From radical resection to organ preservation: the evolution of neoadjuvant therapies in rectal cancer

Abstract Rectal cancer management has progressively shifted from a surgery-first paradigm towards response-adapted strategies that prioritise organ preservation (OP). We provide a narrative, trial-based overview of the evolution of neoadjuvant approaches for extraperitoneal, locally advanced rectal cancer, including short-course radiotherapy (SCRT), long-course chemoradiotherapy (LCRT), and total neoadjuvant therapy (TNT), with particular attention to dose escalation, high-precision techniques, and structured watch-and-wait (WW) pathways. We summarise the evidence supporting organ-preserving approaches, critically appraise the specific challenges of treating frail and elderly patients, and highlight emerging roles for magnetic resonance imaging (MRI) guidance, immunotherapy, and targeted agents. In parallel, we report a single-centre retrospective cohort of 65 patients with locally advanced rectal cancer treated within a TNT-based, organ preservation-oriented pathway that integrated modest radiotherapy dose escalation, induction or consolidation chemotherapy, and a formal WW programme. In this real-world series, clinical complete response (cCR) was achieved in 30 % of patients, pathological complete response (pCR) in 34.5 % of those undergoing surgery, and 50 % of cCR cases were managed non-operatively, with low rates of acute toxicity. Taken together, the literature synthesis and institutional experience illustrate how contemporary multimodality strategies can be individualised to maximise tumour control and quality of life while limiting treatment burden, particularly in older or comorbid patients. This article aims to support multidisciplinary teams in implementing evidence-based organ-preserving pathways and to identify priorities for future clinical trials in rectal cancer.