Objective: To compare long-term efficacy between watch and wait (W&W) strategy and total mesorectal excision (TME) in patients who were diagnosed with locally advanced rectal cancer (LARC) and attained clinical complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT). Methods: A retrospective cohort study was carried out. A total of 238 patients with stage II-III LARC exhibiting cCR after nCRT in Sun Yat-sen University Cancer Center from September 16, 2010 to January 9, 2018 were enrolled. Patients who were diagnosed with other malignant tumor within 5 years, did not receive regular follow-up in our center for more than 1 year and had no complete examination items after nCRT were excluded. Of 238 patients, 151 were male and 87 were female with a median age of 57 (27-83) years old. According to TNM stage, 61 cases were cII, 177 cases were cIII. Concurrent chemoradiotherapy (CCRT) was performed in 20 patients. CCRT plus induction/consolidated chemotherapy was performed in 218 patients. Intensity-modulated radiotherapy (IMRT) was applied to radiotherapy. The median radiation dose was 50 Gy/25 Fr for both the primary tumor and clinical target volumes, and the total dose was 45.0 to 50.6 Gy for 227 patients. In 27 patients, single-agent fluorouracil or capecitabine was used as concurrent chemotherapy. But in the other 211 patients, a combined regimen of oxaliplatin and fluorouracil or capecitabine was used. After nCRT, 59 and 179 patients received W&W (W&W group) and TME 6-12 weeks later (TME group), respectively. After the ending of treatment, patient was interviewed one time every 3 months and after 3 years, one time every six months. Overall survival (OS) rate, distant-metastasis-free survival (DMFS) rate, and local-recurrence-free survival (LRFS) rate were compared between two groups. The salvage treatment and sphincter preservation rate were analyzed. The survival curve was drawn with Kaplan-Meier method and evaluated by log-rank method. Results: In the cases treated with TME, the median interval from nCRT to surgery was 59 days. The postoperative pCR rate was 63.1%(113/179). The median follow-up time of the whole cohort was 41.8 (12.0-99.0) months. The 3-year and 5-year OS rates were 98.4% and 96.5%; the 3-year and 5-year LRFS rates were 96.5% and 96.5%; the 3- and 5-year DMFS rates were 91.0% and 87.9%, respectively. The 3-year OS rates in the W&W group and the TME group were 100% and 97.9%; the 5-year OS rates in W&W group and the TME group were 90.6% and 97.9% (P=0.339); The 3-year local recurrence rate (LRR) in the W&W group was 12.9% (7 cases recurred within 2 years), which was significanthy higher then that in the TME group (0.6%, P=0.003). Salvage surgery was successful in 5/6 cases. After salvage surgery, LRFS rate was not significantly different between the two groups (P=0.137). The 3-year DMFS rate in the W&W group and the TME group were 88.4% and 81.1%, whose difference was not significant (P=0.593). Recurrence with simultaneous metastasis was seen in 3/7 cases of the W&W group. The sphincter was preserved in 89.8% (53/59) of patients in the W&W group, which was significantly higher than 73.7% (132/179) in the TME group (P<0.001). When distance of tumor from the anal verge was ≤ 5 cm, the sphincter preservation rate (SPR) in the W&W group was 88.0% (44/50), which was significantly higher than the 54.4% (56/103) in the TME group (P<0.001). Conclusions: W&W is safe and feasible for patients with LARC and cCR after nCRT. The results should be verified by further clinical trials.
目的： 对比局部进展期期直肠癌患者经新辅助放化疗（nCRT）后获得临床完全缓解（cCR）采用随访等待观察与根治性手术[全直肠系膜切除术（TME）]两种治疗策略的远期临床疗效。 方法： 采用回顾性队列研究。纳入2010年9月16日至2018年1月9日期间，中山大学肿瘤防治中心收治的，接受nCRT并获得cCR的Ⅱ~Ⅲ期局部进展期直肠癌患者，排除5年内确诊其他恶性肿瘤、未在本中心规律随访1年以上以及nCRT后复查项目不全者。共计238例患者入组，男性151例、女性87例；中位年龄57（27~83）岁；临床肿瘤TNM分期Ⅱ期61例、Ⅲ期177例。nCRT采用同期放化疗20例，同期放化疗+诱导/巩固化疗218例。放疗采用调强放射治疗技术，肿瘤靶区（GTV）50 Gy/25次/5周，CTV 45~46 Gy/25次/5周，227例放疗总剂量在45.0~50.6 Gy之间；同期化疗仅氟尿嘧啶或卡培他滨27例，氟尿嘧啶或卡培他滨联合奥沙利铂211例。59例采用等待观察治疗策略（等待观察组），179例在nCRT后6~12周接受TME手术（根治手术组）。两组患者自治疗结束起每3个月随诊1次，至3年后改为每半年随访1次。比较两组的整体生存率（OS）、无远处转移生存率（DMFS）和无局部复发生存率（LRFS）等生存情况，并分析挽救性治疗情况和两组保肛率。采用Kaplan-Meier法绘制生存曲线，并用Log-rank进行时序检验。 结果： 选择TME手术者其nCRT结束距手术的中位时间59 d，术后病理完全缓解（pCR）63.1%（113/179）。中位随访时间41.8（12.0~99.0）个月，全组3、5年OS分别为98.4%和96.5%，3、5年LRFS分别96.5%和96.5%，3、5年无瘤生存率分别为89.8%和88.0%，3、5年DMFS分别为91.0%和87.9%。等待观察组与根治手术组3年OS分别为100%和97.9%，5年OS分别为90.6%和97.9%，差异无统计学意义（P=0.339）。随访期间，等待观察组局部复发7例，均出现在治疗后2年内，3年局部复发率为12.9%，高于根治手术组（0.6%），差异有统计学意义（P=0.003）；挽救手术成功率为5/6，挽救性治疗后，两组的LRFS差异无统计学意义（P=0.137）。等待观察组和根治手术组的3年DMFS分别为88.4%和81.1%，差异无统计学意义（P=0.593）。等待观察组7例局部再生长后发生或同时合并远处转移3例。等待观察组保肛率为89.8%（53/59），高于根治手术组73.7%（132/179），差异有统计学意义（P<0.001）；肿瘤下缘距肛缘≤5 cm患者，等待观察组保肛率88.0%（44/50），显著高于根治手术组54.4%（56/103），差异有统计学意义（P<0.001）。 结论： 经nCRT获得cCR的局部进展期直肠癌患者，选择等待观察治疗策略安全可行、保肛率高，但仍有待进一步临床研究加以确认。.
Keywords: Clinical complete response; Colostomy-free survival; Neoadjuvant chemoradiotherapy; Rectal neoplasms, locally advanced; Watch and wait.