Any form of screening aims to reduce disease-specific and overall mortality, and to improve a person's future quality of life. Screening for prostate cancer has generated considerable debate within the medical and broader community, as demonstrated by the varying recommendations made by medical organizations and governed by national policies. To better inform individual patient decision-making and health policy decisions, we need to consider the entire body of data from randomised controlled trials (RCTs) on prostate cancer screening summarised in a systematic review. In 2006, our Cochrane review identified insufficient evidence to either support or refute the use of routine mass, selective, or opportunistic screening for prostate cancer. An update of the review in 2010 included three additional trials. Meta-analysis of the five studies included in the 2010 review concluded that screening did not significantly reduce prostate cancer-specific mortality. In the past two years, several updates to studies included in the 2010 review have been published thereby providing the rationale for this update of the 2010 systematic review.
To determine whether screening for prostate cancer reduces prostate cancer-specific mortality or all-cause mortality and to assess its impact on quality of life and adverse events.
An updated search of electronic databases (PROSTATE register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CANCERLIT, and the NHS EED) was performed, in addition to handsearching of specific journals and bibliographies, in an effort to identify both published and unpublished trials.
All RCTs of screening versus no screening for prostate cancer were eligible for inclusion in this review.
Data collection and analysis
The original search (2006) identified 99 potentially relevant articles that were selected for full-text review. From these citations, two RCTs were identified as meeting the inclusion criteria. The search for the 2010 version of the review identified a further 106 potentially relevant articles, from which three new RCTs were included in the review. A total of 31 articles were retrieved for full-text examination based on the updated search in 2012. Updated data on three studies were included in this review. Data from the trials were independently extracted by two authors.
Five RCTs with a total of 341,342 participants were included in this review. All involved prostate-specific antigen (PSA) testing, with or without digital rectal examination (DRE), though the interval and threshold for further evaluation varied across trials. The age of participants ranged from 45 to 80 years and duration of follow-up from 7 to 20 years. Our meta-analysis of the five included studies indicated no statistically significant difference in prostate cancer-specific mortality between men randomised to the screening and control groups (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.86 to 1.17). The methodological quality of three of the studies was assessed as posing a high risk of bias. The European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were assessed as posing a low risk of bias, but provided contradicting results. The ERSPC study reported a significant reduction in prostate cancer-specific mortality (RR 0.84, 95% CI 0.73 to 0.95), whilst the PLCO study concluded no significant benefit (RR 1.15, 95% CI 0.86 to 1.54). The ERSPC was the only study of the five included in this review that reported a significant reduction in prostate cancer-specific mortality, in a pre-specified subgroup of men aged 55 to 69 years of age. Sensitivity analysis for overall risk of bias indicated no significant difference in prostate cancer-specific mortality when referring to the meta analysis of only the ERSPC and PLCO trial data (RR 0.96, 95% CI 0.70 to 1.30). Subgroup analyses indicated that prostate cancer-specific mortality was not affected by the age at which participants were screened. Meta-analysis of four studies investigating all-cause mortality did not determine any significant differences between men randomised to screening or control (RR 1.00, 95% CI 0.96 to 1.03). A diagnosis of prostate cancer was significantly greater in men randomised to screening compared to those randomised to control (RR 1.30, 95% CI 1.02 to 1.65). Localised prostate cancer was more commonly diagnosed in men randomised to screening (RR 1.79, 95% CI 1.19 to 2.70), whilst the proportion of men diagnosed with advanced prostate cancer was significantly lower in the screening group compared to the men serving as controls (RR 0.80, 95% CI 0.73 to 0.87). Screening resulted in a range of harms that can be considered minor to major in severity and duration. Common minor harms from screening include bleeding, bruising and short-term anxiety. Common major harms include overdiagnosis and overtreatment, including infection, blood loss requiring transfusion, pneumonia, erectile dysfunction, and incontinence. Harms of screening included false-positive results for the PSA test and overdiagnosis (up to 50% in the ERSPC study). Adverse events associated with transrectal ultrasound (TRUS)-guided biopsies included infection, bleeding and pain. No deaths were attributed to any biopsy procedure. None of the studies provided detailed assessment of the effect of screening on quality of life or provided a comprehensive assessment of resource utilization associated with screening (although preliminary analyses were reported).
