Mesothelioma Recurrence After Pleurectomy Decortication

Page Profile
Recurrence After Pleurectomy/Decortication (P/D)
Anchor study	Paajanen et al., Ann Surg 2026
Cohort	N=436 verified recurrences (of 551 evaluable, 79%)
Local recurrence	85% of recurrences; sole site in 29%
Median DFI	9.8 mo (95% CI 9.0–10.7)
Median PRS	12.7 mo (95% CI 10.6–14.4)
Salvage surgery (PRS)	HR 0.46 (95% CI 0.29–0.74, P=0.0013)
IOHC effect (DFI)	HR 0.60 (P<0.001); PRS HR 0.56 (P<0.001)
Dominant genomic features	Alterations: CDKN2A 49%, BAP1 44%, NF2 33% (980-sample cataloguing)

Executive Summary

Most patients develop mesothelioma recurrence after pleurectomy/decortication (P/D): in a 2026 Brigham and Women's Hospital cohort, 436 of 551 evaluable patients (79%) recurred during follow-up. That cohort, reported by Juuso Paajanen and colleagues in Annals of Surgery, examined 436 patients with verified tumor recurrence from a population of 551 evaluable patients who underwent P/D with macroscopic complete resection (MCR) between 1998 and 2022. The dominant finding is that local recurrence occurred in 85% of patients (N=370) and was the sole site of first recurrence in 29% (N=129), making P/D-associated relapse predominantly a locoregional rather than distant event. This page covers the Paajanen study, how recurrence after P/D differs from recurrence after extrapleural pneumonectomy (EPP), histologic and molecular predictors, intraoperative heated chemotherapy (IOHC), and treatment options at recurrence, including re-resection, hemithoracic intensity-modulated radiation therapy (IMRT), and systemic therapy.

Educational disclaimer: This page is for medical education and is not a substitute for individualized advice from a treating oncologist, thoracic surgeon, or palliative care team. Treatment decisions after P/D recurrence require multidisciplinary evaluation at a specialized mesothelioma program.

At a Glance

Recurrence and post-P/D recurrence at a glance:

• Most patients recur — 436 of 551 evaluable (79%) P/D patients in the Paajanen Brigham cohort developed verified recurrence during a median follow-up of 88.5 months.
• 85% local pattern — local recurrence occurred in 85% of recurrent cases (N=370) and was the sole site of first recurrence in 29% (N=129); residual thoracic cavity (72%), ipsilateral chest wall (55%), and diaphragm (22%) were the leading anatomical sites.
• Histology dominates trajectory — sarcomatoid tumors relapsed earlier and more distantly (P=0.003 for time-to-recurrence; P<0.001 for distant spread); epithelioid tumors relapsed later and predominantly locally.
• Intraoperative heated chemotherapy (IOHC, also known as Hyperthermic Intrathoracic Chemotherapy (HITHOC)) is associated with longer survival — IOHC was independently associated with longer disease-free interval (DFI; HR 0.60, P<0.001) and longer post-recurrence survival (PRS; HR 0.56, P<0.001).
• Salvage re-resection is independently associated with longer survival — among patients with distant or distant+local recurrences, recurrence surgery showed HR 0.46 (95% CI 0.29–0.74, P=0.0013) for PRS.
• 9.8-month median DFI; 12.7-month median PRS — in the recurrent cohort overall; 1-year recurrence-free survival 39%, 3-year 9%.
• P/D ≠ EPP geography — contralateral chest recurrence is roughly half as common after P/D (18%) than after EPP (38%) from the Brigham comparison cohort; abdominal recurrence is 24% after P/D vs. 54% after EPP.
• Modified Response Evaluation Criteria in Solid Tumours (mRECIST) — the Byrne and Nowak modified RECIST criteria are the standard for measuring tumor change in post-treatment surveillance imaging.
• Soluble Mesothelin-Related Peptides (SMRP / MESOMARK) — described as the only U.S. Food and Drug Administration (FDA)-approved biomarker for diagnosis of pleural mesothelioma and the most used for monitoring treatment.
• Circulating tumor DNA (ctDNA) — in a Johns Hopkins phase 2 perioperative immune checkpoint blockade trial, patients with undetectable ctDNA during neoadjuvant immunotherapy had significantly longer progression-free survival; overall survival was numerically longer but not statistically significant.

