Watari Hidemichi, Todo Yukiharu, Takeda Mahito, Ebina Yasuhiko, Yamamoto Ritsu, Sakuragi Noriaki
Department of Obstetrics and Gynecology, Hokkaido University School of Medicine, North 15, West 7, Kita-Ku, Sapporo, 060-8638, Japan.
Gynecol Oncol. 2005 Mar;96(3):651-7. doi: 10.1016/j.ygyno.2004.11.026.
The aim of this study was to determine pathologic variables associated with disease-specific survival of node-positive patients with endometrial carcinoma treated with combination of surgery including pelvic and para-aortic lymphadenectomy and adjuvant chemotherapy.
Survival of 55 node-positive endometrial carcinoma patients prospectively treated with surgery and adjuvant chemotherapy between 1982 and 2002 at Hokkaido University Hospital was compared to various histopathologic variables. All patients underwent primary surgical treatment including pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Survival analyses were performed by the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis using a forward stepwise selection.
Among 303 consecutive endometrial cancer patients treated during the period of this study, 55 patients (18.2%), including 44 without peritoneal metastasis (FIGO stage IIIc) and 11 with peritoneal metastasis (FIGO stage IV), were found to have retroperitoneal lymph node metastasis. Multivariate Cox regression analysis revealed that peritoneal metastasis and lymph-vascular space invasion (LVSI) were independently related to poor survival in node-positive endometrial carcinoma. The estimated 5-year survival rate of stage IIIc patients with or without moderate/prominent LVSI was 50.9% and 93.3%, respectively with statistically significant difference (P=0.0024). The estimated 5-year survival rate of stage IV patients was 20.0%. Prognosis of stage IIIc patients could be stratified into three groups by the number of positive para-aortic node (PAN) with an estimated 5-year survival rate of 86.4% for no positive PAN (n = 23), 60.4% for one positive PAN (n = 13), and 20.0% for > or = 2 positive PAN (n = 8). The difference of survival rate between no or one positive PAN and > or = 2 positive PAN was statistically significant (P = 0.0007 for no positive PAN vs > or = 2 positive PAN, P = 0.0319 for one positive PAN vs > or = 2 positive PAN). Multivariate analysis including number of positive PAN groups showed that LVSI, number of positive PAN groups were independent prognostic factors for survival. Survival of patients with stage IIIc disease could be stratified into three groups by combination of LVSI and number of positive PAN groups with an estimated 5-year survival rate of 93.3% for no or one positive PAN group with nil or minimal LVSI, 62.6% for no or one positive PAN group with intermediate or prominent LVSI, and 20.0% for > or = 2 positive PAN groups irrespective of LVSI (P = 0.0002 for no or one positive PAN group with nil or minimal LVSI vs > or = 2 positive PAN groups, P = 0.0223 for no or one positive PAN group with nil or minimal LVSI vs no or one positive PAN group with intermediate or prominent LVSI, P = 0.0388 for no or one positive PAN group with intermediate or prominent LVSI vs > or = 2 positive PAN groups).
LVSI and number of positive PAN groups were independent prognostic factors for stage IIIc endometrial cancer patients. Postoperative therapy and follow-up modality need to be individualized according to LVSI and the number of positive PAN for stage IIIc patients. New molecular markers to predict the prognosis of endometrial cancer patients preoperatively should be found for individualization of treatment. New chemotherapy regimen including taxane needs to be considered as an adjuvant therapy for patients with node-positive endometrial cancer.
本研究旨在确定与接受包括盆腔和腹主动脉旁淋巴结清扫术及辅助化疗在内的联合手术治疗的子宫内膜癌淋巴结阳性患者的疾病特异性生存相关的病理变量。
将1982年至2002年在北海道大学医院接受手术和辅助化疗的55例淋巴结阳性子宫内膜癌患者的生存情况与各种组织病理学变量进行比较。所有患者均接受了包括盆腔和腹主动脉旁淋巴结清扫术在内的初次手术治疗,随后接受由静脉注射顺铂、多柔比星和环磷酰胺组成的辅助化疗。采用Kaplan-Meier曲线和对数秩检验进行生存分析。通过向前逐步选择的多变量Cox回归分析确定独立的预后因素。
在本研究期间接受治疗的303例连续子宫内膜癌患者中,发现55例(18.2%)有腹膜后淋巴结转移,其中44例无腹膜转移(国际妇产科联盟(FIGO)IIIc期),11例有腹膜转移(FIGO IV期)。多变量Cox回归分析显示,腹膜转移和淋巴血管间隙浸润(LVSI)与淋巴结阳性子宫内膜癌患者的不良生存独立相关。IIIc期有或无中度/显著LVSI的患者的估计5年生存率分别为50.9%和93.3%,差异有统计学意义(P = 0.0024)。IV期患者的估计5年生存率为20.0%。IIIc期患者的预后可根据腹主动脉旁阳性淋巴结(PAN)的数量分为三组,无阳性PAN(n = 23)的估计5年生存率为86.4%,1个阳性PAN(n = 13)的为60.4%,≥2个阳性PAN(n = 8)的为20.0%。无或1个阳性PAN与≥2个阳性PAN之间的生存率差异有统计学意义(无阳性PAN与≥2个阳性PAN相比,P = 0.0007;1个阳性PAN与≥2个阳性PAN相比,P = 0.0319)。包括阳性PAN组数量的多变量分析显示,LVSI、阳性PAN组数量是生存的独立预后因素。IIIc期疾病患者的生存可根据LVSI和阳性PAN组数量的组合分为三组,无或1个阳性PAN组且LVSI为无或最小的估计5年生存率为93.3%,无或1个阳性PAN组且LVSI为中度或显著的为62.6%,≥2个阳性PAN组无论LVSI情况如何均为20.0%(无或1个阳性PAN组且LVSI为无或最小与≥2个阳性PAN组相比,P = 0.0002;无或1个阳性PAN组且LVSI为无或最小与无或1个阳性PAN组且LVSI为中度或显著相比,P = 0.0223;无或1个阳性PAN组且LVSI为中度或显著与≥2个阳性PAN组相比,P = 0.0388)。
LVSI和阳性PAN组数量是IIIc期子宫内膜癌患者的独立预后因素。对于IIIc期患者,术后治疗和随访方式需要根据LVSI和阳性PAN的数量进行个体化。应寻找新的分子标志物以在术前预测子宫内膜癌患者的预后,从而实现治疗个体化。对于淋巴结阳性的子宫内膜癌患者,需要考虑将包括紫杉烷在内的新化疗方案作为辅助治疗。