宫颈癌2018与2009 FIGO分期的比较及预后因素分析

摘要/Abstract

摘要：

目的比较宫颈癌患者在2009和2018两版国际妇产科联盟(FIGO)分期的分布和预后差异,并分析宫颈癌患者的预后因素。方法回顾性分析2010年1月至2018年12月苏州大学附属第一医院收治的524例宫颈癌患者的临床资料,按照2009和2018 FIGO分期分别对病例进行分期,计算Kendall τb系数比较两种分期病例分布的一致性;采用Kaplan-Meier法进行生存分析,log-rank检验各期预后差异。采用Cox比例风险回归模型分析宫颈癌患者的预后因素。结果2009 FIGO分期中有1例ⅠB1期因镜下浸润深度<5 mm降至ⅠA1期,51例ⅠB1期因2 cm<肿瘤最大径≤4 cm上升至ⅠB2期,43例ⅠB2期因肿瘤最大径>4 cm上升至ⅠB3期,119例因盆腔淋巴结转移上升至ⅢC1期,11例因腹主动脉旁淋巴结转移上升至ⅢC2期。两种分期病例分布一致性较好(τb=0.61,P<0.001)。2018(ⅠA、ⅠB、Ⅱ、ⅢA、ⅢB、ⅢC1、ⅢC2、Ⅳ)、2009(ⅠA、ⅠB、Ⅱ、ⅢA、ⅢB、Ⅳ)FIGO各期患者以及不同T分期(T₁、T₂、T₃、T₄)患者的总生存期(OS)(χ²=107.13,P<0.001;χ²=93.02,P<0.001;χ²=92.74,P<0.001)和无进展生存期(PFS)(χ²=91.95,P<0.001;χ²=77.69,P<0.001;χ²=73.27,P<0.001)差异均有统计学意义,其中2018 FIGOⅠB和ⅢC期的OS(χ²=20.71,P<0.001)与PFS(χ²=24.25,P<0.001)差异均有统计学意义,ⅢC1期和ⅠB2期的OS差异有统计学意义(χ²=6.18,P=0.013)。多因素分析结果显示,年龄(HR=1.88,95%CI为1.08~3.28,P=0.026)、病理类型(HR=2.11,95%CI为1.04~4.27,P=0.038)、淋巴结转移(HR=2.18,95%CI为1.34~3.56,P=0.002)、宫旁扩散(HR=2.56,95%CI为1.52~4.29,P<0.001)、肿瘤最大径(HR=1.98,95%CI为1.18~3.30,P=0.009)、治疗后鳞状细胞癌相关抗原(SCCA)阳性(HR=4.49,95%CI为2.09~9.68,P<0.001)、治疗前血红蛋白(HB)水平(HR=0.58,95%CI为0.35~0.96,P=0.035)均为影响宫颈癌患者OS的独立危险因素。按2018 FIGO分期,ⅠB1、ⅠB2、ⅠB3期患者5年OS率分别为100%、97.1%、87.9%,差异有统计学意义(χ²=7.79,P=0.020),ⅠB1和ⅠB3期差异有统计学意义(χ²=5.55,P=0.019);按2009 FIGO分期,ⅠB1、ⅠB2期患者5年OS率分别为95.7%、84.3%,差异有统计学意义(χ²=9.08,P=0.003)。