Key Facts

Metric	Finding
Anchor study	Paajanen J, Richards WG, Xie Y, Mazzola E, Sidopoulos K, Kuckelman J, Gill RR, Bueno R. Annals of Surgery 2026. Single-center retrospective cohort, International Mesothelioma Program, Brigham and Women's Hospital / Harvard Medical School.
Recurrence rate	436 of 551 evaluable (79%) over median follow-up 88.5 months (95% CI 80.9–127.0).
Local recurrence rate	85% of recurrent cases; sole site of first recurrence in 29%.
Median disease-free interval (DFI)	9.8 months (95% CI 9.0–10.7); 1-year recurrence-free survival 39%, 3-year 9%.
Median post-recurrence survival (PRS)	12.7 months (95% CI 10.6–14.4).
Salvage surgery effect on PRS	HR 0.46 (95% CI 0.29–0.74, P=0.0013) in patients with distant ± local recurrences.
Chemotherapy at recurrence effect on PRS	HR 0.69 (95% CI 0.54–0.92, P=0.005).
Histology distribution	Epithelioid 63%, biphasic 31%, sarcomatoid 6%.
Genomic landscape	Alterations in CDKN2A 49%, BAP1 44%, CDKN2B 42%, MTAP 34%, NF2 33%, TP53 18% in a cataloguing of 980 pleural mesothelioma samples (2023 review).
Germline BAP1 survival advantage	~7-fold improved long-term survival in germline BAP1 carriers (5-year survival 47% vs. 6.7% in SEER controls).
CheckMate 743	First-line nivolumab + ipilimumab vs. chemotherapy in unresectable MPM (N=605); median overall survival (OS) 18.1 vs. 14.1 months; HR 0.74; P=0.0020.
MARS2 trial	Extended P/D + chemo vs. chemo alone in resectable MPM; median OS 19.3 vs. 24.8 months; restricted mean survival difference −1.9 months; serious adverse events more common in surgery arm.
Imaging modalities at recurrence	Computed tomography (CT) 51%, Positron Emission Tomography–CT (PET-CT) 45%, magnetic resonance imaging (MRI) 2%, physical exam 1%, exploratory surgery 2%.
Standard response criteria	Modified RECIST (Byrne and Nowak, Annals of Oncology 2004); mRECIST 1.1 revision (Armato, J Thorac Oncol 2018).
Approved biomarker	Soluble Mesothelin-Related Peptides (SMRP / MESOMARK): the only FDA-approved biomarker for diagnosis of pleural mesothelioma and the most used for monitoring treatment.

Why Is the Paajanen 2026 Study the Anchor for Post-P/D Recurrence Care?

The Paajanen 2026 paper analyzed recurrence patterns in a P/D-only cohort and found, on multivariable analysis, that recurrence surgery was independently associated with longer post-recurrence survival.

A 2026 cohort study by Lang-Lazdunski, Zhang, and Nicholson reported long-term outcomes in 152 consecutive P/D patients treated October 2004 – October 2019: median overall survival of 31.7 months overall (35.0 months in the 70.4% epithelioid subset; 18.3 months in the 29.6% non-epithelioid subset), and nil 90-day mortality.

Study population and design

From 1,920 patients in the Brigham International Mesothelioma Program (IMP) surgical database, 709 (37%) underwent complete (extended) P/D. After excluding 148 patients with insufficient endpoint data, 4 with non-diffuse pleural mesothelioma (PM) diagnoses, and 6 with concurrent metastatic malignancies, 551 patients were available for analysis. Of these, 436 (79%) developed verified recurrence and form the analytical cohort. Median follow-up from surgery was 88.5 months (95% confidence interval (CI) 80.9–127.0). Mean patient age was 68 ± 9.7 years; 76% male; histology distribution was epithelioid 63% (N=275), biphasic 31% (N=136), and sarcomatoid 6% (N=25).

