Efficacy of postoperative hyperthermic intraperitoneal chemotherapy in patients with early stage epithelial ovarian cancer

doi:10.3877/cma.j.issn.1673-5250.2026.02.004

Objective

To evaluate the efficacy of postoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with early-stage [International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ-Ⅱ] epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer.

Methods

A total of 243 patients with pathologically confirmed FIGO stage Ⅰ-Ⅱ epithelial ovarian, fallopian tube, or primary peritoneal cancer who underwent surgery at West China Second University Hospital, Sichuan University, between July 2022 and April 2025 were retrospectively enrolled. Patients were divided into study group (n=105, who received postoperative HIPEC treatment) and control group (n=138, who did not receive postoperative HIPEC treatment) based on whether they received HIPEC after surgery. Due to the similar biological behaviors and essentially identical treatment principles of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer, and given that epithelial ovarian cancer accounts for >90% of ovarian cancer cases, these three malignancies were studied as a whole in this research. Hereinafter, epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer were collectively referred to as epithelial ovarian cancer. Clinical data and progression-free survival (PFS) of patients in two groups were collected by retrospective method. Propensity score matching (PSM) was performed at a 1∶1 ratio between the two groups to balance baseline characteristics (including age, FIGO stage, and histologic type, etc.), with a caliper width set at 0.1 times the standard deviation of the propensity score. After PSM, Kaplan-Meier method was used to plot the PFS curves of the two groups of patients, and the PFS period of two groups of patients was compared by the Log-rank test. Univariate Cox regression subgroup analyses were further constructed for subgroup analyses to explore the efficacy of HIPEC across different subgroups. Additionally, a separate PSM was conducted in patients with ovarian clear cell carcinoma, and the effect of HIPEC on PFS in patients with ovarian clear cell carcinoma was evaluated. This study was conducted in accordance with the requirements of the Helsinki Declaration of the World Medical Association revised in 2013.

Results

①After PSM, 158 patients (79 in each group) were included in the final analysis. Post-matching, there were no statistically significant differences between two groups in age, histologic type, FIGO stage, or other clinical characteristics (all P>0.05). With a median follow-up of 19.2 months (0.2-41.8 months), disease progression occurred in 6 patients (7.6%) in study group and 10 patients (12.7%) in control group after PSM. Log-rank test showed no significant difference in PFS between two groups after PSM (χ²=1.11, P=0.291). Univariate Cox regression subgroup analysis showed that there were no statistically significant differences in the proportion of disease progression between the study group and the control group in different clinical subgroups after PSM (P>0.05). ②In the separate PSM analysis of 62 patients with ovarian clear cell carcinoma (31 cases in each group), with a median follow-up of 16.2 months (0.6-39.8 months), disease progression occurred in 3 patients (9.7%) in study group and 8 patients (25.8%) in control group. However, Log-rank test revealed no statistically significant difference in PFS between two groups of patients with ovarian clear cell carcinoma after PSM(χ²=2.77, P=0.096).

Conclusions

In this study, postoperative HIPEC does not demonstrate a significant benefit in improving PFS for patients with FIGO stage Ⅰ-Ⅱ epithelial ovarian, fallopian tube, or primary peritoneal cancer. In patients with FIGO stage Ⅰ-Ⅱ ovarian clear cell carcinoma, HIPEC shows a potential trend toward benefit, although the difference did not reach statistical significance. Larger-scale prospective randomized controlled trials are warranted to further validate these findings.

Key words: Ovarian neoplasms, Early stage ovarian cancer, Hyperthermic intraperitoneal chemotherapy, Ovarian clear cell carcinoma, Propensity score, Neoplasm staging, Female

表1 2组早期上皮性卵巢癌患者PSM前、后相关临床资料比较[例数(%)]

