Background

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.

Objective

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.

Outcome measurements and statistical analysis

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.

Results and limitations

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.

Conclusions

Our data support grade progression, whereby following a prostate over time would reveal transitions from benign to low-grade and then high-grade PCa.

Patient summary

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.

中文翻译：

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前置时间与前列腺癌等级之间的关联：长期随访的大型人群队列研究的等级进展证据，这些人群不受前列腺特异性抗原筛查的影响

背景

提前期（LT）在癌症的早期发现中至关重要，但无法直接测量。我们先前使用来自队列的已归档血液样本进行了多年随访而未进行筛查，从而提供了前列腺癌（PCa）的LT估计值。

客观的

在诊断时确定LT和PCa等级之间的关联，以提供有关等级随着时间推移而发展还是稳定的见解。

设计，设置和参与者

该环境是瑞典的三项长期流行病学研究，包括未接受前列腺特异性抗原（PSA）筛查的男性。该队列包括1041名抽血时PSA为3-10 ng / ml的男性，随后利用现有的分级数据诊断为PCa。

成果测量和统计分析

多变量logistic回归用于预测LT诊断时的高等级（格里森等级组≥2或世界卫生组织等级3）与低等级PCa的对比，LT定义为PSA升高日期与PCa日期之间的时间根据队列和年龄进行诊断。

结果与局限性

LT可使PCa在诊断时为高质量的可能性增加。在所有男性中，随着LT的升高，罹患高危疾病的风险增加（优势比1.13，95％置信区间[CI] 1.10-1.16；p  <0.0001），没有证据显示不同年龄组或人群的疗效差异。较高的PSA预测 每增加1 ng / ml的PSA，LT就会缩短0.46年（95％CI 0.28–0.64；p <0.0001）。但是，PSA和等级之间没有相互作用，这表明高等级肿瘤的较长LT并不仅仅与年龄有关。局限性包括以下假设：PSA升高时，PSA升高且随后被诊断为PCa的男性在活检中可检测到PCa。

结论

我们的数据支持等级进展，从而随着时间的推移追踪前列腺会显示从良性到低等级再到高等级PCa的转变。

病人总结

前列腺特异性抗原升高与随后的前列腺癌诊断之间的准备时间较长的男性在诊断时更可能患有高级别的癌症。