400MO - Curative chemoradiation for low rectal cancer: Early clinical outcomes from a multicentre phase II trial

Background

Watchful waiting without surgery for rectal cancer is an option after complete response to chemoradiation. There is a need for optimising patient selection and radiotherapy to cure more patients with this modality. The aim of the study was to test high-dose radiotherapy of low rectal cancer for organ preservation in a multi-centre setting. The early endpoint of clinical complete response (cCR) at 12 weeks is reported here.

Methods

This prospective trial enrolled patients with rectal cancer 0-6 cm from the anal verge, T1-3 N0-1 M0, performance status 0-2, and adequate organ function. Radiotherapy consisted of 62 and 50.4 Gy to the tumour and regional lymph nodes, respectively, in 28 fractions using intensity-modulated radiation therapy and daily image guidance. Capecitabine 825mg/m² BID was administered on treatment days. Patients with cCR 6-12 weeks from end of treatment judged by MRI, endoscopy, and digital rectal exam were referred to observation without surgery. The patients continue follow-up for recurrence, adverse events, and patient reported outcomes irrespective of treatment.

Results

Three Danish centres enrolled 108 patients from 9/2015 to 12/2019; with 15%/54%/31% T1/T2/T3 tumours; median tumour distance from anal verge 4.5 cm; 29% with N1 disease; 36% female; median age 71 years. 107 patients started treatment, the majority receiving full dose of radiotherapy (n=104) and of chemotherapy (n=80). The most frequent grade 3-4 toxicities were diarrhoea (7%), constipation (2%), and nausea, vomiting, pain, and skin reaction (all 1%). One patient died from other causes and one left the study before evaluation. 12 weeks after end of treatment, 13 patients had residual tumour and were referred for surgery; two had distant metastasis leaving 90 of 108 patients (83.3%) with cCR and allocation to follow-up without surgery.

Conclusions

The unprecedented high cCR rate of 83.3% in this multicentre phase II trial demonstrates that rectal cancer patients can be offered curative chemoradiation. Long-term outcomes, including tumour control, organ function, and quality of life, are still needed to evaluate the full potential of high-dose 62 Gy radiotherapy as a new standard treatment.

Clinical trial identification

NCT02438839.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Danish Cancer Society.

Disclosure

L.H. Jensen: Research grant/Funding (institution): MSD, InCyte, 2cureX, BMS. All other authors have declared no conflicts of interest.