleural effusion, the most common clinical presentation, is frequently attributed to benign causes or other malignancies before mesothelioma is considered.

Tissue confirmation compounds this challenge. Pleural fluid cytology has a sensitivity of only 50–60% for malignant pleural effusion overall, and critically, cytological sensitivity for mesothelioma may be as low as 6% in some series15. Image-guided biopsies achieve diagnostic yields of 84–93%, and medical thoracoscopy achieves sensitivity of approximately 92.6%, but both require specialized infrastructure and operator expertise1. The 2021 Chinese Clinical Practice Guideline explicitly highlights that sarcomatoid subtypes—associated with the worst prognosis—are particularly prone to false-negative cytology, underscoring the need for tissue-based diagnosis with appropriate immunohistochemical panels (calretinin, CK5/6, WT1, mesothelin, and adenocarcinoma markers)15.

Regional differences in diagnostic pathways are clinically significant. In well-resourced US and European centers, a direct-to-thoracoscopy approach is increasingly advocated for suspected mesothelioma with documented asbestos exposure, supported by PET/CT (sensitivity 81–100%, specificity 74–92%) and standardized immunohistochemistry19. In contrast, China's diagnostic infrastructure is more heterogeneous: access to advanced imaging, medical thoracoscopy, and experienced mesothelioma pathologists is unevenly distributed, and formal screening protocols for high-risk asbestos-exposed populations are not routinely recommended due to insufficient evidence of mortality benefit15. Without published, widely accessible national diagnostic algorithms, Chinese practice is likely to reflect institutional variation rather than evidence-based standardization115.

The downstream consequence is direct: late-stage diagnosis reduces eligibility for curative-intent multimodal therapy. The majority of mesothelioma patients in China, the US, and Europe present at stage III–IV, at which point treatment options are confined to systemic therapy and palliation rather than surgery or combined-modality regimens15.

2. Undertreatment in Older Adults

Mesothelioma disproportionately affects older adults; median age at diagnosis is approximately 72–76 years, and in the ASSESS-meso cohort, 89.8% of patients were aged 65 or older1. Yet evidence consistently reveals that older age is an independent barrier to guideline-concordant therapy, driven by comorbidity burden, performance status concerns, and implicit clinician bias rather than explicit medical contraindication.

In the ASSESS-meso cohort, 40.2% of patients carried two or more comorbidities, and 55.1% received chemotherapy or immunotherapy, compared with only 39.6% in the contemporaneous UK National Mesothelioma Audit of 6,950 unselected patients—a gap suggestive of real-world undertreatment1. A Danish nationwide cohort of 880 patients demonstrated that within 180 days of diagnosis, no treatment was recorded for 54% of patients with advanced MPM and 46% with non-advanced MPM3. In the United States, a National Cancer Database analysis of 20,561 patients found that only 20% underwent cancer-directed surgery, and merely 2.6% received trimodality therapy (surgery, chemotherapy, and radiation)2. Independent predictors of trimodality receipt included age under 70, Charlson comorbidity score of 0, and private insurance—confirming that patient age, comorbidity, and socioeconomic status, rather than clinical evidence alone, drive treatment selection2.

Performance status ≥2 was independently associated with a 3.96-fold higher mortality hazard in the ASSESS-meso cohort (adjusted HR 3.96, 95% CI 2.14–7.30)1. Yet the challenge is distinguishing objective functional impairment from age-related clinician assumptions: evidence from CheckMate-743 reported improved overall survival with nivolumab plus ipilimumab compared with chemotherapy in unresectable mesothelioma (median OS approximately 18 months vs 14 months in published results)1015. Systematic geriatric oncology assessment, rather than age-based exclusion, is the evidence-based response to this gap, yet such structured evaluation is rarely embedded in routine mesothelioma care across any of the three regions6.

3. Surveillance and Follow-Up Gaps

Post-treatment surveillance represents one of the most poorly standardized domains in mesothelioma management. No major international guideline—including ASCO 2024, BTS 2018, or the 2021 Chinese guideline—specifies imaging modalities, intervals, or response assessment criteria for routine post-treatment follow-up with sufficient granularity for real-world implementation101315. A 2019 multidisciplinary consensus statement from the National Cancer Institute, IASLC, and Mesothelioma Applied Research Foundation acknowledged explicitly that "detailed guidelines pertaining to radiological assessment of malignant pleural mesothelioma are currently lacking," and that standardized imaging and reporting protocols are absent outside of clinical trial settings13.

The clinical stakes of this gap are quantifiable. A retrospective analysis of 305 patients with epithelioid MPM demonstrated that responders to frontline therapy achieved a median overall survival of 20.6 months versus 9.4 months for nonresponders (HR 0.34, 95% CI 0.24–0.49; p<0.001), with a strong association between tumor burden reduction and survival11. This benefit is only realized if surveillance imaging detects progression early enough for salvage intervention to be feasible. Supporting data from analogous malignancies are instructive: in a gastric cancer cohort, standardized follow-up by a specialized center improved overall survival to 84.9 months versus 38.4 months with non-standardized follow-up (p=0.040)14.

