State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China.
Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou, China.
Cancer Med. 2021 Nov;10(22):8005-8019. doi: 10.1002/cam4.4315. Epub 2021 Oct 12.
The prognostic value of lactate dehydrogenase (LDH) in colorectal cancer patients has remained inconsistent between nonmetastatic and metastatic settings. So far, very few studies have included LDH in the prognostic analysis of curative-intent surgery for colorectal liver metastases (CRLM).
Five hundred and eighty consecutive metastatic colorectal cancer patients who underwent curative-intent CRLM resection from Sun Yat-sen University Cancer Center (434 patients) and Sun Yat-sen University Sixth Affiliated Hospital (146 patients) in 2000-2019 were retrospectively collected. Overall survival (OS) was the primary end point. Cox regression model was performed to identify the prognostic values of preoperative serum LDH levels and other clinicopathology variables. A modification of the established Fong CRS scoring system comprising LDH was developed within this Chinese population.
At the median follow-up time of 60.5 months, median OS was 59.5 months in the pooled cohort. In the multivariate analysis, preoperative LDH >upper limit of normal (250 U/L) was the strongest independent prognostic factor for OS (HR 1.73, 95% confidence interval [CI], 1.22-2.44; p < 0.001). Patients with elevated LDH levels showed impaired OS than patients with normal LDH levels (27.6 months vs. 68.8 months). Five-year survival rates were 53.7% and 22.5% in the LDH-normal group and LDH-high group, respectively. Similar results were also confirmed in each cohort. In the subgroup analysis, LDH could distinguish the survival regardless of most established prognostic factors (number and size of CRLM, surgical margin, extrahepatic metastases, CEA, and CA19-9 levels, etc.). Integrating LDH into the Fong score contributed to an improvement in the predictive value.
Our study implicates serum LDH as a reliable and independent laboratory biomarker to predict the clinical outcome of curative-intent surgery for CRLM. Composite of LDH and Fong score is a potential stratification tool for CRLM resection. Prospective, international studies are needed to validate these results across diverse populations.
乳酸脱氢酶（LDH）在结直肠癌患者中的预后价值在非转移性和转移性环境之间一直不一致。迄今为止，很少有研究将 LDH 纳入结直肠癌肝转移（CRLM）根治性手术的预后分析。
回顾性收集了 2000 年至 2019 年中山大学肿瘤防治中心（434 例）和中山大学第六附属医院（146 例）580 例接受根治性 CRLM 切除术的转移性结直肠癌患者的资料。总生存期（OS）是主要终点。Cox 回归模型用于确定术前血清 LDH 水平和其他临床病理变量的预后价值。在该中国人群中，开发了一种改良的 Fong CRS 评分系统，其中包含 LDH。
在中位随访 60.5 个月时，汇总队列的中位 OS 为 59.5 个月。多变量分析显示，术前 LDH＞正常值上限（250 U/L）是 OS 的最强独立预后因素（HR 1.73，95%置信区间[CI]，1.22-2.44；p＜0.001）。LDH 升高的患者 OS 较 LDH 正常的患者差（27.6 个月比 68.8 个月）。LDH 正常组和 LDH 升高组的 5 年生存率分别为 53.7%和 22.5%。在每个队列中也得到了类似的结果。亚组分析表明，LDH 可区分生存情况，而与大多数既定预后因素（CRLM 的数量和大小、手术切缘、肝外转移、CEA 和 CA19-9 水平等）无关。将 LDH 纳入 Fong 评分有助于提高预测价值。
本研究表明血清 LDH 是预测 CRLM 根治性手术临床结局的可靠且独立的实验室生物标志物。LDH 和 Fong 评分的组合是 CRLM 切除的潜在分层工具。需要进行前瞻性、国际研究，以在不同人群中验证这些结果。
