• Maziak DE, Gagliardi A, Haynes AE, Mackay JA, Evans WK, Lung Cancer Disease Site Group. Surgical management of malignant pleural mesothelioma: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2005 Aug 9. Various p. (Evidence-based series; no. 7-14-2). [43 references]

Malignant pleural mesothelioma

Assessment of Therapeutic Effectiveness
Treatment

Oncology
Pulmonary Medicine
Surgery

Physicians

To evaluate the role of surgery (pleurectomy or extrapleural pneumonectomy) in the treatment of adults with malignant pleural mesothelioma

Adult patients with diffuse or localized malignant pleural mesothelioma

1. Pleurectomy
2. Extrapleural pneumonectomy

• Operative morbidity and mortality
• Recurrence rates
• Survival rates

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

18 studies (eight non-controlled prospective, of which only four were comparative, and 10 retrospective case series) involving both pleurectomy (PL) and extrapleural pneumonectomy (EPP); four studies (two retrospective case series and two including both retrospective and prospective case-series data) examining EPP only; and four prospective non-comparative studies plus eight retrospective case series studies examining PL only were identified.

Expert Consensus (Committee)

Not applicable

Systematic Review with Evidence Tables

A statistical synthesis of the evidence was not conducted because no randomized trials involving surgical treatment for mesothelioma were identified and the prospective and retrospective studies included a variety of adjuvant treatments.

Expert Consensus

The Program in Evidence-based Care (PEBC) reports consist of a comprehensive systematic review of the clinical evidence on a specific cancer care topic, an interpretation of and consensus agreement on that evidence by Disease Site Groups and Guideline Development Groups, the resulting clinical recommendations and an external review by Ontario clinicians in the province for whom the topic is relevant.

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

A draft evidence summary version of this series was reviewed by Ontario practitioners. Any changes made to the report as a result of practitioner feedback are described in the original report. Practitioner feedback was obtained through a mailed survey of 111 practitioners in Ontario (31 surgeons, 36 medical oncologists, 23 radiation oncologists, 20 respirologists, and 1 hematologist). The survey consisted of items evaluating the methods, results, and interpretive summary. Written comments were invited. The practitioner feedback survey was mailed out on June 5, 2003. Follow up reminders were sent out at two weeks (postcard) and four weeks (complete package mailed again). The Lung Disease Site Group (DSG) reviewed the results of the survey.

The evidence summary report was circulated to members of the Practice Guidelines Coordinating Committee (PGCC) for review and approval. Eight of thirteen members of the PGCC returned ballots. Three PGCC members approved the evidence-based series report as written, and five members approved the report conditional on the Lung Disease Site Group addressing specific concerns.

Because of the lack of sufficient high-quality evidence on the surgical management of mesothelioma, the Lung Cancer Disease Site Group opinion is that:

• The role of surgery in the management of malignant pleural mesothelioma cannot be precisely defined. Specifically, the lack of randomised controlled clinical trials makes it impossible to determine whether the use of extrapleural pneumonectomy or pleurectomy improves the survival of patients with malignant pleural mesothelioma or effectively palliates the symptoms of the disease.
• In patients who undergo surgery, combined with chemotherapy and/or radiotherapy, multivariate analysis shows that longer survival is associated with small, epithelial-type, node-negative pleural mesotheliomas.
• This Evidence Summary is confined to the surgical management of malignant pleural mesothelioma. Please refer to Evidence Summary Report #7-14-1 and the Evidence-based Series #7-14-3, to be released shortly, for opinions on the use of systemic therapy and radiation therapy in this disease.
• There is a need for future studies of the role of surgery in the treatment of mesothelioma to include evaluations of quality of life.

None provided

The recommendations are supported by non-controlled prospective studies (including comparative studies), and retrospective case series.

