[Rectum-preserving surgery after consolidation neoadjuvant therapy or totally neoadjuvant therapy for low rectal cancer: a preliminary report].

Objective: To investigate the feasibility and safety of sphincter-preserving surgery after neoadjuvant chemoradiotherapy (nCRT) with consolidation chemotherapy in the interval period or total neoadjuvant therapy (TNT) for low rectal cancer. Methods: A descriptive case series study was carried out. Clinical data of patients with locally advanced low rectal cancer (LALRC) who achieved complete clinical response (cCR) or nearly cCR (near-cCR) after nCRT at the Department of Colorectal Surgery of Fujian Medical University Union Hospital from May 2015 to February 2019 were retrospectively analyzed. Case inclusion criteria: (1) Low rectal adenocarcinoma within 6 cm from the anal verge. (2) After nCRT, tumor presented markedly regression as mucosal nodule or abnormalities, superficial ulcer, scar or a mucosal erythema (< 2 cm); no regional lymph node metastasis or distant metastasis was found in rectal ultrasonography, pelvic MRI and PET-CT; MRI showed obvious fibrosis in the original tumor site; and post-treatment CEA was normal. (3) The patient and the family members adhered to receive the transanal full-thickness local excision with informed consent. (4) When the residual lesions were difficult to detect after nCRT, patients received the watch and wait (W&W) strategy. Exclusion criteria: (1) Before nCRT, pathological results showed poorly differentiated or signet-ring cell carcinoma; lateral lymph node metastasis was suspected. (2) When the residual lesion size was more than 3 cm after nCRT, it was difficult to perform local excision. The consolidation nCRT group received 3-4 cycles of CAPOX regimen (oxaliplatin and capecitabine) or six cycles of mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) combined with the long-course radiotherapy (intensity-modulated radiation therapy with a total dose of 50.4Gy). Patients with concurrent chemotherapy more than or equal to five cycles of CAPOX or eight cycles of mFOLFOX6 were defined as total neoadjuvant therapy (TNT) group. Local resection was recommended for patients who were near-cCR according to modified MSKCC criteria 8-33 weeks after the end of radiotherapy. Patients with a near-cCR, who were judged as ycN0 according to PET-CT and MRI and were ypT0 after local excision, could enter the W&W strategy. Patients with pathologic stage more advanced than ypT1, and those with positive resection margin, or lymphovascular invasion were recommended for salvage radical surgery after local excision. The ypT1 patients with a negative resection margin and without lymphovascular invasion might receive the W&W management carefully if they refused radicalsurgery to sacrifice the sphincter for low rectal cancer. Results: Of 32 patients, 14 were males and 18 were females with the average age of 59 years old. Twenty-three patients underwent consolidation nCRT, and 9 received TNT. The first evaluation after treatments showed 19 cases with cCR and 13 with near-cCR. Twenty-nine patients received local excision while 3 patients with undetectable lesions received W&W policy. Four cases (12.5%) underwent salvage radical surgery with abdominoperineal