JCOG0212
Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial
Phase 3N = 701NCT00190541
- Population
- Patients with clinical stage II/III rectal cancer, lower margin below the peritoneal reflection, without lateral pelvic lymph node enlargement
- Design
- Multicentre, randomised, non-inferiority trial of the Japan Clinical Oncology Group. Eligible patients had histologically proven clinical stage II/III rectal cancer with the lower margin below the peritoneal reflection, no lateral pelvic lymph node enlargement, performance status 0 or 1 and age 20 to 75 years. After surgeons confirmed R0 resection by mesorectal excision, patients were intraoperatively randomised to mesorectal excision with lateral lymph node dissection or mesorectal excision alone; 701 patients from 33 institutions were assigned between June 2003 and August 2010. Primary endpoint relapse-free survival with a non-inferiority margin for the hazard ratio of 1.34; analysis by intention to treat. Roles in this record follow the non-inferiority hypothesis (mesorectal excision alone tested against mesorectal excision with dissection).
- Primary endpoint
- RFS
- Arms
- Mesorectal excision with lateral lymph node dissection (control, n = 351): Mesorectal excision plus lateral lymph node dissection
- Mesorectal excision alone (experimental, n = 350): Mesorectal excision without lateral lymph node dissection
- People
- Fujita S, Colorectal Cancer Study Group of Japan Clinical Oncology Group
RFSHR 1.07Δ 60-month RFS−0.1 pointsΔ 60-month OS−2.4 pointsΔ 60-month Local-recurrence-free survival−5.3 pointsΔ Local recurrence after rectal surgery+5.2 pointsRFSHR 1.09 (95% CI 0.84–1.42)
Show the numbers
| Endpoint | Analysis | Mesorectal excision alone | Mesorectal excision with lateral lymph node dissection | Effect |
|---|---|---|---|---|
| RFS5-year relapse-free survival (primary endpoint) | primaryFujita 2017 | 73.3% at 5 y | 73.4% at 5 y | HR 1.07P=0.0547Hazard ratio 1.07 with a 90.9% confidence interval of 0.84 to 1.36 (not a 95% interval); the abstract does not label its direction, and the 1.34 margin belongs to the non-inferiority hypothesis for mesorectal excision alone relative to mesorectal excision with dissection; p is the 1-sided P value for non-inferiority against a hazard-ratio margin of 1.34. The abstract states that non-inferiority of mesorectal excision alone was not confirmed in the intention-to-treat analysis. |
| OS5-year overall survival (secondary endpoint) | primaryFujita 2017 | 90.2% at 5 y | 92.6% at 5 y | — |
| Local-recurrence-free survival5-year local-recurrence-free survival (secondary endpoint) | primaryFujita 2017 | 82.4% at 5 y | 87.7% at 5 y | — |
| Local recurrence after rectal surgeryProportion of patients with local recurrence; the time point is not stated in the abstract | primaryFujita 2017 | 12.6% | 7.4% | P=0.02426 patients with mesorectal excision plus lateral dissection and 44 with mesorectal excision alone. The abstract's conclusion states a lower local recurrence with dissection, especially in the lateral pelvis. |
| RFS701 patients from 33 institutions assigned to treatment; analysis population not stated in the abstract7-year relapse-free survival (primary endpoint) | long term-updateTsukamoto 2020 | 70.7% at 7 y | 71.1% at 7 y | HR 1.09 (95% CI 0.84–1.42)P=0.064p is the non-inferiority P value. The abstract states that long-term follow-up did not support non-inferiority of mesorectal excision alone. |
| RFSClinical stage III subgroup; subgroup size not given in the abstractRelapse-free survival in the clinical stage III subgroup; the abstract gives a hazard ratio only | exploratoryTsukamoto 2020 | — | — | HR 1.49 (95% CI 1.02–2.17)Subgroup analysis. The abstract describes improved relapse-free survival with mesorectal excision plus lateral dissection compared with mesorectal excision alone (the hazard ratio is read as mesorectal excision alone versus with dissection). It does not state whether the subgroup was prespecified or give a test for interaction. |
| Early urinary dysfunction after surgeryPatients assessed for early urinary dysfunction; numbers assessed are not given in the abstractResidual urine volume of 50 mL or more at least once, or no measurement of residual urine volume (secondary report) | exploratoryIto 2018 | 58% | 59% | Only blood loss of 500 mL or more was independently predictive of early urinary dysfunction (relative risk 1.25, 95% CI 1.10 to 1.55, p = .04). The abstract concludes that lateral dissection was not associated with a significant increase in urinary dysfunction. The abstract does not say whether this analysis was prespecified; 'exploratory' is the nearest available analysis label for a separate report on a trial outcome. |
| Male sexual dysfunction after surgeryMen with no erectile dysfunction before surgery (protocol analysis: 25 with mesorectal excision alone, 29 with dissection); of 472 men, 343 (73%) completed pre- and postoperative questionnairesSexual dysfunction on the IIEF-5 questionnaire one year after surgery, among men with no erectile dysfunction before surgery (secondary report) | exploratorySaito 2016 | 68% (47–85%) | 79% (60–92%) | P=0.37Protocol analysis: 17 of 25 men with mesorectal excision alone and 23 of 29 with dissection. Among 472 men, 343 (73%) completed pre- and postoperative questionnaires. Among men with no or only mild erectile dysfunction before surgery: 59% (48/81) with mesorectal excision alone and 71% (67/95) with dissection (p = 0.15). The abstract concludes that lateral dissection may not increase sexual dysfunction. The abstract does not say whether this analysis was prespecified; 'exploratory' is the nearest available analysis label for a separate report on a trial outcome. |
