簡國龍Chien, Kuo-Liong臺灣大學:預防醫學研究所陳建華Chen, Chien-HuaChien-HuaChen2010-06-022018-06-292010-06-022018-06-292009U0001-1008200918140600http://ntur.lib.ntu.edu.tw//handle/246246/184848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。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。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). 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.ethods: 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.esults: 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). onclusions: Our data demonstrate that initial serum PSA is a significant risk factor for BCP for Taiwanese advanced prostate cancer patients.致謝 I文摘要 IIBSTRACT III容綱要 (Table of Contents) VIGURES VIIABLES VIII一章　緒論 1一節　前言 1二節　研究動機 3二章　文獻探討與研究目的 5一節　攝護腺癌的臨床表徵 5二節　攝護腺特定抗原 6三節　攝護腺癌的診斷 8-3-1　血清攝護腺特定抗原濃度上升超過正常範圍 8-3-2　直腸指檢攝護腺有異常的情形 11-3-3　攝護腺切片 12-3-4　攝護腺癌的病理組織診斷 12-3-5　Gleason分數 (Gleason Score) 13四節　攝護腺癌的分期 14-4-1　TNM的腫瘤分期系統 14-4-2　腫瘤的侵犯程度 (Local extension, T) 14-4-3　局部淋巴結侵犯與否的評估 (Regional lymph nodes, N) 15-4-4　遠處轉移與否的評估 (Distant metastases, M) 18五節　攝護腺癌的治療 20-5-1　早期攝護腺癌的治療 20-5-2　局部侵犯性攝護腺癌的治療 24-5-3　侵犯性攝護腺癌的治療 29-5-4　荷爾蒙治療失效的轉移性攝護腺癌 32六節　預測因子的探討 34七節　研究目的 39三章　材料與方法 40一節　研究流程 40-1-1　問題形成與研究假說 40-1-2　文獻回顧 42-1-3　資料收集 42-1-4　資料分析與模型建立 42二節　資料收集 43-2-1　研究病人的選取與排除條件 43-2-2　病人確定診斷時的臨床資料與變項的定義 44-2-3　研究終點 (Endpoint)的定義 48-2-4　其它病人治療追蹤過程中臨床資料的記錄 49三節　統計方法與資料分析 50-3-1　基本資料的描述 50-3-2　以初始血清PSA濃度高低為主要效應 (Main effect) 51-3-3　單變項的回歸分析 51-3-4　自變項的相關性分析 52-3-5　多變項的回歸分析 53-3-6　生化惡化發生率的計算以及模型進行干擾因子的校正 53-3-7　生化惡化的Kaplan-Meier分析 54四章　研究結果 55一節　研究個案的基本資料描述 55二節　研究個案治療追蹤的結果 56三節　依初始血清PSA濃度高低分組的基本資料比較 56四節　單變項Cox回歸分析的結果 57五節　自變項的相關係數性分析 57六節　多變項Cox回歸分析的結果 58七節　生化惡化發生率與校正干擾因子後的模型 59八節　發生生化惡化的Kaplan-Meier分析 60五章　討論 63一節　研究族群追蹤結果描述性統計的討論 63二節　三個不同初始血清PSA濃度分組的討論 66三節　影響生化惡化的單變項Cox回歸分析 66四節　多變項Cox回歸分析的顯著影響因子 70五節　生化惡化發生率與校正干擾因子後的模型 70六節　研究的強度 (Strength) 71七節　研究的限制 71八節　結論 72考文獻 73application/pdf741230 bytesapplication/pdfen-US攝護腺癌生化惡化攝護腺特定抗原預後因子prostate cancerbiochemical progressionprostate specific antigenprognostic factor[SDGs]SDG3thesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/184848/1/ntu-98-R96846010-1.pdf