Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy Improves Survival for Patients with Peritoneal Carcinomatosis from Colorectal Cancer: A Phase II Study from a Chinese Center

BackgroundPeritoneal carcinomatosis (PC) is a difficult clinical challenge in colorectal cancer (CRC) because conventional treatment modalities could not produce significant survival benefit, which highlights the acute need for new treatment strategies. Our previous case-control study demonstrated the potential survival advantage of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) over CRS alone. This phase II study was to further investigate the efficacy and adverse events of CRS+HIPEC for Chinese patients with CRC PC.MethodsA total of 60 consecutive CRC PC patients underwent 63 procedures consisting of CRS+HIPEC and postoperative chemotherapy, all by a designated team focusing on this combined treatment modality. All the clinico-pathological information was systematically integrated into a prospective database. The primary end point was disease-specific overall survival (OS), and the secondary end points were perioperative safety profiles.ResultsBy the most recent database update, the median follow-up was 29.9 (range 3.5–108.9) months. The peritoneal cancer index (PCI) ≤20 was in 47.0% of patients, complete cytoreductive surgery (CC0-1) was performed in 53.0% of patients. The median OS was 16.0 (95% confidence interval [CI] 12.2–19.8) months, and the 1-, 2-, 3-, and 5-year survival rates were 70.5%, 34.2%, 22.0% and 22.0%, respectively. Mortality and grades 3 to 5 morbidity rates in postoperative 30 days were 0.0% and 30.2%, respectively. Univariate analysis identified 3 parameters with significant effects on OS: PCI ≤20, CC0-1 and adjuvant chemotherapy over 6 cycles. On multivariate analysis, however, only CC0-1 and adjuvant chemotherapy ≥6 cycles were found to be independent factors for OS benefit.DiscussionCRS+HIPEC at a specialized treatment center could improve OS for selected CRC PC patients from China, with acceptable perioperative safety.

研究背景：腹膜癌病（Peritoneal carcinomatosis, PC）是结直肠癌（colorectal cancer, CRC）临床诊疗中的棘手难题，常规治疗手段难以为患者带来显著生存获益，故而亟需探索新型治疗策略。本团队既往开展的病例对照研究显示，相较于单纯肿瘤细胞减灭术（cytoreductive surgery, CRS），肿瘤细胞减灭术联合腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy, HIPEC）具备潜在的生存优势。本项Ⅱ期临床试验旨在进一步探究肿瘤细胞减灭术联合腹腔热灌注化疗用于中国结直肠癌腹膜癌病患者的疗效与不良事件。
研究方法：本研究共纳入60例连续性结直肠癌腹膜癌病患者，实施了共计63次手术操作，涵盖肿瘤细胞减灭术联合腹腔热灌注化疗及术后化疗，所有操作均由专注于该联合治疗方案的固定医疗团队完成。所有临床病理资料均被系统性录入前瞻性数据库。本研究的主要终点为疾病特异性总生存期（overall survival, OS），次要终点为围手术期安全性指标。
研究结果：截至最新数据库更新时，中位随访时间为29.9个月（范围3.5~108.9个月）。47.0%的患者腹膜癌指数（peritoneal cancer index, PCI）≤20，53.0%的患者实现了完全肿瘤细胞减灭术（CC0-1）。中位总生存期为16.0个月（95%置信区间[CI] 12.2~19.8），1年、2年、3年及5年生存率分别为70.5%、34.2%、22.0%及22.0%。术后30天内的死亡率及3~5级并发症发生率分别为0.0%与30.2%。单因素分析显示，腹膜癌指数≤20、完全肿瘤细胞减灭术（CC0-1）以及辅助化疗周期≥6周期这3项参数对总生存期具有显著影响。但多因素分析结果显示，仅完全肿瘤细胞减灭术（CC0-1）与辅助化疗周期≥6周期为总生存期获益的独立影响因素。
讨论：在专业治疗中心开展的肿瘤细胞减灭术联合腹腔热灌注化疗，可改善中国部分符合指征的结直肠癌腹膜癌病患者的总生存期，且围手术期安全性良好。