对于2018 FIGOⅠB期患者,治疗后SCCA阳性(HR=1 172.50,95%CI为10.37~132 554.51,P=0.003)为影响OS的独立危险因素;分化程度(HR=0.09,95%CI为0.01~0.81,P=0.032)、治疗方式(HR=0.17,95%CI为0.04~0.71,P=0.015)、治疗后SCCA阳性(HR=190.68,95%CI为14.27~2 547.67,P<0.001)均为影响PFS的独立危险因素。对于2009 FIGOⅠB期患者,分期(HR=9.56,95%CI为2.38~38.32,P=0.001)、治疗后SCCA阳性(HR=126.32,95%CI为12.36~1 290.60,P<0.001)、淋巴结转移(HR=20.07,95%CI为3.63~111.11,P=0.001)均为影响OS的独立危险因素;分化程度(HR=0.11,95%CI为0.02~0.63,P=0.013)、治疗方式(HR=0.22,95%CI为0.06~0.75,P=0.015)、治疗后SCCA阳性(HR=43.83,95%CI为7.94~241.84,P<0.001)均为影响PFS的独立危险因素。按2018 FIGO分期,ⅡA、ⅡB期患者5年OS率分别为95.7%、75.6%,差异有统计学意义(χ²=13.96,P<0.001);ⅡA、ⅡB期患者5年PFS率分别为83.1%、67.1%,差异有统计学意义(χ²=7.61,P=0.006)。按2009 FIGO分期,ⅡA、ⅡB期患者5年OS率分别为90.9%、75.0%,差异有统计学意义(χ²=8.85,P=0.003);ⅡA、ⅡB期患者5年PFS率分别为75.7%、66.7%,差异有统计学意义(χ²=4.07,P=0.044)。对于2018 FIGOⅡ期患者,病理类型(HR=20.28,95%CI为2.93~140.32,P=0.002)、分期(HR=4.35,95%CI为1.02~18.55,P=0.047)均为影响OS的独立危险因素。对于2009 FIGOⅡ期患者,病理类型(HR=5.82,95%CI为1.62~20.94,P=0.007)为影响OS的独立危险因素;病理类型(HR=3.09,95%CI为1.22~7.85,P=0.017)、淋巴结转移(HR=2.07,95%CI为1.22~3.51,P=0.007)均为影响PFS的独立危险因素。对于2018 FIGOⅢ期患者,肿瘤最大径(HR=3.31,95%CI为1.45~7.56,P=0.005)、治疗后SCCA阳性(HR=4.67,95%CI为1.22~17.86,P=0.024)均为影响患者OS的独立危险因素;病理类型(HR=4.15,95%CI为1.47~11.77,P=0.007)、治疗后SCCA阳性(HR=3.96,95%CI为1.45~10.86,P=0.007)均为影响患者PFS的独立危险因素。结论2018和2009 FIGO分期在宫颈癌患者中分布一致性较好,2018 FIGOⅠB期对预后的判断更具优势,但是ⅢC期并不能准确地判断预后,淋巴结转移情况和肿瘤最大径是较为重要的预后因素。

