A recent clinical trial indicates that immunotherapy,when given both before and after surgery,may offer a notable benefit to patients with operable diffuse pleural mesothelioma. This approach aims to improve outcomes for a cancer that is notoriously difficult to treat.

Mesothelioma is a rare and aggressive cancer affecting the tissue lining various organs in the body.Approximately 30,000 cases are diagnosed globally each year, with the majority affecting the pleura, or lining of the lungs. Exposure to asbestos is a primary risk factor for developing this disease.

According to Dr. Joshua Reuss, MD, the study’s lead author and a thoracic medical oncologist at Georgetown’s lombardi Comprehensive Cancer Center, “Mesothelioma is a difficult tumor to treat. Our study demonstrated the feasibility and safety of using immunotherapy before surgery for patients who have tumors that can potentially be removed surgically.”

Dr. reuss,who also serves as an attending physician at MedStar Georgetown University Hospital,emphasized the growing role of immunotherapy in cancer treatment: “Immunotherapy is making significant contributions to extending the lives of patients with lung cancer and many other solid tumors.This is an vital step in identifying mesothelioma patients who could benefit from immunotherapy in the perioperative period, meaning right before or after their surgery and in choosing patients who are actually candidates for that surgery.”

The clinical trial, designed by Dr. reuss during his fellowship at the Johns Hopkins Kimmel Cancer Center, was a phase II study titled “Neoadjuvant Nivolumab or Nivolumab plus Ipililumab in Resectable Diffuse Pleural Mesothelioma.” The results were presented at the 2025 World Conference on Lung Cancer in Barcelona, Spain, on September 8. The study is also published in the journal Nature Medicine.

Phase II clinical trials are crucial for evaluating the feasibility and safety of new treatments, assessing whether the potential benefits outweigh the adverse effects experienced by patients.

Dr. Reuss noted the ongoing debate surrounding the effectiveness of surgery for mesothelioma: “when looking at patient outcomes to date, the issue of whether any mesothelioma is truly resectable is controversial. Several major studies have not shown enhancement in survival when surgery is incorporated into systemic therapy for mesothelioma.This study incorporates immunotherapy into the treatment of patients who might benefit from surgery.”

“Mesothelioma is a difficult tumor to treat…Our study demonstrated the feasibility and safety of using immunotherapy before surgery.”

dr. Reuss explained the unique growth pattern of mesotheliomas: “since they occur in the tissue that lines the lungs, mesotheliomas don’t grow and spread like other cancers. They don’t typically form solid masses or nodules. These tumors are more fluid, or diffuse throughout the lining of the lung. That makes it more difficult to use our usual methods to determine how extensive a tumor is or to measure whether a treatment is effective by standard imaging assessments.”

The study also incorporated a novel approach by analyzing circulating tumor DNA (ctDNA) in patient blood samples. This collaboration between the clinical team and laboratory scientists aimed to detect microscopic signs of cancer that traditional imaging might miss. While ctDNA analysis is an evolving area, it is indeed especially challenging in mesothelioma due to the low number of detectable cancer mutations.

Dr. Valsamo Anagnostou, MD, PhD, the Alex Grass professor of oncology and co-director of the upper aerodigestive cancers programme at Johns Hopkins, and the study’s senior author, stated, “imaging doesn’t always capture what’s happening with mesothelioma, especially during treatment. By using an ultra-sensitive genome-wide ctDNA sequencing method, we were able to detect microscopic signs of cancer that imaging missed and predict which patients were most likely to benefit from treatment or experience relapse.”

Dr. Reuss suggests that ctDNA analysis could provide a valuable tool for monitoring treatment efficacy: “This approach may give us a baseline to monitor the efficacy of that treatment. If the ctDNA decreases or disappears, it is indeed a good indication that the therapy is working, If not, it indicates a change in therapy might potentially be warranted.” However, he emphasized the need for further validation before it can be routinely used in clinical practice.

According to Dr. Reuss, “These analyses contribute to our understanding of which patients with mesothelioma may be candidates for surgery. Up until now,ctDNA assessments have not been part of the clinical landscape in the management of diffuse pleural mesothelioma,but our analyses suggest this may be nearing a change in the future.”

While Phase II trials are not designed to definitively measure clinical efficacy, both arms of this trial showed improvements in the time until tumor regrowth and overall survival.

Dr. Reuss cautioned against drawing firm conclusions from this data, emphasizing that the results offer encouraging signals regarding the potential of neoadjuvant immunotherapy for mesothelioma patients with surgically removable tumors. He sees this as a stepping stone for future research aimed at developing more effective therapies.

“This is a small study,” he said, “and it does not tell us whether neoadjuvant immunotherapy will improve outcomes for these patients, but it does open windows of opportunity. We need to take what we learned and do further studies, dig deeper so that we can develop better therapies for patients with mesothelioma.”

The study was a collaborative effort across multiple academic cancer centers and was sponsored by Bristol Myers Squibb. Additional funding was provided by various grants and foundations.