临床指标	PSM前					PSM后
临床指标	研究组(n＝105)	对照组(n＝138)	χ²值	P值	SMD	研究组(n＝79)	对照组(n＝79)	χ²值	P值	SMD
保留生育功能			4.78	0.029				<0.01^a	>0.999
否	101(96.2)	122(88.4)			0.407	76(96.2)	77(97.5)			－0.066
是	4(3.8)	16(11.6)			－0.407	3(3.8)	2(2.5)			0.066
卵巢黏液性癌			2.40	0.122				<0.01^a	>0.999
否	100(95.2)	124(89.9)			0.253	75(94.9)	75(94.9)			0
是	5(4.8)	14(10.1)			－0.253	4(5.1)	4(5.1)			0
卵巢透明细胞癌			1.43	0.231				0.11	0.739
否	71(67.6)	83(60.1)			0.160	52(65.8)	50(63.3)			0.053
是	34(32.4)	55(39.9)			－0.160	27(34.2)	29(36.7)			－0.053
卵巢高级别浆液性腺癌			5.61	0.018				0.11	0.737
否	66(62.9)	106(76.8)			－0.289	53(67.1)	51(64.6)			0.054
是	39(37.1)	32(23.2)			0.289	26(32.9)	28(35.4)			－0.054
FIGO临床分期为Ⅱ期			4.59	0.032				0.27	0.602
否	71(67.6)	110(79.7)			－0.258	54(68.4)	57(72.2)			－0.082
是	34(32.4)	28(20.3)			0.258	25(31.6)	22(27.8)			0.082
年龄≥60岁			0.04	0.844				0.04	0.833
否	87(82.9)	113(81.9)			0.026	66(83.5)	65(82.3)			0.034
是	18(17.1)	25(18.1)			－0.026	13(16.5)	14(17.7)			－0.034
改良虚弱指数评分≥1分			1.53	0.217				0.21	0.646
否	87(82.9)	122(88.4)			－0.147	67(84.8)	69(87.3)			－0.071
是	18(17.1)	16(11.6)			0.147	12(15.2)	10(12.7)			0.071
术前SII≥612			<0.01	0.961				0.10	0.746
否	40(38.1)	53(38.4)			－0.006	33(41.8)	31(39.2)			0.051
是	65(61.9)	85(61.6)			0.006	46(58.2)	48(60.8)			－0.051
术前低白蛋白血症			0.18^a	0.675				0.17^a	0.677
否	100(95.2)	134(97.1)			－0.087	75(94.9)	77(97.5)			－0.115
是	5(4.8)	4(2.9)			0.087	4(5.1)	2(2.5)			0.115
手术方式			1.80	0.180				0.03	0.870
腹腔镜	36(34.3)	59(42.8)			－0.178	30(38.0)	31(39.2)			－0.026
开腹	69(65.7)	79(57.2)			0.178	49(62.0)	48(60.8)			0.026
术中PCI评分≥2分			7.86	0.005				0	1.000
否	64(61.0)	107(77.5)			－0.340	56(70.9)	56(70.9)			0
是	41(39.0)	31(22.5)			0.340	23(29.1)	23(29.1)			0
术中同时切除其他器官			<0.01^a	0.975				<0.01^a	>0.999
否	101(96.2)	134(97.1)			－0.048	76(96.2)	75(94.9)			0.066
是	4(3.8)	4(2.9)			0.048	3(3.8)	4(5.1)			－0.066

表1 2组早期上皮性卵巢癌患者PSM前、后相关临床资料比较[例数(%)]

