GRECCAR 2
Phase III Randomized Trial of Local Excision Versus Total Mesorectal Excision in Downstaged T2T3 Low Rectal Cancer After Radiochemotherapy
Phase 3N = 148NCT00427375
- Population
- Adults with T2T3 lower rectal carcinoma of maximum size 4 cm and a good clinical response to chemoradiotherapy (residual tumour 2 cm or less)
- Design
- Prospective, randomised, open-label, multicentre phase 3 trial at 15 tertiary centres in France. Patients with T2T3 lower rectal carcinoma of maximum size 4 cm who had a good clinical response to neoadjuvant chemoradiotherapy (residual tumour 2 cm or less) were randomly assigned by the surgeon before surgery to local excision or total mesorectal excision (permuted blocks of eight, not stratified); in the local excision group a completion total mesorectal excision was required if the tumour stage was ypT2-3. 186 patients received chemoradiotherapy, 148 were randomised, 3 were excluded after randomisation and 145 were analysed (74 and 71). Primary endpoint: a composite of death, recurrence, morbidity and side-effects at 2 years after surgery, to show superiority of local excision (modified intention-to-treat). The 5-year report analyses local recurrence, metastatic disease, disease-free survival, overall survival and cancer-specific mortality, which were secondary endpoints of the trial.
- Primary endpoint
- Composite of death, recurrence, morbidity and side-effects at 2 years
- Arms
- Local excision (experimental, n = 74): Local excision after chemoradiotherapy, with completion total mesorectal excision if the tumour stage was ypT2-3
- Total mesorectal excision (control, n = 71): Total mesorectal excision after chemoradiotherapy
- People
- Rullier E, senior author Doussau A
Δ Composite of death, recurrence, morbidity and side-effects at 2 years+8 pointsLocal recurrence of rectal cancerHR 0.71 (95% CI 0.19–2.58)Δ 60-month Local recurrence of rectal cancer0 pointsMetastatic diseaseHR 0.86 (95% CI 0.36–2.06)Δ 60-month Metastatic disease−1 pointsOSHR 0.92 (95% CI 0.38–2.22)
Show the numbers
| Endpoint | Analysis | Local excision | Total mesorectal excision | Effect |
|---|---|---|---|---|
| Composite of death, recurrence, morbidity and side-effects at 2 yearsModified intention-to-treat population at 2 years: 73 patients in the local excision group and 69 in the total mesorectal excision groupAt least one component of the composite outcome (death, recurrence, morbidity, side-effects) at 2 years after surgery (primary endpoint) | primaryRullier 2017 | 56% | 48% | P=0.4341 of 73 patients versus 33 of 69. Odds ratio 1.33 (95% CI 0.62 to 2.86). The abstract states that there was no difference in any component of the composite outcome and that superiority of local excision was not shown; 26 patients in the local excision group had a completion total mesorectal excision. |
| Local recurrence of rectal cancerModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year local recurrence (secondary endpoint of GRECCAR 2, primary objective of the 5-year report) | long term-updatemedian follow-up 60 monthsRullier 2020 | 7% at 5 y (3–16%) | 7% at 5 y (3–16%) | HR 0.71 (95% CI 0.19–2.58)P=0.60Adjusted hazard ratio as printed in the abstract; the abstract lists the local excision group first and does not state the direction separately. Median follow-up 60 months in each group (IQR 58 to 60 and 57 to 60). The 26 patients with a completion total mesorectal excision remain in the local excision group in this analysis. |
| Metastatic diseaseModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year metastatic disease (secondary endpoint) | long term-updatemedian follow-up 60 monthsRullier 2020 | 18% at 5 y (11–30%) | 19% at 5 y (11–31%) | HR 0.86 (95% CI 0.36–2.06)P=0.73Adjusted hazard ratio as printed in the abstract. |
| OSModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year overall survival (secondary endpoint) | long term-updatemedian follow-up 60 monthsRullier 2020 | 84% at 5 y (73–91%) | 82% at 5 y (71–90%) | HR 0.92 (95% CI 0.38–2.22)P=0.85Adjusted hazard ratio as printed in the abstract; 23 patients died and five were lost to follow-up (both groups together). |
| DFSModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year disease-free survival (secondary endpoint) | long term-updatemedian follow-up 60 monthsRullier 2020 | 70% at 5 y (58–79%) | 72% at 5 y (60–82%) | HR 0.87 (95% CI 0.44–1.72)P=0.68Adjusted hazard ratio as printed in the abstract. |
| Cancer-specific mortalityModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year cancer-specific mortality (secondary endpoint) | long term-updatemedian follow-up 60 monthsRullier 2020 | 7% at 5 y (3–17%) | 10% at 5 y (5–20%) | HR 0.65 (95% CI 0.17–2.49)P=0.53Adjusted hazard ratio as printed in the abstract. |
| Endpoint | Analysis | Local excision | Total mesorectal excision | Effect |
|---|---|---|---|---|
| Composite of death, recurrence, morbidity and side-effects at 2 yearsModified intention-to-treat population at 2 years: 73 patients in the local excision group and 69 in the total mesorectal excision groupAt least one component of the composite outcome (death, recurrence, morbidity, side-effects) at 2 years after surgery (primary endpoint) | primaryRullier 2017 | 56% | 48% | P=0.4341 of 73 patients versus 33 of 69. Odds ratio 1.33 (95% CI 0.62 to 2.86). The abstract states that there was no difference in any component of the composite outcome and that superiority of local excision was not shown; 26 patients in the local excision group had a completion total mesorectal excision. |
| Local recurrence of rectal cancerModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year local recurrence (secondary endpoint of GRECCAR 2, primary objective of the 5-year report) | long term-updatemedian follow-up 60 monthsRullier 2020 | 7% at 5 y (3–16%) | 7% at 5 y (3–16%) | HR 0.71 (95% CI 0.19–2.58)P=0.60Adjusted hazard ratio as printed in the abstract; the abstract lists the local excision group first and does not state the direction separately. Median follow-up 60 months in each group (IQR 58 to 60 and 57 to 60). The 26 patients with a completion total mesorectal excision remain in the local excision group in this analysis. |
| Metastatic diseaseModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year metastatic disease (secondary endpoint) | long term-updatemedian follow-up 60 monthsRullier 2020 | 18% at 5 y (11–30%) | 19% at 5 y (11–31%) | HR 0.86 (95% CI 0.36–2.06)P=0.73Adjusted hazard ratio as printed in the abstract. |
| OSModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year overall survival (secondary endpoint) | long term-updatemedian follow-up 60 monthsRullier 2020 | 84% at 5 y (73–91%) | 82% at 5 y (71–90%) | HR 0.92 (95% CI 0.38–2.22)P=0.85Adjusted hazard ratio as printed in the abstract; 23 patients died and five were lost to follow-up (both groups together). |
| DFSModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year disease-free survival (secondary endpoint) | long term-updatemedian follow-up 60 monthsRullier 2020 | 70% at 5 y (58–79%) | 72% at 5 y (60–82%) | HR 0.87 (95% CI 0.44–1.72)P=0.68Adjusted hazard ratio as printed in the abstract. |
| Cancer-specific mortalityModified intention-to-treat population: 145 patients analysed (74 local excision, 71 total mesorectal excision)5-year cancer-specific mortality (secondary endpoint) | long term-updatemedian follow-up 60 monthsRullier 2020 | 7% at 5 y (3–17%) | 10% at 5 y (5–20%) | HR 0.65 (95% CI 0.17–2.49)P=0.53Adjusted hazard ratio as printed in the abstract. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| Local recurrence of rectal cancer | 0.71 | 0.19–2.58 |
| Metastatic disease | 0.86 | 0.36–2.06 |
| OS | 0.92 | 0.38–2.22 |
| DFS | 0.87 | 0.44–1.72 |
| Cancer-specific mortality | 0.65 | 0.17–2.49 |
Appears in
Sources
Rullier E, Rouanet P, Tuech JJ, Valverde A, Lelong B, Rivoire M, et al. Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial. Lancet. 2017;390(10093):469-479.
Rullier E, Vendrely V, Asselineau J, Rouanet P, Tuech JJ, Valverde A, et al. Organ preservation with chemoradiotherapy plus local excision for rectal cancer: 5-year results of the GRECCAR 2 randomised trial. Lancet Gastroenterol Hepatol. 2020;5(5):465-474.