Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5-year overall surgery, 57.5%; P = 0.167). Patients who underwent R0 resection showed significantly longer OS than did those who underwent R1, R2, or no resection (P = 0.001). In multivariate analysis using age, perioperative chemotherapy, depth of invasion, LN metastasis, surgical radicality, postoperative pneumonia, and anastomotic leakage as covariates, LN metastasis [cN2: hazard ratio (HR), 1.389; P = 0.309; cN3: HR, 16.019; P = 0.012] and surgical radicality (R1: HR, 3.949; P = 0.009; R2 or no resection: HR, 2.912; P = 0.022) were shown to be significant independent prognostic factors. In clinical stage III ESCC patients, no significant difference in OS was observed between NAC and upfront surgery. Although potential patient selection bias might be a factor in this retrospective analysis, the noncurative resection rate was higher after NAC than after upfront surgery. The survival benefit of more intensive NAC needs to be further evaluated.

Matsuda S ，Tsubosa Y ，Sato H ，Takebayashi K ，Kawamorita K ，Mori K ，Niihara M ，Tsushima T ，Yokota T ，Onozawa Y ，Yasui H ，Takeuchi H ，Kitagawa Y ... -  《-》

Failure of neoadjuvant chemotherapy for resectable esophageal squamous cell carcinoma.

Neoadjuvant treatment has become standard care for patients with resectable esophageal cancer. However, some patients cannot undergo surgery or curative resection because of disease progression during neoadjuvant treatment. The aim of this study is to identify the pretreatment characteristics of patients in whom neoadjuvant treatment failed. The study enrolled 231 patients who underwent chemotherapy with cisplatin and 5-fluorouracil (CF) as neoadjuvant therapy for T1N1-3 or T2-3 any-N esophageal squamous cell carcinoma (ESCC). Of these patients, 201 (87.0%) underwent curative resection (R0) and 30 (13.0%) could not undergo curative resection; 19 patients (8.2%) underwent incomplete resection (R1 or R2), and 11 patients (4.8%) could not undergo surgery because of disease progression. We compared clinical characteristics and survival between patients who underwent curative resection (curative group) and those who could not undergo curative resection (noncurative group) to determine the factors predicting noncurative treatment. The noncurative group had significantly worse disease-specific survival than the curative group (P < 0.001). All patients in the noncurative group had cT3 tumors. In 141 patients with cT3 tumors, those in the noncurative group were more likely to have higher serum SCC antigen concentration (P = 0.021), location of the main tumor in the upper to the middle third of the esophagus (P = 0.071), intramural metastases (P < 0.001), advanced N category (P = 0.016), and bulky lymph node metastases (P = 0.060). Multivariate logistic regression analysis identified location of the main tumor in the upper to the middle third of the esophagus (P = 0.047), intramural metastases (P = 0.002), and nodal metastases (N1, P = 0.014; N2, P = 0.015, respectively) as independent predictors of treatment failure in patients with cT3 tumors. Neoadjuvant CF therapy alone may not be effective for patients with cT3 tumors accompanied by these risk factors, and the efficacy of alternative strategies, such as triplet chemotherapy or chemoradiotherapy, should be evaluated.

Okamura A ，Watanabe M ，Mine S ，Kurogochi T ，Yamashita K ，Hayami M ，Imamura Y ，Ogura M ，Ichimura T ，Takahari D ，Chin K ... -  《-》

The prognostic significance of the positive circumferential resection margin in pathologic T3 squamous cell carcinoma of the esophagus with or without neoadjuvant chemotherapy.

To improve the therapeutic strategy for esophageal squamous cell carcinoma (ESCC), combined neoadjuvant chemotherapy (NAC) followed by operative surgical resection has been applied recently to patients at clinical stages II/III. Our study aimed to elucidate the impact of the circumferential resection margin (CRM) status of surgically resected specimens on the prognosis of patients undergoing neoadjuvant therapy. We enrolled 160 consecutive ESCC patients who underwent esophagectomy. The CRM status of specimens obtained was examined pathologically according to both the College of American Pathologists (CAP) and the Royal College of Pathologists (RCP) criteria. We examined the relationship between CRM status and several clinicopathologic factors among ESCC patients with or without NAC. The local recurrence rate was significantly higher in patients with R1 compared with that of patients with R0 according to CAP criteria (12.5% vs 0.7%; P = .02; Chi-square test). Regarding the prognosis of all patients, Kaplan-Meier analyses showed that there were significant differences between R0 and R1 groups by CAP or RCP criteria (CAP, P < .001; RCP, P = .017). Additionally, Kaplan-Meier analyses showed that R1 was a significant prognostic factor for poor survival, judged by CAP criteria in both surgery alone (P < .001) and NAC plus surgery subgroups (P < .001). Positive CRM according to CAP criteria after multimodality treatment significantly affects the overall and relapse-free survival of ESCC patients.