关键词:宫颈肿瘤,肿瘤分期,FIGO,预后

Abstract:

ObjectiveTo compare the differences in distribution and prognosis of cervical cancer patients in the 2009 and 2018 editions of International Federation of Gynecology and Obstetrics (FIGO) staging, and to analyze the prognostic factors of cervical cancer patients.MethodsThe clinical data of 524 cervical cancer patients admitted to the First Affiliated Hospital of Soochow University from January 2010 to December 2018 were retrospectively analyzed. The cases were staged according to the 2009 and 2018 FIGO staging, and the Kendall τb coefficient was calculated to compare the consistency of the distribution of the two stages. Kaplan-Meier was used for survival analysis, and log-rank test was used to test the difference of prognosis in each stage. Cox-regression was used to analyze the prognostic factors of cervical cancer patients.ResultsIn the 2009 FIGO edition of staging, 1 case of stage ⅠB1 was reduced to stage ⅠA1 due to the microscopic infiltration depth <5 mm, 51 cases of stage ⅠB1 were raised to stage ⅠB2 due to 2 cm4 cm. A total of 119 cases raised to stage ⅢC1 due to pelvic lymph node metastasis, and 11 cases raised to stage ⅢC2 due to para-aortic lymph node metastasis. The distribution of cases in the two stages was consistent (τb=0.61,P<0.001). There were statistically significant differences in overall survival (OS) (χ²=107.13,P<0.001;χ²=93.02,P<0.001;χ²=92.74,P<0.001) and progression-free survival (PFS) (χ²=91.95,P<0.001;χ²=77.69,P<0.001;χ²=73.27,P<0.001) among patients with different stages of FIGO in 2018 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, ⅢC1, ⅢC2, Ⅳ) and 2009 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, Ⅳ) and patients with different T stages (T₁, T₂, T₃, T₄). There were statistically significant differences in OS (χ²=20.71,P<0.001) and PFS (χ²=24.25,P<0.001) in 2018 FIGOⅠB and ⅢC stages, and there was a statistically significant difference in OS between stage ⅢC1 and stage ⅠB2 (χ²=6.18,P=0.013). Multivariate analysis showed that age (HR=1.88, 95%CI: 1.08-3.28,P=0.026), pathological type (HR=2.11, 95%CI: 1.04-4.27,P=0.038), lymph node metastasis (HR=2.18, 95%CI: 1.34-3.56,P=0.002), parametrial spread (HR=2.56, 95%CI: 1.52-4.29,P<0.001), maximum tumor diameter (HR=1.98, 95%CI: 1.18-3.30,P=0.009), squamous cell carcinoma antigen (SCCA) positive after treatment (HR=4.49, 95%CI: 2.09-9.68,P<0.001) and Hemoglobin (HB) level before treatment (HR=0.58, 95%CI: 0.35-0.96,P=0.035) were independent risk factors for OS in patients with cervical cancer. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅠB1, ⅠB2, ⅠB3 were 100%, 97.1% and 87.9% respectively, with a statistically significant difference (χ²=7.79, P=0.020), and there was a statistically significant difference between stage ⅠB1 and ⅠB3 (χ²=5.55, P=0.019). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅠB1 and ⅠB2 were 95.7% and 84.3% respectively, with a statistically significant difference (χ²=9.08,P=0.003). For patients with 2018 FIGO stage ⅠB, SCCA positive after treatment (HR=1 172.50, 95%CI: 10.37-132 554.51,P=0.003) was an independent risk factor for OS, and differentiation degree (HR=0.09, 95%CI: 0.01-0.81,P=0.032), treatment method (HR=0.17, 95%CI: 0.04-0.71,P=0.015) and SCCA positive after treatment (HR=190.68, 95%CI: 14.27-2 547.67,P<0.001) were independent risk factors for PFS. For patients with 2018 FIGO stage ⅠB, stage (HR=9.56, 95%CI: 2.38-38.32,P=0.001), SCCA positive after treatment (HR=126.32, 95%CI: 12.36-1 290.60,P<0.001) and lymph node metastasis (HR=20.07, 95%CI: 3.63-111.11,P=0.001) were independent risk factors for OS, and differentiation degree (HR=0.11, 95%CI: 0.02-0.63,P=0.013), treatment method (HR=0.22, 95%CI: 0.06-0.75,P=0.015) and SCCA positive after treatment (HR=43.83, 95%CI: 7.94-241.84,P<0.001) were independent risk factors for PFS. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 95.7% and 75.6% respectively, with a statistically significant difference (χ²=13.96,P<0.001). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 83.1% and 67.1% respectively, with a statistically significant difference (χ²=7.61,P=0.006). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 90.9% and 75.0% respectively, with a statistically significant difference (χ²=8.85,P=0.003). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 75.7% and 66.7% respectively, with a statistically significant difference (χ²=4.07,P=0.044). For patients with 2018 FIGO stage Ⅱ, pathological type (HR=20.28, 95%CI: 2.93-140.32,P=0.002) and stage (HR=4.35, 95%CI: 1.02-18.55,P=0.047) were independent risks factors for OS. For patients with 2009 FIGO stage Ⅱ, pathological type (HR=5.82, 95%CI: 1.62-20.94,P=0.007) was an independent risk factor for OS, and pathological type (HR=3.09, 95%CI: 1.22-7.85,P=0.017) and lymph node metastasis (HR=2.07, 95%CI: 1.22-3.51,P=0.007) were independent risk factors for PFS. For patients with 2018 FIGO stage Ⅲ, maximum tumor diameter (HR=3.31, 95%CI: 1.45-7.56,P=0.005) and SCCA positive after treatment (HR=4.67, 95%CI: 1.22-17.86,P=0.024) were independent risk factors for OS, and pathological type (HR=4.15, 95%CI: 1.47-11.77,P=0.007) and SCCA positive after treatment (HR=3.96, 95%CI: 1.45-10.86, P=0.007) were independent risk factors for PFS.ConclusionThe 2018 and 2009 FIGO staging have a good distribution consistency in the cervical cancer patients, and the 2018 FIGO stage ⅠB has more advantages in judging the prognosis, but stage ⅢC cannot accurately judge the prognosis. Lymph node metastasis and maximum tumor diameter are more important prognostic factors.

