Abstract
Survival benefit of adjuvant chemotherapy (ACT) remained controversial in patients with stage II/III rectal cancer (RC) who received neoadjuvant therapy and surgery. This study aimed to investigate the guiding role of elevated pretreatment serum carcinoembryonic antigen (CEA) levels for receiving ACT in yield pathological Tis-3N0 (ypTis-3N0) RC patients after neoadjuvant radiotherapy and surgery. Between 2004 and 2015, 10,973 RC patients with ypTis-3N0 who received neoadjuvant radiotherapy and radical surgery were retrospectively analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. Compared with CEA-normal group, elevated-CEA patients had worse 5-year CSS rate (90.1 vs 83.5%). The 5-year CSS rates were 86.3 and 87.4% for ypTis-3N0M0 patients with or without ACT, respectively. Patients receiving ACT had a comparable 5-year CSS rate compared to those who did not regardless of CEA levels in ypTis-3N0M0 RC patients (CEA elevation group: 76.4 vs. 83.5%, P = 0.305; CEA normal group: 90.0 vs. 90.1%, P = 0.943). Intriguingly, ypT3N0M0 RC patients with elevated CEA levels may benefit from ACT (5-year CSS: 69.1 vs. 82.9%, P = 0.045), while those with normal CEA levels did not (5-year CSS: 89.3 vs. 89.3%, P = 0.885). Multivariate Cox analysis demonstrated that ACT tended to be a protective factor in elevated-CEA ypT3N0M0 RC patients (HR = 0.633, 95% CI = 0.344–1.164, P = 0.141), while ACT was not associated with improved CSS in normal-CEA ypT3N0M0 RC patients (HR = 1.035, 95% CI = 0.487–2.202, P = 0.928). Elevated pretreatment serum CEA levels may serve as a promising biomarker guiding ACT in rectal cancer patients with ypT3N0M0.
Highlights
Based on the results from the German Rectal Cancer Study Group that demonstrated preoperative chemoradiotherapy (CRT) could decrease local recurrence among patients with locally advanced rectal cancer compared to postoperative chemoradiotherapy [1, 2], neoadjuvant CRT followed by radical resection has been established as a standard strategy for locally advanced rectal cancer.Satisfactory regression has often been observed after neoadjuvant radiotherapy (RT), and some patients even achieved clinical complete response (CCR) or pathological complete response (PCR), which brings debates to the choice of adjuvant chemotherapy (ACT) [3]
According to the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) eighth edition colorectal cancer TNM staging system, rectal cancer can be divided into stages 0–IV according to the severity
The treatment of rectal cancer is a comprehensive treatment based on surgery, including chemotherapy and radiotherapy
Summary
Satisfactory regression has often been observed after neoadjuvant radiotherapy (RT), and some patients even achieved clinical complete response (CCR) or pathological complete response (PCR), which brings debates to the choice of adjuvant chemotherapy (ACT) [3]. Survival benefit of ACT has been observed for patients with ‘highrisk’ stage II and stage III disease [5]. According to yield pathological stage, ACT will no longer be needed in patients with ypTis-2N0 and “low-risk” ypT3N0. The National Comprehensive Cancer Network (NCCN) recommended use of ACT for patients with stage II/III rectal cancer regardless of postoperative yield pathology if the patient did not receive neoadjuvant chemotherapy. The European Society for Medical Oncology (ESMO) indicated that it was reasonable to consider ACT in rectal cancer patients after preoperative chemoradiotherapy with yp stage III and “high-risk” yp stage II. The role of ACT in patients after neoadjuvant CRT and surgery has not been well established
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