Malignant mesothelioma-a cancer of the mesothelium that lines the lung, chest wall, and abdomen-is a relatively rare disease in the U.S. with about 3,000 new cases diagnosed each year, according to the American Cancer Society. The major risk factor of the disease is asbestos exposure, and diagnosis usually occurs decades after initial exposure. While this disease was first limited to asbestos workers, diagnoses grew with an increase in non-occupational exposure.
A recent essay published in The Lancet Oncology, written by Nico van Zandwijk, MD, PhD, FRACP, FCCP, Professor Emeritus in the Faculty of Medicine and Health at The University of Sydney, and colleagues, highlighted the role asbestos continues to play in a global malignant mesothelioma epidemic, while also discussing carcinogenesis, prevention, and novel treatments (2022; https://doi.org/10.1016/S1470-2045(22)00269-8).
"Despite the acknowledgment by WHO and the International Agency for Research on Cancer, more than 40 years ago, that all forms of asbestos are carcinogenic, global asbestos use increased exponentially, leading to an almost ubiquitous presence of these minerals in homes, commercial buildings, ships, vehicles, and thousands of products," Van Zandwijk and colleagues wrote. "When asbestos bans were introduced in Europe and Australia, their use surged in countries where traders suggested that chrysotile asbestos were safe."
Many countries, despite the evidence of carcinogenicity, have not recognized the urgent need for an asbestos ban, according to the review authors. To this day, 10 countries continue to block a 15-year-old UN motion to label chrysotile asbestos as "especially hazardous," Van Zandwijk reported.
"As the global malignant mesothelioma epidemic shows no sign of abating, oncologists should reinforce the idea that the continued harm caused by asbestos cannot be reduced without ceasing all asbestos mining and trade, increasing public awareness, enforcing regulations, and improving diagnosis and treatment," the authors emphasized in their paper.
What to Know About Asbestos
In their review, Van Zandwijk and colleagues noted that the evidence has demonstrated that both amphibole and serpentine asbestos fibers are carcinogenic and even small exposure is linked to increased risk of cancer.
"Although amphibole fibers might pose a higher malignant mesothelioma risk than chrysotile fibers do, epidemiological studies suggest that the lung cancer risk of chrysotile might approach that of amphiboles," they explained while discussing past and current research.
The review also highlighted the ongoing role of the pro-asbestos lobby. "Although many high-income countries banned all forms of asbestos after its carcinogenicity became evident, asbestos use surged in many low-income and middle-income countries," Van Zandwijk and colleagues said. "Weak occupational and environmental regulations combined with dubious studies sponsored by the pro-asbestos lobby were used to promote chrysotile trade."
In the U.S., the government continues to allow the importation and restricted use of asbestos, according to the review authors, who also noted that the Environmental Protection Agency (EPA) intended to loosen asbestos policies in 2018. "Facing legal pressure, the EPA agreed in 2020 to broaden their ongoing risk evaluation for asbestos under the Toxic Substances Control Act."
Treatment Advancements
A turning point in the treatment of malignant mesothelioma has been the introduction of immune checkpoint inhibitors, according to Van Zandwijk and colleagues.
"Monoclonal antibodies directed against PD-1, its cognate ligand PD-L1, CTLA4, or all of these were active in subgroups of patients, progressing after chemotherapy," they reported. "Nivolumab alone and nivolumab plus ipilimumab showed clear activity in relapsing patients with malignant mesothelioma and the CheckMate 743 trial showed that survival with nivolumab plus ipilimumab was better than with nivolumab alone or standard chemotherapy in first-line treatment."
While a number of other studies have also demonstrated better disease control among patients who receive immune checkpoint inhibitors, the review authors noted that a significant number of malignant mesothelioma patients do not respond to this approach.
"Multiple immune pathways will probably need to be restored before immunotherapy can show curative potential in malignant mesothelioma," they suggested in their review. "More positively, a portfolio of novel immune-based treatments is currently entering clinical trials, with mesothelin-directed CAR T-cell therapy (NCT03054298 and NCT04577326) a prominent example."
A Call to Action
The malignant mesothelioma epidemic is fueled by the ongoing distribution of asbestos, according to Van Zandwijk and colleagues. "Clinicians, health officials, and the public should reiterate that asbestos exposure and asbestos-related cancers are not issues of the past, and that this epidemic continues because of an absence of regulations, lack of awareness, and disinformation from pro-asbestos lobbyists," they urged.
Another critical issue is the failure to safely dispose of asbestos waste. This, the review authors noted, has created an environmental problem. While they acknowledged that a worldwide consensus on an immediate asbestos ban will not address the risks associated with asbestos currently in the environment, they emphasized the work of grassroots organizations around the world to increase awareness of the harms of asbestos.
"Strong international collaboration and major political pressure will be needed to establish preventive measures in developing countries and to guarantee that the Rotterdam Convention will succeed in banning all asbestos trade," Van Zandwijk and colleagues concluded. "Stricter regulations and an intensification of translational and clinical research into prevention and treatment will all be needed to reduce the deadly impact of the continuing self-inflicted malignant mesothelioma epidemic."
Catlin Nalley is a contributing writer.