Key words:Cervical neoplasms,Neoplasm staging,FIGO,Prognosis

袁晨阳, 周菊英, 杜霄, 纪环, 赵天翼. 宫颈癌2018与2009 FIGO分期的比较及预后因素分析[J]. 国际肿瘤学杂志, 2022, 49(3): 151-163.

Yuan Chenyang, Zhou Juying, Du Xiao, Ji Huan, Zhao Tianyi. Comparison of 2018 and 2009 FIGO staging system of cervical cancer and analysis of prognostic factors[J]. Journal of International Oncology, 2022, 49(3): 151-163.

图/表17

表1

524例宫颈癌患者2009 FIGO和2018 FIGO分期病例分布情况(例)"

2018 FIGO分期	2009 FIGO分期													合计
2018 FIGO分期	ⅠA1	ⅠA2	ⅠB1	ⅠB2	ⅠB3	ⅡA	ⅡB	ⅢA	ⅢB	ⅢC1	ⅢC2	ⅣA	ⅣB	合计
ⅠA1	3	0	1	0	0	0	0	0	0	0	0	0	0	4
ⅠA2	0	5	0	0	0	0	0	0	0	0	0	0	0	5
ⅠB1	0	0	50	0	0	0	0	0	0	0	0	0	0	50
ⅠB2	0	0	51	0	0	0	0	0	0	0	0	0	0	51
ⅠB3	0	0	0	43	0	0	0	0	0	0	0	0	0	43
ⅡA	0	0	0	0	0	102	0	0	0	0	0	0	0	102
ⅡB	0	0	0	0	0	0	68	0	0	0	0	0	0	68
ⅢA	0	0	0	0	0	0	0	17	0	0	0	0	0	17
ⅢB	0	0	0	0	0	0	0	0	23	0	0	0	0	23
ⅢC1	0	0	33	8	0	47	24	1	6	0	0	0	0	119
ⅢC2	0	0	0	2	0	6	2	0	1	0	0	0	0	11
ⅣA	0	0	0	0	0	0	0	0	0	0	0	15	0	15
ⅣB	0	0	0	0	0	0	0	0	0	0	0	0	16	16
合计	3	5	135	53	0	155	94	18	30	0	0	15	16	524

表1

图1

图2

图3

图4

表2

524例宫颈癌患者OS单因素和多因素分析"

影响因素	单因素分析				多因素分析
影响因素	HR值	95%CI	P值		HR值	95%CI	P值
年龄(≥60岁/<60岁)	1.74	1.06~2.86	0.029	1.88		1.08~3.28	0.026
病理类型
腺癌/鳞状细胞癌	2.28	1.23~4.23	0.009	2.11		1.04~4.27	0.038
腺鳞状细胞癌/鳞状细胞癌	0.60	0.08~4.36	0.617	0.69		0.09~5.17	0.719
分化程度
中分化/低分化	0.91	0.42~1.95	0.802	-		-	-
高分化/低分化	0.84	0.20~3.55	0.814	-		-	-
人乳头状瘤病毒(阳性/阴性)	0.24	0.08~0.73	0.012	0.36		0.11~1.18	0.091
淋巴结转移(阳性/阴性)	2.26	1.44~3.57	<0.001	2.18		1.34~3.56	0.002
宫旁扩散(阳性/阴性)	3.35	2.13~5.29	<0.001	2.56		1.52~4.29	<0.001
肿瘤最大径(>4 cm/≤4 cm)	2.88	1.77~4.68	<0.001	1.98		1.18~3.30	0.009
治疗后SCCA(阳性/阴性)	4.62	2.28~9.38	<0.001	4.49		2.09~9.68	<0.001
治疗前CEA(阳性/阴性)	2.81	1.41~5.59	0.003	1.38		0.64~2.98	0.414
治疗前HB(>110 g/L/≤110 g/L)	0.41	0.26~0.66	<0.001	0.58		0.35~0.96	0.035

