Pathological complete response after neoadjuvant/induction treatment: where is its place in the lung cancer staging system?†

Abstract

OBJECTIVES Prognosis for patients with non-small-cell lung cancer (NSCLC) who, after neoadjuvant/induction and surgery, have a pathological complete response (pCR) is expected to be improved. However, the place of the pCR patients in the context of the tumour, lymph node and metastasis (TNM) staging system is still not defined. The aim of this study is to investigate the long-term survival of NSCLC patients with pCR and to find their appropriate staging category within the TNM staging system. METHODS We retrospectively reviewed the prospectively recorded data of 1076 patients undergoing surgery (segmentectomy or more) for NSCLC between 1996 and 2016. Patients were divided into 2 groups. Group 1: clinical early-stage patients who underwent direct surgical resection (n = 660); group 2: patients who received neoadjuvant/induction treatment before surgical resection for locally advanced NSCLC (n = 416). Morbidity, mortality, survival rates and prognostic factors were analysed and compared. RESULTS Postoperative histopathological evaluation revealed pCR in 72 (17%) patients in group 2. Overall 5-year survival was 58.7% (group 1 = 62.3%, group 2 = 52.8%, P = 0.001). Of note, 5-year survival was 72.2% for pCRs. In addition, 5-year survival for stage 1a disease was 82.6% in group 1 and 63.2% in group 2 (P = 0.008); 70.3% in group 1 and 60.5% in group 2 for stage 1b (P = 0.08). Patients with stage II had a 5-year survival of 53.9% in group 1 and 51.1% in group 2 (P = 0.36). CONCLUSIONS This study shows that patients with locally advanced NSCLC developing a pCR after neoadjuvant/induction treatment have the best long-term survival and survival similar that of to stage Ib patients.

Prognostic Factors and Long-Term Survival in Locally Advanced NSCLC with Pathological Complete Response after Surgical Resection Following Neoadjuvant Therapy

“…Firstly, we observed that initial single-level N2 disease is associated with improved OS. This factor was not previously explored in other series on pCR patients and seems to be a promising and easy-to-use prognostic factor in this subset of patients [10,[16][17][18]20]. Other authors have reported better survival results in patients with persistent N2 disease after IT and followed by surgery, when a single N2 station is involved [21].…”

“…From a theoretical point of view, the IT in LA-NSCLC should have the following purposes: (i) to increase resectability by downstaging lung cancer, (ii) to reduce the extent of resection, (iii) to reduce the local and distance recurrence rate, by controlling microscopic distant metastastic spread, and (iv) to increase the overall survival. Robust evidence suggests that better long-term outcomes could be expected after surgery in patients who presented with a downstaging after neoadjuvant therapy (i.e., mediastinal downstaging) [8,10,13]. Although it does not represent the primary goal of neoadjuvant therapy, one of its potential outcomes is the achievement of pathological complete response (defined as the absence of any residual neoplastic cell in the surgical specimen), which represents the best scenario with the highest survival probabilities.…”

“…Although it does not represent the primary goal of neoadjuvant therapy, one of its potential outcomes is the achievement of pathological complete response (defined as the absence of any residual neoplastic cell in the surgical specimen), which represents the best scenario with the highest survival probabilities. In particular, reviewing the largest clinical series reported in the literature, the rates of pCR for patients with LA-NSCLC treated with neoadjuvant therapy range between 8% and 45%, depending on the IT approach used [10,11,13,[16][17][18]. Our data confirm from a long-term experience that pCR may be obtained in a significant proportion of patients treated with an IT protocol (22% of all patients who underwent surgery in our cohort) and this result may be achieved with acceptable treatment-related toxicity and surgical morbidity rates (see consort diagram in Figure 1).…”

“…Our data confirm the existence of a clinical rationale of this treatment even in pCR patients, but our results are limited and not robust enough to draw definitive conclusions on this issue. Concerning the improved survival in pCR patients treated with adjuvant therapy after surgery, the results reported in the literature are not univocal [10,[16][17][18]. Indeed, while its role is substantially accepted in NSCLC patients with persistence of N2 disease after neoadjuvant therapy, the published experiences are contradictory in pCR patients [18].…”

“…Fundamentally, the higher the IT response, the better survival results are expected after complete surgical resection. Thus, LA-NSCLC patients with pathological complete response (pCR) are therefore optimal candidates to undergo surgery after IT, achieving good to very good long-term survival [9][10][11].…”