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.

We conducted a randomized controlled trial (JCOG0212) to determine whether the outcome of mesorectal excision (ME) alone for rectal cancer is not inferior to that of ME with lateral lymph node dissection (LLND). The present study focused on male sexual dysfunction after surgery. Eligibility criteria included clinical stage II/III rectal cancer, the lower margin of the lesion below the peritoneal reflection, the absence of lateral pelvic lymph node enlargement, and no preoperative radiotherapy. After confirmation of R0 resection by ME, patients were intraoperatively randomized. Questionnaires using the International Index of Erectile Function (IIEF-5) about the sexual function of men were collected before and 1 year after surgery. Sexual dysfunction incidence was defined as the ratio of patients showing sexual dysfunction after surgery relative to the number who had no erectile dysfunction before surgery. Among 701 patients enrolled between June 2003 and August 2010, 472 males were included. Among them, 343 (73%) completed preoperative and postoperative questionnaires. According to the study protocol, the incidences of sexual dysfunction in patients who underwent ME alone and ME with LLND were 68% (17/25; 95%CI, 47-85%) and 79% (23/29; 95%CI, 60-92%), respectively (p = 0.37). Incidences of sexual dysfunction in patients with no or only mild erectile dysfunction before surgery who underwent ME alone and ME with LLND were 59% (48/81) and 71% (67/95), respectively (p = 0.15). Multivariate analysis identified age as the only risk factor for sexual dysfunction after surgery (p = 0.02). LLND may not increase sexual dysfunction incidence after rectal cancer surgery. This incidence is associated with increased age. This trial is registered with ClinicalTrials.gov, number NCT00190541 and University Hospital Medical Information Network Clinical Trials Registry, number C000000034.

Saito S ，Fujita S ，Mizusawa J ，Kanemitsu Y ，Saito N ，Kinugasa Y ，Akazai Y ，Ota M ，Ohue M ，Komori K ，Shiozawa M ，Yamaguchi T ，Akasu T ，Moriya Y ，Colorectal Cancer Study Group of Japan Clinical Oncology Group ... -  《-》

Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): results from a multicentre, randomised controlled, non-inferiority trial.

Mesorectal excision is the international standard surgical procedure for lower rectal cancer. However, lateral pelvic lymph node metastasis occasionally occurs in patients with clinical stage II or stage III rectal cancer, and therefore mesorectal excision with lateral lymph node dissection is the standard procedure in Japan. We did a randomised controlled trial to confirm that the results of mesorectal excision alone are not inferior to those of mesorectal excision with lateral lymph node dissection. This study was undertaken at 33 major hospitals in Japan. Eligibility criteria included histologically proven rectal cancer of clinical stage II or stage III, with the main lesion located in the rectum with the lower margin below the peritoneal reflection, and no lateral pelvic lymph node enlargement. After surgeons had confirmed macroscopic R0 resection by mesorectal excision, patients were intraoperatively randomised to mesorectal excision alone or with lateral lymph node dissection. The groups were balanced by a minimisation method according to clinical N staging (N0 or N1, 2), sex, and institution. Allocated procedure was not masked to investigators or patients. This study is now in the follow-up stage. The primary endpoint is relapse-free survival and will be reported after the primary analysis planned for 2015. Here, we compare operation time, blood loss, postoperative morbidity (grade 3 or 4), and hospital mortality between the two groups. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00190541. 351 patients were randomly assigned to mesoretcal excision with lateral lymph node dissection and 350 to mesorectal excision alone, between June 11, 2003, and Aug 6, 2010. One patient in the mesorectal excision alone group underwent lateral lymph node dissection, but was analysed in their assigned group. Operation time was significantly longer in the mesorectal excision with lateral lymph node dissection group (median 360 min, IQR 296-429) than in the mesorectal excision alone group (254 min, 210-307, p<0·0001). Blood loss was significantly higher in the mesorectal excision with lateral lymph node dissection group (576 mL, IQR 352-900) than in the mesorectal excision alone group (337 mL, 170-566; p<0·0001). 26 (7%) patients in the mesorectal excision with lateral lymph node dissection group had lateral pelvic lymph node metastasis. Grade 3-4 postoperative complications occurred in 76 (22%) patients in the mesorectal excision with lateral lymph node dissection group and 56 (16%) patients in the mesorectal excision alone group. The most common grade 3 or 4 postoperative complication was anastomotic leakage (18 [6%] patients in the mesorectal excision with lateral lymph node dissection group vs 13 [5%] in the mesorectal excision alone group; p=0·46). One patient in the mesorectal excision with lateral lymph node dissection group died of anastomotic leakage followed by sepsis. Mesorectal excision with lateral lymph node dissection required a significantly longer operation time and resulted in significantly greater blood loss than mesorectal excision alone. The primary analysis will help to show whether or not mesorectal excision alone is non-inferior to mesorectal excision with lateral lymph node dissection. National Cancer Center, Ministry of Health, Labour and Welfare of Japan.

