Objective: To investigate the value of colonoscopic assessment in "watch and wait" strategy for mid-lower rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: A single-center retrospective case series study was performed. Database of mid-lower rectal cancer patients at Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute from March 2011 to June 2017 was retrieved. Inclusion criteria: (1) nCRT was completed (50.6 Gy/22 f, plus oral capecitabine); (2) radical surgery was performed within 12 weeks after nCRT treatment; (3) clinical response to nCRT was determined as clinical complete response (cCR) or near-cCR. Patients who did not undergo colonoscopy and MRI in our center during initial assessment and follow-up, or whose colonoscopy data were unable to re-evaluated, were excluded. Initial evaluation of nCRT response was carried out between 6 and 16 weeks after nCRT. The results of endoscopy (eCR, near-eCR and non-eCR) and MRI (mCR, near-mCR and non-mCR) were compared to local lesion relapse during follow-up. The consistency of the results of colonoscopy and MRI was evaluated by Kappa test (Kappa value of 0.21 to 0.40 indicates general consistency, 0.41 to 0.60 moderate consistency, and 0.61 to 0.80 high consistency). The non-regrowth disease-free survival (NR-DFS) curves of the eCR group and the near-eCR group were plotted by Kaplan-Meier method and compared by log-rank test. Clinical significance of colonoscopy examination in the following "watch and wait" strategy during follow-up period was analyzed. Results: A total of 32 patients were enrolled in the study, including 21 (65.6%) males and 11 (34.4%) females with a median age of 57 years old. The differentiated type of rectal cancer included 1 (3.1%) case of well-differentiated, 26 (81.2%) of moderately differentiated and 5 (15.6%) of poorly differentiated. Clinical stage of the patients included 9 (28.1%) cases of T2-3N0 and 23 (71.9%) of T2-3N+. Median follow-up period was 48 (18 to 80) months. The local regrowth rate was 34.4% (11/32) and median interval of local regrowth was 10.0 (4 to 37) months. Initial colonoscopy evaluation was carried out at a median time of 9 (5 to 19) weeks after nCRT was completed. According to endoscopic findings, patients were divided into 3 groups, including 15 cases in eCR group, 15 cases in near-eCR group and 2 cases in non-eCR group. According to the appearance of MRI, patients were divided into 3 groups, including 8 cases in mCR group, 21 cases in near-mCR group and 3 cases in non-mCR group. The regrowth rate of eCR group was lower than that of mCR group (1/15 vs. 1/8) without significant difference (P=1.000). The regrowth rate of near-eCR group was higher than that of near-mCR group [9/15 vs. 42.9% (9/21)] without significant difference as well (P=0.500). The consistency between colonoscopy and MRI in response evaluation of cCR or near-cCR after nCRT was unsatisfactory (Kappa=0.341, P=0.011). After initial evaluation, 31 patients underwent watch and wait strategy, and 1 underwent local resection. The 1- and 3-year NR-DFS in the eCR group was both 100%, which was higher than that in the near-eCR group (53.3% and 38.9%, respectively), and the difference was statistically significant (P=0.001). During watch and wait period, 11 cases developed local regrowth by colonoscopy examination and the biopsy result included 4 case of high-grade intraepithelial neoplasia (HIN), 6 cases of adenocarcinoma and 1 case of chronic mucosal inflammation. Meanwhile lateral developmental tumor of ascending colon in 1 case and of sigmoid in a case was found by colonoscopy and confirmed as HIN by postoperative pathology. Besides, 4 cases developed colonic multiple adenoma and all underwent endoscopic resection. Conclusion: Colonoscopy examination plays an important role in both initial assessment and regrowth monitoring during watch and wait strategy after nCRT treatment.
目的： 探讨肠镜检查在接受新辅助治疗后"等待观察"疗法中的评估作用。 方法： 采用单中心回顾性描述性病例系列研究方法。检索2011年3月至2017年6月期间北京大学肿瘤医院胃肠肿瘤中心的中低位直肠癌患者数据库，纳入完成新辅助放化疗（nCRT，放疗50.6 Gy/22 f，加卡培他滨口服）、nCRT结束12周内未接受根治性手术、临床综合评估符合临床完全缓解（cCR）及近cCR（near-cCR）的患者；排除初始评估及随访未接受本中心肠镜和MRI检查、或肠镜资料无法重新评估的患者。初始评效在nCRT结束后6~16周进行，将nCRT后初始疗效评估中肠镜检查结果为eCR、near-eCR和non-eCR及MRI检查的结果mCR、near-mCR和non-mCR与通过随访获得的局部病灶再发情况进行比较。肠镜与MRI两种手段评估结果的一致性采用Kappa检验（Kappa值为0.21~0.40表明一般的一致性，0.41~0.60表示中等的一致性，0.61~0.80表示高度的一致性）；采用Kaplan-Meier法绘制eCR组和near-eCR组的非肿瘤再生无病生存率（NR-DFS）曲线，log-rank检验进行比较；分析肠镜检查在后续"等待观察"随访中的临床意义。 结果： 共筛选出32例患者纳入本研究，其中男21例（65.6%），女11例（34.4%）；中位年龄57岁。肿瘤高分化者1例（3.1%），中分化26例（81.2%），低分化5例（15.6%）；肿瘤临床分期T(2~3)N(0)期者9例（28.1%），T(2~3)N+期者23例（71.9%）。全组患者的中位随访时间为48（18~80）个月，局部肿瘤再生率为34.4%（11/32），局部肿瘤再生的中位时间为10.0（4~37）个月。本组病例初始评估中位时间为nCRT结束后第9（5~19）周，根据内镜表现，eCR组、near-eCR组和non-eCR组分别有15例、15例和2例；根据MRI表现，mCR组、near-mCR组和non-mCR组分别有8例、21例和3例。eCR组肿瘤局部再生比例低于mCR组（1/15比1/8），但差异无统计学意义（P=1.000）；near-eCR组肿瘤局部再生率高于near-mCR组[9/15比42.9%（9/21）]，差异也无统计学意义（P=0.500）。肠镜与MRI对于nCRT后cCR或near-cCR的判断评估结果一致性欠佳（Kappa=0.341，P=0.011）。经初始评估后，共有31例患者接受"等待观察"治疗，1例行局部切除。eCR组的1年及3年NR-DFS均为100%，高于near-eCR组的53.3%和38.9%，差异具有统计意义（P=0.001）。"等待观察"过程中，肠镜检查发现符合肿瘤局部再生表现者11例，活检结果分别为4例高级别上皮内瘤变、6例腺癌和1例黏膜慢性炎。此外，复查过程中通过肠镜检查发现升结肠及乙状结肠侧向发育型肿瘤各1例，术后病理均为高级别上皮内瘤变；另发现结肠多发腺瘤4例，均接受内镜下切除治疗。 结论： 肠镜检查在nCRT后疗效判断以及"等待观察"随访过程中的临床作用不可或缺。.
Keywords: "Watch and wait"strategy; Colonoscopy; Neoadjuvant therapy; Rectal neoplasms.