Radiotherapy Dose Escalation Did Not Improve Efficacy/QOL in Anal Cancer

For patients with T3/T4 and Tany N-positive anal cancer, the use of radiotherapy dose escalation from 53.2 Gy to 58.8 Gy or 61.6 Gy in 28 fractions did not improve outcomes at 6 months, according to results from the phase 3 PLATO ACT 5 trial (ISRCTN88455282) presented at the 2026 American Society of Clinical Oncology Gastrointestinal Cancer Symposium.

A complete response was noted in 72.7% of patients received 53.2 Gy, 70.3% receiving 58.8 Gy, and 63.6% receiving 61.6 Gy. The complete clinical response MRI of TRG 1 or 2 with no visible T2 weighted nodes was 64.9%, 66.5%, and 65.6%, respectively.

The patient reported outcomes (PROs) for global health status/quality of life assessed pain, sexual function by sex, bowel function in non-stoma participants, and diarrhea. Maria A. Hawkins, professor in radiation oncology at the University of College London, noted that there was no impact up to 6 months for these results.

Toxicity was also assessed at 6 months among the 3 treatment regimens. During treatment, grade 1/2 and grade 3/4 adverse effects (AEs) were noted in 44.6% vs 55.4% in the 53.2 Gy group, 46.4% vs 53.6% in the 58.8 Gy group, and 47.9% vs 52.1% in the 61.6 Gy group. At 6 weeks, grade 1/2 and grade 3 AEs were noted in 78.2% vs 2.9%, 69.7% vs 12.9%, and 72.9% vs 9.4%, respectively, with no archive records noted in 15.9%, 15.2%, and 16.5%. At 3 months, the rates of grade 1/2 and grade 3 AEs were 62.3% vs 2.9%, 62.9% vs 3.0%, and 60.7% vs 6.3%, with no archive records at that timepoint in 33.3%, 32.6%, and 29.9%. At 6 months, grade 1/2 and grade 3 AEs were noted in 65.1% vs 3.6%, 62.3% vs 3.8%, and 55.2% vs 7.1%; there were not archive records at that timepoint in 37.7%, 41.7%, and 33.9%.

Investigators highlighted that the grade 3/4 rates during treatment were at the peak of toxicity, and a reduction occurred in subsequent timepoints. After radiotherapy completion, there were no grade 4 AEs.

In the ACT 5 portion of the PLAT trial, patients were randomly assigned 1:1:1 to either the 53.2 Gy group (n = 154), 58.8 Gy group (n = 154), or the 61.6 Gy group (n = 153), all given in 28 fractions. The total of 459 patients, with a 10% drop out, compared each experimental arm with standard dose intensity modulated radiotherapy for 3-year locoregional-free survival. The 6-month end points were acute toxicity, treatment compliance, radiological and clinical complete response rates, and PROs.

In total, 73.4% of patients were female, 73.0% had an ECOG performance status of 0, and the mean age was 60.9 years old. Additionally, 98.5% of patients were human immunodefiency virus (HIV)-negative. Patients were enrolled at 34 UK sites between February 2017 and August 2023. Hawkins highlighted that 82% of patients were given capecitabine (Xeloda) plus radiotherapy, and 18% were given 5-fluorouracil (5-FU) plus radiotherapy.

Disease characteristics of the tumor site in total included 6.9% in the anal margin and 93.1% in the anal canal. In total, 0.2% had T1 stage, 32.0% had T2 stage, 37.4% had T3 stage, and 30.5% had T4 stage. Regarding N stage, 16.4% had N0, 44.5% had N1, 17.9% had N2, and 21.2% had N3.

A total of 100% of patient received treatment, and 24.4% had radiotherapy interruptions. Capecitabine reduction occurred in 9.0% of patients, 36.0% had capecitabine omission, and 20.4% had capecitabine omission or reduction due to toxicity. Additionally, 9.9% of patients had 5-FU reduction, and 7.4% had 5-FU omission.

Hawkins has no relationships to disclose.

Reference

Hawkins MA, Gilbert A, Adams R, et al. Early outcomes of the PLATO ACT5 randomised trial: personalizing anal cancer radiotherapy dose. J Clin Oncol. 2026;44(suppl 1):1. 10.1200/JCO.2026.44.2_suppl.1