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Prior paradigms of radiographic response per RECIST criteria may no longer be sufficient to predict survival in an age of neoadjuvant chemoimmunotherapy for non-small cell lung cancer (NSCLC). Even PD-L1 and tumor muatoin burden fell short as predictive biomarkers. And while pathologic complete response may be predictive in other cancers (breast, melanoma), long-term overall survival results for NSCLC are mixed.

It appears that circulating tumor (ct)DNA levels is our best tool for predicting treatment efficacy. In the , neoadjuvant carboplatin-paclitaxel plus nivolumab demonstrated outstanding overall survival rates, most notably for patients with undetectable ctDNA levels prior to surgery with HR of 0.04.

Low pre-treatment ctDNA levels likewise were associated with improved survival outcomes. Questions remain how to appropriately use this early surrogate endpoint. When could we adjust surgical and adjuvant therapies? Should we push for ctDNA levels to be tested routinely pre- and/or post-neoadjuvant therapy? How should we standardize this predictive tool?

Furthermore, are all surgical candidates even discussing the option of neoadjuvant chemoimmunotherapy and how this may impact survival?

This is an ongoing call for multidisciplinary collaboration and precision across the spectrum of lung cancer care.

Claire L. Hiles, MD, is a hematologist/oncologist at David Grant Medical Center at Travis AFB in California.

Read the study here and an interview about it here.