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Randomized Controlled Trial
. 2023 Oct 1;278(4):e766-e772.
doi: 10.1097/SLA.0000000000005799. Epub 2023 Jan 20.

Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial

Esmée A Dijkstra  1 , Per J Nilsson  2 , Geke A P Hospers  1 , Renu R Bahadoer  3 , Elma Meershoek-Klein Kranenbarg  3 , Annet G H Roodvoets  3 , Hein Putter  4 , Åke Berglund  5 , Andrés Cervantes  6 , Rogier M P H Crolla  7 , Mathijs P Hendriks  8 , Jaume Capdevila  9 , Ibrahim Edhemovic  10 , Corrie A M Marijnen  11   12 , Cornelis J H van de Velde  3 , Bengt Glimelius  5 , Boudewijn van Etten  13 ; Collaborative Investigators
Affiliations
Randomized Controlled Trial

Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial

Esmée A Dijkstra et al. Ann Surg. .

Abstract

Objective: To analyze risk and patterns of locoregional failure (LRF) in patients of the RAPIDO trial at 5 years.

Background: Multimodality treatment improves local control in rectal cancer. Total neoadjuvant treatment (TNT) aims to improve systemic control while local control is maintained. At 3 years, LRF rate was comparable between TNT and chemoradiotherapy in the RAPIDO trial.

Methods: A total of 920 patients were randomized between an experimental (EXP, short-course radiotherapy, chemotherapy, and surgery) and a standard-care group (STD, chemoradiotherapy, surgery, and optional postoperative chemotherapy). LRFs, including early LRF (no resection except for organ preservation/R2 resection) and locoregional recurrence (LRR) after an R0/R1 resection, were analyzed.

Results: Totally, 460 EXP and 446 STD patients were eligible. At 5.6 years (median follow-up), LRF was detected in 54/460 (12%) and 36/446 (8%) patients in the EXP and STD groups, respectively ( P =0.07), in which EXP patients were more often treated with 3-dimensional-conformed radiotherapy ( P =0.029). In the EXP group, LRR was detected more often [44/431 (10%) vs. 26/428 (6%); P =0.027], with more often a breached mesorectum (9/44 (21%) vs. 1/26 (4); P =0.048). The EXP treatment, enlarged lateral lymph nodes, positive circumferential resection margin, tumor deposits, and node positivity at pathology were the significant predictors for developing LRR. Location of the LRRs was similar between groups. Overall survival after LRF was comparable [hazard ratio: 0.76 (95% CI, 0.46-1.26); P =0.29].

Conclusions: The EXP treatment was associated with an increased risk of LRR, whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated.

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Conflict of interest statement

P.J.N. reports honoraria from Ethicon, Johnson & Johnson, and Amgen. GAPH reports consulting fees from Roche, MSD, Amgen, and Novartis; consulting fees and research support to their institution from Bristol Myers Squibb; and research support to their institution from Seerave Foundation. A.G.H.R. and C.J.H.v.d.V. were partially funded by the EU’s Horizon 2020 research and innovation program under a Marie SkłodowskaCurie grant award (H2020MSCAITN2019, grant agreement number 857894; project acronym: CAST). M.P.H. reports consulting fees from MSD. J.C. reports consulting fees, travel expenses, and research support to their institution from Pfizer, Ipsen, and Eisai; consulting fees and research support to their institution from Bayer, Novartis, and Advanced Accelerator Applications; consulting fees from Sanofi, Exelixis, and Merck Serono; and research support to their institution from AstraZeneca. B.G. reports research support from the Swedish Cancer Society. The remaining authors report no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Consort diagram. Patients entering a W&W program or who “refused surgery” according to the case record forms were grouped together since the predominant reason for the refusers was no remaining tumor/no need for surgery. These patients were included in the LRR analysis. The 2 patients who initially entered a W&W strategy/refused surgery but later developed regrowth without having surgery were scored as LRR. When W&W patients with tumor regrowth underwent a curative resection, this was not scored as LRR. However, when regrowth was subsequent to a radical resection in W&W patients, this was scored as LRR. F-UP indicates follow-up; IC, informed consent; PD progressive disease.
FIGURE 2
FIGURE 2
Plot development of locoregional failure against time in years after randomization. Red: no resection surgery for other reasons than entering a W&W strategy (5 vs. 5). Light blue: R2 (residual tumor locally (all these patients also had distant metastases) (5 vs. 5). Green: locoregionally progressive disease after having refused surgery (0 vs. 2, referred to the LRR group) Dark blue: LRR after an R0 resection (28 vs. 15). Pink: LRR after an R1 resection (16 vs. 9).
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References

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