Patients with malignant pleural mesothelioma (MPM) lived 6 months longer, on average, when they had surgery in addition to chemotherapy, a large retrospective analysis showed.
The addition of surgery to combination chemotherapy resulted in a median overall survival (OS) of 22 months as compared with 16 months with chemotherapy alone. Twice as many patients remained alive at 5 years with surgery, and four times as many lived 10 years or longer if they underwent surgery, although long-term survival remained poor, with or without surgery, reported Ahmed Alnajar, MD, of the University of Miami, at the virtual World Conference on Lung Cancer (WCLC).
“Our study demonstrated how poor survival rates were associated with MPM, as an overall survival outcome,” said Alnajar. “However, surgical treatment has played a role in improving survival, and academic programs improved survival, based on their overall management plans.”
The findings added some positive data to a persisting controversy over surgery’s role in the management of MPM. A decade ago, the Mesothelioma and Radical Surgery (MARS) study showed not only that radical surgery did not improve outcomes in MPM but conferred a high morbidity that precluded future large randomized trials. However, other feasibility trials and prospective studies showed more positive outcomes with surgery, including median OS exceeding 2 years, said Alnajar.
The study is the latest, and one of the largest, to examine the role of surgery for MPM, said WCLC invited discussant Francoise Galateau-Sallé, MD, of Leon Berard Cancer Center in Lyon, France. The size of the patient population, use of propensity matching, and identification of risk factors that influence survival after surgery are the principal strengths and clearly showed a benefit of surgery.
But those have to be balanced against the possible confounding effects of selection bias, lack of details about histologic features, and lack of information about characteristics of long survival that distinguish responders and nonresponders, Galateau-Sallé noted.
Recent reviews have come down on both sides of the issue, Galateau-Sallé said. Authors of a review published in 2020 found a lack of supporting evidence for surgery from randomized trials. Literature that supports surgical resection “is biased by patient selection for the earliest stage, healthiest patients.”
On the other hand, two articles published in 2019 — a 10-year retrospective review and another analysis of National Cancer Database (NCDB) data — showed survival benefits with surgery, albeit with fairly high surgical mortality in the NCDB analysis.
Continuing the investigation of surgery’s role in MPM, Alnajar and colleagues retrospectively reviewed the NCDB to identify patients with resectable stage I-IIIa MPM from 2004 to 2017. The query included patients who underwent pleurectomy, decortication, or extrapleural pneumonectomy. Patients who had palliative surgery were excluded. All patients received standard-of-care chemotherapy.
They examined data from 4,036 patients and performed propensity score matching to adjust for surgical treatment allocation confounders, resulting in 1,402 matched pairs to estimate OS and identify predictors of survival.
The analysis yielded 5-year survival estimates of 23.9% with surgery versus 11.2% with chemotherapy alone, and 10-year estimates of 14.2% and 3.6%, respectively. The 6-month difference in median OS represented a 40% decrease in the survival hazard in favor of surgery.
Multivariable analysis showed that the combination of surgery and chemotherapy had the greatest impact on survival (HR 0.606, P<0.001), followed by receipt of trimodal therapy (surgery, chemotherapy, and radiotherapy), which reduced the survival hazard by 27.2%. Analysis of risk factors associated with survival showed that men had a 57% higher survival hazard, and that treatment at a community (versus academic) center increased the hazard by 14%, and older age increased the hazard by 2% per year.
“We look forward to future larger clinical trials in these patients to have better-quality evidence,” Alnajar said.
He acknowledged several study limitations, including its retrospective design and variation in data precision reported to the NCDB over the study period. Propensity matching might have helped reduce the influence of selection bias.
“The next step will be to evaluate the impact of innovative therapies, such as immunotherapy and CAR T cells, and the results of the [ongoing] MARS2 trial,” said Galateau-Sallé.
Alnajar and Galateau-Sallé disclosed no relationships with industry.