表2

图5

图6

表3

144例2018 FIGOⅠB期宫颈癌患者OS、PFS多因素分析"

影响因素	OS								PFS
影响因素	HR值		95%CI		P值				HR值	95%CI		P值
年龄(≥60岁/<60岁)	0.33	0.02~4.71		0.414				1.07		0.23~5.05		0.936
病理类型
腺癌/鳞状细胞癌	3.63	0.04~378.08		0.587				0.27		0.03~2.32		0.233
腺鳞状细胞癌/鳞状细胞癌	0.00	-		0.996				0.00		-		0.991
影响因素	OS									PFS
影响因素	HR值		95%CI		P值	HR值				95%CI	P值
分化程度
中分化/低分化	0.01		0.00~4.06		0.128		0.09				0.01~0.81	0.032
高分化/低分化	0.00		-		0.996		0.00				-	0.989
治疗方式
根治性放疗±化疗/根治术±化疗	2.63		0.00~10 012.04		0.819		2.86				0.21~38.05	0.427
根治术+放疗±化疗/根治术±化疗	0.04		0.00~23.24		0.323		0.17				0.04~0.71	0.015
单纯外照射/根治术±化疗	0.00		-		0.996		1.46				0.04~47.97	0.832
分期
ⅠB2/ⅠB1	1 030.14		0~9.60×10³⁴		0.853		0.37				0.08~1.70	0.200
ⅠB3/ⅠB1	12 395.02		0~1.19×10³⁶		0.802		0.65				0.15~2.74	0.557
治疗后SCCA(阳性/阴性)	1 172.50		10.37~132 554.51		0.003		190.68				14.27~2 547.67	<0.001

表3

表4

188例2009 FIGOⅠB期宫颈癌患者OS、PFS多因素分析"

影响因素	OS				PFS
影响因素	HR值	95%CI	P值		HR值	95%CI	P值
年龄(≥60岁/<60岁)	1.22	0.21~7.20	0.827	1.11		0.32~3.93	0.867
病理类型
腺癌/鳞状细胞癌	2.78	0.18~42.16	0.461	0.36		0.04~3.00	0.347
腺鳞状细胞癌/鳞状细胞癌	0.00	0.00~6.50×10⁵²	0.849	0.00		-	0.975
分化程度
中分化/低分化	0.09	0.01~1.68	0.107	0.11		0.02~0.63	0.013
高分化/低分化	0.00	-	0.995	0.00		-	0.993
治疗方式
根治性放疗±化疗/根治术±化疗	3.13	0.11~85.88	0.499	0.85		0.12~6.26	0.872
根治术+放疗±化疗/根治术±化疗	0.23	0.01~4.03	0.315	0.22		0.06~0.75	0.015
单纯外照射/根治术±化疗	0.00	-	0.995	0.49		0.03~7.67	0.610
分期(ⅠB2/ⅠB1)	9.56	2.38~38.32	0.001	2.02		0.76~5.37	0.161
治疗后SCCA(阳性/阴性)	126.32	12.36~1 290.60	<0.001	43.83		7.94~241.84	<0.001
淋巴结转移(阳性/阴性)	20.07	3.63~111.11	0.001	2.22		0.84~5.83	0.107

表4

图7

图8

表5

170例2018 FIGO Ⅱ期宫颈癌患者OS、PFS多因素分析"

