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Information from PDQ -- for Health Professionals
Malignant mesothelioma
208/01071
** GENERAL INFORMATION **
Prognosis in this disease is difficult to assess consistently because there
is great variability in the time before diagnosis and the rate of disease
progression. Various surgical procedures may be possible in selected patients,
providing long-term survival without cure. In large retrospective series of
pleural mesothelioma patients, important prognostic factors were found to be
stage, age, performance status, and histology.[1,2] For patients treated with
aggressive surgical approaches, factors associated with improved long-term
survival include epithelial histology, negative lymph nodes, and negative
surgical margins.[3,4] For those patients treated with aggressive surgical
approaches, nodal status is an important prognostic factor.[3] Median survival
for malignant local pleural disease has been reported as 16 months and
extensive disease as 5 months. In some instances the tumor grows through the
diaphragm making the site of origin difficult to assess. Cautious
interpretation of treatment results in this disease is imperative because of
the selection differences among series. Effusions, both pleural and
peritoneal, represent major symptomatic problems for at least two thirds of the
patients. A history of asbestos exposure is reported in about 70% to 80% of
all cases of mesothelioma.[1,5,6]
References:
1. Ruffie P, Feld R, Minkin S, et al.: Diffuse malignant mesothelioma of the
pleura in Ontario and Quebec: a retrospective study of 332 patients.
Journal of Clinical Oncology 7(8): 1157-1168, 1989.
2. Tammilehto L, Maasilta P, Kostiainen S, et al.: Diagnosis and prognostic
factors in malignant pleural mesothelioma: a retrospective analysis of
sixty-five patients. Respiration 59: 129-135, 1992.
3. Sugarbaker DJ, Strauss GM, Lynch TJ, et al.: Node status has prognostic
significance in the multimodality therapy of diffuse, malignant
mesothelioma. Journal of Clinical Oncology 11(6): 1172-1178, 1993.
4. Sugarbaker D, Harpole D, Healey E, et al.: Multimodality treatment of
malignant pleural mesothelioma (MPM): results in 94 consecutive
patients. Proceedings of the American Society of Clinical Oncology 14:
A-1083, 356, 1995.
5. Chailleux E, Dabouis G, Pioche D, et al.: Prognostic factors in diffuse
malignant pleural mesothelioma: a study of 167 patients. Chest 93(1):
159-162, 1988.
6. Adams VI, Unni KK, Muhm JR, et al.: Diffuse malignant mesothelioma of
pleura: diagnosis and survival in 92 cases. Cancer 58(7): 1540-1551,
1986.
** CELLULAR CLASSIFICATION **
Histologically, these tumors are composed of fibrous or epithelial elements or
both. The epithelial form occasionally causes confusion with peripheral
anaplastic lung carcinomas or metastatic carcinomas. Attempts at diagnosis by
cytology or needle biopsy of the pleura are often unsuccessful. It can be
especially difficult to differentiate mesothelioma from adenocarcinoma on small
tissue specimens. Thoracoscopy can be valuable in obtaining adequate tissue
specimens for diagnostic purposes.[1] Examination of the gross tumor at
surgery and use of special stains or electron microscopy can often help. The
special stains reported to be most useful include periodic acid-Schiff
diastase, hyaluronic acid, mucicarmine, CEA, and Leu M1.[2] Histologic
appearance appears to be of prognostic value, with most clinical studies
showing that epithelial mesotheliomas have a better prognosis than sarcomatous
or mixed histology mesotheliomas.[2-4]
References:
1. Boutin C, Rey F: Thoracoscopy in pleural malignant mesothelioma: a
prospective study of 188 consecutive patients - part 1: diagnosis.
Cancer 72(2): 389-393, 1993.
2. Chahinian AP: Malignant Mesothelioma. In: Holland JF, Frei E, Bast RC,
et al., eds.: Cancer Medicine. Philadelphia: Lea & Febiger, 3rd ed.,
1993, pp: 1337-1355.
3. Nauta RJ, Osteen RT, Antman KH, et al.: Clinical staging and the tendency
of malignant pleural mesotheliomas to remain localized. Annals of
Thoracic Surgery 34(1): 66-70, 1982.
4. Sugarbaker DJ, Strauss GM, Lynch TJ, et al.: Node status has prognostic
significance in the multimodality therapy of diffuse, malignant
mesothelioma. Journal of Clinical Oncology 11(6): 1172-1178, 1993.
