PDS或IDS联合HIPEC在新诊断晚期上皮性卵巢癌治疗中的疗效观察

Efficacy of primary or interval debulking surgery combined with hyperthermic intraperitoneal chemotherapy in the treatment of newly diagnosed advanced epithelial ovarian cancer: an observational study

摘要:

目的 探讨初次肿瘤细胞减灭术（PDS）或间歇性肿瘤细胞减灭术（IDS）联合腹腔热灌注化疗（HIPEC）治疗晚期上皮性卵巢癌的安全性和治疗效果。方法 回顾性分析2013年2月—2023年2月在中南大学湘雅医院就诊的419例晚期上皮性卵巢癌患者的临床资料。所有患者在术前接受全面的检查和评估，以确定减瘤满意手术的可能性，据此接受PDS或IDS，并在术后行常规化疗。303例患者接受PDS，其中121例术后联合HIPEC（PDS+HIPEC组），182例术后未联合HIPEC（PDS组）。116例患者接受IDS，其中42例术后联合HIPEC（IDS+HIPEC组），74例术后未联合HIPEC（IDS组）。分别比较两组患者的无疾病进展生存期（PFS）和总生存期（OS）及不良反应事件的发生情况。并进行亚组分析，探究不同亚组在肿瘤细胞减灭术后联合HIPEC对PFS、OS的影响。结果 PDS组与PDS+HIPEC组年龄、体质量指数（BMI）、病理类型、国际妇产科联合会（FIGO）分期、有无腹水、乳腺癌易感基因（BRCA）状态、治疗前糖类抗原125（CA125）、治疗前人附睾蛋白4（HE4）、治疗前血红蛋白、治疗前血肌酐水平、手术残留病灶和静脉化疗次数比较，差异均无统计学意义（P >0.05）。IDS组与IDS+HIPEC组年龄、BMI、病理类型、FIGO分期、有无腹水、BRCA状态、治疗前CA125、治疗前HE4、治疗前血红蛋白、治疗前血肌酐、手术残留病灶、新辅助化疗次数和静脉化疗次数比较，差异均无统计学意义（P >0.05）。PDS组与PDS+HIPEC组中位PFS、OS比较，差异无统计学意义（P >0.05）。IDS组与IDS+HIPEC组中位PFS、OS比较，差异有统计学意义（P <0.05）。多因素一般Cox回归分析结果显示，年龄≥ 55岁［H^R =1.621（95% CI：1.093，2.403）］、手术残留病灶≥R1［H^R =2.007（95% CI：1.322，3.047）］为接受PDS治疗的晚期上皮性卵巢癌患者预后的独立危险因素（P <0.05）；手术残留病灶≥ R1［H^R =1.873（95% CI：1.046，3.356）］为接受IDS治疗的晚期上皮性卵巢癌患者预后的独立危险因素（P <0.05），术后联合HIPEC［H^R =0.561（95% CI：0.326， 0.967）］为保护因素（P <0.05）。亚组分析显示，IDS治疗的患者病理类型为浆液性癌、FIGO Ⅳ期和手术残留病灶≥ R1的患者从HIPEC中生存获益显著（P <0.05）。PDS组与PDS+HIPEC组、IDS组与IDS+HIPEC组之间，贫血、腹泻、便秘、肠梗阻、血栓形成、急性肾功能损伤、肝功能异常、电解质紊乱发生率比较，差异均无统计学意义（P >0.05）。结论 接受IDS治疗的晚期上皮性卵巢癌患者可从HIPEC中获得显著生存获益，而对PDS治疗的患者生存改善尚不明确。HIPEC未增加不良反应，其疗效可能受病理类型、FIGO分期、手术残留病灶状况的影响。

Abstract:

Objective To investigate the safety and efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with primary debulking surgery (PDS) or interval debulking surgery (IDS) in the treatment of advanced epithelial ovarian cancer.Methods A retrospective analysis was conducted on the clinical data of 419 patients with advanced epithelial ovarian cancer treated at Xiangya Hospital, Central South University, from February 2013 to February 2023. All patients underwent comprehensive preoperative evaluations to determine the feasibility of optimal cytoreduction and were subsequently categorized into PDS or IDS groups. Postoperatively, all patients received conventional chemotherapy. Among the 303 patients who underwent PDS, 121 received HIPEC post-surgery (PDS + HIPEC group), while 182 did not receive HIPEC (PDS group). Among the 116 patients who underwent IDS, 42 received HIPEC post-surgery (IDS + HIPEC group), while 74 did not receive HIPEC (IDS group). Progression-free survival (PFS), overall survival (OS), and the incidence of adverse events were compared between the respective groups. Subgroup analyses were performed to evaluate the impact of HIPEC on PFS and OS in different subgroups.Results No statistically significant differences were observed in terms of age, BMI, pathological type, FIGO stage, presence of ascites, BRCA status, levels of CA125, HE4, hemoglobin, and serum creatinine before treatment, residual lesions after surgery, and the number of intravenous chemotherapy sessions between the PDS group and the PDS + HIPEC group (P > 0.05). Similarly, no statistically significant differences were found in these parameters as well as the number of neoadjuvant chemotherapy sessions between the IDS group and the IDS + HIPEC group (P > 0.05). There were no statistically significant differences in median PFS or OS between the PDS group and the PDS + HIPEC group (P > 0.05). In contrast, statistically significant differences were observed in median PFS and OS between the IDS group and the IDS + HIPEC group (P < 0.05). Multivariable Cox regression analysis revealed that age ≥ 55 years [H^R = 1.621 (95% CI: 1.093, 2.403) ] and residual lesions after surgery ≥ R1 [H^R = 2.007 (95% CI: 1.322, 3.047) ] were independent risk factors for poor prognosis in patients with advanced ovarian cancer treated with PDS (P < 0.05). For patients undergoing IDS, residual lesions after surgery ≥ R1 [H^R = 1.873 (95% CI: 1.046, 3.356) ] was identified as an independent risk factor for poor prognosis (P < 0.05). Postoperative HIPEC [H^R = 0.561 (95% CI: 0.326, 0.967) ] was associated with a protective effect on patient outcomes (P < 0.05). Subgroup analysis further demonstrated that patients treated with IDS who had serous carcinoma, FIGO stage Ⅳ tumors, and residual lesions after surgery ≥ R1 derived significant survival benefits from HIPEC (P < 0.05). No statistically significant differences were observed in the incidence rates of anemia, diarrhea, constipation, intestinal obstruction, thrombosis, acute renal function injury, liver function abnormalities, and electrolyte disorders between the PDS group and the PDS + HIPEC group, or between the IDS group and the IDS + HIPEC group (P > 0.05).Conclusions Patients with advanced ovarian cancer undergoing IDS demonstrate significant improvements in survival following the addition of HIPEC. However, the survival advantage in those receiving PDS remains inconclusive. Notably, HIPEC does not increase the incidence of adverse events, and its therapeutic efficacy may be affected by factors such as pathological subtype, FIGO stage, and the extent of residual lesions after cytoreductive surgery.