New
therapy approaches in the treatment of surgically resectable
non-small cell lung cancer (NSCLC) challenge the traditional handling and examination of pathology specimens. The increasingly common use of
neoadjuvant therapies before surgical resection, due to advantages in novel
drug administration, tolerance, and measurement of radiographic and pathologic response compared to adjuvant treatment, has the potential to alter the microscopic
tumor appearance and its biology. Currently, many clinical trials use pathologic response as a
surrogate endpoint of clinical efficacy, since the extent of residual viable
tumor appears to correlate with outcome in patients treated with
neoadjuvant chemotherapy. Consequently, pathologic assessment of the extent of residual viable
tumor is of paramount importance. However, high level evidence-based guidelines on how to process and evaluate such specimens are lacking. Moreover, while pathologic response has been shown to be associated with survival after
chemotherapy, its significance after
immunotherapy remains to be determined. Additionally, many clinical trials do not routinely include pathologists in trial design, which may lead to non-standardized evaluation of pathologic response. Although recently, several algorithms have been proposed to address these issues, none of them represents evidence-based recommendations or is universally applied. Therefore, controversies and challenges continue to exist, raising concerns about the validity, reproducibility, and comparability of the results of many neoadjuvant clinical trials. Herein, we discuss the current difficulties in pathologic specimen evaluation following
neoadjuvant therapy in NSCLC and propose potential approaches to overcome these challenges.