Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Urol Oncol. 2019 Nov;37(11):809.e19-809.e25. doi: 10.1016/j.urolonc.2019.07.020. Epub 2019 Sep 5.
Germ cell tumor patients with intermediate prognosis (IPGCT) according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification represent a heterogeneous group with different clinical features. This analysis was performed to investigate the prognostic impact of different tumor marker levels prior to first line chemotherapy within IPGCT.
For this study an international registry for IPGCT was established. Eligibility criteria were intermediate prognosis according to IGCCCG criteria, nonseminomatous histology, male sex, and age ≥ 16 years. Uni- and multivariate analysis were conducted to identify characteristics associated with survival outcomes. Receiver-Operating-Characteristic curve analysis was applied to find cut-off parameters. Five-year overall survival (OS) rate was the primary and 5-year progression-free survival rate the secondary endpoint.
This database included 634 IPGCT with a median follow-up of 9.0 years (interquartile range: 14.35). Patients received first line treatment with platinum based chemotherapy, associated with a 5-year OS rate of 87%. The stratification of patients according to AFP levels revealed a correlation between AFP levels and outcome, associated with 5-year OS rates of 88% for AFP levels <1,000 IU/ml (n = 303), 89% for 1,000 to 2,000 IU/ml (n = 82), 87% for >2,000 to 6,000 IU/ml (n = 121), and 82% for >6,000 IU/ml (n = 57) prior first course of chemotherapy, respectively (P= 0.013). LDH levels prior fist course of chemotherapy also correlated with outcome associated with 5-year OS rates of 92% for <2 UNL (n = 271), 89% for ≥2 to 3 UNL (n = 85), 78% for >3 to 4 UNL (n = 34), and 77% for >4 UNL (n = 79), respectively (P= 0.03). Different HCG levels prior chemotherapy were not associated with outcome. In multivariable analysis AFP levels >6,000 IU/ml (P= 0.023; hazard ratio HR 2.263) or >1,982 IU/ml (P= 0.031; HR 1.722), and LDH levels >3 UNL (P< 0.001; HR 2.616) were independent prognosticators for OS.
Prognostication according to LDH and AFP levels prior chemotherapy could offer a new approach to stratify patients within the intermediate prognosis cohort. According to our findings, patients with AFP values above 6,000 IU/ml or/and LDH > 3 UNL represent an independent high risk cohort. Our results need to be confirmed in the upcoming IGCCCG reclassification.
根据国际生殖细胞癌协作组（IGCCCG）分类，具有中间预后（IPGCT）的生殖细胞肿瘤患者是一组具有不同临床特征的异质群体。进行这项分析是为了研究在一线化疗前不同肿瘤标志物水平对 IPGCT 患者预后的影响。
为此研究建立了一个 IPGCT 的国际登记处。入选标准为符合 IGCCCG 标准的中间预后、非精原细胞瘤组织学、男性和年龄≥16 岁。进行单变量和多变量分析以确定与生存结果相关的特征。应用受试者工作特征曲线分析寻找截断参数。5 年总生存率（OS）是主要终点，5 年无进展生存率是次要终点。
该数据库包括 634 例 IPGCT，中位随访时间为 9.0 年（四分位间距：14.35）。患者接受了基于铂类的一线化疗，5 年 OS 率为 87%。根据 AFP 水平对患者进行分层显示 AFP 水平与预后相关，分别有 88%的 AFP<1000IU/ml（n=303）、89%的 AFP 为 1000-2000IU/ml（n=82）、87%的 AFP>2000-6000IU/ml（n=121）和 82%的 AFP>6000IU/ml（n=57）患者在一线化疗前有 5 年 OS 率（P=0.013）。一线化疗前 LDH 水平也与预后相关，分别有 92%的 LDH<2UNL（n=271）、89%的 LDH≥2-3UNL（n=85）、78%的 LDH>3-4UNL（n=34）和 77%的 LDH>4UNL（n=79）患者有 5 年 OS 率（P=0.03）。化疗前不同的 HCG 水平与预后无关。多变量分析显示 AFP>6000IU/ml（P=0.023；风险比 HR 2.263）或>1982IU/ml（P=0.031；HR 1.722）和 LDH>3UNL（P<0.001；HR 2.616）是 OS 的独立预后因素。
根据化疗前 LDH 和 AFP 水平进行预后评估可能为中间预后队列中的患者提供一种新的分层方法。根据我们的发现，AFP 值高于 6000IU/ml 和/或 LDH>3UNL 的患者代表一个独立的高危人群。我们的结果需要在即将到来的 IGCCCG 重新分类中得到证实。