** STAGE INFORMATION **
Patients with stage I disease have a significantly better prognosis than those
with more advanced stages. However, because of the relative rarity of this
disease, exact survival information based upon stage is limited.[1] A proposed
staging system based upon thoracic surgery principles and clinical data is
shown below.[2] It is a modification of the older system proposed by Butchart
et al.[3] Other staging systems that have been employed, including a proposed
new international TNM staging system, are summarized by the International
Mesothelioma Interest Group.[4]
Stage I: Disease confined within the capsule of the parietal pleura:
ipsilateral pleura, lung, pericardium, and diaphragm
Stage II: All of stage I with positive intrathoracic (N1 or N2) lymph nodes
Stage III: Local extension of disease into the following: chest wall or
mediastinum; heart or through the diaphragm, peritoneum; with or without
extrathoracic or contralateral (N3) lymph node involvement
Stage IV: Distant metastatic disease
--Localized malignant mesothelioma--
See description of stage I above.
--Advanced malignant mesothelioma--
See descriptions of stages II, III, and IV above.
For the purposes of the discussion of treatment in this summary, the disease is
categorized as either localized or advanced.
References:
1. Chahinian AP: Malignant Mesothelioma. In: Holland JF, Frei E, Bast RC,
et al., eds.: Cancer Medicine. Philadelphia: Lea & Febiger, 3rd ed.,
1993, pp: 1337-1355.
2. Sugarbaker DJ, Strauss GM, Lynch TJ, et al.: Node status has prognostic
significance in the multimodality therapy of diffuse, malignant
mesothelioma. Journal of Clinical Oncology 11(6): 1172-1178, 1993.
3. Butchart EG, Ashcroft T, Barnsley WC, et al.: Pleuropneumonectomy in the
management of diffuse malignant mesothelioma of the pleura: experience
with 29 patients. Thorax 31(1) 15-24, 1976.
4. Rusch VW: A proposed new international TNM staging system for malignant
pleural mesothelioma. Chest 108(4): 1122-1128, 1995.
** TREATMENT OPTION OVERVIEW **
Standard treatment for all but localized mesothelioma is generally not
curative. Although some patients will experience long-term survival with
aggressive treatment approaches, it remains unclear if overall survival has
been significantly altered by the different treatment modalities or by
combinations of modalities. Extrapleural pneumonectomy in selected patients
with early stage disease may improve recurrence-free survival, but its impact
on overall survival is unknown.[1] Pleurectomy and decortication can provide
palliative relief from symptomatic effusions, discomfort caused by tumor
burden, and pain caused by invasive tumor. Operative mortality from
pleurectomy/decortication is less than 2%,[2] while mortality from extrapleural
pneumonectomy has ranged from 6% to 30%.[1,3] The addition of radiation
therapy and/or chemotherapy following surgical intervention has not
demonstrated improved survival.[2] The use of radiation therapy in pleural
mesothelioma has been shown to alleviate pain in the majority of patients
treated. However, the duration of symptom control is short-lived.[4,5] Single
agent and combination chemotherapy have been evaluated in single and combined
modality studies. The most studied agent is doxorubicin, which has produced
partial responses in approximately 15% to 20% of patients studied.[6] Some
combination chemotherapy regimens have been reported to have higher response
rates in small phase II trials. However the toxicity reported is also higher
and there is no evidence that combination regimens result in longer survival or
longer control of symptoms.[6,7]. Recurrent pleural effusions may be treated
with pleural sclerosing procedures; however, failure rates are usually
secondary to the bulk of the tumor, which precludes pleural adhesion due to the
inability of the lung to fully expand.
The designations in PDQ that treatments are "standard" or "under clinical
evaluation" are not to be used as a basis for reimbursement determinations.
References:
1. Rusch VW, Piantadosi SP, Holmes EC: The role of extrapleural
pneumonectomy in malignant pleural mesothelioma. Journal of Thoracic
and Cardiovascular Surgery 102(1): 1-9, 1991.
2. Rusch V, Saltz L, Venkatraman E, et al.: A phase II trial of
pleurectomy/decortication followed by intrapleural and systemic
chemotherapy for malignant pleural mesothelioma. Journal of Clinical
Oncology 12(6): 1156-1163, 1994.
3. Sugarbaker DJ, Mentzer SJ, DeCamp M, et al.: Extrapleural pneumonectomy
in the setting of a multimodality approach to malignant mesothelioma.
Chest 103(4, Suppl): 377s-381s, 1993.
