252 Chapter 17 This thesis investigated three histopathological aspects in resected NSCLC specimens, relevant to diagnosis, prognosis, and staging. In part I, the aim was to establish criteria for the pathologic response effect after neoadjuvant therapy by examining whether histopathological findings such as the percentage of tumor rest, proliferative activity, as well as including morphometric properties may lead to a refinement in the prognosis of patients with NSCLC. In addition, the modified criteria from TNM-7 to TNM-8 were examined in a Dutch cohort as a kind of validation. Neoadjuvant therapy and postoperative pathologic staging Approximately 25-30% of non-small cell lung cancer (NSCLC) patients are diagnosed in the early stage (IA-IIB), and most of them undergo surgical treatment with a curative intention2. Also, patients with stage IIIA can be treated by surgery. However, a significant number of these patients will during follow-up develop distant metastases, resulting in a low 5-year overall survival (OS) rate (<35%) for those with stage IIIA disease16. Platinum-based adjuvant chemotherapy showed a positive impact, raising the 5-year survival rate by an additional 5%351. In the absence of randomized studies to compare both of them, adjuvant and neoadjuvant approaches could be valid. Several studies have compared adjuvant treatment to neoadjuvant (preoperative) treatment in different study populations, but they have not shown any significant differences in effectiveness between the two approaches. Both adjuvant and neoadjuvant chemotherapy for resected NSCLC increase the 5 years OS by 4% to 5% 352 353. Importantly, neoadjuvant treatment has several advantages over adjuvant therapy, such as reducing the tumor size and stage (thereby increasing the possibility of complete surgical removal), treating micrometastatic disease early, after resection evaluating the response to systemic therapy in the surgical specimen, and improving the patient’s preoperative performance status, which may improve adherence to the treatment plan354 355. The introduction of immune checkpoint inhibitors, which have been shown to significantly prolong survival in many patients, is changing the treatment options for advanced NSCLC356, 357. Recently, Forde et al. reported the Checkmate 816 trial, showing a significant increase in the median event free survival in patients treated with chemotherapy combined with immunotherapy (Nivolumab) compared to chemotherapy alone (31.6 vs 20.8 months)358. Thorough investigation is warranted to examine the histopathologic effects of these changes in adjuvant schemes. Also, for patients with more advanced stage III disease, such as those with a Pancoast tumor in the upper lung sulcus, neoadjuvant therapy can be advantageous. This type of treatment may change the status of the tumor from irresectable to resectable. The standard of care for these patients still involves trimodality therapy, which involves concurrent chemotherapy and radiotherapy with cisplatin/etoposide, followed by surgery63. It is likely that immunotherapy will also play a part in altering
RkJQdWJsaXNoZXIy MTk4NDMw