The first positive trials of neoadjuvant immunotherapy for lung cancer have highlighted both the potential benefits of immunotherapy before surgery and the looming gap between emerging clinical practice and thoracic pathology.
“All indications from the early data are that neoadjuvant immunotherapy is a key advance,” said Keith Kerr, MB, ChB, FRCPath, Professor and Honorary Chair of Pathology at Abeerdeen University School of Medicine, Foresterhill, UK.
Neoadjuvant therapies have a long history in lung cancer but have never been popular with surgeons or patients. Surgeons were unhappy about operating on patients who had recently undergone chemotherapy, and patients were unhappy at having to delay surgery, Dr. Kerr said.
And neoadjuvant chemotherapy was a coin toss. About half of patients benefited, but there were no reliable prognostic biomarkers.
Adding neoadjuvant immunotherapy has improved success rates, but prognostic factors remain uncertain. Early trials suggest that pathology can help identify patients more likely to benefit.
“Some of the treatments being used in the neoadjuvant space rely on the presence of some kind of predictive biomarkers that the pathologist might identify before the patient has surgery,” Dr. Kerr said. “We don’t have data from many trials yet, but clearly pathology is involved in identifying those alterations in the tumor in order to select for a particular neoadjuvant treatment.” Dr. Kerr will discuss the role of pathology in the setting of neoadjuvant treatment during “Closing Plenary Session 6: Advances in Lung Cancer Pathology,” which will take place from 15:45 – 16:45 SGT on Tuesday, September 12, in Room 406. The session will be livestreamed and available on-demand for virtual attendees.
Closing Plenary Session 6: Advances in Lung Cancer Pathology
15:45–16:45 SGT, Tuesday, September 12, Room 406
There is also a clear role for pathology in assessing neoadjuvant treatment response. Pathological response at the microscopic level can be a surrogate for postoperative survival. Complete pathologic response (CPR) is the optimum response, major pathologic response (MPR) suggests a positive prognosis.
The problem is interpreting what surgical specimens have to say. The IASLC Pathology Committee developed uniform criteria for processing of resected specimens and uniform histological assessment that showed promise in a few single-institution studies, but there has been no global, multicenter trial. Until now.
“Breast cancer and other cancers have standardized, detailed guidelines for pathologic assessment of response to neoadjuvant therapies,” said Sanja Dacic, MD, PhD, Professor, Vice Chair, and Director of Anatomic Pathology at the Yale School of Medicine, New Haven, Connecticut. “There are many reproducibility studies in breast cancer telling us how pathologists are doing these assessments. Similar reproducibility studies in lung cancer are limited.”
Dr. Dacic will present results of the global IASLC Interobserver Study from a panel of 11 pathologists in Asia, Europe, and North America assessing pathologic response using specimens from six neoadjuvant immunotherapy trials in lung cancer.
“What is unique about this study is a web-based MPR calculator that takes into account the proportion of the tumor represented by each slide,” Dr. Dacic explained. “What we did as pathologists was to measure the size of the surgical bed based on these slides.”
The panel made two histological assessments for each patient. A weighted assessment was based on the size of the tumor bed and the percentages of the different components. An unweighted assessment was based on an average of the slides without reference to bed size.
“You will have to come to the plenary to see the results,” Dr. Dacic said. “These results are absolutely necessary for the community because so many of these neoadjuvant protocols are effectively standard of care. It is important to ensure that in clinical practice, we are all implementing the same best practices for our patients.”