Anatomic recurrence map

Among the 436 patients with verified recurrence:

Recurrence category	Frequency (N, %)
Local — residual thoracic cavity (pleura)	N=314 (72%)
Local — ipsilateral chest wall	N=241 (55%)
Local — diaphragm	N=96 (22%)
Local — interlobar fissures	N=69 (16%)
Local — pericardium	N=57 (13%)
Local — direct lung invasion	N=43 (10%)
Local — mediastinal soft tissue mass	N=28 (6%)
Local — spinal cord/thoracic vertebrae (adjacent)	N=20 (5%)
Local — direct abdominal extension (liver)	N=30 (7%)
Lymphatic — any nodal recurrence	N=217 (50%)
Lymphatic — mediastinal lymph nodes (specifically)	N=177 (41%)
Hematogenous — abdomen	N=105 (24%)
Hematogenous — metastatic lung nodules	N=91 (21%)
Hematogenous — contralateral hemithorax (CHT)	N=77 (18%)
Hematogenous — distant musculoskeletal	N=27 (6%)
Hematogenous — central nervous system (CNS)	N=18 (4%)
Port-site recurrence (any port)	N=65 (15%)
Multifocal recurrence (more than one site)	N=402 (92%)

Multivariable predictors

Multivariable Cox proportional hazards modeling identified the following independent predictors:

Predictor	Outcome	Hazard ratio (HR) (95% CI)	P-value
Age (continuous)	Shorter DFI	1.02 (1.00–1.03)	0.015
Preoperative tumor volume (TV)	Shorter DFI	1.00 (1.00–1.01)	<0.001
Epithelioid vs. biphasic	Longer DFI	0.62 (0.49–0.77)	<0.001
Intraoperative heated chemotherapy (IOHC)	Longer DFI	0.60 (0.45–0.79)	<0.001
Tumor-Node-Metastasis (TNM) Stage IV vs. I	Shorter DFI	4.69 (1.69–13.01)	0.003
Eastern Cooperative Oncology Group performance status (ECOG PS) >1 at recurrence	Worse PRS	2.01 (1.50–2.70)	<0.001
TNM Stage IV vs. I	Worse PRS	5.00 (1.47–17.01)	0.010
Sarcomatoid vs. biphasic	Worse PRS	1.81 (1.09–3.01)	0.021
Epithelioid vs. biphasic	Better PRS	0.62 (0.49–0.80)	<0.001
IOHC (yes)	Better PRS	0.56 (0.42–0.75)	<0.001
Multifocal recurrence	Worse PRS	1.74 (1.08–2.82)	0.024
Recurrence surgery (distant ± local)	Better PRS	0.46 (0.29–0.74)	0.0013
Chemotherapy at recurrence	Better PRS	0.69 (0.54–0.92)	0.005

Abstract conclusion (verbatim)

"PM is frequently associated with local recurrence. Repeat surgical resection is feasible and can achieve good local control in selected cases."

How Does P/D Recurrence Differ From EPP Recurrence?

P/D is a parietal and visceral pleurectomy to remove all gross tumor while preserving the lung; extended P/D also resects the diaphragm and/or pericardium as needed. The goal is macroscopic complete resection, which the Paajanen paper classifies as an R1 resection. After P/D, 85% of patients who recurred had local recurrence.

A 94-patient Italian (Padova) comparative recurrence analysis by Bellini and colleagues, reporting separate first-relapse patterns for P/D (N=45) and EPP (N=49) groups, found local-only relapse rates of 42.2% (P/D) versus 16.3% (EPP) and combined local+distant rates of 48.9% versus 36.7%, mirroring the Brigham pattern. A Japanese single-center series by Nakamura and colleagues of 90 P/D patients reported 68.4% local, 10.5% distant, and 21.1% local+distant recurrences among 57 patients who relapsed. The Brigham EPP comparison cohort had contralateral chest recurrence in 38% (vs. 18% after P/D) and abdominal recurrence in 54% (vs. 24% after P/D).

For comparison of the operations themselves, see Pleurectomy/Decortication and Extrapleural Pneumonectomy. For the MARS2 trial controversy on whether extended P/D produces a net survival benefit, see MARS Trial and the MARS2 results published by Lim and colleagues in Lancet Respiratory Medicine 2024.

What Are the Predictors of Recurrence After P/D?

Histologic subtype dominates

In the Paajanen cohort, histologic subtype was independently associated with both disease-free interval and post-recurrence survival.

Epithelioid mesothelioma (63% of the Paajanen cohort) is independently associated with longer DFI (HR 0.62 vs. biphasic, P<0.001) and better PRS (HR 0.62 vs. biphasic, P<0.001). Epithelioid tumors recur later and predominantly locally.

