Efficacy and safety of short-course radiotherapy versus total neoadjuvant therapy in older rectal cancer patients: a randomised pragmatic trial (SHAPERS).

Although total neoadjuvant therapy (TNT) is a new standard of care for locally advanced rectal cancer (LARC), there are no data to confirm the safety and efficacy of this approach in older patients. SHAPERS is a multicentre, open-label, randomised pragmatic trial, aiming to assess whether neoadjuvant short-course radiotherapy (SCRT) is a better trade-off between safety and efficacy than TNT in LARC patients aged ≥70 years. Eligible patients are randomised in a 1 : 1 ratio to SCRT followed by surgery [or watch & wait (w&w)] ± adjuvant chemotherapy or TNT (either SCRT followed by 12-18 weeks of chemotherapy, or long-course chemoradiotherapy followed or preceded by 16 weeks of chemotherapy, based on the investigator's choice) followed by surgery (or w&w). The primary endpoint is the net treatment benefit, a multicomponent measure of treatment effect based on generalised pairwise comparisons, and defined by four prioritised outcome measures: (i) overall survival at 3 years; (ii) progression-free survival at 3 years; (iii) increased-grade peripheral sensory neuropathy at 3 years; (iv) grade ≥3 toxicities during treatment. The study sample size includes 230 eligible patients, to be recruited at 15-20 centres in Belgium. The trial is registered with ClinicalTrials.gov (NCT06052332).