Minimal Residual Disease Enhances Prognostic Stratification beyond Pathologic Response in Resectable Non–Small Cell Lung Cancer
Year: 2026
Type: article
Abstract: PURPOSE: Perioperative chemoimmunotherapy is the standard of care for resectable, locally advanced non-small cell lung cancer (NSCLC). Although pathologic complete response (pCR) correlates with excellent survival outcomes, some patients without pCR still exhibit long-term survival. In this study, we evaluate the added value of minimal residual disease (MRD). EXPERIMENTAL DESIGN: MRD was assessed in 60 patients from the NADIM II trial (NCT03838159) using the Guardant Reveal assay. In NADIM II, patients with NSCLC without EGFR or ALK alterations were randomly assigned to receive neoadjuvant nivolumab plus chemotherapy (experimental arm) or chemotherapy alone, followed by surgery. Patients in the experimental arm with R0 resection received adjuvant nivolumab. RESULTS: The MRD detection rate was 9.6%. MRD after surgery or during adjuvant treatment was associated with inferior event-free survival (EFS) and overall survival [OS; hazard ratio (HR): 10.2; 95% confidence interval (CI), 3.7-28.3 and HR: 10.0; 95% CI, 2.0-49.9, respectively]. All patients with MRD-negative plasma samples in at least two time points were alive [HR: not estimable (NE), P < 0.001], with only one relapse (HR: 41.6; 95% CI, 5.0-348.8), corresponding to a patient relapsing with a single brain metastasis. MRD enhanced the prognostic value of pCR for both EFS (P < 0.001) and OS (P = 0.015). Among non-pCR patients, MRD remained a significant prognostic marker (HR: 6.2; 95% CI, 2.2-17.1 and HR: 6.5; 95% CI, 1.3-32.5, for EFS and OS respectively). All non-pCR patients with MRD-negative results in at least two time points were alive (HR: NE, P = 0.025), with one relapse (HR: 19.9; 95% CI, 2.4-165.6), corresponding to the aforementioned case. CONCLUSIONS: MRD may refine prognostic evaluation beyond pCR in resectable NSCLC undergoing perioperative chemoimmunotherapy.
Source: Clinical Cancer Research
Authors: Mariano Provencio, Roberto Serna-Blasco, Ernest Nadal, José Luis González Larriba, Alex Martínez-Martí, Reyes Bernabé Caro, Joaquim Bosch-Barrera, Virginia Calvo, Amelia Insa Molla, Noemí Reguart, Javier de Castro Carpeño, Carlos Aguado de la Rosa, Ramón Palmero Sanchez, Florentino Hernando Trancho, Javier Martín-López, Alejandro Rodríguez-Festa, Pilar Mediavilla-Medel, Martín Lázaro, Jim Hayes, Alberto Cruz-Bermúdez, Bartomeu Massutí, Atocha Romero
Institutions: Hospital Universitario Puerta de Hierro Majadahonda, Institut Català d'Oncologia, Duran i Reynals Hospital, Hospital Clínico San Carlos, Vall d'Hebron Hospital Universitari, Hospital Universitario Virgen del Rocío, Institut d'Investigació Biomèdica de Girona, Hospital Universitari de Girona Doctor Josep Trueta, Hospital Clínico Universitario de Valencia, Hospital Clínic de Barcelona, Hospital Universitario La Paz, Guardant (United States), Hospital General Universitario de Alicante Doctor Balmis
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Bristol-Myers Squibb Foundation, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Gilead Sciences, F. Hoffmann-La Roche, Regeneron Pharmaceuticals, Les Laboratories Pierre Fabre, Centres de Recerca de Catalunya, Apollomics, European Commission, Daiichi-Sankyo, Fundació Institut de Recerca Hospital Universitari Vall d’Hebron, PharmaMar, Ipsen, Instituto de Salud Carlos III, European Regional Development Fund, Agencia Estatal de Investigación, Cilag
Awards: G2956895487, G434337789, Quimio-inmunoterapia en estadios localmente avanzados de CPCNP: validación de marcadores derivados del ctDNA y el microambiente tumoral., Papel de la microbiota intestinal en la respuesta a la quimio-inmunoterapia en cáncer de pulmón de células no pequeñas, G7063755300, Cancer Long Survivors Artificial Intelligence Follow Up, Biomarkers4Cure: Biomarcadores predictivos de respuesta a combinaciones de inmunoterapia mas quimioterapia neoadyuvante en pacientes con cáncer de pulmón operable
OpenAlex ID: W7124315299