Malignant mesothelioma: options for management

Our plain-English summary of Malignant mesothelioma: options for management, by S. Singhal, L.R. Kaiser (The Surgical Clinics of North America, 2002).

The study

• Authors: S. Singhal, L.R. Kaiser
• Journal: The Surgical Clinics of North America
• Published: 2002;82(4):797-831
• Type of article: Review
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In the past, there has been a tendency to think of diffuse malignant pleural mesothelioma as one disease in therapeutic terms, regardless of histological type and tumor stage. This does not happen with other tumors, yet it is equally illogical and inappropriate in mesothelioma. As with other tumors, early diagnosis-while the disease is still in stage I, or even at an in situ stage-must be the goal so that therapy can be maximized, particularly if immunotherapy or gene therapy is to be used. Patients with pure epithelial mesothelioma have a better prognosis and respond better to trimodality therapy. Stage I patients who meet fitness criteria should be offered the option of radical surgery in combination with chemotherapy and radiotherapy. Further research is required to determine the optimum neoadjuvant and adjuvant modalities, particularly the timing of individual drugs, use of hyperthermia, and route of administration. The place of immunotherapy and gene therapy as adjunctive treatments also remains to be defined. For example, it may be possible to reduce tumor bulk and perhaps downstage the disease with immunotherapy before radical surgery, if treatment is started early enough. Gene therapy may have a role either preoperatively or in destroying the microscopic disease that remains after radical surgery. These and other combinations of treatment need to be tested in well-designed clinical trials, probably on a multicenter basis (to enroll a sufficient number of patients). Finding the means to improve treatment for sarcomatous and mixed histology mesothelioma remains a challenge. At present, radical surgery does not seem worthwhile for these patients when combined with currently employed chemotherapy and radiotherapy; however, chemotherapy combinations used for treating other sarcomas need to be evaluated as adjunctive therapy before radical surgery is abandoned altogether as a mode of treatment. A collaborative approach involving thoracic surgeons, basic scientists and oncologists, and physicians with experience in treating mesothelioma is essential. Despite its increasing frequency, mesothelioma is still a relatively rare tumor, so treatment should be concentrated in relatively few supraregional centers to maximize expertise and allow innovative treatment combinations to be implemented with the greatest chance of success. Evaluation of new therapeutic approaches will be achieved more rapidly if these supraregional centers collaborate in multicenter trials. The nihilistic approach of simply waiting until the mesothelioma epidemic eventually begins to decline spontaneously in 20 or 30 years is untenable in view of the hundreds of thousands of deaths that will result if no effective treatment is found.

In plain English

This article was a narrative review of treatment options for malignant pleural mesothelioma, written by authors from the Department of Surgery at the University of Pennsylvania. It did not study asbestos exposure and reported no new patient data. Its figures came from earlier studies it cited. According to those reports, median survival without treatment was 6 to 8 months, chemotherapy had limited effect, and external radiation alone did not extend survival. Published surgical series reported median survival of 9 to 18 months after pleurectomy and 4 to 21 months after extrapleural pneumonectomy. In one cited series of 183 patients treated with surgery, chemotherapy and radiation, median survival was 19 months. In 31 of those patients, who had epithelial tumors, clear surgical margins and no spread to extrapleural lymph nodes, two-year survival was 68%. The authors noted that many studies were small and hard to interpret. They concluded that fit stage I patients should be offered radical surgery with chemotherapy and radiotherapy, that pure epithelial tumors carry a better outlook, and that treatment should be concentrated in a few specialist centers running multicenter trials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of the published literature on treating malignant mesothelioma (mainly pleural). There were no original patient data, and the article does not describe how studies were selected.
• Who was studied: No study population of its own. The review covered published reports on patients with malignant pleural mesothelioma, many of them small series.
• Exposure: Asbestos exposure was not examined. The review covered treatments: chemotherapy, radiotherapy, surgery (pleurectomy or decortication, and extrapleural pneumonectomy), combined-modality therapy, immunotherapy, gene therapy, photodynamic therapy and palliative care.
• Main results:
  • Cited studies put median survival for untreated patients at 6 to 8 months.
  • The authors stated that the maximal response rate with any single chemotherapy agent had been 20%. Elsewhere, the article cites higher ranges for some individual drugs.
  • The authors stated that external radiation alone did not extend survival.
  • Studies of pleurectomy with or without decortication reported median survival of 9 to 18 months.
  • Series of extrapleural pneumonectomy (EPP) reported median survival of 4 to 21 months.
  • In a cited Chicago series, 40 EPP patients had 13.3-month median survival and 22.5% two-year survival. The 56 pleurectomy patients had 9-month median survival and 8.9% two-year survival. The difference did not reach statistical significance.
  • In a cited series of 183 EPP patients given trimodal therapy, median survival was 19 months, with 2-year survival of 38% and 5-year survival of 15%.
  • Within that series, 31 patients had epithelial type, negative resection margins and no extrapleural lymph node involvement. They had 68% two-year survival, 46% five-year survival and 51-month median survival.
  • In a cited Memorial Sloan-Kettering series of 231 patients who underwent thoracotomy, median survival was 29.9 months for stage I, 19 months for stage II, 10.4 months for stage III and 8 months for stage IV.
  • In a cited chemoimmunotherapy study, median survival was 11.5 months for 43 treated patients and 7.0 months for 19 patients given supportive therapy alone. The difference was not significant.
  • In cited phase I gene therapy trials in patients with pleural mesothelioma, two patients remained tumor-free 3 years after treatment.
• The authors' conclusion: The authors concluded that patients with pure epithelial mesothelioma have a better prognosis and respond better to trimodality therapy, and that fit stage I patients should be offered radical surgery with chemotherapy and radiotherapy. They also concluded that radical surgery does not currently seem worthwhile for sarcomatous and mixed tumors, and that treatment should be concentrated in supraregional centers collaborating in multicenter trials.
• Limitations the authors state:
  • The authors stated that interpretation of almost all published surgical series is hindered by problems such as missing staging and performance-status information, selection bias, imprecise histological typing, and varied surgical technique and adjuvant therapy.
  • The authors noted that many studies were very small.
  • The authors noted that the 183-patient trimodal series changed protocol over time without separating the data, so it is impossible to tell which drug combination worked best.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Pleural Mesothelioma, Mesothelioma, Immunotherapy, Prognosis, Trimodality Therapy, Chemotherapy, Clinical Trial.

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