New conversations in an old argument: Lessons learnt from the PIONEER randomised feasibility study in resectable...

Stage III-N2 non-small cell lung cancer (NSCLC) accounts for ∼ 6% of NSCLC cases in the UK. Despite decades of research, no clear survival advantage has been demonstrated between surgical and non-surgical treatment strategies in cases considered resectable. The impact of these regimens on health-related quality of life (HRQoL) remains poorly understood. The PIONEER trial aimed to assess the feasibility of a future phase III randomised controlled trial (RCT) comparing surgical versus non-surgical multimodality treatment with HRQoL as a potential primary outcome.

PIONEER was a UK-based, 8-centre feasibility RCT recruiting patients with resectable stage III-N2 NSCLC. Patients were randomised 1:1 to surgical multimodality treatment or non-surgical treatment. Feasibility outcomes included recruitment rate, treatment adherence, and completion of HRQoL questionnaires (EORTC QLQ-C30).

Of 276 screened patients, 52 (19%) were eligible, and 28 (54%) of these consented and were randomised. Uptake of randomised treatment was high (93%), but only 50% and 57% completed HRQoL questionnaires at 3 and 6 months, respectively. Completion of planned multimodality treatment occurred in 50% (surgery arm) and 65% (non-surgical arm). Central review showed 12% of "unresectable" patients were potentially eligible and highlighted variability between multi-disciplinary teams.

A future phase III trial is unlikely to be feasible. We suggest future work in this area considers leveraging high-quality, real-world data to offer valuable insights into treatment patterns and outcomes in unselected populations.