Radiotherapy Dose Escalation for Non-operative Management of Unresectable Locally Recurrent Rectal Cancer (STEP-UP)

The optimal curative-intent management of locally recurrent rectal cancer (LRRC) typically involves multimodality therapy, comprising neoadjuvant therapy and subsequent salvage surgery. However, in patients with unresectable LRRC, where surgical intervention is not feasible, management is limited to non-operative bimodality therapy with systemic therapy and radiotherapy. For this patient group, evidence guiding the optimisation of non-operative management remains limited, particularly regarding strategies to optimise radiotherapy and achieve durable control. In this context, the therapeutic goal is to achieve prolonged local control while minimising treatment-related toxicity. Radiotherapy dose escalation has been proposed as a potential strategy to achieve this balance. However, its feasibility and safety in the non-operative management of unresectable LRRC have not yet been established. As such, this study aims to evaluate the feasibility and safety of this radiotherapeutic approach, and to determine its impact on both symptomatic control and oncological outcomes.