临床指标	PSM前					PSM后
临床指标	研究组(n＝105)	对照组(n＝138)	χ²值	P值	SMD	研究组(n＝79)	对照组(n＝79)	χ²值	P值	SMD
保留生育功能			4.78	0.029				<0.01^a	>0.999
否	101(96.2)	122(88.4)			0.407	76(96.2)	77(97.5)			－0.066
是	4(3.8)	16(11.6)			－0.407	3(3.8)	2(2.5)			0.066
卵巢黏液性癌			2.40	0.122				<0.01^a	>0.999
否	100(95.2)	124(89.9)			0.253	75(94.9)	75(94.9)			0
是	5(4.8)	14(10.1)			－0.253	4(5.1)	4(5.1)			0
卵巢透明细胞癌			1.43	0.231				0.11	0.739
否	71(67.6)	83(60.1)			0.160	52(65.8)	50(63.3)			0.053
是	34(32.4)	55(39.9)			－0.160	27(34.2)	29(36.7)			－0.053
卵巢高级别浆液性腺癌			5.61	0.018				0.11	0.737
否	66(62.9)	106(76.8)			－0.289	53(67.1)	51(64.6)			0.054
是	39(37.1)	32(23.2)			0.289	26(32.9)	28(35.4)			－0.054
FIGO临床分期为Ⅱ期			4.59	0.032				0.27	0.602
否	71(67.6)	110(79.7)			－0.258	54(68.4)	57(72.2)			－0.082
是	34(32.4)	28(20.3)			0.258	25(31.6)	22(27.8)			0.082
年龄≥60岁			0.04	0.844				0.04	0.833
否	87(82.9)	113(81.9)			0.026	66(83.5)	65(82.3)			0.034
是	18(17.1)	25(18.1)			－0.026	13(16.5)	14(17.7)			－0.034
改良虚弱指数评分≥1分			1.53	0.217				0.21	0.646
否	87(82.9)	122(88.4)			－0.147	67(84.8)	69(87.3)			－0.071
是	18(17.1)	16(11.6)			0.147	12(15.2)	10(12.7)			0.071
术前SII≥612			<0.01	0.961				0.10	0.746
否	40(38.1)	53(38.4)			－0.006	33(41.8)	31(39.2)			0.051
是	65(61.9)	85(61.6)			0.006	46(58.2)	48(60.8)			－0.051
术前低白蛋白血症			0.18^a	0.675				0.17^a	0.677
否	100(95.2)	134(97.1)			－0.087	75(94.9)	77(97.5)			－0.115
是	5(4.8)	4(2.9)			0.087	4(5.1)	2(2.5)			0.115
手术方式			1.80	0.180				0.03	0.870
腹腔镜	36(34.3)	59(42.8)			－0.178	30(38.0)	31(39.2)			－0.026
开腹	69(65.7)	79(57.2)			0.178	49(62.0)	48(60.8)			0.026
术中PCI评分≥2分			7.86	0.005				0	1.000
否	64(61.0)	107(77.5)			－0.340	56(70.9)	56(70.9)			0
是	41(39.0)	31(22.5)			0.340	23(29.1)	23(29.1)			0
术中同时切除其他器官			<0.01^a	0.975				<0.01^a	>0.999
否	101(96.2)	134(97.1)			－0.048	76(96.2)	75(94.9)			0.066
是	4(3.8)	4(2.9)			0.048	3(3.8)	4(5.1)			－0.066

图1 PSM后2组早期上皮性卵巢癌患者PFS曲线比较注：研究组为术后接受HIPEC治疗的早期(FIGO临床分期为Ⅰ~Ⅱ期)上皮性卵巢癌患者，对照组为术后未接受HIPEC治疗的早期(FIGO临床分期为Ⅰ~Ⅱ期)上皮性卵巢癌患者。PSM为倾向性评分匹配，PFS为无进展生存，FIGO为国际妇产科联盟，HIPEC为腹腔热灌注化疗

表2 PSM后研究组与对照组早期上皮性卵巢癌患者疾病进展影响因素的单因素Cox回归亚组分析

临床指标	例数	研究组疾病进展比例(n/n′)	对照组疾病进展比例(n/n′)	HR值(95%CI)	P值	交互作用P值
所有患者	158	6/79	10/79	0.584(0.212~1.606)	0.297	—
保留生育功能						1.000
否	153	6/76	10/77	0.601(0.219~1.655)	0.325
是	5	0/3	0/2	NA
卵巢黏液性癌						1.000
否	150	6/75	10/75	0.571(0.207~1.570)	0.277
是	8	0/4	0/4	NA
卵巢透明细胞癌						0.239
否	102	3/52	2/50	1.413(0.236~8.456)	0.705
是	56	3/27	8/29	0.372(0.098~1.403)	0.144
卵巢高级别浆液性腺癌						0.478
否	104	4/53	8/51	0.463(0.139~1.539)	0.209
是	54	2/26	2/28	1.073(0.151~7.627)	0.944
FIGO临床分期为Ⅱ期						0.673
否	111	4/54	8/57	0.516(0.155~1.715)	0.280
是	47	2/25	2/22	0.826(0.116~5.868)	0.849
年龄≥60岁						0.881
否	131	5/66	7/65	0.647(0.205~2.040)	0.458
是	27	1/13	3/14	0.583(0.059~5.738)	0.644
改良虚弱指数评分≥1分						0.998
否	136	6/67	9/69	0.656(0.234~1.844)	0.424
是	22	0/12	1/10	NE	1.000
SII≥612						0.866
否	64	2/33	3/31	0.675(0.113~4.044)	0.667
是	94	4/46	7/48	0.552(0.161~1.887)	0.343
术前低白蛋白血症						1.000
否	152	6/75	10/77	0.595(0.216~1.637)	0.315
是	6	0/4	0/2	NA
手术方式						0.761
腹腔镜	61	2/30	4/31	0.472(0.086~2.580)	0.387
开腹	97	4/49	6/48	0.654(0.184~2.321)	0.512
术中PCI评分≥2分						0.997
否	112	6/56	7/56	0.851(0.286~2.532)	0.771
是	46	0/23	3/23	NE	0.999
术中同时切除其他器官						0.998
否	151	5/76	10/75	0.473(0.162~1.384)	0.172
是	7	1/3	0/4	NE	1.000