Sarcomatoid mesothelioma (6% of the Paajanen cohort) is independently associated with worse PRS (HR 1.81 vs. biphasic, P=0.021) and more frequent distant spread (P<0.001). Among sarcomatoid patients, 76% experienced early recurrence (DFI < 9.8 months).

Biphasic mesothelioma (31% of the Paajanen cohort) is the reference group for these comparisons.

BAP1 (BRCA1-Associated Protein-1)

The 2016 comprehensive genomic analysis of 216 pleural mesothelioma tumors by Bueno and colleagues (Nature Genetics) found BAP1 among the significantly mutated genes. A 2023 review cites a cataloguing of 980 pleural mesothelioma samples in which 44% had BAP1 alterations and 49% had CDKN2A alterations.

Testa and colleagues reported germline BAP1 mutations in two families with a high incidence of mesothelioma in Nature Genetics in 2011. Mesothelioma patients with germline BAP1 mutations show an approximately 7-fold improved long-term survival compared with sporadic mesothelioma, with 5-year survival of 47% versus 6.7% in Surveillance, Epidemiology, and End Results (SEER) Program controls (Baumann et al., Carcinogenesis 2015).

CDKN2A (p16/INK4a) homozygous deletion

A 2023 review states that there is strong evidence that homozygous loss of cyclin-dependent kinase inhibitor 2A (CDKN2A) is a significant independent adverse prognostic factor. The frequent alteration of CDKN2A, CDKN2B, and methylthioadenosine phosphorylase (MTAP) reflects their co-location on chromosome 9p21.

Intraoperative heated chemotherapy (IOHC / HITHOC)

Intraoperative heated chemotherapy — heated cisplatin at 175 milligrams per square meter (mg/m²) at the Brigham — was administered in 80% of the Paajanen cohort (N=349) and was independently associated with both longer DFI (HR 0.60, P<0.001) and better PRS (HR 0.56, P<0.001). A National Cancer Database analysis of 1,632 patients undergoing radical surgery confirmed HITHOC's overall survival advantage (HR 0.72, P=0.004 in propensity-matched radical surgery subgroup).

For more on the genomic landscape, see BAP1 and Mesothelioma and Genetic Testing for Mesothelioma.

How Are Patients Monitored for Recurrence After P/D?

Imaging surveillance

The U.S. National Comprehensive Cancer Network (NCCN) Guidelines for Mesothelioma: Pleural (Version 3.2026) include supportive-care and survivorship recommendations. The European Respiratory Society (ERS) / European Society of Thoracic Surgeons (ESTS) / European Association for Cardio-Thoracic Surgery (EACTS) / European Society for Radiotherapy and Oncology (ESTRO) 2020 guidelines identify performance status, histological subtype, and tumour volume as the main prognostic factors of clinical importance in routine management.

In the Paajanen 2026 dataset, recurrence was detected by CT in 51% of cases, by PET-CT in 45%, by MRI in 2%, by physical examination in 1%, and by exploratory surgery in 2%, with pathologic or cytologic confirmation obtained in 42% of cases.

Modified RECIST (mRECIST)

Standard World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumours (RECIST) criteria do not apply to pleural mesothelioma because of its non-spherical, rind-like growth pattern. Byrne and Nowak developed the modified RECIST (mRECIST) system, published in Annals of Oncology 2004: tumor thickness perpendicular to the chest wall or mediastinum is measured at two positions at three separate levels on thoracic CT, creating a six-point unidimensional sum. A 2018 revision, mRECIST 1.1, published by Armato and Nowak in the Journal of Thoracic Oncology, addresses practical issues including the definitions of minimally measurable disease and of measurable lesions.

Soluble mesothelin-related peptides (SMRP / MESOMARK)

SMRP — the Mesomark® assay — is described in a 2021 pilot study as the only FDA-approved biomarker for diagnosis of pleural mesothelioma and the most used for monitoring treatment; the study notes its poor performance as a screening test because of low sensitivity.

