Prognostic Features of Long-term Survivors After Surgical Management of Malignant Pleural Mesothelioma

doi:10.1016/j.athoracsur.2009.01.026

The Annals of Thoracic Surgery

Volume 87, Issue 5, May 2009, Pages 1552-1556

https://doi.org/10.1016/j.athoracsur.2009.01.026 Get rights and content

Background

The primary aim of this study was to evaluate prognostic features of long-term survivors with pleural mesothelioma.

Methods

Overall survival outcome was analyzed in 456 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP), pleurectomy/decortications, or pleurodesis/biopsy with at least 18 months of follow-up. Prospectively collected clinicopathologic and treatment data were assessed for their correlations with actual 18-month survivors in both univariate and multivariate analyses.

Results

The actual 18-month survival was 28%. Epithelial subtype was present in 185 patients (41%) and nonepithelial subtype in 183 (40%). Procedures were EPP in 59 patients (13%), pleurectomy/decortication in 250 (55%), and pleurodesis/biopsy in 147 (32%). Forty-two patients (9%) underwent positron emission tomography (PET) scanning. Forty patients (9%) received adjuvant radiotherapy and 45 (10%) received postoperative pemetrexed combination chemotherapy. In univariate analysis, age 65 years or younger (p < 0.001), malignant pleural effusion (p = 0.041), epithelial subtype (p < 0.001), EPP (p < 0.001), PET scan (p = 0.012), adjuvant radiotherapy (p = 0.042), and postoperative pemetrexed combination chemotherapy (p = 0.035) were strongly associated with 18-month survivors. In multivariate analysis, epithelial histopathologic subtype (p < 0.001) and EPP (p < 0.001) were independently associated with 18-month survivors.

Conclusions

The actual 18-month survival was 28% in 456 pleural mesothelioma patients who underwent operation. Epithelial histologic subtype and EPP were identified as independent predictors for 18-month survivors.

Section snippets

Patients

Between March 1984 and December 2007, 540 patients with MPM were surgically managed at the Royal Prince Alfred Hospital in Sydney, Australia. Informed consent was obtained from all patients before operation. Patient characteristics and clinical data were recorded in a prospective electronic database. Eligible patients were those with a tissue diagnosis of MPM confirmed by immunohistochemistry. These patients underwent extensive preoperative investigations, which included a review of all prior

Results

A total of 456 consecutive patients who underwent surgical management of MPM were prospectively observed for at least 18 months. All patients were monitored until December 2007 or until death, and the median follow-up period was 32 months (range, 18 to 115 months). At the time of the last follow-up, 20 patients (4.4%) remained alive. The actual 18-month survival was 28%, with an estimated 3-year survival of 10%. Perioperatively, 18 patients (4%) died, including 4 who underwent EPP.

Comment

This current study on a prospectively collected cohort of 456 patients who underwent surgical management of MPM revealed an absolute 18-month survival of 28%. It also showed that epithelial subtype and EPP were the favorable variables independently associated with 18-month survivors. These survival results could serve as more precise reference data for future studies on the prognosis after surgical treatments for MPM.

Several studies have consistently demonstrated the significance of epithelial

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Cited by (25)