表2 PSM后研究组与对照组早期上皮性卵巢癌患者疾病进展影响因素的单因素Cox回归亚组分析

临床指标	例数	研究组疾病进展比例(n/n′)	对照组疾病进展比例(n/n′)	HR值(95%CI)	P值	交互作用P值
所有患者	158	6/79	10/79	0.584(0.212~1.606)	0.297	—
保留生育功能						1.000
否	153	6/76	10/77	0.601(0.219~1.655)	0.325
是	5	0/3	0/2	NA
卵巢黏液性癌						1.000
否	150	6/75	10/75	0.571(0.207~1.570)	0.277
是	8	0/4	0/4	NA
卵巢透明细胞癌						0.239
否	102	3/52	2/50	1.413(0.236~8.456)	0.705
是	56	3/27	8/29	0.372(0.098~1.403)	0.144
卵巢高级别浆液性腺癌						0.478
否	104	4/53	8/51	0.463(0.139~1.539)	0.209
是	54	2/26	2/28	1.073(0.151~7.627)	0.944
FIGO临床分期为Ⅱ期						0.673
否	111	4/54	8/57	0.516(0.155~1.715)	0.280
是	47	2/25	2/22	0.826(0.116~5.868)	0.849
年龄≥60岁						0.881
否	131	5/66	7/65	0.647(0.205~2.040)	0.458
是	27	1/13	3/14	0.583(0.059~5.738)	0.644
改良虚弱指数评分≥1分						0.998
否	136	6/67	9/69	0.656(0.234~1.844)	0.424
是	22	0/12	1/10	NE	1.000
SII≥612						0.866
否	64	2/33	3/31	0.675(0.113~4.044)	0.667
是	94	4/46	7/48	0.552(0.161~1.887)	0.343
术前低白蛋白血症						1.000
否	152	6/75	10/77	0.595(0.216~1.637)	0.315
是	6	0/4	0/2	NA
手术方式						0.761
腹腔镜	61	2/30	4/31	0.472(0.086~2.580)	0.387
开腹	97	4/49	6/48	0.654(0.184~2.321)	0.512
术中PCI评分≥2分						0.997
否	112	6/56	7/56	0.851(0.286~2.532)	0.771
是	46	0/23	3/23	NE	0.999
术中同时切除其他器官						0.998
否	151	5/76	10/75	0.473(0.162~1.384)	0.172
是	7	1/3	0/4	NE	1.000

图2 PSM后2组早期卵巢透明细胞癌患者PFS曲线比较注：研究组为术后接受HIPEC治疗的早期(FIGO临床分期为Ⅰ~Ⅱ期)卵巢透明细胞癌患者，对照组为术后未接受HIPEC治疗的早期(FIGO临床分期为Ⅰ~Ⅱ期)卵巢透明细胞癌患者。PSM为倾向性评分匹配，PFS为无进展生存，FIGO为国际妇产科联盟，HIPEC为腹腔热灌注化疗

表3 PSM前、后，研究组与对照组早期卵巢透明细胞癌患者相关临床指标比较[例数(%)]

