Role of ctDNA for the detection of minimal residual disease in resected non-small cell lung cancer: a systematic review

Abstract

Background: Operable stage I-III non-small cell lung cancer (NSCLC) has a high risk of recurrence, mainly due to remnant clones of the disease defined as minimal residual disease (MRD). Adjuvant chemotherapy has a limited efficacy in reducing the risk of relapse, and prognostic as well as predictive biomarkers in this context are currently missing.Methods: We performed a systematic review to evaluate the state of the art about the role of circulating tumor DNA detection through liquid biopsy for the assessment of MRD in resected early-stage NSCLC patients.Results: Among the 650 studies identified, 13 were eligible and included. Although highly heterogeneous, all the studies demonstrated a poor prognosis in patients with post-operative MRD, with a detection rate ranging from 6% to 45%. MRD detection preceded radiographic/clinical recurrence by a mean of 5.5 months. MRD positive patients were most likely to benefit from adjuvant treatment in terms of recurrence-free survival (RFS). Consistently, adjuvant therapy did not minimize the risk of relapse in the MRD negative group.Conclusions: Liquid biopsy has a relevant role in assessing post-surgical MRD in resected NSCLC. Since currently there are no criteria other than stage and risk factors for the choice of adjuvant treatment in this setting, post-operative assessment of MRD through liquid biopsy might be a promising approach to guide the decision.

The use of minimal residual disease in thoracic oncology: Gaps between promises and the on‐the‐ground reality of daily practice

“…The clinical utility of cf‐DNA for the evaluation of MRD has been investigated in many studies, which show a significant association between circulating tumour‐DNA (ct‐DNA) and decreased recurrence‐free survival 7 . Post‐radical treatment, the analysis of cf‐DNA has the potential to become a highly valuable tool to guide treatment and surveillance.…”

Molecular minimal residual disease in resected non-small cell lung cancer (NSCLC): results of specifically designed interventional clinical trials eagerly awaited

“…Molecular minimal residual disease in resected non-small cell lung cancer (NSCLC): results of specifically designed interventional clinical trials eagerly awaited are presented in the review (10). We might also have in the near future results from clinical trials evaluating different treatments in the adjuvant setting, such as the ADAURA trial for EGFR-mutated NSCLC patients (13), and the Impower010 trial evaluating adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA NSCLC (14).…”

“…Verzè and her colleagues performed a systematic review of these studies (10). They selected and included 13 studies in their analysis.…”

“…The performance of ctDNA detection for the assessment of MRD (molecular MRD) in resected early-stage NSCLC patients has been evaluated in several studies. Michela Verzè and her colleagues performed a systematic review of these studies ( 10 ). They selected and included 13 studies in their analysis.…”

Rapid Advances in Resectable Non–Small Cell Lung Cancer

“…We expect many clinicians to advocate treatment beyond 3 years and possibly indefinitely for patients tolerating it well longitudinally, despite the attendant cost and toxic effects. 7 Although we can envision a future when the duration of treatment may be informed by the presence or absence of circulating tumor DNA (ctDNA) in minimal residual disease (MRD) assays, 8 this is not our current reality.…”