Defining oligometastatic non-small cell lung cancer: concept versus biology, a literature review

Abstract

In this review, the concept of (synchronous) oligometastatic disease in patients with nononcogene-driven non-small cell lung cancer (NSCLC) will be placed in the context of tumor biology and metastatic growth patterns. We will also provide considerations for clinical practice and future perspectives, which will ultimately lead to better patient selection and oligometastatic disease outcome. Background:The treatment landscape of metastasized NSCLC has moved from "one-size fits all" to a personalized approach. Prognosis has traditionally been poor but new treatment options, such as immunotherapy and targeted therapy, brighten future perspectives. Another emerging development is the recognition of patients with so-called "oligometastatic" state of disease. Oligometastatic disease has been recognized as a distinct clinical presentation in which the tumor is stated to be early in its evolution of metastatic potential. It is suggested that this stage of disease has an indolent course, comes with a better prognosis and therefore could be considered for radical multimodality treatment.Methods: Narrative overview of the literature synthesizing the findings of literature retrieved from searches of computerized databases, hand searches, and authoritative texts.Conclusions: Oligometastatic NSCLC is a broad spectrum disease, with a variable prognosis. Although the biology and behavior of "intermediate state" of metastatic disease are not fully understood, there is evidence that a subgroup of patients can benefit from local radical treatment when integrated into a multimodality regime. The consensus definition of oligometastatic NSCLC, including accurate staging, may help to uniform future trials. The preferable treatment strategy seems to sequential systemic treatment with subsequent local radical treatment in patients with a partial response or stable disease. Prognostic factors such as N-stage, number and site of distant metastases, tumor volume, performance status, age, and tumor type should be considered. The local radical treatment strategy has to be discussed in a multidisciplinary team meeting, taking into account patient characteristics and invasiveness of the procedure. However, many aspects remain to be explored and learned about the cancer biology and characteristics of intermediate state tumors.

Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC

“…Over the past 30 years oligometastatic NSCLC has been recognized as a unique clinical entity [3][4][5]11,25]. Several retrospective series and some prospective studies have demonstrated the efficacy and safety of aggressive approaches in selected patients with OMD and supported the use of metastasis-directed ablative radiotherapy alone, or in addition to a primary therapy to consolidate all sites of gross disease [26][27][28][29][30][31][32].…”

“…The definition and management of oligometastatic NSCLC have been incorporated into current guidelines on lung cancer, supporting the use of a definitive treatment with curative intent directed to primary disease and including focal ablation of all sites of oligometastatic involvement [8][9][10][11]. In the pre-immunotherapy era, prospective phase 2 randomized trials have shown an increase in progression free survival (PFS) and overall survival (OS) for oligometastatic patients receiving radiotherapy (RT) as local ablative treatment (LAT) in combination with systemic therapy [12][13][14].…”

Immunotherapy with radiotherapy fails to improve prognosis of patients with stage IV non-small cell lung cancer: a retrospective cohort analysis of the THUNDER-2 study

“…The primary implanted particle in patients treated with RPI was 125 I, and the median number of particle implantation was 1 time (range,1–4 times). Oligometastatic status was defined as a maximum of 5 metastases in 3 organs, but diffuse plasma membrane (meningeal, pleural, pericardial, and mesenteric) or bone marrow metastases were not included in this definition ( 18 ). Based on the peak timing of RT to promote tumor-specific antigen release, we preliminarily explored the optimal timing of immune drug intervention.…”

Oligometastatic Non-Small Cell Lung Cancer: A Practical Review of Prospective Trials

“…These categories included (1) synchronous oligometastatic disease where oligometastasis and the primary tumor are detected concurrently at the time of diagnosis, (2) metachronous oligometastatic or oligo-recurrent disease where oligometastatic lesions are detected three months after the initial diagnosis while the primary tumor is controlled, (3) oligo-progressive metastatic disease where progression after systemic therapy occurs in a limited number of metastases, and (4) oligo-persistent metastatic disease where oligo-metastases persist after systemic therapy [ 18 ]. Nevertheless, a universal definition of oligometastatic disease has not been adopted yet, and discrepancy regarding the number of organs involved, the volume of the metastasis, and the response of the primary tumor persists, in addition to the patient’s performance status and the likelihood of tolerating local ablative therapies [ 3 ].…”

“…Despite the current advances in lung cancer screening, at least 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) will present with metastatic disease at diagnosis [ 1 ]. Among those patients, approximately 37.5% will present with a limited metastatic state referred to as “oligometastatic” [ 2 ], requiring a multidisciplinary treatment approach with systemic agents combined with potential metastasis-directed local ablative therapies [ 3 ].…”