1月6日,，《國立癌癥研究所雜志》在線發(fā)表的有關前列腺,、肺,、結直腸和卵巢(PLCO)篩查試驗的13年隨訪結果"Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after 13 Years of Follow-up"表明，每年接受前列腺癌篩查者死于前列腺癌的幾率并不低于接受常規(guī)隨訪和隨機篩查的男性,。
這項研究由華盛頓大學圣路易斯分校的Gerald L. Andriole博士及其同事進行,，共納入76,693名55~74歲的男性，旨在評價在既有隨機篩查基礎上增加每年1次篩查的效果并比較兩者的預后。這些男性被隨機分成2組,，干預組(n=38,343)接受為期6年的每年1次前列腺特異性抗原(PSA)篩查和為期4年的每年1次直腸指檢,，對照組(n=38,350)接受常規(guī)隨訪(包括醫(yī)生建議的篩查)。在研究開始前,，44%的受試者曾接受PSA篩查,。研究期間，對照組與干預組接受PSA檢查的受試者比例分別為52%和100%,。
研究者此前曾報道了隨訪7年和10年的結果,。隨訪7年的結果顯示，與常規(guī)處理相比,，每年1次篩查與前列腺癌診斷率增加有關,，但2組的前列腺癌死亡率和全因死亡率相同。同樣,，隨訪10年的結果顯示,，干預組死亡率與對照組無明顯差異(N. Engl. J. Med. 2009;360:1320-1328)。
截至2009年12月31日的13年隨訪結果顯示,，干預組38,340名受試者中的4,250名和對照組38,345名受試者中的3,815名被診斷為前列腺癌,。干預組和對照組的前列腺癌累計發(fā)生率分別為108.4/10,000(人·年) 和97.1/10,000(人·年),，干預組的發(fā)生率相對明顯增加12%,。在前列腺癌診斷方面，干預組401例受試者和對照組454例受試者被診斷為高級別前列腺癌,，Gleason評分為8~10分,。隨訪13年時，干預組和對照組的死亡例數(shù)分別為158例和145例,，前列腺癌累計死亡率分別為3.7/ 10,000(人·年)和3.4/ 10,000(人·年),，組間差異不顯著。研究者采用泊松回歸模型分析各組前列腺癌死亡率和相對死亡風險與年齡,、合并癥和試驗前PSA檢查之間的交互作用,，但未發(fā)現(xiàn)顯著交互作用。2組的全因死亡(除了前列腺癌,、肺癌和結直腸癌所致死亡之外)率存在臨界統(tǒng)計學差異,，干預組和對照組的死亡例數(shù)分別為5,783例和5,982例。干預組和對照組的非PLCO癌癥死亡率分別為23%和22%,，缺血性心臟病死亡率分別為21%和19%,。
該研究的局限性在于混雜的診斷效應可能掩蓋了前列腺癌死亡率的降低。換言之,，干預組有較多死亡歸因于前列腺癌,。支持這種可能性的依據(jù)在于干預組的全因死亡率顯著低于對照組。干預組其他原因所致的死亡率較高，因此死亡歸因方面的錯誤或許不是干預組前列腺癌死亡率高的原因,。
研究者計劃將隨訪時間延長至15年,，以進一步觀察死亡率。（生物谷Bioon.com）
doi:10.1093/jnci/djr500
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Prostate Cancer Screening in the Randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: Mortality Results after 13 Years of Follow-up
Gerald L. Andriole, E. David Crawford, Robert L. Grubb III, Saundra S. Buys, David Chia, Timothy R. Church, Mona N. Fouad, Claudine Isaacs,et al.
Background The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7–10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial.
Methods A total of 76 685 men, aged 55–74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided.
Results Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (Pinteraction = .81), pretrial PSA testing (Pinteraction = .52), and comorbidity (Pinteraction = .68).
Conclusions After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing.
