台灣賀爾蒙治療骨轉移攝護腺癌預後因子之評估

背景與目的：在台灣，初診斷即為攝護腺癌即為第四期骨骼轉移的比率比美國高。本研究之目的為統計中部某醫學中心接受荷爾蒙治療之骨轉移攝護腺癌的存活狀態，並分析死亡族群與存活族群之間之差異，同時探討治療前後血清攝護腺抗原值、骨轉移之緩解性放射治療及化學治療與預後之關係，以期確認影響骨轉移攝護腺癌存活的預後因子。方法：本研究以中部某醫學中心為對象，統計自民國七十二年元月到民國九十七年十二月底，共有257位病患初診斷即為骨轉移攝護腺癌接受荷爾蒙治療及追蹤之病例，進行存活分析。研究採病例回朔性、橫斷式之分析，統計則包括跨描述性統計、雙變項分析並以Cox 回歸模型以及 Kaplan-Meier 存活分析來評估臨床因子與存活的相關性。結果：病人的平均年齡為72 歲(±8.4歲)。初始血清攝護腺特定抗原值的中位數則是 155 ng/mL(Q1-Q3 為92.04至600 ng/mL)。在平均追蹤時間為36.4個月(±29.1個月) 而追蹤時間的中位數為58.08個月。。根據 Kaplan-Meier 存活分析顯示整體五年總存活率為60%，十年為33%。治療後最低血清攝護腺特定抗原值，小於1 ng/mL、1-10 ng/mL及大於10 ng/mL之五年存活率分別為70%、61%及52%( p= 0.113)。多變項Cox proportional hazard model結果顯示，治療前初始血清攝護腺特定抗原值大於300 ng/mL病例之預後優於初始血清攝護腺特定抗原值小於100 ng/mL病例(死亡相對危險性：0.66， 95%信賴區間：0.35-1.23，p= 0.187)。治療後最低血清攝護腺特定抗原值大於10 ng/mL病例相較於最低血清攝護腺特定抗原值小於1 ng/mL病例，預後較差(死亡相對危險性：3.07，95%信賴區間：1.47-6.43，p= 0.003)。接受合併男性荷爾蒙阻斷療法治療者預後較僅接受去勢治療者佳(死亡相對危險性：0.37，95%信賴區間：0.19-0.72，p= 0.003)。而有接受骨轉移之緩解性放射治療(死亡相對危險性：1.78， 95%信賴區間：0.96-3.30，p= 0.070)及化學治療(死亡相對危險性：1.79，95%信賴區間：0.96-3.33，p= 0.065)者，為預後不良之相關因子。結論：本研究顯示治療前初始血清攝護腺特定抗原值、治療後血清攝護腺特定抗原最低值、是否接受合併男性荷爾蒙阻斷療法、緩解性放射治療及化學治療，將對於初始診斷為骨骼轉移攝護腺癌病患的預後有影響。最低血清攝護腺特定抗原值為一有效的預後因子，將有助於判定哪些病患對治療效果較差，進而規劃下一步的治療計畫。

關鍵字

攝護腺癌；骨骼轉移；預後因子；存活分析；攝護腺特定抗原值

並列摘要

Background and Objectives:The proportion of men with metastatic prostate cancer disease at first diagnosis is greater in Taiwanese men than in American men. This study aims to determine the survival rate of metastatic prostate cancer treated with hormone therapy patient treated and followed in a medical center of central Taiwan. Furthermore, this study wants to discover the differences between the death group and the survival group. Finally , this study attempts to investigate if various clinical parameters in patients with bone metastatic prostate cancer and determine whether the pretreatment and nadir serum PSA level, palliative metastatic radiotherapy for metastatic bone and advanced chemotherapy can be used as a prognostic factor. Methods:From January 1983 to December 2008, there were total 257 patients admitted to cased hospital diagnosed as having bone metastatic prostate cancer treated with hormone therapy. Charts records were retrospectively. Statistical methods included descriptive statistics, bibariate analyses, Kaplan-Meier survival analyses and Cox regression analysis for investgating the relationship between the clinical factors and disease survival. Results:The average age was 72 years(±8.4 years). The median value of pretreatment serum PSA level was 155 ng/mL(Q1-Q3 92.04-600 ng/mL). The average follow-up times was 36.4 months (±29.1 months) and median survival times was 58.08 months . Using Kaplan-Meier survival analyses, the overall 5-year survival rate was 60%. The 5-year survival rates for nadir PSA level less than 1ng/mL,1-10 ng/mL and more than 10ng/mL were 70%、61%及52% (P_ 0.113) . Multivariate Cox regressionhazard model revealed that those pretreatment serum PSA level more than 300ng/mL tended to have good prognosis than those less than 100ng/mL (HR：0.66， 95% CI：0.35-1.23，p= 0.187). In addition, those post-treatment nadir serum PSA level more than 10ng/mL have higher death probability than those less than 1ng/mL (HR：3.07， 95% CI：1.47-6.43，p= 0.003). Further significant factors include: those treated with combined androgen blockade had higher survival rate when compared with those treated with castration only (HR：0.37， 95%CI：0.19-0.72，p= 0.003). In those with palliative radiotherapy for metastatic bone will have shorter survival periods than those without radiotherapy (HR：1.78， 95%CI：0.96-3.30，p= 0.070). Moreover, those with advanced chemotherapy will have poorer prognosis when comparing with those without chemotherapy (HR：1.79， 95%CI：0.96-3.33，p= 0.065). Conclusions: This study found that pretreatment serum PSA level, post-treatment nadir serum PSA level and the treatment modality significantly influenced the survival of patient with bone metastatic prostate cancer . Prognostic factors are also helpful in identifying which patients are less likely to respond to treatment; this information also would help to counsel patients. The nadir PSA level is a valuable prognostic factor for survival in patients initially diagnosed with bone metastatic prostate cancer treated with hormone therapy.