Weissferdt Annikka, Pataer Apar, Swisher Stephen G, Heymach John V, Gibbons Don L, Cascone Tina, Sepesi Boris
Department of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Cardiovascular and Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA.
Department of Cardiovascular and Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, USA.
Lung Cancer. 2021 Apr;154:76-83. doi: 10.1016/j.lungcan.2021.02.014. Epub 2021 Feb 17.
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.
可手术切除的非小细胞肺癌（NSCLC）的新治疗方法对病理标本的传统处理和检查提出了挑战。与辅助治疗相比，由于新药物给药、耐受性以及影像学和病理反应测量方面的优势，手术切除前新辅助治疗的使用越来越普遍，这有可能改变肿瘤的微观外观及其生物学特性。目前，许多临床试验将病理反应作为临床疗效的替代终点，因为残余存活肿瘤的范围似乎与接受新辅助化疗患者的预后相关。因此，对残余存活肿瘤范围进行病理评估至关重要。然而，目前缺乏关于如何处理和评估此类标本的高水平循证指南。此外，虽然病理反应已被证明与化疗后的生存相关，但其在免疫治疗后的意义仍有待确定。此外，许多临床试验在试验设计中没有常规纳入病理学家，这可能导致病理反应评估不规范。尽管最近有人提出了几种算法来解决这些问题，但它们都不是基于证据的建议，也没有被普遍应用。因此，争议和挑战仍然存在，引发了人们对许多新辅助临床试验结果的有效性、可重复性和可比性的担忧。在此，我们讨论NSCLC新辅助治疗后病理标本评估目前存在的困难，并提出克服这些挑战的潜在方法。
