Long-Term Survival in Patients with Oligometastatic Non-Small Cell Lung Cancer by a Multimodality Treatment—Comparison with Stage III Disease

Abstract

Background: In patients with oligometastatic NSCLC, a cT3–cT4 primary tumor or an cN2/cN3 lymph node status was reported to be associated with unfavorable outcome. The aim of this study was to assess the importance of definitive or neoadjuvant thoracic radiochemotherapy for long-term outcome of these patients in order to find more appropriate treatment schedules. Methods: Analysis of the West Cancer Centre (WTZ) institutional database from 08/2016 to 08/2020 was performed. Patients with primary synchronous OMD, all without actionable driver mutations, who received definitive thoracic radiochemotherapy (RCT) or neoadjuvant RCT followed by surgery (trimodality treatment) were included. Survival outcome is compared with stage III NSCLC. Results: Altogether, 272 patients received concurrent radiochemotherapy. Of those, 220 presented with stage III (158 with definitive RCT, 62 with trimodality approach). A total of 52 patients had OMD patients with cT3/cT4 or cN2/cN3 tumors. Overall survival (OS) at five years for OMD patients was 28.3% (95%-CI: 16.4–41.5%), which was not significantly different from OS of patients with stage III NSCLC treated with definitive or neoadjuvant RCT (34.9% (95%-CI: 27.4–42.8%)). However, the PFS of OMD patients at five years or last follow-up was significantly worse than that of stage III patients (13.0% vs. 24.3%, p = 0.0048). The latter was due to a higher cumulative incidence of distant metastases in OMD patients (50.2% vs. 20.4% at 48 months, p < 0.0001) in comparison to stage III patients. A cross-validated classifier that included severe comorbidity, ECOG performance status, gender and pre-treatment serum CRP level as the most important factors in the univariable analysis, was able to divide the OMD patient group into two equally sized groups with a four-year survival rate of 49.4% in the good prognosis group and 9.9% in the poor prognosis group (p = 0.0021). Laboratory chemistry and clinical parameters, in addition to imaging and high-precision therapies, can help to predict and improve prognosis. Conclusions: A multimodality treatment approach and local metastases-directed therapy in addition to chemoimmunotherapy can lead to good long-term survival in patients with cT3/cT4 or cN2/cN3 OMD NSCLC without severe comorbidities and in good performance status and is therefore recommended.

C-reactive protein as robust laboratory value associated with prognosis in patients with stage III non-small cell lung cancer (NSCLC) treated with definitive radiochemotherapy

“…In a prior investigation we found that severe comorbidity, ECOG performance status, sex and pre-treatment serum CRP level as the most important factors in the univariable analysis in a consecutive cohort of de-novo oligometastatic NSCLC treated at our centre 22 . Also other study groups found the predictive value of baseline CRP levels on the efficacy of chemotherapy plus immune checkpoint inhibitors in patients with advanced lung squamous cell carcinoma.…”

“…However, limitations exist due to the study's retrospective design. In addition external validation by an independent larger cohort was not conducted in stage III but up to now CRP at base line was also analyzed so far in oligometastatic NSCLC patients treated with thoracic radiochemotherapy and found to be prognostic 22 . Furthermore, various other biomarkers and prognostic parameters should be investigated in more detail as e.g.…”

“…Laboratory parameters, such as leukocytosis 13 , lymphocytopenia 14 , neutropenia 15 , elevation of lactate dehydrogenase (LDH) 16 , C-reactive protein (CRP) changes 17 – 19 , thrombocytosis 20 , and low hemoglobin (Hb) 21 , have been identified as prognostic factors in stage III NSCLC patients. In a prior investigation we found in de-novo oligo-metastatic disease that severe comorbidity, ECOG performance status, sex and pre-treatment serum CRP level as the most important factors in the univariable analysis in consecutive cohort treated at our centre 22 .…”