大腸直腸癌篩檢策略之評估

Evaluation of Strategy of Colorectal Cancer Screening

邱瀚模(Han-Mo Chiu)

指導教授 ： 陳秀熙 ； 林肇堂

國立臺灣大學/公共衛生學院/預防醫學研究所/博士(2010年)

https://doi.org/10.6342/NTU.2010.00006

摘要

大腸直腸癌是目前世界上最常見的惡性腫瘤之一，也是亞洲地區近年來增加速度最快速的癌症。根據衛生署的統計，目前大腸直腸癌已高居國人十大癌症死因第三名，也是每年新增個案最多的癌症。由於大腸直腸癌有較長的癌前時期與前臨床期，又有一些明確的危險因子，因此不論是初段預防或次段預防都有可以著力的地方。目前衛生署國民健康局也提供五十歲以上民眾接受每兩年一次的糞便潛血檢查並對一等親有大腸直腸癌家族病史之高危險群提供每五年一次的大腸鏡檢。本論文主要的研究主題在於探討現行高危險群篩檢策略的妥當性及藉由決策分析探討以新內視鏡技術篩檢應用於高危險群之可行性。

針對高危險群施以內視鏡篩檢，如能配合影像強化內視鏡技術，預期能夠減少對非腫瘤性病灶的過度治療（over-treatment）與腫瘤性病灶的治療不足（under- treatement），得到較佳的成本效果比。我們的決策分析比較無篩檢、每年糞便潛血檢查、每五年一次之傳統白光內視鏡、染色內視鏡與窄帶內視鏡（narrow band imaging, NBI）五種篩檢策略。

在這個成本效果分析當中，吾人以七階段馬可夫電腦模式來比較各種篩檢策略。假設提供免疫法糞便潛血檢查、傳統白光大腸鏡（white light endoscopy, WLE）、染色內視鏡NBI給大於五十歲高危險群十萬人進行篩檢，直至六十九歲為止，所有在篩檢當中所發現或診斷的腫瘤性病灶均予以切除並依現行監測指針進行追蹤。高危險群的腫瘤性病灶盛行率根據過去台灣內視鏡篩檢的結果與文獻上與一般危險性族群比較之相對風險。轉移速率與機率的估計乃根據過去台灣社區篩檢的結果以及針對高危險群研究的結果。篩檢相關成本資料根據健保局給付規定，而各病期大腸直腸癌的治療費用則以隨機抽樣方式來估算。本成本效果分析研究是根據支付者觀點進行。

研究結果顯示篩檢可以有效降低大腸直腸癌的發生率與死亡率，其中糞便潛血檢查、傳統白光內視鏡、染色內視鏡與NBI內視鏡篩檢，與無篩檢策略相較後大腸直腸癌之發生率分別下降63.8、76.8、80.8及79.9%，死亡率則分別下降63.8、77.3、81.2及80.3%。與無篩檢策略相比之增量效果比（Incremental cost-effectivenss ratio，ICER）分別為每增加一單位之平均餘命需花費美元6,511、2,064、3,072與3,310元。與糞便潛血檢查相比，傳統內視鏡、染色內視鏡及NBI之ICER則分別為美金279、402與394元。敏感度分析顯示大腸直腸腫瘤的盛行率與對大腸鏡檢之順從性、傳統白光內視鏡對小腺瘤之偵測率與敏感度，對於以內視鏡方式進行篩檢之策略的ICER有顯著的影響。雖然影像強化內視鏡與傳統白光內視鏡給付或價格上並無不同，但如影像強化內視鏡相對於傳統白光內視鏡的價格則對以影像強化內視鏡進行篩檢之ICER有顯著影響。根據可接受曲線（accceptability）分析，當願意付出之最高金額（maximum willing to pay）為美金700元或以下時，糞便潛血檢查最符合成本效果，1,000元以上時則以影像強化內視鏡最符合成本效果。

現行以大腸鏡進行大腸直腸癌高危險群的篩檢是妥當且在低增量成本的情況下可以有效降低發生率與死亡率。在合理增加成本之情況下，運用影像強化內視鏡則可進一步提高內視鏡篩檢之成本效果。至於運用影像強化內視鏡於一般危險性族群之可行性則有待更進一步研究。

