Reduced-dose chemoradiotherapy and non-surgical strategies show promising outcomes with fewer long-term side-effects in lower gastrointestinal cancers
Two major clinical trials recently presented at ESTRO 2025, the annual congress of the European Society for Radiotherapy and Oncology (ESTRO), are setting new standards in the treatment of lower gastrointestinal cancers, offering patients less invasive options while maintaining oncological safety.
Final results from the ACT4 trial, showed that a reduced-dose, shorter-course regimen of chemoradiotherapy using intensity-modulated radiotherapy (IMRT) is as effective as the current standard in early-stage anal cancer (Lancet Oncol. 2025 May 2:S1470-2045(25)00213-X). ACT4 is part of the Personalising Radiotherapy in Anal Cancer (PLATO) trial designed as an umbrella trial to optimise radiotherapy treatment for patients with anal cancer.
The randomised phase II trial enrolled 163 patients across 28 UK centres, randomising them to receive either standard-dose IMRT (50.4 Gy over 5.5 weeks) or a reduced dose (41.4 Gy over 4.5 weeks), both combined with chemotherapy. After three years, pelvic disease control was observed in 87.6% of patients in the reduced-dose group and 83.6% in the standard group. All major survival outcomes—including progression-free, disease-free, colostomy-free, and overall survival—were comparable.
Crucially, the shorter regimen improved short term toxicity and demonstrated a trend towards better sexual function in men and women. Patients used a newly developed questionnaire (EORTC QLQ-ANL27) to report on their side-effects before, during and after treatment, so for the first time the true impact of the disease and treatment on patient experience has been recognised. Also, the practice-changing results show promise in reducing treatment burden and improving healthcare resource allocation. “For the first time, we have shown that a shorter, lower-dose course of radiotherapy is safe and effective for early-stage anal cancer,” said Prof. David Sebag-Montefiore, University of Leeds, UK, presenting the results. “This could lead to a global shift in how we treat these patients.”
Also presented at the congress, the international STAR-TREC trial (NCT02945566) has demonstrated that selected patients with early- to intermediate-stage rectal cancer can safely avoid radical surgery if they achieve a complete response after radiotherapy-based treatment. Radical surgery has been the standard treatment in this patient group and while effective, is associated with long-term complications including the need for permanent stomas.
The phase II/III study, which enrolled 344 patients across 37 international centres, compared two non-surgical strategies, short-course radiotherapy (five radiotherapy sessions) versus long-course chemoradiotherapy (25 lower-dose radiotherapy sessions with chemotherapy). At one year, 80% of patients treated with long-course chemoradiotherapy and 61% of those receiving short-course radiotherapy were able to avoid surgery altogether. Both regimens were well tolerated with minimal short-term toxicity.
“Avoiding surgery helps preserve bowel function and quality of life,” said Prof. Corrie Marijnen, Netherlands Cancer Institute, presenting the results. “This study shows that radiotherapy-based strategies, whether alone with a more intensive treatment course or combined with chemotherapy, can be a viable alternative for many patients.”
This trial evaluates a smaller radiotherapy field size with the aim of reducing both short- and longer-term side effects for patients. The STAR-TREC results challenge the long-standing paradigm that surgery is essential for all rectal cancer patients, offering a more patient-centred, quality-of-life-focused approach. Ongoing follow-up will assess long-term cancer control, but the 12-month results set the stage for integrating organ-preserving strategies into standard care pathways.
Both ACT4 and STAR-TREC reflect a broader movement in radiation oncology toward personalised de-escalation, where treatment intensity is adjusted based on patient and tumour characteristics. These strategies aim not only to cure, but also to preserve organ function and quality of life.
(With the kind contribution of Alexandra Gilbert, University of Leeds, UK)