4. Bissett D, Macbeth FR, Cram I: The role of palliative radiotherapy in
malignant mesothelioma. Clinical Oncology (Royal College of
Radiologists) 3(6): 315-317, 1991.
5. Ball DL, Cruickshank DG: The treatment of malignant mesothelioma of the
pleura: review of a 5-year experience, with special reference to
radiotherapy. American Journal of Clinical Oncology 13(1): 4-9, 1990.
6. Weissmann LB, Antman KH: Incidence, presentation and promising new
treatments for malignant mesothelioma. Oncology (Huntington NY) 3(1):
67-72, 1989.
7. Ong ST, Vogelzang NJ: Chemotherapy in malignant pleural mesothelioma: a
review. Journal of Clinical Oncology 14(3): 1007-1017, 1996.
** LOCALIZED MALIGNANT MESOTHELIOMA (STAGE I) **
Standard treatment options:[1]
1. Solitary mesotheliomas: Surgical resection en bloc including contiguous
structures to ensure wide disease-free margins. Sessile polypoid lesions
should be treated with surgical resection to ensure maximal potential for
cure.[2]
2. Intracavitary mesothelioma:
A. Palliative surgery (pleurectomy and decortication) with or without
postoperative radiation therapy
B. Extrapleural pneumonectomy
C. Palliative radiation therapy
Treatment options under clinical evaluation:
1. Intracavitary chemotherapy following resection.[3,4]
2. Multimodality therapy.[4-6]
3. Other clinical trials.
References:
1. Antman KH, Li FP, Osteen R, et al.: Mesothelioma. Cancer: Principles and
Practice of Oncology Updates 3(1): 1-16, 1989.
2. Martini N, McCormack PM, Bains MS, et al.: Pleural mesothelioma. Annals
of Thoracic Surgery 43(1): 113-120, 1987.
3. Markman M, Kelsen D: Efficacy of cisplatin-based intraperitoneal
chemotherapy as treatment of malignant peritoneal mesothelioma. Journal
of Cancer Research and Clinical Oncology 118(7): 547-550, 1992.
4. Rusch V, Saltz L, Venkatraman E, et al.: A phase II trial of
pleurectomy/decortication followed by intrapleural and systemic
chemotherapy for malignant pleural mesothelioma. Journal of Clinical
Oncology 12(6): 1156-1163, 1994.
5. Sugarbaker DJ, Mentzer SJ, DeCamp M, et al.: Extrapleural pneumonectomy
in the setting of a multimodality approach to malignant mesothelioma.
Chest 103(4, Suppl): 377s-381s, 1993.
6. Vogelzang NJ: Malignant mesothelioma: diagnostic and management
strategies for 1992. Seminars in Oncology 19(4, Suppl 11): 64-71, 1992.
** ADVANCED MALIGNANT MESOTHELIOMA (STAGES II, III, AND IV) **
Standard treatment options:
1. Symptomatic treatment to include drainage of effusions, chest tube
pleurodesis, or thoracoscopic pleurodesis.[1]
2. Palliative surgical resection in selected patients.[2,3]
3. Palliative radiation therapy.[4,5]
4. Single-agent chemotherapy. Partial responses have been reported with
doxorubicin,epirubicin, mitomycin, cyclophosphamide, cisplatin, carboplatin,
and ifosfamide.[6-8]
5. Combination chemotherapy (under clinical evaluation).[6,7] Information
about ongoing clinical trials is available from the NCI
(http://cancer.gov/clinical_trials).
6. Multimodality clinical trials.[9-13]
7. Intracavitary therapy. Intrapleural or intraperitoneal administration of
chemotherapeutic agents (e.g., cisplatin, mitomycin, and cytarabine) has been
reported to produce transient reduction in the size of tumor masses and
temporary control of effusions in small clinical studies.[14-16] Additional
studies are needed to define the role of intracavitary therapy.
References:
1. Boutin C, Viallat JR, Rey R: Thoracoscopy in Diagnosis, Prognosis and
Treatment of Mesothelioma. In: Antman K, Aisner J, eds.:
Asbestos-Related Malignancy. Orlando,Fla: Grune & Stratton, 1987, pp:
301-321.
2. Butchart EG, Ashcroft T, Barnsley WC, et al.: The role of surgery in
diffuse malignant mesothelioma of the pleura. Seminars in Oncology
8(3): 321-328, 1981.
3. Martini N, McCormack PM, Bains MS, et al.: Pleural mesothelioma. Annals
of Thoracic Surgery 43(1): 113-120, 1987.