• Three prospective studies that involved both extrapleural pneumonectomy and pleurectomy, along with adjuvant chemotherapy, radiotherapy, or photodynamic therapy, directly compared the two surgical treatments. Longer survival was reported with pleurectomy in all three studies; however, caution must be exercised in interpreting those comparisons because the patients were not randomly allocated to the surgical procedure, and thus survival outcomes may have been influenced by pre-surgery patient characteristics.
• Median survival was reported in four non-controlled, non-comparative prospective studies examining pleurectomy combined with intrapleural chemotherapy (13 to 27 patients per study) and was 9 months, 11.5 months, and 18.3 months in those four studies. Three of those studies also reported two-year survival (12% to 40%) and local recurrence rates (75% to 80%) for this combined-modality approach.
• Seven non-controlled prospective and five retrospective case-series studies explored the effect of prognostic factors on survival using multivariate analyses. Of the prospective studies, three were non-comparative studies, one had comparison groups that were not of interest and three had relevant comparison groups but they assigned patients based on disease characteristics. Seven of those studies included treatment type as a potential prognostic variable; three specifically examined the type of surgery. The factors most commonly associated with longer survival included epithelial-type mesothelioma (five studies), earlier stage of disease (five studies), use of adjuvant or combined modality treatment (five studies), and good performance status (four studies). Factors adversely associated with survival included high pre-treatment platelet count (three studies), positive nodal status (two studies), larger preoperative tumour volume (two studies), and larger postoperative residual tumour volume (one study). The type of surgery did not have a significant impact on survival in any of the three studies that examined that association.
• Two prospective and two retrospective non-comparative surgical studies, three including adjuvant chemotherapy or radiotherapy, reported the palliation of signs or symptoms of malignant mesothelioma following treatment. Pleural fluid control improved in 98% of 50 patients and 96% of 54 patients; the recurrence of pleural effusion was prevented in 80% of 20 patients; dyspnea improved in 47% of 20 patients and 100% of 37 patients; and pain improved in 21% of 19 patients and 85% of 71 patients. However, none of the studies described the methods of symptom assessment in detail.

• Operative mortality for both types of surgery was reported in two non-controlled, comparative prospective studies and in two non-controlled, non-comparative prospective studies. Operative mortality ranged from 0% (two studies) to 3% (one study) following pleurectomy and from 4% to 14% following extrapleural pneumonectomy. In one study, operative morbidity was 5% following pleurectomy and 18% to 36% following extrapleural pneumonectomy; in a second study, the rates were 39% and 71%, respectively.
• Operative mortality was similar in two non-controlled, non-comparative prospective studies examining pleurectomy combined with intrapleural chemotherapy (one patient death in each study), although morbidity varied between 8% and 44% and included hemorrhage, renal toxicity, cardiac events, air leaks, and wound infections.

Care has been taken in the preparation of the information contained in this document. Nonetheless, any person seeking to apply or consult the evidence-based series is expected to use independent medical judgment in the context of individual clinical circumstances or seek out the supervision of a qualified clinician. Cancer Care Ontario makes no representation or guarantees of any kind whatsoever regarding their content or use or application and disclaims any for their application or use in any way.

An implementation strategy was not provided.

Living with Illness

Effectiveness

• Maziak DE, Gagliardi A, Haynes AE, Mackay JA, Evans WK, Lung Cancer Disease Site Group. Surgical management of malignant pleural mesothelioma: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2005 Aug 9. Various p. (Evidence-based series; no. 7-14-2). [43 references]

Not applicable: The guideline was not adapted from another source.

2005 Aug 9

Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]

The Program in Evidence-based Care (PEBC) is a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Cancer Care Ontario
Ontario Ministry of Health and Long-Term Care

Provincial Lung Cancer Disease Site Group

The members of the Lung Disease Site Group (DSG) disclosed potential conflicts of interest relating to the topic of this evidence-based series. No potential conflicts were declared.

None available

This summary was completed by ECRI on January 24, 2006. The information was verified by the guideline developer on February 23, 2006.