Fosså S D, Stenning S P, Gerl A, Horwich A, Clark P I, Wilkinson P M, Jones W G, Williams M V, Oliver R T, Newlands E S, Mead G M, Cullen M H, Kaye S B, Rustin G J, Cook P A
Department of Medical Oncology and Radiotherapy, The Norwegian Radium Hospital, Montebello, Oslo.
Br J Cancer. 1999 Jul;80(9):1392-9. doi: 10.1038/sj.bjc.6690534.
The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.
本研究的目的是确定接受铂类诱导化疗（无论是否接受手术）后病情进展的恶性生殖细胞肿瘤患者的生存预后参数。在795例接受铂类诱导化疗（无论是否接受手术）治疗转移性生殖细胞恶性肿瘤的患者中，共确定了164例病情进展的患者（睾丸肿瘤：83%，性腺外肿瘤：17%）。“疾病进展”包括先前部分或完全缓解后病情进展的患者以及初始治疗失败的患者。挽救性化疗采用“传统”铂类化疗。通过单因素和多因素分析评估生存预后因素。所得的预后模型在66例类似患者的独立数据集中进行了验证。对于所有164例患者，从诱导化疗开始到病情进展的中位时间为10个月（范围：0 - 99个月）。38例（23%）患者在2年后复发。所有病情进展患者的5年生存率为30%（95%置信区间23% - 38%）。在单因素分析中，以下因素对预后不良的预测最为重要：无进展生存期<2年、初始预后不良类别（MRC标准）、诱导化疗未达完全缓解、20世纪80年代初开始初始治疗以及在“小型”中心接受治疗。多因素分析中保留了三个预后因素：无进展生存期、诱导治疗反应以及复发时血清人绒毛膜促性腺激素（hCG）和甲胎蛋白（AFP）水平。根据这些特征可将124例患者分类。无进展生存期<2年、诱导化疗未达完全缓解且复发时标志物水平高（AFP>100 kU l⁻¹或hCG>100 IU l⁻¹）的患者形成了一个预后不良的30例患者组，其中无一例在3年后存活。这三个危险因素中最多有两个的患者形成了一个预后良好的94例患者组（76%），其5年生存率为47%（37% - 56%）。来自预后良好组的38例无进展生存期>2年的患者2年生存率为74%（60% - 88%），5年生存率为61%。这些预后组在独立数据集中得到了验证，其中预后良好和不良风险组的5年生存率分别为51%和0%。三分之一在铂类诱导化疗期间或之后病情进展的转移性生殖细胞恶性肿瘤患者可通过重复“传统”铂类化疗治愈。良好的预后参数为：无进展生存期>2年、诱导治疗达完全缓解且复发时血清标志物正常或低水平（hCG<100 IU l⁻¹且AFP<100 kU l⁻¹）。应在这些预后因素的背景下解释大剂量挽救性化疗的结果。
