Patient-reported symptom monitoring in patients with lung cancer (SYMPRO-Lung trial): long-term, post-hoc survival results of a multicentre, stepped-wedged, cluster-randomised clinical trial.

BACKGROUND: Patient-reported outcome (PRO) symptom monitoring has been shown to improve overall survival. Yet, available evidence largely derives from resource-intensive studies limited to patients with advanced cancer. We aimed to assess the effect of PRO symptom monitoring on overall and progression-free survival in patients with stage I-IV lung cancer in a real-world clinical setting, with follow-up extending to 5 years. METHODS: The SYMPRO-Lung trial was a multicentre, stepped-wedged, cluster-randomised clinical trial across 14 medical centres in the Netherlands. Patients were eligible for inclusion if they were aged 18 years or older with stage I-IV lung cancer (new-onset or recurrent; cytologically or histologically confirmed or radiological suspected) and were starting new treatment. All hospitals started with a control period (standard of care) and, according to randomisation by a computer-generated allocation sequence, crossed over at predefined timepoints to the intervention period (completing weekly online symptom assessments for 1 year). The primary outcome for SYMPRO-Lung trial was health-related quality of life, which has been previously reported. In this post-hoc analysis, we assessed long-term survival outcomes of overall survival and progression-free survival, with overall survival as the primary outcome. Survival analyses in the intention-to-treat population was performed using Cox mixed-effects modelling, adjusted for age, sex, stage, histology, Eastern Cooperative Oncology Group performance status, systemic treatment line, and a random effect for site clustering. The study is registered with Netherlands Trial Register, NL7897, and is complete. FINDINGS: Of the 515 patients initially enrolled to the SYMPRO-Lung trial between Oct 24, 2019, and Sept 16, 2021, 446 (87%) patients were included in this post-hoc analysis (230 [52%] male; 216 [48%] female). 235 (53%) were assigned to the pooled intervention group and 211 (47%) patients to the control group. 69 (13%) of 515 patients were excluded due to the absence of informed consent for the use of their data in follow-up research or because linkage to the Netherlands Cancer Registry could not be established. At a median follow-up 50 months (IQR 46-55), median overall survival was 26 months in the intervention group (IQR 9-not reached, 95% CI 21-33) compared with 21 months (IQR 10-54, 95% CI 17-26) in the control group. Analyses adjusting for confounders showed that PRO symptom monitoring might be associated with improved overall survival (hazard ratio [HR] 0·80, 95% CI 0·63-1·00, p=0·049). Analyses adjusting for confounders showed that PRO symptom monitoring showed no significant difference in progression-free survival between groups (0·86, 0·70-1·07; p=0·18). INTERPRETATION: Weekly PRO symptom monitoring was associated with meaningful improvement in long-term overall survival among patients with stage I-IV lung cancer. Median overall survival was 5 months longer in the intervention group than in the control group. These findings underscore the value of implementing PRO symptom monitoring within routine care for patients with lung cancer. FUNDING: Roche Netherlands, Stichting Kwaliteitsgelden Medisch Specialisten, and Zorginnovatiefonds. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.