Enblad Malin, Cashin Peter, Ghanipour Lana, Graf Wilhelm
Department of Surgical Sciences, Colorectal Surgery, Uppsala University, Uppsala, Sweden.
Ann Surg Oncol. 2025 May;32(5):3638-3647. doi: 10.1245/s10434-024-16860-y. Epub 2025 Jan 22.
Prediction of open-close and long-term outcome is challenging in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic scores often include factors not known at baseline. Therefore, we aimed to analyze whether patterns of preoperative tumor markers could aid in prediction of open-close surgery and outcome in patients with pseudomyxoma peritonei (PMP) or colorectal peritoneal metastases (PM).
All patients accepted for CRS and HIPEC for PMP or colorectal PM at Uppsala University Hospital in 2013-2021 were included. The tumor markers CEA, CA19-9, CA125, CA72-4, and CA15-3 were clustered using the k-means algorithm; the average silhouette width determined the optimal numbers of clusters.
Clustering of patients with PMP (n = 138) and colorectal PM (n = 213) resulted in two clusters each. PMPCluster-1 (n = 124) had a 5-year overall survival (OS) of 77% (95% CI 69-85%), 11 (9%) open-close surgeries, and a median peritoneal cancer index (PCI) of 17. PMPCluster-2 (n = 14) patients had poorer prognosis (36%, 95% CI 15-85%, p = 0.003), more often open-close (n = 6, 43%, p = 0.002), and higher PCI (median 36, p < 0.001). ColorectalCluster-1 (n = 191) had a 5-year OS of 28% (95% CI 21-37%), median PCI of 11, and 38 (20%) open-close surgeries. ColorectalCluster-2 (n = 22) had poorer prognosis (10%, 95% CI 3-36%, p = 0.02), higher PCI (median 26, p < 0.001), higher completeness of cytoreduction score (p = 0.005), but no difference in open-close surgery (n = 6, 27%, p = 0.411). PMPCluster-2 and ColorectalCluster-2 were characterized by markedly elevated tumor markers. Open-close surgery was unusual in cases of normal CA72-4.
Elevation of several preoperative tumor markers is associated with poor prognosis and increased risk of open-close. CA72-4 deserves increased attention.
对于接受细胞减灭术（CRS）和热灌注化疗（HIPEC）的患者，预测手术的开合情况及长期预后具有挑战性。预后评分通常包含基线时未知的因素。因此，我们旨在分析术前肿瘤标志物的模式是否有助于预测腹膜假黏液瘤（PMP）或结直肠癌腹膜转移（PM）患者的手术开合情况及预后。
纳入2013年至2021年在乌普萨拉大学医院接受CRS和HIPEC治疗的PMP或结直肠癌PM患者。使用k均值算法对肿瘤标志物癌胚抗原（CEA）、糖类抗原19-9（CA19-9）、糖类抗原125（CA125）、糖类抗原72-4（CA72-4）和糖类抗原15-3（CA15-3）进行聚类分析；平均轮廓宽度确定聚类的最佳数量。
对PMP患者（n = 138）和结直肠癌PM患者（n = 213）进行聚类分析，均得到两个聚类。PMP聚类1（n = 124）的5年总生存率（OS）为77%（95%置信区间69 - 85%），有11例（9%）手术开合情况，腹膜癌指数（PCI）中位数为17。PMP聚类2（n = 14）患者预后较差（36%，95%置信区间15 - 85%，p = 0.003），手术开合情况更常见（n = 6，43%，p = 0.002），PCI更高（中位数36，p < 0.001）。结直肠癌聚类1（n = 191）的5年OS为28%（95%置信区间21 - 37%），PCI中位数为11，有38例（20%）手术开合情况。结直肠癌聚类2（n = 22）预后较差（10%，95%置信区间3 - 36%，p = 0.02），PCI更高（中位数26，p < 0.001），细胞减灭术完成度评分更高（p = 0.005），但手术开合情况无差异（n = 6，27%，p = 0.411）。PMP聚类2和结直肠癌聚类2的特点是肿瘤标志物显著升高。CA72-4正常的病例中手术开合情况不常见。
术前多种肿瘤标志物升高与预后不良及手术开合风险增加相关。CA72-4值得更多关注。