Fujita S ，Akasu T ，Mizusawa J ，Saito N ，Kinugasa Y ，Kanemitsu Y ，Ohue M ，Fujii S ，Shiozawa M ，Yamaguchi T ，Moriya Y ，Colorectal Cancer Study Group of Japan Clinical Oncology Group ... -  《-》

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).

Postoperative urinary dysfunction is a major complication of rectal cancer surgery. A randomized controlled trial (JCOG0212) concluded that the noninferiority of mesorectal excision alone to mesorectal excision with lateral lymph node dissection was not confirmed in terms of relapse-free survival. Eligibility criteria included histologically proven clinical stage II/III rectal cancer, a main lesion located in the rectum with the lower margin below the peritoneal reflection, and the absence of lateral lymph node enlargement. After confirming R0 resection by mesorectal excision, patients were randomized intraoperatively. The residual urine volume was measured three times. Urinary dysfunction was defined as ≥50 mL residual urine occurring at least once or no measurement of residual urinary volume. This trial was registered with the UMIN Clinical Trials Registry, number C000000034. In the mesorectal excision alone and the mesorectal excision with lateral lymph node dissection groups, the incidence of early urinary dysfunction were 58% and 59%, respectively. A tumor location in the lower rectum (vs. upper rectum) and a blood loss of ≥500 mL (vs. <500 mL) were associated with an increased risk of early urinary dysfunction. However, only blood loss was independently predictive of early urinary dysfunction (relative risk, 1.25 [95% CI: 1.10-1.55], p = .04). Mesorectal excision with lateral lymph node dissection is not associated with a significant increase in the incidence of urinary dysfunction. Urinary dysfunction is associated with tumor location and blood loss.

Ito M ，Kobayashi A ，Fujita S ，Mizusawa J ，Kanemitsu Y ，Kinugasa Y ，Komori K ，Ohue M ，Ota M ，Akazai Y ，Shiozawa M ，Yamaguchi T ，Akasu T ，Moriya Y ，Colorectal Cancer Study Group of Japan Clinical Oncology Group ... -  《-》

Mesorectal Excision With or Without Lateral Lymph Node Dissection for Clinical Stage II/III Lower Rectal Cancer (JCOG0212): A Multicenter, Randomized Controlled, Noninferiority Trial.

Fujita S ，Mizusawa J ，Kanemitsu Y ，Ito M ，Kinugasa Y ，Komori K ，Ohue M ，Ota M ，Akazai Y ，Shiozawa M ，Yamaguchi T ，Bandou H ，Katsumata K ，Murata K ，Akagi Y ，Takiguchi N ，Saida Y ，Nakamura K ，Fukuda H ，Akasu T ，Moriya Y ，Colorectal Cancer Study Group of Japan Clinical Oncology Group ... -  《-》

Long-term follow-up of the randomized trial of mesorectal excision with or without lateral lymph node dissection in rectal cancer (JCOG0212).

Japan Clinical Oncology Group (JCOG) 0212 (ClinicalTrials.gov NCT00190541) was a non-inferiority phase III trial of patients with clinical stage II-III rectal cancer without lateral pelvic lymph node enlargement. The trial compared mesorectal excision (ME) with ME and lateral lymph node dissection (LLND), with a primary endpoint of recurrence-free survival (RFS). The planned primary analysis at 5 years failed to confirm the non-inferiority of ME alone compared with ME and LLND. The present study aimed to compare ME alone and ME with LLND using long-term follow-up data from JCOG0212. Patients with clinical stage II-III rectal cancer below the peritoneal reflection and no lateral pelvic lymph node enlargement were included in this study. After surgeons confirmed R0 resection by ME, patients were randomized to receive ME alone or ME with LLND. The primary endpoint was RFS. A total of 701 patients from 33 institutions were assigned to ME with LLND (351) or ME alone (350) between June 2003 and August 2010. The 7-year RFS rate was 71.1 per cent for ME with LLND and 70·7 per cent for ME alone (hazard ratio (HR) 1·09, 95 per cent c.i. 0·84 to 1·42; non-inferiority P = 0·064). Subgroup analysis showed improved RFS among patients with clinical stage III disease who underwent ME with LLND compared with ME alone (HR 1·49, 1·02 to 2·17). Long-term follow-up data did not support the non-inferiority of ME alone compared with ME and LLND. ME with LLND is recommended for patients with clinical stage III disease, whereas LLND could be omitted in those with clinical stage II tumours.

Tsukamoto S ，Fujita S ，Ota M ，Mizusawa J ，Shida D ，Kanemitsu Y ，Ito M ，Shiomi A ，Komori K ，Ohue M ，Akazai Y ，Shiozawa M ，Yamaguchi T ，Bando H ，Tsuchida A ，Okamura S ，Akagi Y ，Takiguchi N ，Saida Y ，Akasu T ，Moriya Y ，Colorectal Cancer Study Group of Japan Clinical Oncology Group ... -  《-》