临床指标	PSM前					PSM后
临床指标	研究组(n＝34)	对照组(n＝55)	χ²值	P值	SMD	研究组(n＝31)	对照组(n＝31)	χ²值	P值	SMD
保留生育功能			<0.01^a	>0.999				0.52^a	0.471
否	33(97.1)	53(96.4)			0.041	30(96.8)	30(96.8)			0
是	1(2.9)	2(3.6)			－0.041	1(3.2)	1(3.2)			0
FIGO临床分期为Ⅱ期			0.11^a	0.735				<0.01^a	>0.999
否	30(88.2)	51(92.7)			－0.139	27(87.1)	28(90.3)			－0.096
是	4(11.8)	4(7.3)			0.139	4(12.9)	3(9.7)			0.096
年龄≥60岁			0.18	0.670				0.41	0.520
否	29(85.3)	45(81.8)			0.098	26(83.9)	24(77.4)			0.175
是	5(14.7)	10(18.2)			－0.098	5(16.1)	7(22.6)			－0.175
改良虚弱指数≥1			1.50^a	0.221				0.41	0.520
否	27(79.4)	50(90.9)			－0.284	24(77.4)	26(83.9)			－0.154
是	7(20.6)	5(9.1)			0.284	7(22.6)	5(16.1)			0.154
全身免疫炎症指数≥612			3.94	0.047				0	1.000
否	17(50.0)	16(29.1)			0.418	14(45.2)	14(45.2)			0
是	17(50.0)	39(70.9)			－0.418	17(54.8)	17(54.8)			0
术前低白蛋白血症			0.61^a	0.435				—^b	1.000
否	34(100.0)	52(94.5)			0.306	31(100.0)	30(96.8)			0.258
是	0(0)	3(5.5)			－0.306	0(0)	1(3.2)			－0.258
手术方式			2.08	0.149				0	1.000
腹腔镜	17(50.0)	19(34.5)			0.309	14(45.2)	14(45.2)			0
开腹	17(50.0)	36(65.5)			－0.309	17(54.8)	17(54.8)			0
术中PCI指数≥2分			0.81	0.368				0.73	0.393
否	23(67.6)	42(76.4)			－0.186	21(67.7)	24(77.4)			－0.207
是	11(32.4)	13(23.6)			0.186	10(32.3)	7(22.6)			0.207
术中同时切除其他器官			<0.01^a	>0.999				0.52^a	0.471
否	33(97.1)	53(96.4)			－0.048	30(96.8)	30(96.8)			0
是	1(2.9)	2(3.6)			0.048	1(3.2)	1(3.2)			0

表3 PSM前、后，研究组与对照组早期卵巢透明细胞癌患者相关临床指标比较[例数(%)]

临床指标	PSM前					PSM后
临床指标	研究组(n＝34)	对照组(n＝55)	χ²值	P值	SMD	研究组(n＝31)	对照组(n＝31)	χ²值	P值	SMD
保留生育功能			<0.01^a	>0.999				0.52^a	0.471
否	33(97.1)	53(96.4)			0.041	30(96.8)	30(96.8)			0
是	1(2.9)	2(3.6)			－0.041	1(3.2)	1(3.2)			0
FIGO临床分期为Ⅱ期			0.11^a	0.735				<0.01^a	>0.999
否	30(88.2)	51(92.7)			－0.139	27(87.1)	28(90.3)			－0.096
是	4(11.8)	4(7.3)			0.139	4(12.9)	3(9.7)			0.096
年龄≥60岁			0.18	0.670				0.41	0.520
否	29(85.3)	45(81.8)			0.098	26(83.9)	24(77.4)			0.175
是	5(14.7)	10(18.2)			－0.098	5(16.1)	7(22.6)			－0.175
改良虚弱指数≥1			1.50^a	0.221				0.41	0.520
否	27(79.4)	50(90.9)			－0.284	24(77.4)	26(83.9)			－0.154
是	7(20.6)	5(9.1)			0.284	7(22.6)	5(16.1)			0.154
全身免疫炎症指数≥612			3.94	0.047				0	1.000
否	17(50.0)	16(29.1)			0.418	14(45.2)	14(45.2)			0
是	17(50.0)	39(70.9)			－0.418	17(54.8)	17(54.8)			0
术前低白蛋白血症			0.61^a	0.435				—^b	1.000
否	34(100.0)	52(94.5)			0.306	31(100.0)	30(96.8)			0.258
是	0(0)	3(5.5)			－0.306	0(0)	1(3.2)			－0.258
手术方式			2.08	0.149				0	1.000
腹腔镜	17(50.0)	19(34.5)			0.309	14(45.2)	14(45.2)			0
开腹	17(50.0)	36(65.5)			－0.309	17(54.8)	17(54.8)			0
术中PCI指数≥2分			0.81	0.368				0.73	0.393
否	23(67.6)	42(76.4)			－0.186	21(67.7)	24(77.4)			－0.207
是	11(32.4)	13(23.6)			0.186	10(32.3)	7(22.6)			0.207
术中同时切除其他器官			<0.01^a	>0.999				0.52^a	0.471
否	33(97.1)	53(96.4)			－0.048	30(96.8)	30(96.8)			0
是	1(2.9)	2(3.6)			0.048	1(3.2)	1(3.2)			0

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