Non-Operative Management Shows Strong Outcomes in Rectal Cancer Patients With Complete Clinical Response

A non-operative, “watch-and-wait” approach may provide excellent disease control for selected patients with rectal cancer who achieve a clinical complete response after total neoadjuvant therapy, according to results from a phase 2 trial published in The Lancet Oncology.

In the investigator-initiated, multicentre study, non-operative management was associated with a 95% distant relapse-free survival rate at 30 months among patients with stage II–III rectal cancer who showed a clinical complete response to neoadjuvant treatment. Importantly, patients who experienced local tumour regrowth retained the option of successful salvage surgery.

Study design and treatment

The trial enrolled 180 patients (median age 62 years; 44% women) with stage II–III adenocarcinoma of the lower-to-middle rectum across four cancer centres in Italy between June 2018 and August 2023. Treatment consisted of induction chemotherapy with capecitabine and oxaliplatin, followed by chemoradiotherapy (50–54 Gy over 5 weeks).

Of the 179 evaluable patients, 47 (26%) achieved a clinical complete response and were assigned to non-operative management, 107 (60%) underwent surgery after neoadjuvant therapy, and 18 (10%) underwent surgery after discontinuing the study. The primary endpoint was 30-month distant relapse-free survival in the non-operative group.

Key outcomes

After a median follow-up of 35 months, the 30-month distant relapse-free survival rate was 95% in the non-operative management group, compared with 74% in both the surgery group and the overall study population.

Among patients managed non-operatively, 15% experienced local tumour regrowth within two years, corresponding to a 2-year local regrowth risk of 17%. In the surgery group, cumulative risks of local relapse were 11% at 2 years and 16% at 3 years.

Safety and biomarkers

Grade 3–4 adverse events were relatively uncommon, with diarrhoea, lymphopenia, and neutropenia each occurring in about 4% of patients. Overall, 17% experienced serious adverse events, most commonly bowel obstruction (4%) and thromboembolism (3%).

The study also highlighted the prognostic value of circulating tumour DNA (ctDNA). Patients with positive ctDNA after neoadjuvant therapy had significantly worse distant relapse-free survival (P = .0032) and progression-free survival (P = .0028) in the non-operative management group.

Clinical implications

“Non-operative management ensures excellent distant disease control with organ preservation after clinical complete response,” the authors wrote. As the watch-and-wait strategy gains recognition in international guidelines, they noted that integrating ctDNA and other emerging biomarkers could enhance risk stratification and support more personalised treatment decisions.

The study was led by Alessio Amatu, MD, and Giorgio Patelli, MD, from the Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy, and was published online in December 2025.

Source

Non-Operative Management Effective in Patients With Rectal Cancer Showing Clinical Complete Response to Neoadjuvant Therapy - Medscape - December 08, 2025.