Evidence from MPM patients who relapse after surgical multimodality therapy is particularly sobering: median overall survival from relapse was only 4.8 months, and 62% of relapsed patients received no systemic therapy due to poor performance status at recurrence12. The authors of this analysis explicitly called for "prompt detection of recurrence with early and regular postoperative imaging," concluding that earlier surveillance could identify disease at lower burden, preserving functional status and salvage therapy eligibility12. In China, the 2021 guideline acknowledges the absence of high-level evidence to support a specific surveillance schedule, offering only that CT every 3–6 months may be appropriate in responding patients—a vague recommendation that invites inconsistent implementation15.

4. Referral Patterns and Access to Specialized Centers

Centralized, multidisciplinary care is the structural prerequisite for optimal mesothelioma management, yet geographic and systemic barriers limit its reach across all three regions. Mesothelioma requires coordinated input from thoracic surgery, peritoneal surface oncology, medical oncology, interventional radiology, specialist pathology, and palliative care. Specialized mesothelioma multidisciplinary team (MDT) meetings are linked to improved staging accuracy, treatment intensity, and clinical trial enrollment1.

For PeM specifically, cytoreductive surgery combined with HIPEC (CRS/HIPEC) is the standard of care for selected patients and the procedure most capable of achieving long-term survival. However, a survey of 116 physicians in the Washington, D.C. metropolitan region found that only 50% would consider CRS/HIPEC referral for peritoneal mesothelioma (vs. 75% for appendiceal peritoneal metastasis)4. The primary barrier was lack of access to a HIPEC specialist (47%), followed by perceived insufficient evidence (31%). Critically, more than half of respondents underestimated 5-year survival after CRS/HIPEC and overestimated 30-day mortality—demonstrating that physician knowledge gaps directly translate into withheld referrals4.

In China, the prevalence of PeM is estimated at approximately 2.6 per million population, yet formal, specialized peritoneal mesothelioma treatment infrastructure is critically inadequate1. No retrieved evidence provides a precise count of functioning HIPEC/CRS programs in China, itself a reflection of the infrastructure and data gap. In the US, although mesothelioma centers of excellence exist, they are concentrated in major academic centers; rural and underinsured populations face travel burdens and financial barriers that translate into lower rates of surgical and trimodality treatment—the National Cancer Database analysis confirmed that travel distance greater than 26 miles to a treatment facility paradoxically predicted trimodality therapy receipt, indicating that patients willing to travel to specialized centers had better access to intensive treatment2.

Access to immunotherapy introduces an additional layer of regional disparity. The ASCO 2024 guideline designates nivolumab plus ipilimumab as preferred first-line therapy for unresectable mesothelioma10. In the United States and parts of Europe, access is generally available in academic and community oncology settings, though rural access and reimbursement restrictions persist. In China, while the 2021 guideline formally incorporates dual immunotherapy, the real-world reimbursement status and patient-level availability of nivolumab plus ipilimumab on China's National Reimbursement Drug List remain incompletely characterized in the available evidence base15. This gap between guideline recommendation and actual drug access represents a tangible inequity that may restrict Chinese patients to chemotherapy-only regimens.

5. Outcome Impact and Practical Implications for Clinicians

The cumulative effect of these gaps is measurable across every outcome dimension. Diagnostic delays shift presentation toward advanced stage, reducing eligibility for surgery and trimodality treatment. Undertreatment in older adults denies patients a median 2.8-month overall survival benefit from pemetrexed-platinum doublet chemotherapy over single-agent therapy, and substantially greater benefit from immunotherapy in fit patients1. Surveillance deficiencies allow recurrence to accumulate to high disease burden before detection, at which point performance status deterioration forecloses salvage therapy options12. Referral barriers to specialized centers exclude patients from CRS/HIPEC, clinical trials, and mesothelioma-specific nursing support.

For clinicians across all three regions, priority areas for quality improvement include: (1) implementing standardized diagnostic algorithms with rapid access to thoracoscopy and expert immunohistochemistry, particularly in China where heterogeneous infrastructure creates diagnostic inconsistency; (2) using objective fitness assessment tools—geriatric screening instruments, comorbidity indices, performance status evaluation—to replace implicit age-based exclusion with individualized treatment selection; (3) establishing surveillance protocols that specify contrast-enhanced CT at minimum every 3 months for the first two years post-treatment, with clear criteria for escalation to MRI or PET/CT; (4) creating regional mesothelioma MDT networks with formalized referral pathways to CRS/HIPEC centers for PeM and to high-volume thoracic centers for PM; and (5) ensuring equitable access to immunotherapy through reimbursement advocacy and health policy engagement, particularly in China.

"Best practice" in this disease demands more than guideline publication—it requires infrastructure investment, physician education targeted at community oncologists and surgeons who underutilize CRS/HIPEC referral, and prospective outcomes research to close evidence gaps in second-line therapy, surveillance efficacy, and immunotherapy outcomes in peritoneal disease. Until these systemic and knowledge-based barriers are systematically addressed, the translational distance between what evidence-based medicine can offer and what most mesothelioma patients actually receive will remain one of oncology's most consequential unmet needs.