Combined versus staged resection of synchronous rectal cancer liver metastases: national target trial emulation
Francesco Marchegiani, Alix Dhote, Alexandra Nassar, Vincent Mallet, Anna Pellat, Heithem Jeddou, Ugo Marchese, Romain Coriat, David Fuks, Karim Boudjema, Emilie Lanoy, Sandrine Katsahian, Stylianos TzedakisAbstract
Background
Optimal sequencing of rectal and liver resection for patients with resectable synchronous liver metastases (SLM) from rectal cancer remains controversial, and rectal-specific evidence is limited.
Methods
A nationwide target trial (METASYNC-R) was emulated using the French national discharge database (2014–2023). Adults undergoing both rectal and liver resection for rectal cancer with SLM were eligible. Combined resection was compared with staged strategies (rectum- or liver-first within 14 weeks). Inverse probability of treatment weighting (IPTW) estimated the average treatment effect. Thirty-day severe complications (Clavien–Dindo grade ≥III) were analysed using marginal logistic regression with robust variance; overall survival was analysed using IPTW Cox proportional hazards models with cluster-robust standard errors. Landmark analyses at 3, 6, 12, and 24 months addressed potential immortal time bias.
Results
Among 9632 patients undergoing both resections, 3057 had SLM and 1872 met the eligibility criteria (median age of 64 years); 1365 (73%) underwent combined resection and 507 (27%) underwent staged resection. Severe complications occurred in 39.7% versus 45.3% (P = 0.20); combined surgery was not associated with an increased risk of severe complications (adjusted OR 0.82 (95% c.i. 0.58 to 1.16); P = 0.27). Major hepatectomy independently increased the risk of severe complications (adjusted OR 1.81 (95% c.i. 1.06 to 3.08); P = 0.029). Thirty-day mortality was similar (1.8% versus 1.5%). Median overall survival was 52.4 months (combined) versus 57.3 months (staged) (P = 0.30). Combined surgery was not associated with worse survival (adjusted HR 0.88 (95% c.i. 0.65 to 1.19); P = 0.40), with consistent findings across landmark analyses.
Conclusion
In this nationwide rectal cancer cohort, combined and staged strategies were associated with comparable morbidity and long-term survival. Surgical sequencing should be individualized within multidisciplinary decision-making.