Coexistence of Perineural Invasion and Lymph Node Metastases Is a Poor Prognostic Factor in Patients with Locally Advanced Rectal Cancer after Preoperative Chemoradiotherapy Followed by Radical Resection and Adjuvant Chemotherapy

Objective: To determine the role of lymph node metastases (ypN) and perineural invasion (PNI) in patients with locally advanced rectal cancer (LARC). Subjects and Methods: Eighty-eight LARC patients receiving preoperative chemoradiotherapy from April 2006 to November 2011 were enrolled in this study. Univariate and multivariate analyses were conducted to determine the association between clinicopathologic features and clinical outcome. Results: The presence of ypN (p = 0.011) and PNI (p = 0.032) was a significant adverse Received: January 21, 2014 Accepted: May 11, 2014 Published online: July 5, 2014 Prof. Jaw-Yuan Wang, MD, PhD Division of Gastrointestinal and General Surgery, Department of Surgery Kaohsiung Medical University Hospital, Kaohsiung Medical University No. 100 Tzyou 1st Road, Kaohsiung 807, Taiwan (ROC) E-Mail cy614112 @ ms14.hinet.net © 2014 S. Karger AG, Basel 1011–7571/14/0235–0465$39.50/0 www.karger.com/mpp Th is is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Huang /Huang /Huang /Lin /Chen /Yeh / Ma /Huang /Wang Med Princ Pract 2014;23:465–470 DOI: 10.1159/000363604 466 Introduction Preoperative chemoradiotherapy (CRT) has improved the locoregional control rate but not the overall survival (OS) rate in patients with locally advanced rectal cancer (LARC) compared with postoperative CRT [1, 2] . Distant recurrence is at present the leading cause of treatment failure in the preoperative CRT era, and distant failure rates range from 30 to 40% [1] . However, the benefit of postoperative adjuvant chemotherapy in LARC patients undergoing preoperative CRT remains controversial [3– 6] . Therefore, it is crucial to identify such patients at high risk of distant recurrence after multimodality therapy. The high-risk patients theoretically benefit from adjuvant chemotherapy. The most significant prognostic factors in patients with LARC are lymph node metastases [7–9] . Patients with lymph node metastases have significantly worse disease-free (DFS) and OS rates compared with those without lymph node metastases. For rectal cancer, several reports have suggested the presence of perineural invasion (PNI) as an independent prognostic factor for predicting survival time [7, 10] . No relevant studies have investigated the correlation between ypN and PNI status, and the effect of their coexistence on the oncologic outcome in LARC patients after multimodality therapy. Hence, the purpose of this study was to evaluate the impact of the coexistence of ypN+ and PNI+ on the clinical outcome in LARC patients undergoing preoperative CRT followed by radical resection and adjuvant chemotherapy. Subjects and Methods Patients and Evaluation This was a retrospective study that reviewed LARC patients treated with preoperative CRT followed by radical resection and adjuvant chemotherapy. The inclusion criteria for the study were as follows: (1) biopsy-proven rectal adenocarcinoma; (2) locally advanced diseases (clinical T3–4 or nodal involvement); (3) tumors located within 10 cm of the anal verge; (4) Eastern Cooperative Oncology Group performance status ≤ 2, and (5) no evidence of distant metastasis. Exclusion criteria included local excision of tumor, radiation dose <45 Gy, a positive surgical margin, history of earlier pelvic irradiation, and history of malignancies other than rectal cancer. The medical records of 103 patients from April 2006 to November 2011 were reviewed, and the Institutional Review Board approved the study. Treatment All patients had received preoperative CRT followed by radical resection and adjuvant chemotherapy. The details of the treatment course were reported previously [11] . In brief, radiotherapy (RT) was administered to the whole pelvis at a dose of 45 Gy in 25 fractions with or without a boost of 5.4 Gy in 3 fractions to the primary tumor. Of the 88 patients, 42 patients were treated with 5-fluorouracil (350 mg/m 2 intravenous bolus) and leucovorin (20 mg/m 2 intravenous bolus) during RT. Forty-six patients received capecitabine (850 mg/m 2 , twice daily, 5 days per week). Patients underwent total mesorectal excision 6–10 weeks after the completion of CRT. Four to 6 weeks after radical surgery, all patients received the same adjuvant chemotherapy regimens as before surgery. Table 1. Clinicopathologic characteristics of 88 patients Median age (range), years Gender Males Females Pre-CRT CEA, ng/ml <5 ≥5 Clinical tumor stage cT1 – 2 cT3 cT4 Clinical nodal stage cN0 cN1 cN2 Distance of tumor from anal verge, cm <5 5 – 10 Pathologic T category ypT0 ypT1 ypT2 ypT3 ypT4 Pathologic N category ypN0 ypN1 ypN2 Tumor gradea Low High PNI Negative Positive Lymphovascular invasion Negative Positive 64.5 (34 – 85)