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Surgery-based regimen improves survival in malignant pleural mesothelioma
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Carefully selected patients with malignant pleural mesothelioma benefited from a surgery-based treatment modality, according to results from a propensity score matching analysis published in Journal of Clinical Oncology.
Previous studies investigated whether surgery may extend survival among patients with malignant pleural mesothelioma; however, limitations exist — such as poor patient accrual and higher than expected mortality rates — and it is unclear if these results are generalizable.
“As such, additional efforts to show the efficacy of surgical therapy for mesothelioma are needed,” Boris Sepesi, MD, FACS, assistant professor in the department of thoracic and cardiovascular surgery at The University of Texas MD Anderson Cancer Center, and colleagues wrote. “For such a disease process with a limited incidence, complex therapy and high mortality as with mesothelioma, a well-constructed database study that pools outcomes from multiple institutions can potentially offer more detailed results.”
Sepesi and colleagues used the National Cancer Data Base to identify patients with microscopically proven malignant pleural mesothelioma. Researchers evaluated survival following cancer-directed surgery, as well as surgery interaction with chemotherapy or radiation therapy.
A logistic regression model — designed to predict the likelihood of patients undergoing cancer-directed surgery — created a propensity score to match 6,645 patients 1:2 to comprise a surgical and nonsurgical cohort. These cohorts included:
- 2,166 patients who received no therapy;
- 850 who underwent surgery alone;
- 2,015 who had chemotherapy only;
- 85 patients treated with radiation only;
- 988 patients who underwent surgery and chemotherapy; and
- 274 patients who had a trimodality regimen.
The surgical cohort demonstrated mortality rates of 6.3% at 30 days and 15.5% at 90 days following surgery, “which underscores the magnitude of treatment insult with cancer-directed surgery,” Sepesi and colleagues wrote.
Thirty-day readmission occurred in 4.8% of patients; an additional 1.9% of patients had planned 30-day readmission (median length of hospital stay, 6 days).
Increased risk for death occurred among patients with sarcomatoid histology (HR = 2.24; 95% CI, 2.06-2.45) and stage IV disease (HR = 1.56; 95% CI, 1.42-1.7). However, each treatment option improved survival, including cancer-directed surgery (HR = 0.77; 95% CI, 0.72-0.81), chemotherapy (HR = 0.74; 95% CI, 0.69-0.78) and radiation therapy (HR = 0.88; 95% CI, 0.8-0.97).
Researchers then conducted a subgroup analysis to determine whether the survival benefit of each treatment modality interacted with one another. Results showed cancer-directed surgery (HR = 0.77; 95% CI, 0.7-0.84) and chemotherapy alone (HR = 0.73; 95% CI, 0.68-0.78) improved survival, whereas radiation therapy alone did not (HR = 0.93; 95% CI, 0.73-1.18).
The addition of chemotherapy to cancer-directed surgery led to a greater impact on survival (HR = 0.56; 95% CI, 0.51-0.61). However, the greatest estimated treatment effect on survival occurred with the combination of cancer-directed surgery, chemotherapy and radiation (HR = 0.52; 95% CI, 0.45-0.6), underscoring the importance of trimodality therapy, the researchers wrote.
According to stratified analysis of histology, cancer-directed surgery led to a durable improvement in survival across all histologic subtypes, with the most favorable survival found in patients with the epithelial subtype (HR = 0.8; 95% CI, 0.73-0.88).
Patients who underwent cancer-directed surgery achieved superior median OS (13.9 months; 95% CI, 13-14.7) compared with those who did not (10.5 months; 95% CI, 10-10.9).
Trimodality therapy extended median survival from 11.2 months (95% CI, 10.8-11.6) to 20.8 months (95% CI, 18.4-22.5) among all patients, and from 14.5 months (95% CI, 13.7-15.1) to 23.4 months (95% CI, 20.7-25.4) for epithelial subtype.
“Ultimately, mesothelioma is a rapidly progressive and often fatal disease, and despite much effort over the last several decades, survival outcomes have not changed significantly,” Sepesi and colleagues wrote. “Continued research on new approaches, including immunotherapy, will be essential to improving prognosis.”
These data identify patients who may benefit from cancer-directed surgery, the researchers wrote.
“Our results demonstrate that a small proportion of patients demonstrate improved survival after surgery-based multimodality therapy, and indicate that well-selected patients seem to benefit from aggressive therapy and should likely play a role in future clinical trials,” they added. “We recommend that all patients with malignant pleural mesothelioma are evaluated by multidisciplinary teams that are experienced in the management of mesothelioma for consideration of surgery-based multimodality therapy and potential clinical trial enrollment.” – by Kristie L. Kahl
Disclosures: Sepesi reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
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Alex Spira
Mesothelioma is one of the most challenging malignancies for patients and oncologists. Many patients are older, and access to experts, especially surgeons, with experience in this disease is limited. Only a handful of surgeons in the United States can truly classify themselves as experts in mesothelioma surgery. Radiation for patients with mesothelioma is challenging and is emerging as a possible indication for proton therapy. In addition, clinical studies of novel agents beyond platinum and pemetrexed are few and far between.
Results of the analysis by Nelson and colleagues demonstrated that patients who underwent more — “trimodality” — therapy lived longer than those that underwent fewer therapies. Those patients with the less aggressive epithelioid subtype who underwent triomodality therapy lived on average 8 months longer than those who did not.
It is unclear whether this represents a selection bias for patients who were in better medical shape, better able to undergo this difficult therapy or more likely to get themselves to specialty surgical centers. The numbers of patients, as well as the complexity of the cases, makes the concept of a randomized study looking at these individual factors impossible. The take-home message is, be more aggressive in those patients who are able to withstand it to give them a fighting chance with the necessary specialty referrals as needed.
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