Organ preservation in rectal cancer following clinical complete response after short-course radiotherapy-based total neoadjuvant therapy

Background and purpose Organ preservation after total neoadjuvant therapy (TNT) is feasible in patients with locally advanced rectal cancer (LARC) who achieve a clinical complete response (cCR). However, most watch-and-wait (WW) evidence derives from long-course chemoradiotherapy (LCCRT), with limited data regarding short-course radiotherapy (SCRT)-based TNT. We evaluated response-adapted organ preservation following SCRT-based TNT in a public, resource-limited healthcare setting. Materials and methods This retrospective cohort included consecutive patients with stage II–III LARC (cT3-T4 and/or N+) with palpable tumors ≤8 cm from the anal verge treated between 2020 and 2023. All patients received SCRT (25 Gy in five fractions) followed by consolidation chemotherapy (FOLFOX or CAPOX). Tumor response was assessed 8–12 weeks after TNT using digital rectal examination, pelvic MRI, flexible sigmoidoscopy and CEA levels. Patients achieving a cCR were managed with a structured WW protocol; others underwent total mesorectal excision (TME). Time-to-event outcomes were estimated descriptively. Results Among 51 evaluable patients, 19 (37.3%) achieved cCR and 18 (35.3%) were managed with WW. After a median follow-up of 43.2 months (IQR 34.1–51.5), 3 WW patients (16.7%) developed local regrowth, all successfully salvaged with R0 resection. The estimated 24-month local regrowth-free survival was 82.2% (95% CI 65.8–100%). One WW patient died from systemic progression after salvage surgery. In the surgical group, 4 patients (12.1%) achieved a pathological complete response (pCR). Overall, 13 of 18 WW patients (72.2%) maintained sustained cCR without any oncologic event during follow-up. Conclusions Hypofractionated SCRT integrated into a TNT strategy enabled response-adapted organ preservation with acceptable local regrowth-free survival in selected patients with LARC. This strategy was deliverable within a public healthcare system and achieved acceptable mid-term oncologic control. Prospective validation with longer follow-up is warranted.