以攝護腺特定抗原做為侵犯性攝護腺癌患者接受荷爾蒙療法後發生生化惡化的預後因子之研究

Abstract

背景與目的: 侵犯性攝護腺癌患者接受雄性激素剝奪療法的預後差異性很大，造成在病人諮詢上的困難。本研究目的在確認影響侵犯性攝護腺癌患者發生化惡化的預後因子。 方法：從台灣北部兩所醫學中心電腦登錄系統回溯性地查詢於1995年11月到2008年4月曾經使用leuprorelin acetate (Leuplin Depot®, 3.75 mg)治療攝護腺腺癌的病患。共有107位符合初診斷為侵犯性(cT3 以上)或是轉移性攝護腺癌的病人接受評估影響發生生化惡化與總存活的相關因子。所有病患都有檢測初始血清攝護腺特定抗原 (prostate specific antigen, PSA)。並以Cox 回歸模型以及 Kaplan-Meier 分析來評估臨床因子與發生生化惡化的關係。 結果：病人年齡的中位數是74.6 歲。初始血清攝護腺特定抗原的中位數則是 105 ng/mL(Q1-Q3 為39.8至372 ng/mL)。在追蹤時間的中位數為46.1個月這段期間，總共有54位病人 (50.5%) 有發生生化惡化的情形。在多變項分析中，初始血清PSA值大於105 ng/mL (相對危險比, RR, 3.23; 95% 信賴區間, 95% CI, 1.66, 6.29)、病理性骨折 (RR, 2.73; 95% CI, 1.37, 5.44)、以及血色素濃度小於或是等於12.7 g/dL (RR, 2.05; 95% CI, 1.10, 3.81) 是影響發生生化惡化的預後因子。與血清PSA最低三分位分組比較，在血清PSA最高三分位分組的病人，經校正年齡以及身體質量指數，發生生化惡化的危險比超過三倍 (RR, 3.16, 95% CI, 1.38, 7.22). 進一步校正攝護腺體積、診斷方式、Gleason 分數、是否有骨骼轉移以及病理性骨折，稍微減弱了發生生化惡化的危險比。再進一步校正血色素以及臨床疾病狀態，發生生化惡化的危險比依然顯著(RR, 3.68, 95% CI, 1.33, 10.0). 結論：本研究顯示初始血清PSA濃度的高低確實可以做為影響台灣侵犯性攝護腺癌患者發生生化惡化的危險因子。

Background and Objectives: The prognosis of men with advanced prostate cancer receiving androgen deprivation therapy is highly variable, and it is difficult to counsel a man who is in non-curative treatments. The aim of this study is to identify prognostic factors affecting biochemical progression (BCP) of advanced prostate cancer patients in Taiwan. Methods: Working with 2 medical centers within north Taiwan, a cohort of men diagnosed with prostate adenocarcinoma ever receiving leuprorelin acetate (Leuplin Depot®, 3.75 mg) between November 1995 and April 2008 was collected from the computerized registry system of the two medical centers. A total of 107 eligible patients with newly diagnosed advanced (cT3 above) or metastatic prostate cancer were assessed for the development of BCP and overall survival. All men had initial serum prostate specific antigen (PSA) measurements. Cox regression model and Kaplan-Meier analysis were used to evaluate the relationship between the clinical parameters and the BCP. Results: The median age of the included men was 74.6 years. The median value of initial PSA was 105 ng/mL (Q1-Q3, 39.8 to 372 ng/mL). A total of 54 patients (50.5%) had BCP during a median 46.1 months’ follow-up. In a multivariate analysis, initial serum PSA greater than 105 ng/mL (relative risk [RR], 3.23; 95% confidence interval [CI], 1.66, 6.29), pathological bone fracture (RR, 2.73; 95% CI, 1.37, 5.44), and hemoglobin 12.7 g/dL or less (RR, 2.05; 95% confidence interval, CI, 1.10, 3.81) were prognostic factors of BCP. As compared with those in the lowest tertile, participants in the highest tertile of initial PSA had nearly 3 times the age and body mass index (BMI)-adjusted risk of BCP (RR, 3.16; 95% CI, 1.38, 7.22). Further adjustment for prostate volume, method of diagnosis, Gleason score, bone metastasis and pathologic bone fracture slightly attenuated the risk. However, after adjusting for hemoglobin and the clinical diseases, the relative risk of developing BCP remained significant (RR, 3.68; 95% CI, 1.33 to 10.0). Conclusions: Our data demonstrate that initial serum PSA is a significant risk factor for BCP for Taiwanese advanced prostate cancer patients.