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
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Neoadjuvant versus adjuvant chemoradiation for stage II-III esophageal squamous cell carcinoma: a single institution experience.
Esophageal cancer is the eighth most common cancer worldwide. It is the fourth most common cause of cancer death in China and esophageal squamous cell carcinoma (ESCC) is the most prevalent histologic type. Many clinical trials have explored the value of neoadjuvant or adjuvant chemoradiation therapy in potentially resectable ESCC; however, these studies have produced conflicting results. This retrospective study was performed to investigate whether patients with resectable stage II/III ESCC should receive neoadjuvant or adjuvant therapy in addition to surgery. A review of stage II/III thoracic ESCC patients who underwent esophagectomy and either neoadjuvant or adjuvant chemoradiation was performed. Chemotherapy regimen consisted of cisplatin 75 mg/m2 divided into 3 days and fluorouracil 500 mg/m2 on days 1 to 5. The patients who underwent neoadjuvant therapy were treated with one cycle of chemotherapy concurrently with radiotherapy (40 Gy in 20 fractions, 5 days/week), and those receiving adjuvant therapy were treated with two cycles of chemotherapy concurrently with radiotherapy (46-50 Gy in 23-25 fractions, 5 days/week). A total of 122 patients met inclusion criteria, of which 49 underwent neoadjuvant chemoradiation and 73 underwent adjuvant chemoradiation. Median follow up was 36.5 months. The median survival times and 3, 5-year overall survival (OS) rates for the neoadjuvant and adjuvant groups were 39.3 versus 31.5 months, and 53.0%, 45.7% versus 42.9%, 29.7%, respectively (P = 0.091). For the patients with stage III ESCC, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 39.3 versus 21.3 months, and 43.4% versus 21.0%, respectively (P = 0.021). Among lymph node-positive patients, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 55.6 versus 23.7 months, and 43.0% versus 25.7%, respectively (P = 0.085). The incidence of perioperative and postoperative complications was comparable between the two groups (P > 0.05). For patients with resectable stage II/III ESCC, neoadjuvant chemoradiation does not increase postoperative complications and is associated with a trend toward better OS when compared to adjuvant chemoradiation.
Chen Y
，Hao D
，Wu X
，Xing W
，Yang Y
，He C
，Wang W
，Liu J
，Wang J
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Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Docetaxel/Cisplatin/5-Fluorouracil Followed by Surgery.
Preoperative therapy followed by surgery has become the clinical standard for resectable advanced esophageal cancer. Several studies showed that neoadjuvant docetaxel/cisplatin/5-fluorouracil (DCF) resulted in a high response rate and prolonged relapse-free survival, but what constitutes appropriate additional therapy is unknown.
A total of 101 consecutive patients with cStage I B-III esophageal cancer were treated with preoperative DCF between April 2011 and December 2015. After completing 2 cycles of DCF neoadjuvant chemotherapy (NAC), esophagectomy was performed. We investigated prognostic factors and recurrence patterns in patients with resectable esophageal cancer who underwent DCF NAC followed by surgery.
Univariate analysis showed that performance status (hazard ratio, HR 2.85; p = 0.033), clinical response (HR 2.16; p = 0.048), pT stage (HR 2.20; p = 0.047), pN stage (HR 5.83; p< 0.001), pathological curability (HR 5.64; p = 0.038), and histological grade (HR 1.92; p = 0.048) were significant factors. Multivariate prognostic analysis revealed that pN stage and pathological curability were significant prognostic factors (HR 11.20; p < 0.001, and HR 27.41; p = 0.007, respectively). In addition, based on the number of metastatic lymph nodes (LNs), the difference in overall survival was the largest between patients with ≤2 and ≥3 metastatic LNs (HR 5.83; p< 0.001). Distant metastatic recurrence increased significantly in patients with 3 or more pathologically confirmed metastatic LNs (p = 0.008).
Distant recurrence occurred more frequently and prognosis was poorer in patients with 3 or more pathologically confirmed metastatic LNs; they might need additional systemic therapy.
Sugimura K
，Miyata H
，Shinno N
，Ushigome H
，Asukai K
，Yanagimoto Y
，Hasegawa S
，Takahashi Y
，Yamada D
，Yamamoto K
，Nishimura J
，Motoori M
，Wada H
，Takahashi H
，Yasui M
，Omori T
，Ohue M
，Yano M
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