| Endpoint | Analysis | Mesorectal excision alone | Mesorectal excision with lateral lymph node dissection | Effect |
|---|---|---|---|---|
| RFS5-year relapse-free survival (primary endpoint) | primaryFujita 2017 | 73.3% at 5 y | 73.4% at 5 y | HR 1.07P=0.0547Hazard ratio 1.07 with a 90.9% confidence interval of 0.84 to 1.36 (not a 95% interval); the abstract does not label its direction, and the 1.34 margin belongs to the non-inferiority hypothesis for mesorectal excision alone relative to mesorectal excision with dissection; p is the 1-sided P value for non-inferiority against a hazard-ratio margin of 1.34. The abstract states that non-inferiority of mesorectal excision alone was not confirmed in the intention-to-treat analysis. |
| OS5-year overall survival (secondary endpoint) | primaryFujita 2017 | 90.2% at 5 y | 92.6% at 5 y | — |
| Local-recurrence-free survival5-year local-recurrence-free survival (secondary endpoint) | primaryFujita 2017 | 82.4% at 5 y | 87.7% at 5 y | — |
| Local recurrence after rectal surgeryProportion of patients with local recurrence; the time point is not stated in the abstract | primaryFujita 2017 | 12.6% | 7.4% | P=0.02426 patients with mesorectal excision plus lateral dissection and 44 with mesorectal excision alone. The abstract's conclusion states a lower local recurrence with dissection, especially in the lateral pelvis. |
| RFS701 patients from 33 institutions assigned to treatment; analysis population not stated in the abstract7-year relapse-free survival (primary endpoint) | long term-updateTsukamoto 2020 | 70.7% at 7 y | 71.1% at 7 y | HR 1.09 (95% CI 0.84–1.42)P=0.064p is the non-inferiority P value. The abstract states that long-term follow-up did not support non-inferiority of mesorectal excision alone. |
| RFSClinical stage III subgroup; subgroup size not given in the abstractRelapse-free survival in the clinical stage III subgroup; the abstract gives a hazard ratio only | exploratoryTsukamoto 2020 | — | — | HR 1.49 (95% CI 1.02–2.17)Subgroup analysis. The abstract describes improved relapse-free survival with mesorectal excision plus lateral dissection compared with mesorectal excision alone (the hazard ratio is read as mesorectal excision alone versus with dissection). It does not state whether the subgroup was prespecified or give a test for interaction. |
| Early urinary dysfunction after surgeryPatients assessed for early urinary dysfunction; numbers assessed are not given in the abstractResidual urine volume of 50 mL or more at least once, or no measurement of residual urine volume (secondary report) | exploratoryIto 2018 | 58% | 59% | Only blood loss of 500 mL or more was independently predictive of early urinary dysfunction (relative risk 1.25, 95% CI 1.10 to 1.55, p = .04). The abstract concludes that lateral dissection was not associated with a significant increase in urinary dysfunction. The abstract does not say whether this analysis was prespecified; 'exploratory' is the nearest available analysis label for a separate report on a trial outcome. |
| Male sexual dysfunction after surgeryMen with no erectile dysfunction before surgery (protocol analysis: 25 with mesorectal excision alone, 29 with dissection); of 472 men, 343 (73%) completed pre- and postoperative questionnairesSexual dysfunction on the IIEF-5 questionnaire one year after surgery, among men with no erectile dysfunction before surgery (secondary report) | exploratorySaito 2016 | 68% (47–85%) | 79% (60–92%) | P=0.37Protocol analysis: 17 of 25 men with mesorectal excision alone and 23 of 29 with dissection. Among 472 men, 343 (73%) completed pre- and postoperative questionnaires. Among men with no or only mild erectile dysfunction before surgery: 59% (48/81) with mesorectal excision alone and 71% (67/95) with dissection (p = 0.15). The abstract concludes that lateral dissection may not increase sexual dysfunction. The abstract does not say whether this analysis was prespecified; 'exploratory' is the nearest available analysis label for a separate report on a trial outcome. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| RFS | 1.09 | 0.84–1.42 |
| RFS | 1.49 | 1.02–2.17 |
Appears in
Sources
Fujita S, Mizusawa J, Kanemitsu Y, Ito M, Kinugasa Y, Komori K, et al. Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial. Ann Surg. 2017;266(2):201-207.
Tsukamoto S, Fujita S, Ota M, Mizusawa J, Shida D, Kanemitsu Y, et al. Long-term follow-up of the randomized trial of mesorectal excision with or without lateral lymph node dissection in rectal cancer (JCOG0212). Br J Surg. 2020;107(5):586-594.
Ito M, Kobayashi A, Fujita S, Mizusawa J, Kanemitsu Y, Kinugasa Y, et al. Urinary dysfunction after rectal cancer surgery: Results from a randomized trial comparing mesorectal excision with and without lateral lymph node dissection for clinical stage II or III lower rectal cancer (Japan Clinical Oncology Group Study, JCOG0212). Eur J Surg Oncol. 2018;44(4):463-468.
Saito S, Fujita S, Mizusawa J, Kanemitsu Y, Saito N, Kinugasa Y, et al. Male sexual dysfunction after rectal cancer surgery: Results of a randomized trial comparing mesorectal excision with and without lateral lymph node dissection for patients with lower rectal cancer: Japan Clinical Oncology Group Study JCOG0212. Eur J Surg Oncol. 2016;42(12):1851-1858.