早期子宫颈神经内分泌癌的术后放疗价值及预后影响因素分析

Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix

目的探讨早期子宫颈神经内分泌癌(NECC)术后放疗的价值,并分析高危病理因素对预后的影响。方法本研究为单中心回顾性队列研究,收集2011年1月至2022年4月中国医学科学院北京协和医院收治的早期(Ⅰ~Ⅱa2期)NECC患者,均行子宫广泛性切除术±辅助治疗,根据术后是否放疗分为术后未放疗组和术后放疗组,对术后复发的相关因素进行单因素及多因素logistic回归分析;采用Kaplan-Meier法计算并比较两组患者的无进展生存(PFS)时间、总生存(OS)时间、复发率和死亡率。结果(1)共62例早期NECC患者纳入本研究,其年龄为(43.6±11.7)岁;其中,术后未放疗组33例、术后放疗组29例。(2)术后中位随访时间为37个月(范围:12~116个月),随访期内23例(37%)复发,其中7例(11%)为盆腔内复发、20例(32%)为盆腔外复发[其中4例(6%)盆腔内、外均有复发]。与未放疗组相比,术后放疗组的盆腔内复发率(18%、3%,P=0.074)降低,盆腔外复发率(24%、41%,P=0.150)和总复发率(33%、41%,P=0.513)均升高,但两组分别比较,差异均无统计学意义。单因素分析显示,淋巴脉管间隙浸润、子宫颈间质浸润≥1/2均为显著影响早期NECC患者术后复发的危险因素(P均<0.05);多因素分析显示,淋巴脉管间隙浸润为影响早期NECC患者术后复发的独立危险因素(OR=23.03,95%CI为3.55~149.39,P=0.001)。(3)随访期内18例(29%,18/62)死亡,术后未放疗组10例(30%,10/33)、术后放疗组8例(28%,8/29),两组比较,差异无统计学意义(P=0.814)。62例早期NECC患者的3年生存率为79.2%,5年生存率为60.8%。对不同高危病理因素进行亚组分析显示,与术后未放疗组相比,术后放疗组中子宫颈间质浸润≥1/2所占比例更高(27%、64%;P=0.011),此类患者术后放疗使PFS时间(32.3、53.9个月)和OS时间(39.4、73.4个月)有延长趋势,但分别比较,差异均无统计学意义(P=0.704,P=0.371);有淋巴脉管间隙浸润患者中,与术后未放疗患者相比,术后放疗患者并未改善PFS时间(54.5、37.3个月,P=0.860)和OS时间(56.2、62.4个月,P=0.550)。结论早期NECC手术后放疗有减少盆腔内复发的趋势,但未能降低盆腔外复发率和总复发率,未能改善死亡率;对于子宫颈间质浸润≥1/2的患者,术后放疗有延长PFS时间和OS时间的趋势;淋巴脉管间隙浸润为术后肿瘤复发的独立危险因素,但此类患者术后放疗并无生存获益。

Objective To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix(NECC).Methods A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled.The patients were treated with radical hysterectomy±adjuvant treatment.They were divided into postoperative non-radiation group and postoperative radiation group.The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression.The Kaplan-Meier method was used to analyze the progression free survival(PFS),overall survival(OS),recurrence rate,and mortality rate.Results(1)Sixty-two cases were included in the study,including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group.(2)The median follow-up time was 37 months(ranged 12-116 months),with 23 cases(37%)experienced recurrences.There were 7 cases(11%)pelvic recurrences and 20 cases(32%)distant recurrences,in which including 4 cases(6%)both pelvic and distant recurrences.Compared with postoperative non-radiation group,the postoperative radiation group had a lower pelvic recurrence rate(18%vs 3%;P=0.074)but without statistic difference,a slightly elevated distant recurrence rate(24%vs 41%;P=0.150)and overall recurrence rate(33%vs 41%;P=0.513)without statistically significances.Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence(all P<0.05).Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence(OR=23.03,95%CI:3.55-149.39,P=0.001).(3)During the follow-up period,18 cases(29%,18/62)died with tumor,with 10 cases(30%,10/33)in postoperative non-radiation group and 8 cases(28%,8/29)in postoperative radiation group,without significant difference(P=0.814).The postoperative 3-year and 5-year survival rate was 79.2%,60.8%.The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group(27%vs 64%;P=0.011),and postoperative radiation in such patients showed an extended trend in PFS(32.3 vs 53.9 months)and OS(39.4 vs 73.4 months)but without statistic differences(P=0.704,P=0.371).Compared with postoperative non-radiation group,the postoperative radiation did not improve PFS(54.5 vs 37.3 months;P=0.860)and OS(56.2 vs 62.4 months;P=0.550)in patients with lymph-vascular space invasion.Conclusions Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence,and has not improved mortality.For patients with the depth of cervical stromal invasion≥1/2,postoperative radiation has a trend of prolonging OS and PFS but without statistic difference.Lymph-vascular space invasion is an independent predictor for postoperative recurrence,but postoperative radiation in such patients does not seem to have any survival benefits.