Organ-preserving regimens in rectal cancer

The phase 2 NO-CUT and phase 3 OPERA results showed that both total neoadjuvant therapy (TNT) and contact x-ray brachytherapy (CXB) are effective organ-preserving approaches in the non-operative management of patients with rectal cancer.

Non-operative management after clinical complete response to TNT is gaining consensus in locally advanced rectal cancer. The phase 2, single-arm NO-CUT trial (NCT03565029) assessed whether non-operative management negatively affects the risk of distant relapse. Dr Alessio Amatu (Niguarda Cancer Center, Italy) presented the first results [1].

Of 180 enrolled participants with rectal adenocarcinoma (mid/low cT3–4, cN1–2, cM0, pMMR/MMS), 46 (26%) achieved clinical complete response at 30 weeks after starting TNT and proceeded with non-operative management. At 30 months, distant relapse-free survival was 96.9% in participants in the non-operative management arm and 76.7% in the full study cohort, meeting the primary endpoint of the study. The organ preservation rate in participants receiving non-operative management was 85% (39/46). All participants with local regrowth underwent rescue surgery.

Likewise, the phase 3 OPERA trial (NCT02505750) has shown that a CXB boost with chemoradiotherapy was able to increase the 3-year rate of organ preservation for early rectal adenocarcinoma from 59% to 81% (HR 0.36; P=0.0026) [2]. Dr Syrine Ben Dhia (Antoine Lacassagne Center, France) presented the 5-year results of OPERA [3].

OPERA enrolled 141 participants with rectal adenocarcinoma (mid/low cT2–T3b, cN0–1). The 5-year organ preservation rate in participants who underwent CXB (n=72) was 79%, versus 56% for participants in the control arm (n=69) (HR 0.4; 95% CI 0.21–0.75; P=0.0039). In participants with a tumour of <3 cm, organ preservation rates were 93% and 54%, respectively (HR 0.12; P<0.006). “Of note, rectal bleeding dissolved after 3 years,” Dr Ben Dhia said. In addition, a CXB boost decreased local recurrence at 5 years (16% vs 33%; P=0.002) and improved disease-free survival (73% vs 46%; P=0.003).

1. Amatu A, et al. Total neoadjuvant treatment (TNT) with non-operative management (NOM) for proficient mismatch repair locally advanced rectal cancer (pMMR LARC): First results of NO-CUT trial. Abstract 509O, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
2. Gérard JP, et al. Lancet Gastroenterol Hepatol. 2023;8:356-367.
3. Ben Dhia S, et al. Organ preservation in early rectal adenocarcinoma: 5-year results of the randomized opera trial. Abstract 508MO, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

Copyright ©2024 Medicom Medical Publishers



Posted on 4 November 20244 November 2024