Department of Surgery, Catharina Cancer Institute, Eindhoven, the Netherlands.
Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, the Netherlands.
JAMA Oncol. 2020 Aug 1;6(8):e202701. doi: 10.1001/jamaoncol.2020.2701. Epub 2020 Aug 13.
To date, there are no data on the value of adjuvant systemic chemotherapy following up-front resection of isolated synchronous colorectal peritoneal metastases.
To assess the association between adjuvant systemic chemotherapy and overall survival following up-front resection of isolated synchronous colorectal peritoneal metastases.
DESIGN, SETTING, AND PARTICIPANTS: In this population-based, observational cohort study using nationwide data from the Netherlands Cancer Registry (diagnoses between January 1, 2005, and December 31, 2017; follow-up until January 31, 2019), 393 patients with isolated synchronous colorectal peritoneal metastases who were alive 3 months after up-front complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy were included. Patients allocated to the adjuvant systemic chemotherapy group were matched (1:1) with those allocated to the active surveillance group by propensity scores based on patient-, tumor-, and treatment-level covariates.
Adjuvant systemic chemotherapy, defined as systemic chemotherapy without targeted therapy, starting within 3 months postoperatively.
Overall survival was compared between matched groups using Cox proportional hazards regression analysis adjusted for residual imbalance. A landmark analysis was performed by excluding patients who died within 6 months postoperatively. A sensitivity analysis was performed to adjust for unmeasured confounding by major postoperative morbidity.
Of 393 patients (mean [SD] age, 61 [10] years; 181 [46%] men), 172 patients (44%) were allocated to the adjuvant systemic chemotherapy group. After propensity score matching of 142 patients in the adjuvant systemic chemotherapy group with 142 patients in the active surveillance group, adjuvant systemic chemotherapy was associated with improved overall survival compared with active surveillance (median, 39.2 [interquartile range, 21.1-111.1] months vs 24.8 [interquartile range, 15.0-58.4] months; adjusted hazard ratio [aHR], 0.66; 95% CI, 0.49-0.88; P = .006), which remained consistent after excluding patients who died within 6 months postoperatively (aHR, 0.68; 95% CI, 0.50-0.93; P = .02) and after adjustment for major postoperative morbidity (aHR, 0.71; 95% CI, 0.53-0.95).
Findings of this study suggest that in patients undergoing up-front resection of isolated synchronous colorectal peritoneal metastases, adjuvant systemic chemotherapy appeared to be associated with improved overall survival. Although randomized trials are needed to address the influence of potential residual confounding and allocation bias on this association, results of this study may be used for clinical decision-making in this patient group for whom no data are available.
迄今为止，尚无关于初始根治性切除孤立性同步结直肠腹膜转移后辅助全身化疗价值的数据。
评估初始根治性切除孤立性同步结直肠腹膜转移后辅助全身化疗与总生存期之间的关系。
设计、地点和参与者：这是一项基于人群的观察性队列研究，使用荷兰癌症登记处（2005 年 1 月 1 日至 2017 年 12 月 31 日期间的诊断；随访至 2019 年 1 月 31 日）的全国性数据，纳入 393 例接受初始完全细胞减灭术联合腹腔内热疗后 3 个月存活的孤立性同步结直肠腹膜转移患者。将接受辅助全身化疗的患者（定义为无靶向治疗的全身化疗，术后 3 个月内开始）与接受主动监测的患者（按患者、肿瘤和治疗水平的协变量进行倾向评分匹配）进行匹配（1:1）。
辅助全身化疗。
采用 Cox 比例风险回归分析比较匹配组之间的总生存期，并根据术后残留不平衡情况进行调整。通过排除术后 6 个月内死亡的患者进行了 landmark 分析。进行敏感性分析以调整主要术后发病率的未测量混杂因素。
在 393 例患者（平均[标准差]年龄，61[10]岁；181[46%]为男性）中，172 例（44%）被分配到辅助全身化疗组。对辅助全身化疗组的 142 例患者和主动监测组的 142 例患者进行倾向评分匹配后，与主动监测相比，辅助全身化疗与改善的总生存期相关（中位，39.2[四分位距，21.1-111.1]个月比 24.8[四分位距，15.0-58.4]个月；调整后的危险比[aHR]，0.66；95%CI，0.49-0.88；P=0.006），排除术后 6 个月内死亡的患者后（aHR，0.68；95%CI，0.50-0.93；P=0.02）和调整主要术后发病率后（aHR，0.71；95%CI，0.53-0.95）仍保持一致。
本研究结果表明，在接受初始根治性切除孤立性同步结直肠腹膜转移的患者中，辅助全身化疗似乎与总生存期的改善相关。尽管需要随机试验来解决潜在残余混杂因素和分配偏倚对这种关联的影响，但本研究的结果可用于该患者群体的临床决策，因为目前尚无数据。
