Editor’s Note: Get more highlights from ELCC 2022 from Lung Cancer Considered, IASLC’s podcast.
Biological features, pathological characteristics, and molecular drivers should be incorporated into the upcoming 9th edition of the anatomical lung cancer TNM classification, attendees agreed during a session designed to address this controversial issue during the European Lung Cancer Congress (ELCC).
Polled on the topic before and after the March 31 session titled “New TNM Classification: Anatomical vs. Biological,” attendees were swayed toward supporting such changes after hearing talks by Ramon Rami-Porta, MD, PhD, of the Thoracic Surgery Service at the Hospital Universitari Mutua Terrassa in Barcelona, Spain, and Raymond U. Osarogiagbon, MD, of the Multidisciplinary Thoracic Oncology Program at Baptist Cancer Center in Memphis, Tennessee.
The attendees considered three questions posed by session chair Valerie Rusch, MD, of Memorial Sloan Kettering Cancer Center:
- Are additional refinements to the current anatomical lung cancer TNM staging system needed?
- Should some of the biological/pathological features known to have prognostic importance in lung cancer—such as the presence of carcinoma in the endothelial lining or vascular wall, or histological subtypes of NSCLC—be added?
- Should well-described molecular alterations such as EGFR, KRAS, and ALK be incorporated?
The yes/maybe/no votes, respectively, were:
- Question 1: 33%/33%/33% before the talks versus 100%/0%/0% after
- Question 2: 60%/20%/20% initially versus 86%/14%/0% after the presentations
- Question 3: 40%/30%/30% at the outset of the session versus 72%/22%/6% afterwards.
Dr. Osarogiagbon said these types of updates to the staging system will improve its quality for the benefit of all stakeholders.
“The goal of quality improvement is two-fold,” he said. “One is to improve the outcomes for the individual person, and the other is to help us get a new threshold of universal quality upon which we can then construct the next generation of studies that allow us to get to the heart of the biologic drivers of outcomes differences, thus giving us the ability to apply rational knowledge of cancer biology to ultimately overcome cancer.”
The existing staging system measures the burden of disease by analyzing the anatomic extent of a lung cancer. In so doing, it sheds light on treatment options. Within this system, T indicates the primary tumor, including size, location, and invaded structures; N refers to regional lymph nodes and their location; and M describes metastases and their number and location.
“While additional prognostic information based on the biology of lung cancer should prove useful, the staging system, if it grows too complicated, runs the risk of becoming unwieldy and difficult to navigate. The next iteration ideally needs to address these challenges.”
— Corey J. Langer, MD, FACP, Editor
First generated in 1943, the staging system was updated most recently in 2016, based on information entered an international database managed by the IASLC. A team of experts including Dr. Rami-Porta is preparing a 9th edition for publication in 2024.
Although the TNM system successfully classifies cancers into stages associated with distinct prognoses, Dr. Rami-Porta said, the recent incremental gains in prognostic value from edition to edition indicate room for improvement. The 9th edition should include not only anatomical information, he said, but also the characteristics of tumors (such as stage, histotype, and grade), patients (for instance, performance status and age), and tumor environment (i.e., the adequacy of margin resection)—information that is largely available within the IASLC’s database.
He recommended that the updated staging system include measurements of lymphatic invasion, venous invasion, perineural invasion, and residual tumor, as well as any genetic biomarkers, copy number alterations, or protein alterations present in 1% or more of patients who have lung cancer.
Dr. Osarogiagbon agreed with the need to incorporate biomarker-driven strategies backed by global datasets. Since 2012, he said, molecular unknowns in lung cancer have dwindled from 50% to 11% and the role of these drivers in patient outcomes has become clearer.
“How can we apply EGFR pathologic TNM subsets identically to non-EGFR mutation positive TNM subsets in light of their radically different survival expectations?” he asked.
Dr. Osarogiagbon also suggested that the TNM system be improved by better defining and applying N staging, as failure to examine lymph nodes is common and reduces patient survival rates. To correct that, he said, the IASLC has proposed a redefinition of the completeness of resection that does not strictly consider margin status but also incorporates an assessment of the thoroughness of nodal staging.
Once new parameters have been chosen for inclusion in the staging system, Dr. Rami-Porta suggested, the factors should be categorized into their own buckets but then considered together in comprehensive prognostic groupings.
He predicted that a biological classification will not quickly replace the TNM staging system, which retains a key role because it can be used in any medical setting and is crucial in designing clinical trials of precision treatments.
For more, this lecture and other ELCC 2022 presentations are available on-demand for attendees on OncologyPro.