4. Bissett D, Macbeth FR, Cram I: The role of palliative radiotherapy in
malignant mesothelioma. Clinical Oncology (Royal College of
Radiologists) 3(6): 315-317, 1991.
5. Ball DL, Cruickshank DG: The treatment of malignant mesothelioma of the
pleura: review of a 5-year experience, with special reference to
radiotherapy. American Journal of Clinical Oncology 13(1): 4-9, 1990.
6. Chahinian AP, Antman K, Goutsou M, et al.: Randomized phase II trial of
cisplatin with mitomycin or doxorubicin for malignant mesothelioma by
the Cancer and Leukemia Group B. Journal of Clinical Oncology 11(8):
1559-1565, 1993.
7. Ong ST, Vogelzang NJ: Chemotherapy in malignant pleural mesothelioma: a
review. Journal of Clinical Oncology 14(3): 1007-1017, 1996.
8. Lerner HJ, Schoenfeld DA, Martin A, et al.: Malignant mesothelioma: the
Eastern Cooperative Group (ECOG) experience. Cancer 52(11): 1981-1985,
1983.
9. Mattson K, Holsti LR, Tammilehto L, et al.: Multimodality treatment
programs for malignant pleural mesothelioma using high-dose hemithorax
irradiation. International Journal of Radiation Oncology, Biology,
Physics 24(4): 643-650, 1992.
10. Weissmann LB, Antman KH: Incidence, presentation and promising new
treatments for malignant mesothelioma. Oncology (Huntington NY) 3(1):
67-72, 1989.
11. Vogelzang NJ: Malignant mesothelioma: diagnostic and management
strategies for 1992. Seminars in Oncology 19(4, Suppl 11): 64-71, 1992.
12. Sugarbaker D, Harpole D, Healey E, et al.: Multimodality treatment of
malignant pleural mesothelioma (MPM): results in 94 consecutive
patients. Proceedings of the American Society of Clinical Oncology 14:
A-1083, 356, 1995.
13. Sugarbaker DJ, Mentzer SJ, DeCamp M, et al.: Extrapleural pneumonectomy
in the setting of a multimodality approach to malignant mesothelioma.
Chest 103(4, Suppl): 377s-381s, 1993.
14. Markman M, Kelsen D: Efficacy of cisplatin-based intraperitoneal
chemotherapy as treatment of malignant peritoneal mesothelioma. Journal
of Cancer Research and Clinical Oncology 118(7): 547-550, 1992.
15. Markman M, Cleary S, Pfeifle C, et al: Cisplatin administered by the
intracavitary route as treatment for malignant mesothelioma. Cancer
58(1): 18-21, 1986.
16. Rusch VW, Figlin R, Godwin D, et al.: Intrapleural cisplatin and
cytarabine in the management of malignant pleural effusions: a Lung
Cancer Study Group trial. Journal of Clinical Oncology 9(2): 313-319,
1991.
** RECURRENT MALIGNANT MESOTHELIOMA **
Treatment of recurrent mesothelioma usually utilizes procedures and/or agents
not previously employed in the initial treatment attempt. No standard
treatment approaches have been proven to improve survival or control symptoms
for a prolonged period of time. These patients should be considered candidates
for phase I and II clinical trials evaluating new biologicals, chemotherapeutic
agents, or physical approaches.[1-5] Information about ongoing clinical trials
is available from the NCI (http://cancer.gov/clinical_trials).
References:
1. Rusch V, Saltz L, Venkatraman E, et al.: A phase II trial of
pleurectomy/decortication followed by intrapleural and systemic
chemotherapy for malignant pleural mesothelioma. Journal of Clinical
Oncology 12(6): 1156-1163, 1994.
2. Markman M, Kelsen D: Efficacy of cisplatin-based intraperitoneal
chemotherapy as treatment of malignant peritoneal mesothelioma. Journal
of Cancer Research and Clinical Oncology 118(7): 547-550, 1992.
3. Weissmann LB, Antman KH: Incidence, presentation and promising new
treatments for malignant mesothelioma. Oncology (Huntington NY) 3(1):
67-72, 1989.
4. Boutin C, Viallat JR, Van Zandwijk N, et al.: Activity of intrapleural
recombinant gamma-interferon in malignant mesothelioma. Cancer 67(8):
2033-2037, 1991.
5. Ong ST, Vogelzang NJ: Chemotherapy in malignant pleural mesothelioma: a
review. Journal of Clinical Oncology 14(3): 1007-1017, 1996.
Date Last Modified: 05/2002
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