Histopathological features of epithelioid malignant pleural mesotheliomas in patients with extended survival
2020, Human Pathology
Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, wherein the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. To study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival more than five years (LTSs) and compared the findings with 84 tumors from a reference group (RG) with average survival. We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34, 90%) and a tubulopapillary growth pattern (n = 30, 70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49, 61%) and solid growth pattern (n = 59, 70%) were more frequent in the RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (P < 0.001) and the presence of necrosis (P = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (P < 0.001) and presence of exophytic polypoid growth (P = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.
Amount of Epithelioid Differentiation Is a Predictor of Survival in Malignant Pleural Mesothelioma
2017, Annals of Thoracic Surgery
Citation Excerpt :
The absence of these prognostic factors has commonly been used to exclude patients from radical surgical treatment. Therefore, many patients with nonepithelioid histology are not considered for such therapy, even though surgical intervention has been observed to prolong survival and improve quality of life [19]. Our results support that a better stratification of biphasic patients should be pursued.
Macroscopic complete surgical resection with adjuvant chemotherapy can provide a survival advantage in patients with malignant pleural mesothelioma (MPM). Patients with nonepithelioid histology are largely excluded from such radical operations even though they might benefit. The degree of epithelioid differentiation varies in biphasic histology. We report the outcomes of pleurectomy and decortication and the effect of epithelioid differentiation on overall survival of patients with MPM.
This report is based on the outcomes of 144 patients who underwent pleurectomy and decortication at a single institution between 2008 and 2015. The variables assessed were age, gender, histology, and pathologic T and N stage. No patients with pure sarcomatoid histology were included. Two independent pathologists estimated the percentage of epithelioid histology. A Cox regression model was used to identify significant predictors of survival. The Kaplan-Meier method was used to summarize overall and subgroup survival.
Included were 116 men and 28 women with a median age of 69 years (range, 43 to 88 years). The 2-year survival from pleurectomy and decortication was 20%. Median survival overall was 13.34 months and was 20.1 months for the 100% epithelioid subgroup (n = 77), 11.8 months for the 51% to 99% epithelioid subgroup (n = 39), and 6.62 months for the less than 50% epithelioid subgroup (n = 28). The amount of epithelioid differentiation was a significant predictor of survival (p < 0.001). Differences in survival based on the T, but N stage, were not statistically significant.
The percentage of epithelioid differentiation is an independent predictor of survival in MPM and should be taken into careful consideration when recommending surgical treatment for patients with biphasic MPM.
Current Treatment of Mesothelioma: Extrapleural Pneumonectomy Versus Pleurectomy/Decortication
2016, Thoracic Surgery Clinics
Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma
2015, Annals of Thoracic Surgery
This comprehensive meta-analysis was conducted to answer the question as to which procedure, pleurectomy decortication (P/D) or extrapleural pneumonectomy (EPP) is more beneficial to malignant pleural mesothelioma patients’ outcome.
Original research studies that evaluated long-term outcomes of P/D versus EPP were identified, from January 1990 to January 2014. The combined percent perioperative and 2-year mortality, and median survival were calculated according to both a fixed and a random effect model. The Q statistics and I² statistic were used to test for heterogeneity between the studies.
There were 24 distinct data sets, for a total of 1,512 patients treated with P/D, and 1,391 treated with EPP. There was a significantly higher proportion of short-term deaths in the EPP group versus the P/D group (percent mortality meta estimate; 4.5% vs 1.7%; p < 0.05). There was no statistically significant difference in 2-year mortality between the 2 groups, but there was significant heterogeneity.
The reanalysis of the large number of studies comparing P/D to EPP suggests that P/D is associated with a 2 ½-fold lower short-term mortality (perioperatively and within 30 days) than EPP. Pleurectomy decortication should therefore be preferred when technically feasible.
Supplementary prognostic variables for pleural mesothelioma: A report from the IASLC staging committee
2014, Journal of Thoracic Oncology
The staging system for malignant pleural mesothelioma is controversial. To revise this system, the International Association for the Study of Lung Cancer Staging Committee developed an international database. This report analyzes prognostic variables in a surgical population, which are supplementary to previously published CORE variables (stage, histology, sex, age, and type of procedure).
Supplementary prognostic variables were studied in three scenarios: (1) all data available, that is, patient pathologically staged and other CORE variables available (2) only clinical staging available along with CORE variables, and (3) only age, sex, histology, and laboratory parameters are known. Survival was analyzed by Kaplan–Meier, prognostic factors by log rank and stepwise Cox regression modeling after elimination of nonsignificant variables. p value less than 0.05 was significant.
A total of 2141 patients with best tumor, node, metastasis (TNM) stages (pathologic with/without clinical staging) had nonmissing age, sex, histology, and type of surgical procedure. Three prognostic models were defined. Scenario A (all parameters): best pathologic stage, histology, sex, age, type of surgery, adjuvant treatment, white blood cell count (WBC) (≥15.5 or not), and platelets (≥400 k or not) (n = 550). Scenario B (no surgical staging): clinical stage, histology, sex, age, type of surgery, adjuvant treatment, WBC, hemoglobin (<14.6 or not), and platelets (n = 627). Scenario C (limited data): histology, sex, age, WBC, hemoglobin, and platelets (n = 906).
Refinement of these models could define not only the appropriate patient preoperatively for best outcomes after cytoreductive surgery but also stratify surgically treated patients after clinical and pathologic staging who do or do not receive adjuvant therapy.
A systematic review of extrapleural pneumonectomy for malignant pleural mesothelioma
2010, Journal of Thoracic Oncology
Citation Excerpt :
However, the practice of routine mediastinoscopy and exclusion of patients with mediastinoscopy-positive N2 disease from undergoing EPP remains controversial.25 Median follow-up of all the studies in the current systematic review ranged from 8.8 to 31.2 months but varied greatly in the form and frequency of radiologic follow-up.6–63 Partly because of this, recurrence rates and disease-free survival should be interpreted with caution.
The primary objective of the present systematic review was to evaluate the safety and efficacy of extrapleural pneumonectomy (EPP) for patients with malignant pleural mesothelioma.
A systematic review of relevant studies identified through five online search databases was performed. Two reviewers independently appraised each study.
Thirty-four of 58 relevant studies from 26 institutions containing the most updated data were evaluated for survival and perioperative outcomes after EPP. The median overall survival varied from 9.4 to 27.5 months, and 1-, 2-, and 5-year survival rates ranged from 36 to 83%, 5 to 59%, and 0 to 24%, respectively. Overall perioperative mortality rates ranged from 0 to 11.8%, and the perioperative morbidity rates ranged from 22 to 82%. Quality of life assessments from three studies reported improvements in nearly all domains at 3 months postoperatively. Patients who underwent trimodality therapy involving EPP and adjuvant chemoradiotherapy had a median overall survival of 13 to 23.9 months.
The current evidence suggests that selected patients with malignant pleural mesothelioma may benefit from EPP, especially when combined with neoadjuvant or adjuvant chemotherapy and adjuvant radiotherapy.

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Original articleGeneral thoracicPrognostic Features of Long-term Survivors After Surgical Management of Malignant Pleural Mesothelioma

Background

Methods

Results

Conclusions

Section snippets

Patients

Results

Comment

Lancet

J Thorac Cardiovasc Surg

Int J Radiat Oncol Biol Phys

Ann Oncol

Lung Cancer

J Thorac Oncol

Original article
General thoracic
Prognostic Features of Long-term Survivors After Surgical Management of Malignant Pleural Mesothelioma