Emerging: circulating tumor DNA (ctDNA)

A perioperative ctDNA study in resectable pleural mesothelioma was published by the Johns Hopkins Kimmel Cancer Center team in Nature Medicine. The phase 2 trial combined neoadjuvant immune checkpoint blockade with ultra-sensitive tumor-informed whole-genome sequencing of cell-free DNA to detect minimal residual disease. Patients with undetectable ctDNA at cycle 3 or before surgery had longer progression-free survival (P=0.027 and P=0.0059). Overall survival was numerically longer with undetectable pre-surgery ctDNA but not statistically significant (median 27.73 vs. 15.47 months, P=0.16). The significant overall-survival result was narrower: among patients who underwent resection, those with a ≥95% reduction in cell-free DNA tumor fraction before surgery or undetectable ctDNA throughout neoadjuvant therapy had longer overall survival (median 27.73 vs. 14.95 months, P=0.031).

How Is Recurrence Treated After P/D?

Local recurrence — salvage surgery

Re-resection was independently associated with longer post-recurrence survival in the Paajanen 2026 dataset (HR 0.46, 95% CI 0.29–0.74, P=0.0013 for PRS, in the distant ± local subgroup). A systematic review by Bellini and colleagues of second surgery for recurrent pleural mesothelioma — six studies of 365 relapsed patients, 89 of whom had a second operation — reported median PRS after recurrence surgery ranging from 14.5 to 23.5 months, with chest wall resection the most common procedure (70.8%). In the Paajanen cohort, recurrence surgery was done in 33% of patients with only local recurrence and 13% of those with distant ± local recurrence, and the authors note that patient selection is crucial.

For the operative considerations and the natural history of the index P/D operation, see Pleurectomy/Decortication.

Hemithoracic intensity-modulated radiation therapy (IMRT)

Hemithoracic pleural IMRT after P/D was evaluated by Chance and colleagues in 24 patients treated to 45 Gray (Gy) to the involved hemithorax, compared with 24 matched patients who had received EPP-IMRT. The IMPRINT phase II study by Rimner and colleagues evaluated hemithoracic IMRT as part of multimodality P/D-based treatment (median progression-free survival 12.4 months, median overall survival 23.7 months).

Photodynamic therapy (PDT)

The Penn Medicine team led by Joseph Friedberg has studied intraoperative PDT combined with lung-sparing radical pleurectomy. The 38-patient Penn series reported median survival of 31.7 months for all patients and 41.2 months for the 31 patients with epithelial subtypes.

Systemic therapy for distant or distant+local recurrence

CheckMate 743 (nivolumab + ipilimumab)

Baas, Scherpereel, and colleagues reported the phase III CheckMate 743 trial in Lancet 2021: N=605 unresectable mesothelioma patients; first-line nivolumab plus ipilimumab vs. platinum + pemetrexed chemotherapy. Median overall survival 18.1 vs. 14.1 months; HR 0.74; P=0.0020. Two-year overall survival 41% vs. 27%. CheckMate 743 enrolled only unresectable MPM patients without prior systemic therapy; its relevance to post-P/D recurrence is an extrapolation. Among Paajanen patients who received systemic therapy for distant ± local recurrence, median post-recurrence survival did not differ between chemotherapy (11.8 months) and immune checkpoint inhibitors (10.2 months; P=0.900).

MAPS — bevacizumab + cisplatin/pemetrexed

Zalcman and colleagues reported the phase III Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS) trial in Lancet 2016: N=448 unresectable MPM; bevacizumab 15 mg/kg every 21 days added to cisplatin/pemetrexed vs. cisplatin/pemetrexed alone. Median overall survival 18.8 vs. 16.1 months; HR 0.77; P=0.0167.

RAMES — ramucirumab + gemcitabine (second-line)

The phase II RAMES trial reported by Pinto, Zucali, and colleagues in Lancet Oncology compared gemcitabine plus ramucirumab vs. gemcitabine plus placebo in the second-line setting after first-line platinum-based chemotherapy. Median overall survival was 13.8 months with ramucirumab versus 7.5 months with placebo.

ATOMIC-Meso — pegargiminase (ADI-PEG 20)

Szlosarek and colleagues reported the ATOMIC-Meso phase II/III randomized clinical trial (NCT02709512) in JAMA Oncology. Pegargiminase (pegylated arginine deiminase 20, ADI-PEG 20) plus pemetrexed and platinum (cisplatin or carboplatin) vs. placebo plus the same chemotherapy in non-epithelioid mesothelioma, 60% of which was deficient in argininosuccinate synthetase 1 (ASS1) in the trial report. Results: median overall survival 9.3 vs. 7.7 months (HR for death 0.71) and median progression-free survival 6.2 vs. 5.6 months (HR 0.65), with 3- to 4-fold more patients alive at 36 months (11.9% vs. 3.3%).