Prostate cancer screening did not significantly decrease prostate cancer-specific mortality in a combined meta-analysis of five RCTs. Only one study (ERSPC) reported a 21% significant reduction of prostate cancer-specific mortality in a pre-specified subgroup of men aged 55 to 69 years. Pooled data currently demonstrates no significant reduction in prostate cancer-specific and overall mortality. Harms associated with PSA-based screening and subsequent diagnostic evaluations are frequent, and moderate in severity. Overdiagnosis and overtreatment are common and are associated with treatment-related harms. Men should be informed of this and the demonstrated adverse effects when they are deciding whether or not to undertake screening for prostate cancer. Any reduction in prostate cancer-specific mortality may take up to 10 years to accrue; therefore, men who have a life expectancy less than 10 to 15 years should be informed that screening for prostate cancer is unlikely to be beneficial. No studies examined the independent role of screening by DRE.
為試著找出已出版與尚未出版的試驗，除了人工搜尋特定的期刊與參考書目之外，也針對電子資料庫做了最新的搜尋(PROSTATE register、Cochrane Central Register of Controlled Trials (CENTRAL)、MEDLINE、EMBASE、CANCERLIT以及 NHS EED等資料庫)。
本文獻收錄了5個包括341,342位受試者的RCTs。雖然進一步評估的間隔與門檻會因試驗而不同，但全部的試驗都有包括或不包括肛門指診(DRE)的攝護腺特異性抗原(PSA)測試。受試者的年齡範圍由45歲至80歲，後續追蹤期則為7年至20年。5個收錄研究的統合分析指出，攝護腺癌死亡率在男性隨機篩檢組與對照組之間，沒有統計上的顯著差異(危險率比(RR) 1.00, 95% 信賴區間(CI) 0.86至1.17)。3個研究的研究方法品質被評估為高偏誤風險。歐洲前列腺癌篩檢的隨機研究(European Randomized Study of Screening for Prostate Cancer (ERSPC))以及美國的攝護腺癌、肺癌、大腸癌與卵巢癌篩檢試驗(Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial)皆被評估為低偏誤風險，但仍提供了矛盾的結果。ERSPC研究記錄了攝護腺癌死亡率的顯著降低(RR 0.84, 95% CI 0.73至0.95)，然而PLCO研究則沒有斷定顯著的效益(RR 1.15, 95% CI 0.86至1.54)。在預先指定、男性55至69歲的次群組中，ERSPC是本文獻收錄的5個研究裡唯一一個記錄攝護腺癌死亡率顯著降低的。整體偏誤風險的敏感度分析指出，當只提到ERSPC與PLCO試驗資料的統合分析時，攝護腺癌死亡率沒有顯著的差異(RR 0.96, 95% CI 0.70至1.30)。次群組分析指出，攝護腺癌死亡率不受篩檢受試者的年齡影響。4個調查總死亡率的研究之統合分析，沒有判定出隨機篩檢的男性與對照組之間有任何顯著的差異(RR 1.00, 95% CI 0.96至1.03)。男性隨機篩檢相較於隨機對照組，攝護腺癌的診斷明顯更多(RR 1.30, 95% CI 1.02至1.65)。隨機篩檢的男性較常被診斷出局限性攝護腺癌(RR 1.79, 95% CI 1.19至2.70)，然而篩檢組中的男性被診斷出嚴重攝護腺癌的人數，比做為對照組的男性顯著較少(RR 0.80, 95% CI 0.73至0.87)。篩檢對於癌症嚴重性與持續期造成一系列被認為是輕微到重大的傷害。篩檢常見的輕微傷害包括出血、瘀青以及短期焦慮；常見的重大傷害則有過度診斷與過度治療，包括感染、需要輸血的出血、肺炎、勃起困難以及失禁。篩檢的傷害包括PSA測試的偽陽性結果以及過度診斷(在ERSPC研究中有高達50%)。與經直腸超音波(TRUS)攝護腺切片相關的不良事件包括感染、出血以及疼痛。任何一種切片程序皆無造成死亡。沒有研究提供篩檢對生活品質影響的詳細評估，或是與篩檢相關資源利用的全面評估(雖然初步分析已記錄)。