Assel Melissa, Dahlin Anders, Ulmert David, Bergh Anders, Stattin Pär, Lilja Hans, Vickers Andrew J
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Clinical Microbiology, Lund University, Skåne University Hospital, Malmö, Sweden.
Eur Urol. 2018 Jun;73(6):961-967. doi: 10.1016/j.eururo.2017.10.004. Epub 2017 Oct 21.
Lead time (LT) is of key importance in early detection of cancer, but cannot be directly measured. We have previously provided LT estimates for prostate cancer (PCa) using archived blood samples from cohorts followed for many years without screening.
To determine the association between LT and PCa grade at diagnosis to provide an insight into whether grade progresses or is stable over time.
DESIGN, SETTING, AND PARTICIPANTS: The setting was three long-term epidemiologic studies in Sweden including men not subject to prostate-specific antigen (PSA) screening. The cohort included 1041 men with PSA of 3-10 ng/ml at blood draw and subsequently diagnosed with PCa with grade data available.
Multivariable logistic regression was used to predict high-grade (Gleason grade group ≥2 or World Health Organization grade 3) versus low-grade PCa at diagnosis in terms of LT, defined as the time between the date of elevated PSA and the date of PCa diagnosis with adjustment for cohort and age.
The probability that PCa would be high grade at diagnosis increased with LT. Among all men combined, the risk of high-grade disease increased with LT (odds ratio 1.13, 95% confidence interval [CI] 1.10-1.16; p<0.0001), with no evidence of differences in effect by age group or cohort. Higher PSA predicted shorter LT by 0.46 yr (95% CI 0.28-0.64; p<0.0001) per 1 ng/ml increase in PSA. However, there was no interaction between PSA and grade, suggesting that the longer LT for high-grade tumors is not simply related to age. Limitations include the assumption that men with elevated PSA and subsequently diagnosed with PCa would have had biopsy-detectable PCa at the time of PSA elevation.
Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa.
Men with a longer lead time between elevated prostate-specific antigen and subsequent prostate cancer diagnosis were more likely to have high-grade cancers at diagnosis.
提前期（LT）在癌症早期检测中至关重要，但无法直接测量。我们之前利用多年来未进行筛查的队列中存档的血液样本，对前列腺癌（PCa）的提前期进行了估计。
确定提前期与诊断时前列腺癌分级之间的关联，以深入了解分级随时间推移是进展还是稳定。
设计、设置和参与者：研究设置为瑞典的三项长期流行病学研究，研究对象为未接受前列腺特异性抗原（PSA）筛查的男性。该队列包括1041名男性，他们在抽血时PSA为3 - 10 ng/ml，随后被诊断为前列腺癌且有分级数据。
多变量逻辑回归用于根据提前期预测诊断时的高级别（Gleason分级组≥2或世界卫生组织3级）与低级别前列腺癌，提前期定义为PSA升高日期与前列腺癌诊断日期之间的时间，并对队列和年龄进行调整。
诊断时前列腺癌为高级别的概率随提前期增加。在所有男性中，高级别疾病的风险随提前期增加（优势比1.13，95%置信区间[CI] 1.10 - 1.16；p<0.0001），没有证据表明年龄组或队列之间存在效应差异。PSA每升高1 ng/ml，预测提前期缩短0.46年（95% CI 0.28 - 0.64；p<0.0001）。然而，PSA与分级之间没有相互作用，这表明高级别肿瘤较长的提前期并非仅仅与年龄有关。局限性包括假设PSA升高且随后被诊断为前列腺癌的男性在PSA升高时就患有活检可检测到的前列腺癌。
我们的数据支持分级进展，即随着时间推移对前列腺进行监测会发现从良性到低级别然后到高级别前列腺癌的转变。
前列腺特异性抗原升高与随后前列腺癌诊断之间的提前期较长的男性，在诊断时更有可能患有高级别癌症。