KEYNOTE-028 — pembrolizumab in PD-L1-positive previously treated mesothelioma

Alley and colleagues reported the phase Ib KEYNOTE-028 mesothelioma cohort in Lancet Oncology 2017: N=25 programmed death-ligand 1 (PD-L1)-positive previously treated MPM patients; objective response rate 20%, median duration of response 12.0 months.

LUME-Meso (negative trial)

Scagliotti and colleagues reported the phase III LUME-Meso final results in Lancet Respiratory Medicine 2019: nintedanib + pemetrexed/cisplatin vs. placebo + pemetrexed/cisplatin in N=458 chemotherapy-naïve epithelioid mesothelioma patients. The primary progression-free survival endpoint was not met (median 6.8 vs. 7.0 months).

Intracavitary CAR-T cell therapy (investigational)

Adusumilli and the Memorial Sloan Kettering (MSK) team have led intrapleural delivery of cluster of differentiation 28 (CD28)-costimulated mesothelin-targeted chimeric antigen receptor (CAR) T-cells. The phase I trial (ClinicalTrials.gov identifier NCT02414269): 27 patients (25 with MPM) received 0.3 million to 60 million CAR-T cells per kilogram intrapleurally. No patients experienced cytokine release syndrome above grade 2, neurotoxicity above grade 2, or on-target, off-tumor toxicity; six patients had grade 3 clinical adverse events. CAR-T cells were detected in peripheral blood for more than 100 days in 39% of patients. Among 18 patients with MPM who also received pembrolizumab, median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival 83%), and the best overall response was partial response in 2 of 16 with measurable disease.

The cells were delivered through a pleural catheter or by interventional radiology–guided injection. The evidence is from a phase I, single-center trial.

Intrapleural gene therapy

Sterman and colleagues at the University of Pennsylvania (now New York University Langone) have led intrapleural adenoviral-mediated interferon gene transfer trials. The pilot/phase I/II of adenoviral interferon alpha-2b (Ad.IFN-α2b) plus celecoxib plus chemotherapy in 40 unresectable mesothelioma patients showed an overall response rate of 25% and a disease control rate of 88%, with overall survival significantly higher than historical controls in the second-line group.

When Should Goals-of-Care and Palliative Care Conversations Happen?

In the Paajanen 2026 multivariable model, shorter post-recurrence survival was independently associated with ECOG performance status >1 at recurrence (HR 2.01, P<0.001), original TNM stage IV (HR 5.00, P=0.010) or stage III (HR 1.49, P=0.003), sarcomatoid histology (HR 1.81, P=0.021), and multifocal recurrence (HR 1.74, P=0.024). These features can help frame goals-of-care conversations at recurrence.

Symptomatic re-accumulation of pleural effusion after P/D may be managed with indwelling pleural catheter (IPC) placement. The Second Therapeutic Intervention in Malignant Effusion Trial (TIME2), reported by Davies and colleagues in Journal of the American Medical Association (JAMA) 2012, was a randomized controlled trial (N=106) comparing IPC vs. chest tube plus talc pleurodesis for symptomatic malignant pleural effusion: both strategies were equally effective for dyspnea relief, with IPC avoiding hospitalization but requiring home drain management.

For the broader symptom management framework, see Palliative Care for Mesothelioma.

What Should Patients Know Before Choosing P/D?

Points patients may want to discuss with their surgical team before choosing P/D:

1. Long-term recurrence is highly probable — 79% of evaluable Brigham P/D patients developed verified recurrence during a median 88.5-month follow-up. Among patients who recurred, 39% were recurrence-free at 1 year and 9% at 3 years.
2. The median DFI in the Paajanen recurrent cohort is 9.8 months (95% CI 9.0–10.7).
3. Histology defines trajectory — epithelioid patients recur later, predominantly locally, and have better PRS; sarcomatoid patients recur early (76% within 9.8 months), distantly, and have the worst PRS.
4. IOHC was independently associated with longer DFI and PRS in the Paajanen cohort; ask whether the center offers it.
5. Some patients are candidates for salvage surgery — in the Paajanen dataset, patients with distant ± local recurrence who were treated initially with surgery had the longest median post-recurrence survival on univariable analysis (26.6 months).
6. In comparative series, recurrence after P/D was more often local, and less often contralateral or abdominal, than after EPP.
7. The phase III MARS2 trial reported by Lim and colleagues in Lancet Respiratory Medicine 2024 found that extended P/D was associated with shorter 2-year survival than chemotherapy alone (median overall survival 19.3 vs. 24.8 months; restricted mean survival difference −1.9 months, 95% CI −3.4 to −0.3, P=0.019), with more serious adverse events.