Okada N ，Fujii S ，Fujita T ，Kanamori J ，Kojima T ，Hayashi R ，Daiko H ... -  《-》

Neoadjuvant chemotherapy with irinotecan and nedaplatin in a single cycle followed by esophagectomy on cT4 resectable esophageal squamous cell carcinoma: a prospective nonrandomized trial for short-term outcomes.

Neoadjuvant chemotherapy (NAC) significantly extends survival in advanced esophageal squamous cell carcinoma (ESCC), but the short-term outcomes for cT4 ESCC remain controversial. Many NAC regimens have been previously reported, although no study has reported a regimen of irinotecan and nedaplatin for cT4 potential resectable ESCC. We evaluated the short-term outcomes of NAC with irinotecan and nedaplatin in a single cycle followed by esophagectomy on cT4 resectable ESCC. A total of 51 patients with cT4 potentially resectable ESCC were eligible for this study. Twenty of these patients underwent NAC, and the other 31 patients underwent surgery alone. The toxicities and response of NAC were evaluated. The clinicopathologic characteristics, responses, toxicities, surgical outcomes, postoperative complications, and survival time between the two groups were analyzed. No significant differences were found in clinicopathologic characteristics between the groups (P > 0.05). The response rate of NAC was 75% (15/20). The differences in the long-axis diameter of the tumor and cT stage between pre- and post-NAC were significant (P < 0.05). Twenty-four toxic events occurred in 11 patients of the NAC group, and 20/24 of these were mild. The R0 resection rates in the NAC group and the surgery alone group were 85% and 64.5%, with no statistically significant difference (P > 0.05). Differences in the pathological T stage and pathological tumor-node-metastasis (TNM) stage were significant (P < 0.05). The overall survival (OS) time and mortality in the NAC group versus the surgery alone group were 31.57 ± 3.06 months versus 15.24 ± 1.46 months and 25% versus 61.3%, respectively. The differences in OS and mortality were significant (P < 0.05). The NAC group and R0 resection were significant and independent predictors of positive prognosis. NAC with irinotecan and nedaplatin in a single cycle followed by esophagectomy on cT4 resectable ESCC as a new NAC is safe and effective.

Tian D ，Zhang L ，Wang Y ，Chen L ，Zhang KP ，Zhou Y ，Wen HY ，Fu MY ... -  《-》

Prognostic Advantage of Docetaxel/Cisplatin/ 5-Fluorouracil Neoadjuvant Chemotherapy in Clinical Stage II/III Esophageal Squamous Cell Carcinoma due to Excellent Control of Preoperative Disease and Postoperative Lymph Node Recurrence.

Neoadjuvant chemotherapy (NAC) has become prevalent in esophageal squamous cell carcinoma (ESCC), but its long-term prognostic advantages remain unclear. The latest prognostic outcomes in clinical Stage (cStage) II/III ESCC with NAC were herein elucidated. NAC prior to curative treatment was done in 115 cStage II/III ESCC patients with either cisplatin (CDDP)/5-fluorouracil (5-FU; CF) (n = 41) or docetaxel/CDDP/5-FU (DCF) NAC (n = 74) between 2007 and 2013. (1) Esophagectomy was finally performed in 35 of the 41 CF NAC cases and in 48 of the 74 DCF NAC cases. The preservation rate of the esophagus was higher in the DCF NAC than in the CF NAC (p = 0.018). (2) The overall survival was better in DCF NAC than in CF NAC (p = 0.071), and progression-free survivals were 58.3% with DCF and 30.5% with CF (p = 0.0060). DCF NAC was associated with fewer cases of progression than CF NAC (p = 0.0040), largely due to excellent control of the preoperative disease (p = 0.018) and postoperative lymph node recurrence (p = 0.014). DCF NAC in cStage II/III ESCC could have a great potential to achieve a better prognosis due to suppression of specific progression events with a higher preservation rate of the esophagus.

Yamashita K ，Hosoda K ，Moriya H ，Katada C ，Sugawara M ，Mieno H ，Komori S ，Katada N ，Watanabe M ... -  《-》