Management of Synchronous Extrathoracic Oligometastatic Non-Small Cell Lung Cancer

Abstract

Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of newly diagnosed cases of NSCLC. The oligometastatic state—≤5 extrathoracic metastatic lesions in ≤3 organs—is present in ~25% of patients with stage IV disease and is associated with markedly improved outcomes. We retrospectively identified patients with extrathoracic oligometastatic NSCLC who underwent primary tumor resection at our institution from 2000 to 2018. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Factors associated with EFS and OS were determined using Cox regression. In total, 111 patients with oligometastatic NSCLC underwent primary tumor resection; 87 (78%) had a single metastatic lesion. Local consolidative therapy for metastases was performed in 93 patients (84%). Seventy-seven patients experienced recurrence or progression. The five-year EFS was 19% (95% confidence interval (CI), 12–29%), and the five-year OS was 36% (95% CI, 27–50%). Factors independently associated with EFS were primary tumor size (hazard ratio (HR), 1.15 (95% CI, 1.03–1.29); p = 0.014) and lymphovascular invasion (HR, 1.73 (95% CI, 1.06–2.84); p = 0.029). Factors independently associated with OS were neoadjuvant therapy (HR, 0.43 (95% CI, 0.24–0.77); p = 0.004), primary tumor size (HR, 1.18 (95% CI, 1.02–1.35); p = 0.023), pathologic nodal disease (HR, 1.83 (95% CI, 1.05–3.20); p = 0.033), and visceral-pleural invasion (HR, 1.93 (95% CI, 1.10–3.40); p = 0.022). Primary tumor resection represents an important treatment option in the multimodal management of extrathoracic oligometastatic NSCLC. Encouraging long-term survival can be achieved in carefully selected patients, including those who received neoadjuvant therapy and those with limited intrathoracic disease.

Results of Radiation Therapy as Local Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer

“…Performance status, volume of the primary tumor and receipt of at least 63 Gy to the primary tumor were associated with improved OS in multivariate analysis. This observation of favorable OS outcomes with aggressive treatment of the primary site (with chemotherapy plus surgery and/or radiation) has also been observed in a metanalysis of 668 oligometastatic NSCLC patients [ 27 ], a secondary analysis of two prospective trials involving 274 oligometastatic and Stage IV non-oligometastatic NSCLC patients [ 28 ], and a large retrospective review from the Memorial Sloan Kettering Cancer Center [ 29 ]. These studies align with an earlier study noting that the most common site of recurrence in metastatic NSCLC is at the location of the primary tumor [ 30 ], suggesting the importance of definitive therapy targeting the primary tumor in combination with LAT.…”

“…Systemic therapy is a cornerstone of treatment for metastatic lung cancer. As discussed above, aggressive treatment of the primary site has been associated with improved survival outcomes in retrospective analyses involving patients with oligometastatic lung cancer [ 26 , 27 , 28 , 29 ]. While the previously discussed initial trials did not select patients by the receipt, response or timing of systemic therapy, many more recent prospective studies have included these parameters in an effort to further stratify patients who may benefit from LAT.…”

Patient Selection for Local Aggressive Treatment in Oligometastatic Non-Small Cell Lung Cancer

“…A recent study by Ohtaki et al supports this assumption: In a retrospective cohort of 36 patients who underwent salvage surgery after EGFR- or ALK-TKI treatment, a 3-year OS and PFS of 75.1% and 22.2% were found [ 38 ]. A recent retrospective study by Jones et al additionally supports the concept of a neoadjuvant induction in stage oligometastatic NSCLC by showing that patients who received neoadjuvant therapy had a significantly improved 5-year OS of 40% when compared to the cohort of patients who had received primary surgery (20% 5-year OS) [ 39 ]. However, when compared to neoadjuvant chemotherapy followed by local radiotherapy, primary surgery followed by adjuvant chemotherapy still appears to offer an increased median OS (48 months versus 18 months) [ 40 ].…”

Oligometastatic Cancer: Key Concepts and Research Opportunities for 2021 and Beyond

“…Compared with a leukaemia-like dissemination of many malignant processes, the encouraging aspect of a spatially limited oligometastatic disease has ignited a steep rise of scientific interest with new research questions and challenges. We have divided them in three main categories, summarized in Table 1 [ 2 , 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. One of the major drawbacks of the oligometastatic concept is the current perception relying on therapeutic opportunity and cross-sectional imaging rather than intra- and intercellular processes [ 7 ].…”

“…The body of existing evidence, especially from phase III trials, is far from satisfactory, and improvements are already needed at the level of study design with respect to clinical endpoints and the choice of modalities [ 9 , 24 , 29 ]. The latter aspect may indeed be crucial not only due to the large range of possible treatment options and indications, but also because of various combinations and sequencing schedules [ 9 , 14 , 15 , 16 , 17 , 18 ]. It is therefore noteworthy that local ablation should not be used indiscriminately in the oligometastatic setting.…”