Frequently Asked Questions

How likely is recurrence after pleurectomy/decortication?

In the 2026 Brigham analysis of 551 evaluable P/D patients, 436 (79%) developed verified recurrence during a median follow-up of 88.5 months. The 1-year recurrence-free survival was 39% and the 3-year was 9%, meaning that most P/D patients should expect some recurrence in long-term follow-up.

Where does mesothelioma recur most often after P/D?

The Paajanen 2026 data show that 85% of recurrences are local (the same hemithorax that was operated on), with the residual thoracic cavity (72%), ipsilateral chest wall (55%), and diaphragm (22%) being the leading anatomical sites. Distant spread — most commonly to the abdomen (24%) or contralateral chest (18%) — is less common after P/D than after extrapleural pneumonectomy.

Does salvage surgery for recurrence work?

In the Paajanen 2026 dataset, recurrence surgery was independently associated with improved post-recurrence survival in patients with distant ± local recurrences (HR 0.46, 95% CI 0.29–0.74, P=0.0013). Surgery was performed in only 33% of patients with local-only recurrence and 13% of those with distant ± local recurrence, indicating that careful selection is required: the authors note that patient selection is crucial.

What is the role of intraoperative heated chemotherapy (IOHC)?

IOHC (also called HITHOC) — heated cisplatin at 175 mg/m² at the Brigham — was administered in 80% of the Paajanen cohort. On multivariable analysis it was independently associated with longer disease-free interval (HR 0.60, P<0.001) and post-recurrence survival (HR 0.56, P<0.001).

Does the BAP1 gene affect recurrence after P/D?

BAP1 alterations were found in 44% of 980 pleural mesothelioma samples in a cataloguing cited by a 2023 review. Mesothelioma patients with germline BAP1 mutations had 7-fold improved long-term survival in a 2015 analysis (5-year survival 47% vs. 6.7% in SEER controls).

What new approaches are being investigated for recurrent mesothelioma?

Three avenues are advancing. First, perioperative immune checkpoint blockade combined with circulating tumor DNA (ctDNA) monitoring — the Johns Hopkins phase 2 trial published in Nature Medicine showed that undetectable ctDNA during neoadjuvant immunotherapy was associated with longer progression-free survival. Second, intrapleural mesothelin-targeted CAR T-cell therapy (MSK NCT02414269), delivered into the pleural space. Third, pegargiminase plus chemotherapy in non-epithelioid disease (ATOMIC-Meso), with 11.9% vs. 3.3% of patients alive at 36 months.

Related Resources at WikiMesothelioma

• Pleurectomy/Decortication — the operation itself: indications, technique, perioperative outcomes.
• Extrapleural Pneumonectomy — the alternative operation and its distinct recurrence geography.
• MARS Trial — the MARS and MARS2 trials and their implications for surgery selection.
• BAP1 and Mesothelioma — germline and somatic BAP1 alterations.
• Immunotherapy for Mesothelioma — CheckMate 743 and second-line ICI options.
• Chemotherapy for Mesothelioma — pemetrexed/cisplatin standard-of-care and second-line options.
• Radiation Therapy for Mesothelioma — hemithoracic IMRT and SBRT for focal recurrences.
• Clinical Trials Mesothelioma — finding active trials at recurrence.
• Palliative Care for Mesothelioma — symptom management framework and early integration.
• Mesothelioma Prognosis — overall survival benchmarks across histologies.

External Links

• Danziger & De Llano — mesothelioma and asbestos-related lung disease attorneys, covering asbestos bankruptcy trust funds, civil personal injury and wrongful death lawsuits, and VA disability claims for veterans.
• Mesothelioma Lawyer Center — patient and family resources on diagnosis, treatment, clinical trials, and legal options.
• Mesothelioma.net — comprehensive information on pleural mesothelioma diagnostic workup, treatment, and prognosis.