結合基因及前列腺特異性抗原之個人化前列腺癌篩檢

Abstract

背景：由於實證不足，前列腺癌遺傳風險的角色在亞洲男性中仍然不明。結合亞洲遺傳資訊與前列腺特異性抗原的模擬方法，為亞洲前列腺癌的個人化篩查的發展提供了一條新途徑。根據實證原則，我們使用模擬方法，評估相較於統一性篩檢，使用個人化篩檢在死亡率改善和成本效益分析。 研究方法: 本論文先對基因變異研究和劑量依賴前列腺特異性抗原研究進行系統性回顧，並發展了一個具有亞洲遺傳訊息和全球前列腺特異性抗原資訊的六階段自然病史模型（正常、過度檢測、潛在低惡性和高惡性前列腺癌，臨床的低惡性和高惡性前列腺癌）。這種具有亞洲基因合併全球前列腺特異性抗原資訊 的模型用於個人化風險評估和風險分級。我們接著使用一個由電腦模擬每組 10萬名患者的隨機對照試驗，旨在估計評估三種不同的篩查方法，包括個人化篩檢、統一性篩檢和非篩檢組產生的死亡率差別。另外使用馬可夫決策模型模擬了每種篩選策略的成本及篩檢效益。 結果：10 年內發生前列腺癌的風險從最低風險組的 0.1%增加到高危組的17.2%。對於高風險組，篩檢建議的年齡在50歲，間隔是一年。對於低風險人群，起始年齡延至60歲，篩檢間隔延長至6年。個人化篩檢的前列腺癌死亡率降低效果(分之二十三)統一性篩檢(分之十五)為佳。個人化篩檢可以免除22%不必要的PSA測試，並避免2%過度檢測。與沒有篩檢相比，統一性篩檢每增加壽命年的費用為16,189美元。另外個人化篩檢每增加壽命年花費17,952美元，與統一性篩檢的成本效益相當 結論：跟統一性篩檢比較起來，使用亞洲基因資訊合併前列腺特異性抗原模型的個人化篩檢成本效益相當，並能夠減少不必要的前列腺特異性抗原測試，同時減低更多的亞洲男性死亡率。

Background: The role of genetic risk in prostate cancer (PrCa) still disparities for Asian men due to the limited evidence. A simulation approach for PrCa with a prostate-specific antigen (PSA) test incorporating Asian genetic information provides a new avenue for the development of personalized screening for Asian PrCa . Going by the evidence-based principle, we use the simulation method to evaluate the effectiveness of mortality reduction and cost effective analysis resulting from PSA screening, using a personalized screening regime as opposed to a universal screening program Methods: A six-state (normal, over-detected, low-grade, and high-grade PrCa in pre-clinical phase, and low-grade and high-grade PrCa in clinical phase) Markov model with Asian genetic and global PSA information was developed after a systematic review of genetic variant studies and dose-dependent PSA studies. This Asian gene with global PSA-guided model was used for personalized risk assessment and risk stratification. A computer-based simulated randomized controlled trial with 100000 men in each arm was designed to estimate the reduction of mortality achieved by three different screening methods, personalized screening(PSG), universal screening(USG), and a non-screening group. The cost and effectiveness of each screening strategy were simulated by the Markov decision model. Life-year gained effectiveness was applied in the analyses. The incremental costs required to save one life-year of each screening strategy (ICERs) compared to no screening were calculated. Results: The 10-year risk for prostate cancer increased from 0.1% in the lowest-risk group to 17.2% in the highest-risk group. The recommended age at screening was 50 years old with one-year interval for the highest-risk group. For the low-risk group, the starting age was postponed to 60 years old and the screening interval was lengthened to 6 years. The effectiveness of PrCa mortality reduction for a PSG(23%) was greater to that in the USG(15%). A PSG could dispense with 23% of unnecessary PSA testing, and avoid over-detection by 2%. The USG costs $16,189 per additional life year compared to no screening; and The PSG will cost $17,852 per addition life year, which is equivalent to the strategy of USG. (4) Conclusions: Asian Gene with PSA-guided personalized screening for PrCa leads to fewer unnecessary PSA tests with the additional benefits of mortality reduction for Asian men and offers the consistent ICERs (as happens with the universal screening program)