Clinical trialColorectal cancer

Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery

Annals of Surgery · 2023920 patients randomised; 460 patients in the experimental group and 446 in the standard group were eligible for analysis

Dijkstra EA, Nilsson PJ, Hospers GA, Bahadoer RR, Meershoek-Klein Kranenbarg E, Roodvoets AG, et al. Annals of Surgery. 2023. 278:e766-e772

Study type: Clinical trial
Study name: RAPIDO
Design: 5-year follow-up analysis of a randomised trial (total neoadjuvant therapy versus standard chemoradiotherapy)
Sample size: 920 patients randomised; 460 patients in the experimental group and 446 in the standard group were eligible for analysis
Source: Annals of Surgery · 2023

In plain words

In this study, patients with rectal cancer were treated either with short-course radiotherapy followed by chemotherapy and surgery, or with long-course chemoradiotherapy followed by surgery. After about 5.6 years of follow-up, the tumour came back in and around the rectum slightly more often in the short-course radiotherapy plus chemotherapy group (10% vs 6%). However, survival of the patients who had this local return was similar in the two groups. The researchers say the benefits of this approach in reducing treatment failure and distant spread remained after 5 years, but the treatment needs further improvement.

Key results

54 of 460 (12%) vs 36 of 446 (8%), experimental vs standard group

Locoregional failure (LRF) (median follow-up 5.6 years)

P=0.07

44 of 431 (10%) vs 26 of 428 (6%)

Locoregional recurrence (LRR) after R0/R1 resection

P=0.027

9 of 44 (21%) vs 1 of 26 (4%), experimental vs standard group

Mesorectal breach in patients with LRR

P=0.048

More frequent in the experimental group

Use of 3D conformal radiotherapy

P=0.029

HR 0.76 (95% CI 0.46–1.26)

Overall survival after LRF

P=0.29 (comparable between the two groups)

Drugs in this study:Capecitabine (Xeloda)Fluorouracil (5-FU)Oxaliplatin (Eloxatin)

Dose and schedule cards

Short-course radiotherapy followed by CAPOX or FOLFOX4 (RAPIDO)

High-risk locally advanced rectal adenocarcinoma on MRI (at least one of: cT4a/b, extramural vascular invasion, cN2, mesorectal fascia involvement or enlarged lateral lymph nodes); ECOG 0–1On the page “Colorectal cancer” · Locally advanced rectal cancer: total neoadjuvant therapy (TNT) and immunotherapy

High-risk locally advanced rectal adenocarcinoma on MRI (at least one of: cT4a/b, extramural vascular invasion, cN2, mesorectal fascia involvement or enlarged lateral lymph nodes); ECOG 0–1

Drug	Dose	Route	Schedule
Phase 1
Short-course radiotherapy	5 × 5 Gy	Pelvis	Within a maximum of 8 days
Phase 2: 6 cycles of CAPOX (every 21 days)
Oxaliplatin	130 mg/m²	IV	Day 1
Capecitabine	1000 mg/m² twice daily	Oral	Days 1–14
Or phase 2: 9 cycles of FOLFOX4 (every 14 days)
Oxaliplatin	85 mg/m²	IV	Day 1
Leucovorin	200 mg/m²	IV	Days 1 and 2
Fluorouracil	400 mg/m² bolus, then 600 mg/m² over 22 hours	IV	Days 1 and 2

Cycle length: CAPOX every 21 days; FOLFOX4 every 14 days
Duration: Radiotherapy, then 6 cycles of CAPOX or 9 cycles of FOLFOX4, followed by total mesorectal excision (TME)

Doses and schedule from the RAPIDO publication.

On the page “Colorectal cancer” · Locally advanced rectal cancer: total neoadjuvant therapy (TNT) and immunotherapy

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Experimental group (EXP)

Short-course radiotherapy 5 × 5 Gy (over a maximum of 8 days), then 6 cycles of CAPOX (capecitabine 1000 mg/m² orally twice daily, days 1 to 14; oxaliplatin 130 mg/m² IV on day 1; every 21 days) or 9 cycles of FOLFOX4 (oxaliplatin 85 mg/m² IV on day 1; leucovorin 200 mg/m² IV on days 1 and 2; fluorouracil 400 mg/m² bolus and 600 mg/m² over 22 hours on days 1 and 2; every 14 days), then total mesorectal excision (TME).

2Standard group (STD)

Chemoradiotherapy: 28 fractions of 1.8 Gy (50.4 Gy) or 25 fractions of 2 Gy (50 Gy) with oral capecitabine 825 mg/m² twice daily; then TME and, if hospital policy, adjuvant chemotherapy (8 cycles of CAPOX or 12 cycles of FOLFOX4).

Source of the regimen details: Doses and schedules from the abstract of the original RAPIDO paper (Bahadoer et al, Lancet Oncol 2021; PMID 33301740)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with rectal cancer randomised in the RAPIDO trial (920 patients). The exact eligibility criteria are not given in the abstract and are available in the full text of the paper.

Endpoints

The aim was to analyse the risk and pattern of locoregional failure (LRF) in RAPIDO trial patients at 5 years. LRF comprised early LRF (no resection, except organ preservation, or R2 resection) and locoregional recurrence (LRR) after R0/R1 resection. Overall survival after LRF was also assessed.

Safety and side effects

Information on grade 3 or higher adverse events is not reported in the abstract of this paper.

Clinical significance and place in guidelines

This analysis shows that total neoadjuvant therapy (short-course radiotherapy followed by chemotherapy) was associated with a higher risk of locoregional recurrence, although the difference in overall LRF was not statistically significant. Factors such as enlarged lateral lymph nodes, a positive circumferential resection margin, tumour deposits and nodal involvement were associated with LRR. The authors stress the need to refine TNT further. The status of this approach in clinical guidelines should be checked in up-to-date sources; the abstract gives no information on approvals or guidelines.

Limitations

The abstract is only an exploratory analysis of the pattern of locoregional failure. The EXP group was more often treated with 3D conformal radiotherapy, which may have affected the results. Information on adverse events and dose details are not in the abstract; refer to the full text of the paper.

Original article (DOI)PubMed

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.