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Review
. 2022 Dec;11(12):2588-2600.
doi: 10.21037/tlcr-22-390.

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

Michela Verzè  1   2 , Monica Pluchino  1 , Alessandro Leonetti  1   2 , Matilde Corianò  1   2 , Francesco Bonatti  1   2 , Maria P Armillotta  1 , Fabiana Perrone  1 , Miriam Casali  1   3 , Roberta Minari  1 , Marcello Tiseo  1   2
Affiliations
Review

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

Michela Verzè et al. Transl Lung Cancer Res. 2022 Dec.

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.

Keywords: Non-small cell lung cancer (NSCLC); adjuvant therapy; circulating tumor DNA (ctDNA); minimal residual disease (MRD).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-390/coif). MT serves as an unpaid editorial board member of Translational Lung Cancer Research from December 2021 to November 2023. MT has received speakers’ and/or consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Takeda, Amgen, Merck, and Sanofi. MT received institutional research grants from Astra-Zeneca and Boehringer Ingelheim. AL has received speakers’ fees for Astra-Zeneca and MSD. AL has been on advisory boards for BeiGene and Sanofi. RM has received a payment for manuscript writing from Novartis. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Schematic approach of ctDNA MRD testing in resected NSCLC patients. CT, chemotherapy; RFS, recurrence-free survival; OS, overall survival; MRD, minimal residual disease; NSCLC, non-small cell lung cancer.
Figure 2
Figure 2
Flow diagram. ASCO, American Society of Clinical Oncology; ESMO, European Society of Medical Oncology; IASLC, International Association for the Study of Lung Cancer; NSCLC, non-small cell lung cancer.
Figure 3
Figure 3
Timeline of blood collection before and after surgery.
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