基于前哨淋巴结活检术的早期外阴癌个体化治疗研究

Investigation of individualized treatment based on sentinel lymph node biopsy for early-stage vulvar ;cancer

目的：评估基于前哨淋巴结活检术（SLNB）的不同手术方案治疗早期（临床拟诊为Ⅰ～Ⅱ期）外阴癌的可行性及效果，探讨合适的个体化治疗方案。方法收集2004年1月至2013年12月在中山大学附属肿瘤医院接受手术治疗的早期外阴癌患者的临床病理资料，选择其中行前哨淋巴结（SLN）探查的患者共74例，患者平均年龄为55岁（18～87岁）。手术方式包括SLNB、腹股沟淋巴清扫术（IL）和外阴肿物广泛性切除术，术中对SLN进行快速冰冻病理检查，根据SLN有无转移确定手术治疗方案，回顾性分析患者的围手术期情况、病理检查结果，评估SLNB的价值；中位随访时间为41个月（3～122个月），分析患者的复发和生存情况。结果（1）手术治疗方案：74例行SLN探查的患者中，68例（92%，68/74）患者成功识别至少1枚SLN，随后接受了SLNB，并同时行外阴肿物广泛性切除术。这68例患者中，21例患者SLN有转移，其中12例（A组）SLNB后加行双侧IL，9例（B组）于单纯SLNB后行放疗；47例SLN无转移，其中26例（C组）SLNB后加行双侧IL，发现1例非SLN的淋巴结转移，21例（D组）单纯SLNB后予随访观察。（2）围手术期情况：行SLNB＋IL患者（A组＋C组）的手术时间为（126±38）min，术中出血量为（98±99）ml、平均术后住院时间为32 d（18～62 d），均明显多于单纯SLNB者[B组＋D组；分别为（82±22）min、（45±28）ml、15 d（8～24 d）；P0.05）。多因素分析显示，仅淋巴结转移（RR=21.57，95%CI为2.68～173.10，P=0.002）和肿瘤部位类型（RR=7.85，95%CI为1.79～34.50，P=0.024）是影响患者预后的独立因素。结论淋巴结转移是影响早期外阴癌患者预后的独立因素，SLNB可准确判断早期外阴癌患者的淋巴结转移状态，对SLN无转移的患者免除IL可避免手术并发症的发生，缩短术后恢复时间，且不会显著增加复发的风险。

Objective To evaluate the feasibility and outcomes of different surgical approaches on？the basis of sentinel lymph node biopsy （SLNB） in treating early-stage vulvar cancer, and discuss the proper strategy for individualized treatment. Methods The medical charts of patients with early-stage vulvar cancer treated in Sun Yat-sen University between January 2004 and December 2013 were retrospectively collected. A total of 74 patients who received sentinel lymph node（SLN）detection in primary surgery were enrolled （average age 55）. The surgical approaches contained SLNB, inguinal lymphadenectomy （IL）, and extensive vulvectomy. The SLN were examed on intraoperative frozen sections. The treatment protocols, lymphatic metastasis, postoperative recovery condition, recurrence and survival data were collected and analyzed. Results At least one SLN was successfully detected in 68 （92%,68/74） patients. SLN were positive in 21 patients, of whom 12 （group A） underwent bilateral IL, and 9 （group B） received radiotherapy without performed IL. SLN were negative in 47 patients, of whom 26 （group C） underwent bilateral IL and one of them had a non-SLN metastasis, and 21 （group D） were advised to follow-up. The coincidence of pathological results between frozen and paraffin sections was 100%. The sensitivity and specificity of SLNB for diagnosis of lymph node metastasis were 95% and 100%, respectively. A total of 44 complications happened in patients underwent SLNB and IL （group A and C）, including 16 poor wound healing, 14 lymphedema, 8 lymphatic fistulas, 3 phlebothrombosis and 3 infections. There were no complications happened in patients underwent SLNB alone （group B and D）, among whom the operation time, bleeding amount, and hospital stay were also significantly less than those in patients underwent SLNB and IL. The median follow-up time was 41 months and the 3-year overall survival rate was 85% in the whole series. Recurrences were observed in 11 patients and 9 of them died of the tumor with the median survival time of 15 months. In patients with positive SLN （group A and B）, the 3-year overall survival rate was 58% with 8 patients died of the disease, including 4 in group A and 4 in group B. In patients with negative SLN （group C and D）, the 3-years overall survival rate was 97% with one patient in group D died of the tumor, and significantly higher than that of patients with positive SLN （P=0.003）. The 3-year overall survival rate was significantly difference. In univariate analysis by log-rank test showed that, neither in patients with nor without SLN metastasis the prognosis differed with respect to surgical approaches （group A vs B, P=0.709;group C vs D, P=0.253）. Univariate analysis by log-rank test showed that, lymph node metastasis, pathological grade, depth of invasion, and tumor location could significantly affected survival （P0.05）. Multivariate analysis showed that lymph node metastasis （RR=21.57, 95%CI：2.68-173.10, P=0.002） and tumor location （RR=7.85, 95%CI：1.79-34.50, P=0.024） were the independent factors for overall survival. Conclusions Lymph node metastasis is an independent prognosis factor for patients with early-stage vulvar cancer. SLNB could accurately diagnose the status of lymph nodes and help to decide subsequent treatment. The omissions of IL in patients with negative SLN avoid surgical morbidity and shorten postoperative recovery period without an increased risk of recurrence.