While neoadjuvant chemotherapy (NAC) is used as a standard of care in many resectable cancers, there is no standard of care with respect to its use in resectable malignant pleural mesothelioma (MPM). An intention-to-treat study published in the Journal of the National Cancer Institute aimed to answer whether neoadjuvant chemotherapy improved overall survival and postresection survival for patients with MPM.
The results were surprising. Neoadjuvant chemotherapy was associated with worse postresection survival when compared with patients who underwent surgery sooner, without neoadjuvant chemotherapy treatment.
Current Treatment of Malignant Pleural Mesothelioma
In treating MPM, one of the most important questions for an oncologist to determine with a newly diagnosed patient is whether the patient is a surgical candidate, or whether nonsurgical control of the disease is the goal. Type and stage of the disease factor into the decision about surgery.
Two types of surgeries are offered for patients who are candidates for chemotherapy in the neoadjuvant setting. One is an extrapleural pneumectomy and the other is a pleurectomy and decortication. According to Joel Neal, MD, PhD, a medical oncologist at Stanford University who was not involved in the study, the type of surgery a patient is offered depends as much on the expertise of the surgeon as anything else.
Once a patient is determined to be a surgical candidate, some oncologists may offer NAC prior to surgery to help shrink tumors and ostensibly make the surgery more effective. But previous studies have not definitively answered whether this makes sense as a standard of care for resectable MPM.
Does Neoadjuvant Chemotherapy Before Surgery Improve or Worsen Survival?
The key question the study sought to answer was: is it better to proceed straight to surgery without chemotherapy first, or to give several cycles of chemotherapy during approximately 3 months prior to surgery?
Neoadjuvant chemotherapy is also sometimes given because it has the potential to induce cancer remission in some cases. However, some patients may not be healthy enough to endure the side effects of chemotherapy, and oncologists may recommend immediate surgery instead.
The authors measured survival from the time of surgery. One group had received 3 months of chemotherapy prior to surgery, so choosing surgery as the landmark eliminated the time bias of longer survival for the neoadjuvant group.
The study adjusted for various confounding factors and selection biases. While the study had only 250 patients, they also looked at a group of 2000 patients in the National Cancer Database to see if the results held up with a larger population. While the data were less granular in this larger group, their findings supported the conclusions drawn from the smaller study. Postresection survival was worse for the group that received neoadjuvant chemotherapy compared with the group that received surgery only.
“These are rather surprising results,” said Dr Neal. “Is this going to change how we practice? For medical oncologists like myself, it makes us question whether we should encourage patients to go directly to surgery and not offer neoadjuvant chemotherapy, instead of saying that everyone who is strong enough should go through chemotherapy first.” The authors (and Dr Neal) recommended that care teams discuss the risks and benefits of NAC together and with their patients.
Why would NAC lead to an overall worse outcome? Well, said Dr Neal, the response rate to chemotherapy is rather low in MPM — only about 20% of patients in this particular study had a positive response. The other approximately 80% either remained stable or showed some tumor growth. And chemotherapy is taxing for patients. “It takes energy, possibly making them less fit for surgery, and they may be at higher risk of surgery complications,” he said.
While further research is needed to confirm this initial study’s conclusions, this is important information guiding clinical practice, said Dr Neal. And, although the authors adjusted for certain biases, a randomized trial would provide more objective results. “Studies like that are important and very reasonable to conduct in a randomized way in this field,” said Dr Neal. “It’s still reasonable to try to answer this question definitively.”
Voigt SL, Raman V, Jawitz OK, et al. The role of neoadjuvant chemotherapy in patients with resectable malignant pleural mesothelioma – an institutional and national analysis [published online February 3, 2020]. J Natl Cancer Inst. doi: 10.1093/jnci/djaa002