影响因素	OS				PFS
影响因素	HR值	95%CI	P值		HR值	95%CI	P值
年龄(≥60岁/<60岁)	1.52	0.51~4.539	0.454	0.88		0.40~1.92	0.746
病理类型
腺癌/鳞状细胞癌	20.28	2.93~140.32	0.002	2.19		0.48~9.94	0.308
腺鳞状细胞癌/鳞状细胞癌	9.05	0.52~157.91	0.131	2.19		0.20~23.81	0.521
分化程度
中分化/低分化	0.00	0.00~1.77×10⁵⁴	0.900	0.86		0.22~3.39	0.834
高分化/低分化	2.73	0.25~30.08	0.413	1.13		0.14~9.35	0.913
治疗方式
根治性放疗±化疗/根治术±化疗	19 045.54	0.00~5.18×10⁸⁴	0.917	40 078.09		0.00~1.12×10⁸⁸	0.914
根治术+放疗±化疗/根治术±化疗	3 608.56	0.00~9.81×10⁸³	0.931	23 016.21		0.00~6.43×10⁸⁷	0.918
单纯外照射/根治术±化疗	7 636.34	0.00~2.10×10⁸⁴	0.925	26 263.34		0.00~7.39×10⁸⁷	0.917
分期(ⅡB/ⅡA)	4.35	1.02~18.55	0.047	1.59		0.71~3.58	0.263
治疗后SCCA(阳性/阴性)	1.44	0.17~12.33	0.741	0.64		0.09~4.80	0.663

表5

表6

249例2009 FIGOⅡ期宫颈癌患者OS、PFS多因素分析"

影响因素	OS						PFS
影响因素	HR值	95%CI			P值		HR值	95%CI		P值
年龄(≥60岁/<60岁)	1.29		0.52~3.17	0.586		0.83			0.43~1.59		0.688
病理类型
腺癌/鳞状细胞癌	5.82		1.62~20.94	0.007		3.09			1.22~7.85		0.017
腺鳞状细胞癌/鳞状细胞癌	3.92		0.38~40.77	0.253		1.18			0.14~9.93		0.881
分化程度
中分化/低分化	1.54		0.42~5.69	0.520		1.82			0.82~4.01		0.139
高分化/低分化	3.57		0.65~19.77	0.145		1.40			0.38~5.17		0.616
治疗方式
根治性放疗±化疗/根治术±化疗	2.89		0.49~16.95	0.240		2.37			0.65~8.63		0.191
根治术+放疗±化疗/根治术±化疗	0.89		0.20~3.96	0.875		1.92			0.62~5.96		0.258
单纯外照射/根治术±化疗	1.63		0.11~23.53	0.721		2.06			0.30~14.09		0.461
分期(ⅡB/ⅡA)	1.59		0.65~3.89	0.308		1.39			0.76~2.52		0.282
治疗后SCCA(阳性/阴性)	2.69		0.75~9.70	0.129		1.95			0.74~5.14		0.175
淋巴结(阳性/阴性)	1.63		0.75~3.52	0.219		2.07			1.22~3.51		0.007

表6

图9

图10

表7

170例2018 FIGOⅢ期宫颈癌患者OS、PFS多因素分析"

影响因素	OS				PFS
影响因素	HR值	95%CI	P值		HR值		95%CI	P值
年龄(≥60岁/<60岁)	0.61	0.21~1.73	0.349	0.73		0.34~1.57		0.425
病理类型
腺癌/鳞状细胞癌	3.32	0.80~13.81	0.098	4.15		1.47~11.77		0.007
腺鳞状细胞癌/鳞状细胞癌	0.00	-	0.979	0.00		0.00~4.46×10²⁷⁸		0.970
肿瘤最大径(>4 cm/≤4 cm)	3.31	1.45~7.56	0.005	1.86		0.99~3.47		0.052
治疗方式
根治性放疗±化疗/根治术±化疗	0.51	0.12~2.13	0.353	1.07		0.31~3.65		0.915
根治术+放疗±化疗/根治术±化疗	0.73	0.19~2.74	0.639	1.54		0.49~4.87		0.462
单纯外照射/根治术±化疗	0.00	-	0.993	0.00		-		0.989
分期
ⅢB/ⅢA	1.40	0.38~5.15	0.613	1.74		0.58~5.22		0.323
ⅢC1/ⅢA	0.53	0.13~2.13	0.372	0.79		0.26~2.35		0.666
ⅢC2/ⅢA	1.74	0.30~10.15	0.537	2.27		0.60~8.60		0.226
治疗后SCCA(阳性/阴性)	4.67	1.22~17.86	0.024	3.96		1.45~10.86		0.007

表7

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