Prognostic impact of residual lateral lymph node metastasis after neoadjuvant (chemo)radiotherapy in patients with advanced low rectal cancer.

There is a lack of large studies focusing on the prognostic significance of lateral lymph node (LLN) metastasis following LLN dissection (LLND) in rectal cancer. The aim of this study was to evaluate the prognostic impact of LLN metastases on survival of patients with advanced low rectal cancer. Consecutive patients with locally advanced, but not metastatic, extraperitoneal rectal cancer treated with neoadjuvant (chemo)radiotherapy plus total mesorectal excision between 2004 and 2015 were included in the study. LLND was performed when pretreatment imaging documented enlarged LLNs (7 mm or greater in size). Localization of nodal metastases and long-term outcomes were analysed. Kaplan-Meier analysis was used to compare the survival of patients with ypN0 disease with that of patients with mesorectal ypN+/LLN- status and patients with positive LLNs. The Cox proportional hazards model was used to evaluate predictors of disease-free survival (DFS) and local recurrence. A total of 613 patients were included in the study; LLND was performed in 212 patients (34·6 per cent) and 57 (9·3 per cent) had LLN metastasis. Patients with LLN metastasis had improved DFS and local recurrence cumulative incidence rates compared with patients with mesorectal ypN2+/LLN- disease (DFS: P = 0·014; local recurrence: P = 0·006). Although the DFS rate of patients with LLN metastasis was worse than that of patients with ypN0 disease (P < 0·001), the cumulative incidence of local recurrence was similar (P = 0·491). In multivariable analysis, residual LLN metastasis was not an independent predictor of worse DFS or local recurrence. LLN metastasis is not an independent predictor of local recurrence or survival. Survival of patients presenting with LLN metastasis after (chemo)radiotherapy was intermediate between that of patients with ypN0 status and those with mesorectal ypN2 positivity.

Akiyoshi T ，Toda S ，Tominaga T ，Oba K ，Tomizawa K ，Hanaoka Y ，Nagasaki T ，Konishi T ，Matoba S ，Fukunaga Y ，Ueno M ，Kuroyanagi H ... -  《BJS Open》

Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer.

Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer. Neoadjuvant chemoradiotherapy (NCRT) can effectively reduce the postoperative recurrence rate; thus, NCRT with total mesorectal excision (TME) is the most widely accepted standard of care for rectal cancer. The addition of lateral lymph node dissection (LLND) after NCRT remains a controversial topic. To investigate the surgical outcomes of TME plus LLND, and the possible risk factors for lateral lymph node metastasis after NCRT. This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018. In the NCRT group, TME plus LLND was performed in patients with short axis (SA) of the lateral lymph node greater than 5 mm. In the non-NCRT group, TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm. Data regarding patient demographics, clinical workup, surgical procedure, complications, and outcomes were collected. Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients. LLN metastasis was pathologically confirmed in 35 patients (39.3%): 26 (41.3%) in the NCRT group and 9 (34.6%) in the non-NCRT group. The most common site of metastasis was around the obturator nerve (21/35) followed by the internal iliac artery region (12/35). In the NCRT patients, 46% of patients with SA of LLN greater than 7 mm were positive. The postoperative 30-d mortality rate was 0%. Two (2.2%) patients suffered from lateral local recurrence in the 2-year follow up. Multivariate analysis showed that cT4 stage (odds ratio [OR] = 5.124, 95% confidence interval [CI]: 1.419-18.508; P = 0.013), poor differentiation type (OR = 4.014, 95%CI: 1.038-15.520; P = 0.044), and SA ≥ 7 mm (OR = 7.539, 95%CI: 1.487-38.214; P = 0.015) were statistically significant risk factors associated with LLN metastasis. NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter, poorer histological differentiation, or advanced T stage. Selective LLND for NCRT patients can have a favorable oncological outcome.

Chen JN ，Liu Z ，Wang ZJ ，Mei SW ，Shen HY ，Li J ，Pei W ，Wang Z ，Wang XS ，Yu J ，Liu Q ... -  《-》

Lateral pelvic lymph node dissection after neoadjuvant chemo-radiation for preoperative enlarged lateral nodes in advanced low rectal cancer: study protocol for a randomized controlled trial.

Wei M ，Wu Q ，Fan C ，Li Y ，Chen X ，Zhou Z ，Han J ，Wang Z ... -  《Trials》

Prognostic value of metastatic lymph node regression grade after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.

