Objective: To analyze the prognosis of Ⅰb2 and Ⅱa2 cervical squamous cancer without high risk factors treated with neo-adjuvant chemotherapy (NACT) and radical hysterectomy. Methods: This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ b2 and Ⅱ a2 cervical squamous cancer without high risk factors who underwent platinum-based NACT followed by radical surgery from January 2008 to January 2015. The responses of NACT were observed and compared in their effect on postoperative pathologic risk factors. Kaplan-Meier method and Cox regression analysis were performed to analyze survival status. Results: This study was recruited 282 patients with the average age of (44.4±6.7) years old. After NACT, 42 patients achieved complete response [CR, 14.9% (42/282) ], while 138 patients achieved partial response [PR, 48.9% (138/282) ] and 102 stable disease [SD, 36.2% (102/282) ]. The rate of pathologic diameter ≥4 cm, deep stromal invasion (DSI) positive and lymph-vascular space invasion (LVSI) positive rate decreased significantly in CR and PR group compared with SD group (P<0.05) . The number of postoperative risk factors in CR, PR and SD groups varied significantly (χ(2)=64.869, P=0.000) . Besides, the rate of multiple intermediate risk factors was respectively 0 vs 13.8% vs 45.1% (χ(2)=7.107, P=0.008) . The disease relapsed in 23 patients, and 12 died. On the whole series, 5-year overall survival rate was 91.7%, and 5-year recurrence-free survival rate was 88.9%. The rate of recurrence (P=0.002) and mortality (P=0.036) were higher in LVSI positive patients compared with LVSI negative. And the rate of recurrence was higher in patients with multiple intermediate risk factors, compared with no or one intermediate risk factors (P=0.002) . Univariate analysis revealed that LVSI positive and multiple intermediate risk factors were the factors predicted recurrence and mortality (P<0.05) , and no significance in age, stage, tumor grade, tumor diameter before or after NACT, response to NACT, or DSI positive factors (all P>0.05) . The multivariate analysis showed that, the factor of primary tumor diameter ≥6 cm (P=0.022) and multiple intermediate risk factors (P=0.001) were independent prognostic variables for recurrent-free survival. Besides, multiple intermediate risk factors was independent prognostic variable for overall survival (P=0.034) . After surgery, 107 patients did not receive adjuvant therapy, while 175 patients received adjuvant therapy with 26 radiotherapy, 46 chemotherapy and 103 concurrent radiochemotherapy. On survival analysis of postoperative adjuvant treatment, 5-year recurrence-free survival rate of radiotherapy group was significantly lower in patients with the factor of SD response to NACT (P=0.011) and multiple intermediate risk factors (P=0.008) , while overall no significance in overall survival rate (P>0.05) . Conclusions: NACT may be play beneficial role in relieving the status of intermediate risk factors for stage Ⅰ b2 and Ⅱ a2 cervical squamous cancer without high risk factors. The status of multiple intermediate risk factors is independent prognostic factors for recurrence and mortality. For patients with multiple intermediate risk factors, postoperative adjuvant chemotherapy or concurrent radiochemotherapy might be the better choice to prevent relapse.
目的： 探讨Ⅰb2和Ⅱa2期无术后病理高危因素的子宫颈癌患者接受新辅助化疗联合手术治疗的预后及其影响因素。 方法： 选择2008年1月至2015年1月在中国医学科学院北京协和医学院肿瘤医院接受新辅助化疗联合子宫广泛性切除术治疗的Ⅰb2和Ⅱa2期子宫颈鳞癌患者，排除有术后病理高危因素（包括淋巴结受累、阴道残端受累、宫旁受侵）的患者，将无术后病理危险因素以及有术后病理中危因素[包括新辅助化疗后肿瘤直径≥4 cm、淋巴脉管间隙浸润（LVSI）、深间质浸润（DSI，间质浸润深度≥1/2）]的患者纳入本研究。（1）观察新辅助化疗的疗效，并对不同疗效[分为完全缓解（CR）、部分缓解（PR）、疾病稳定（SD），本研究中无疾病进展的患者]患者存在的术后病理危险因素情况进行比较。（2）观察新辅助化疗后患者的生存情况，并分析其预后影响因素。（3）对接受不同术后辅助治疗方式患者的预后进行比较。 结果： 本研究共纳入282例患者，年龄为（44.4±6.7）岁。（1）282例子宫颈癌患者接受新辅助化疗后，疗效达CR者42例（14.9%，42/282），PR者138例（48.9%，138/282），SD者102例（36.2%，102/282）。新辅助化疗疗效为CR、PR、SD患者的术后肿瘤直径≥4 cm的发生率、LVSI阳性率、DSI阳性率分别比较，差异均有统计学意义（P<0.05）；CR、PR、SD患者间术后病理危险因素数目比较，差异有统计学意义（χ(2)=64.869，P=0.000），其中有多个术后病理中危因素的发生率，CR、PR、SD患者分别为0、13.8%、45.1%，3者比较，差异有统计学意义（χ(2)=7.107，P=0.008）。（2）282例子宫颈癌患者中，随访期内复发23例，死亡12例；其5年总生存率（OS）为91.7%，5年无复发生存率（RFS）为88.9%。LVSI阳性患者的复发率及死亡率均明显高于LVSI阴性者（P=0.002，P=0.036），有多个术后病理中危因素患者的复发率明显高于无术后病理危险因素和仅有1个术后病理中危因素者（P=0.002）。单因素生存分析显示，年龄、临床分期、病理分化程度、新辅助化疗疗效、术后肿瘤直径、术后DSI状态对子宫颈癌患者的5年RFS及5年OS均无明显影响（P>0.05）；术后LVSI阳性、有多个术后病理中危因素对子宫颈癌患者的5年RFS及5年OS均有明显影响（P<0.05）；新辅助化疗前肿瘤直径对子宫颈癌患者的5年RFS有明显影响（P=0.031），而对患者的5年OS无明显影响（P=0.092）。多因素Cox回归法分析显示，初治肿瘤直径≥6 cm（P=0.022）、有多个术后病理中危因素（P=0.001）是影响子宫颈癌患者5年RFS的独立危险因素，而有多个术后病理中危因素是影响子宫颈癌患者5年OS的独立危险因素（P=0.034）。（3）282例子宫颈癌患者中，未接受术后辅助治疗者107例，接受术后辅助治疗者175例（其中术后行单纯放疗者26例、单纯化疗者46例、同步放化疗者103例）。对合并预后危险因素（包括新辅助化疗前肿瘤直径≥6 cm、新辅助化疗疗效、有多个术后病理中危因素）患者在接受不同方式的术后辅助治疗后的生存分析显示，新辅助化疗疗效为SD以及有多个术后病理中危因素者，其术后辅助治疗方式明显影响患者的5年RFS（P<0.05），但未发现对患者5年OS有明显影响（P>0.05）。 结论： 在无术后病理高危因素的Ⅰb2和Ⅱa2期子宫颈癌患者中，新辅助化疗敏感（即达到CR、PR）患者有多个术后病理中危因素的发生率低，而有多个术后病理中危因素患者的复发风险明显增加，故应积极治疗，术后辅助化疗或同步放化疗可能有利于减少复发。.
Keywords: Chemoradiotherapy, adjuvant; Hysterectomy; Prognosis; Risk factors; Uterine cervical neoplasms.