resection. After local excision, 3 cases underwent salvage radical surgery immediately, and the final pathologic result was ypT3N0, ypT2N0, and ypT2N0 respectively, of whom 2 cases were in the group of consolidation CRT and 1 was in the TNT group. Of these 3 cases, 1 case with an initial cT3 stage showed a pathologic stage of ypT1 and a negative circumferential resection margin after consolidation nCRT and local excision, however, the final pathologic stage was ypT3 with fragmented tumor deposits in the mesorectum after the salvage radical surgery. Meanwhile 1 patient in the TNT group receiving W&W suffered from intraluminal regrowth after 7.4 months follow-up and underwent salvage abdominoperineal resection. One patient in the consolidation nCRT group died of stroke 42.5 months after local resection. Another patient in the TNT group had cerebral metastasis 10 months after the W&W policy, but no local recurrence was found in the pelvic cavity, then received resection of the metastatic tumors. The average follow-up for all the patients was 23 (5-51) months. The cumulative local regrowth rate was 5.0%. The overall survival rate was 85.7%, and the sphincter-preservation rate was increased from 25.0% (28/32) in the original plan to 87.5% (28/32) actually. The 3-year disease-free survival rate was 89.7%. The 3-year organ-preserving survival rate was 85.7%, and the 3-year stoma-free survival rate was 82.5%. At present, 31 patients still survived. Conclusions: After nCRT with consolidation chemotherapy or TNT for low rectal cancer, patients with cCR, ycN0 according to PET-CT and MRI, and ypT0 after local excision, can consider the W&W strategy. Strict patient selection with a near-cCR for local resection and sphincter-preserving strategy can reduce the local regrowth of cancer, and the short-term outcomes are satisfactory.目的： 探讨低位直肠癌新辅助放化疗（nCRT）间歇期巩固化疗（强化nCRT）或全程新辅助治疗（TNT）保直肠手术的可行性和安全性。 方法： 采用描述性病例系列研究方法。回顾性分析2015年5月至2019年2月福建医科大学附属协和医院结直肠外科实施nCRT后临床完全缓解（cCR）或接近cCR（near-cCR）的局部进展期低位直肠癌患者的临床资料。病例入选标准：（1）低位直肠腺癌，肿瘤距肛缘≤6 cm。（2）nCRT后，表现为显著消退的、≤2 cm的黏膜结节或异常、浅溃疡、瘢痕样改变或黏膜红斑；直肠腔内彩超、盆腔MRI和PET-CT均未见区域淋巴结转移或远处转移；MRI提示原肿瘤部位明显纤维化；血清癌胚抗原在正常范围。（3）患者及其家属知情同意并坚持实施经肛门全层局部切除手术。（4）nCRT后，残余病灶难以发现，未能实施局部切除者，则选择等待观察。排除标准：（1）nCRT前，病理提示为低分化癌或印戒细胞癌；怀疑侧方淋巴结转移者。（2）nCRT后，残余病灶范围> 3 cm，难以实施局部切除者。强化nCRT采用长程放疗（适形调强放疗，总剂量50.4 Gy）开始联合3~4个周期CAPOX方案（奥沙利铂、卡培他滨）、或6次mFOLFOX6方案（奥沙利铂、亚叶酸钙和氟尿嘧啶）；联合CAPOX方案化疗≥5次或mFOLFOX6方案8次者定义为TNT。放疗结束后8~33周按照改良MSKCC标准评估，对near-cCR患者建议行局部切除术。对于near-cCR、PET-CT结合MRI判定其为ycN(0)期者，局部切除后ypT(0)者采取等待观察策略。对局部切除术后病理分期为ypT(1)以上、切缘阳性、脉管瘤栓者，建议行挽救性根治手术；而部分病理分期为ypT(1)、切缘阴性、无脉管瘤栓、原拟行切除肛门者，若家属拒绝根治手术，需谨慎选择随访。 结果： 全组32例患者，平均年龄59岁，14例男性。23例强化nCRT，9例TNT。治疗后经过初步评估，cCR者19例，near-CR者13例。采用局部切除29例，3例患者因病灶无法探及而选择等待观察。有4例（12.5%）行挽救性根治手术，均行腹会阴联合切除术。局部切除后有3例（2例强化nCRT者，1例TNT者）即行挽救手术，最终病理分期分别为ypT(3)N(0)、ypT(2)N(0)和ypT(2)N(0)；其中1例为初始分期cT(3)的患者，强化nCRT后局部切除病理评估为ypT(1)且切缘阴性，行挽救根治手术后病理发现系膜内肿瘤碎片化残留（ypT(3)）。还有1例（TNT者）为等待观察7.4个月出现肠腔内肿瘤再生长，行挽救性腹会阴联合切除术。1例强化nCRT患者局部切除术后42.5个月死于脑血管意外。还有1例（TNT者）等待观察者10个月出现脑转移，但盆腔未发现局部复发，故行脑转移瘤切除手术。全组平均随访23（5~51）个月，3年累计局部再生率为5.0%，总生存率85.7%，括约肌保留率由原计划25.0%（8/32）升高为87.5%（28/32）。全组3年无病生存率89.7%，3年累计器官保留生存率85.7%，3年累计无造口生存率82.5%。目前31例患者均存活。 结论： 低位直肠癌nCRT后巩固化疗或TNT后cCR者，PET-CT结合MRI判定为ycN(0)以及局部切除后判定为ypT(0)者，可进入等待观察。严格选择near-cCR者行局部切除为主的保直肠治疗策略，可减少肿瘤局部再生，近期疗效满意。.