關鍵字

大腸直腸癌 ； 篩檢 ； 糞便潛血檢查 ； 大腸鏡 ； 影像強化內視鏡 ； 馬可夫模式 ； 成本效果分析

並列摘要

Colorectal cancer (CRC) is one of the most common maligancy worldwide and many of the Asian countries experiences remarkable and rapid rise of CRC incidence in the past decades. According to the national census and cancer registry data, CRC is nowadays the third leading cause of cancer mortality and has the most incident cases among all malignancies in Taiwan. Owing to its long precancerous period and sublinical early stage and identifiable risk factors, there are several points to put our strength in terms of primary and secondary prevention. With many identifiable risk factors which are preventable and modifiable, primary prevention is a feasible way for CRC prevention. Moreover, there are several good tools for CRC screening and early diagnosis which leads to favorable long term outcome. Bureau of Helath Promotion of Department of Health has launched a nation-wide CRC screening program since 2004 which provides biennial fecal occult blood test for average-risk people older than 50 years and 5-yearly primary screening colonoscopy for high-risk population who have CRC family history in their first degree relatives. The focus of this dissertation will be specifically on the research on the appropriateness of current screening policies and elucidate the feasibility of applying new endoscopic technologies for high-risk population via a decision analysis model.

Compared to conventional white light endoscopy, application of IEE for endoscopic screening in high-risk group may be helpful with anticipated reduction of both over-treatment and under-treatment of detected lesions and achieving a better cost-performance. Our decision analysis compared five strategies of CRC screening: no screening, annual fecal occult blood test (FOBT), 5-yearly endoscopic screening with conventional white light endoscopy (WLE), chromoendoscopy and narrow band imaging (NBI).

The cost-effectivenss of the screening strategies were compared by using a computer model of seven-state Markov process. A hypothetical 100,000 high-risk population aged 50 years underwent screening with annual immune FOBT, 5-yearly WLE, 5-yearly chromoendoscopy and 5-yearly NBI till the age of 69. All neoplastic lesions detected at screening were resected and received surveillance according to the current guidelines. Prevalence of colorectal neoplasm in high-risk population was estimated according to previous prevalence study in Taiwanese population and literature review of the relative risk in high-risk popualtion. Transition rates and probabilities were estimated from previous population-based studies in general Taiwanese population and also from studies on high-risk population. Cost ensued by screening were obtained from National Health Insurance reimbursement data and stage-specific CRC treatment cost were estimated from sampling of empirical data. The study was conducted based on a health-care payer perspective.

Base-case anlysis showed that screening is effective in terms of rduction of CRC incidence and mortality. When compared with no screening strategy, the reduction of incidence using FOBT, WLE, chromoendoscopy and NBI was 63.8、76.8、80.8 and 79.9% and mortaily of 63.8, 77.3, 81.2 and 80.3%. Incremental cost-effectivenss ratio (ICER) using FOBT, WLE, chromoendoscopy and NBI was USD 6,511, 2,064，3,072，and 3,310 per life-year gained compared with no screening strategy and ICER of WLE, chromoendoscopy and NBI was USD 279, 402 and 394 when endoscopic strategies were compared with FOBT. Sensitivity analyses showed that screening with endoscopic modalities was more sensitive to the prevalence of adenoma, the compliance to endoscopy, detection rate and sensitivity of small adenoma by colonoscopy. Though insurance reimbursement among WLE and IEE modalities are not different, screening with IEE modalities was more sensitive to the relative cost compared to WLE. WLE was most cost-effective when WTP was less than USD 700 and IEE was more cost-effective when WTP was greater than USD 1000.

Current recommendation of endoscopic screening for high-risk population is optimal as it reduced incidenc and mortality at acceptable incremental costs. Applicaton of IEE can further improve cost-effectiveness of endoscopic screening. Its application in average-risk population need further study.

並列關鍵字

Colorectal cancer (CRC) ； screening ； fecal occult blood test (FOBT) ； colonoscopy ； image enhancing endoscopy (IEE) ； Markov model ； cost-effectivenss analysis

參考文獻

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