The prognostic value of classifying the degree of metastatic lymph node regression grade after neoadjuvant chemoradiotherapy remains unclear. The aim was to assess the prognostic value of lymph node regression grade in patients with rectal cancer treated with chemoradiotherapy. We reviewed a total of 421 patients with rectal cancer who underwent neoadjuvant long-course chemoradiotherapy. All lymph nodes were examined retrospectively for evidence of response to chemoradiotherapy, and lymph node regression grade was scored as lymph node regression grade 0 (normal lymph node), lymph node regression grade 1 (100% fibrosis), lymph node regression grade 2 (< 25% cancer cells), lymph node regression grade 3 (25%-50% cancer cells), lymph node regression grade 4 (50%-75% cancer cells), and lymph node regression grade 5 (> 75% cancer cells). The prognostic importance of lymph node regression grade was evaluated. Among 301 ypN0 patients, 27 patients were scored as lymph node regression grade 1. The 5-year recurrence-free survival and local recurrence rates in lymph node regression grade 1 patients were similar to those in lymph node regression grade 0 patients (96.3% versus 88.1% in recurrence-free survival and 0% versus 2.7% in local recurrence); however, among 120 ypN+ (lymph node regression grade 2-5) patients, the 5-year recurrence-free survival and local recurrence rates were poor regardless of the lymph node regression grade score (38.1%-61.1% in recurrence-free survival and 8.4%-14.0% in local recurrence). In the multivariate analysis, an intensified regimen using systemic chemotherapy was independently associated with more lymph node regression grade 1 (P < .001; odds ratio, 6.06; 95% confidence interval, 2.33-16.20) among patients with lymph node regressions grade 1 through 5. Furthermore, in the multivariate analysis, ypT3-4 (hazard ratio, 7.82; 95% confidence interval, 2.80-27.32; P < .001), lymph node regression grade 1 (hazard ratio, 0.048; 95% confidence interval, 0.002-0.27; P < .001), the number of retrieved lymph nodes < 12 (hazard ratio, 5.48; 95% confidence interval, 1.48-16.38; P = .014), and no perioperative chemotherapy (hazard ratio, 3.01; 95% confidence interval, 1.53-5.68; P = .002) were independent predictors of recurrence-free survival. Complete lymph node regression after chemoradiotherapy is a strong prognostic factor in rectal cancer.

Tominaga T ，Akiyoshi T ，Yamamoto N ，Oba K ，Nagasaki T ，Yamaguchi T ，Konishi T ，Fukunaga Y ，Ueno M ... -  《-》

Local recurrences in western low rectal cancer patients treated with or without lateral lymph node dissection after neoadjuvant (chemo)radiotherapy: An international multi-centre comparative study.

In the West, low rectal cancer patients with abnormal lateral lymph nodes (LLNs) are commonly treated with neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). Additionally, some perform a lateral lymph node dissection (LLND). To date, no comparative data (nCRT vs. nCRT + LLND) are available in Western patients. An international multi-centre cohort study was conducted at six centres from the Netherlands, US and Australia. Patients with low rectal cancers from the Netherlands and Australia with abnormal LLNs (≥5 mm short-axis in the obturator, internal iliac, external iliac and/or common iliac basin) who underwent nCRT and TME (LLND-group) were compared to similarly staged patients from the US who underwent a LLND in addition to nCRT and TME (LLND + group). LLND + patients (n = 44) were younger with higher ASA-classifications and ypN-stages compared to LLND-patients (n = 115). LLND + patients had larger median LLNs short-axes and received more adjuvant chemotherapy (100 vs. 30%; p < 0.0001). Between groups, the local recurrence rate (LRR) was 3% for LLND + vs. 11% for LLND- (p = 0.13). Disease-free survival (DFS, p = 0.94) and overall survival (OS, p = 0.42) were similar. On multivariable analysis, LLND was an independent significant factor for local recurrences (p = 0.01). Sub-analysis of patients who underwent long-course nCRT and had adjuvant chemotherapy (LLND-n = 30, LLND + n = 44) demonstrated a lower LRR for LLND + patients (3% vs. 16% for LLND-; p = 0.04). DFS (p = 0.10) and OS (p = 0.11) were similar between groups. A LLND in addition to nCRT may improve loco-regional control in Western patients with low rectal cancer and abnormal LLNs. Larger studies in Western patients are required to evaluate its contribution.

Kroon HM ，Malakorn S ，Dudi-Venkata NN ，Bedrikovetski S ，Liu J ，Kenyon-Smith T ，Bednarski BK ，Ogura A ，van de Velde CJH ，Rutten HJT ，Beets GL ，Thomas ML ，Kusters M ，Chang GJ ，Sammour T ... -  《-》