Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine; Horten Center for patient orientated research and knowledge transfer, University of Zurich; Department of Urology, University of Zurich, University Hospital, Zurich, Switzerland.
BJU Int. 2014 Apr;113(4):561-7. doi: 10.1111/bju.12131. Epub 2013 Jun 7.
To investigate the association between serum prostate-specific antigen (PSA) concentration at active surveillance (AS) entry and disease reclassification on subsequent AS biopsy ('biopsy reclassification') in men with low PSA density (PSAD). To investigate whether a clinically meaningful PSA threshold for AS eligibility/ineligibility for men with low PSAD can be identified based on risk of subsequent biopsy reclassification.
We included men enrolled in the Johns Hopkins AS Study (JHAS) who had a PSAD of <0.15 ng/mL/g (640 men). We estimated the incidence rates (IRs; per 100 person years) and hazard ratios (HR) of biopsy reclassification (Gleason score ≥ 7, any Gleason pattern 4 or 5, ≥3 positive cores, or ≥50% cancer involvement/biopsy core) for categories of serum PSA concentration at the time of entry into AS. We generated predicted IRs using Poisson regression to adjust for age and prostate volume, mean percentage free PSA (ratio of free to total PSA) and maximum percentage biopsy core involvement with cancer.
The unadjusted IRs (per 100 person years) of biopsy reclassification across serum PSA concentration at entry into JHAS showed, in general, an increase; however, the pattern was not linear with higher IRs in the group ≥ 4 to <6 ng/mL (14.2, 95% confidence interval [CI] 11.8-17.2%) when compared with ≥6 to <8 ng/mL (8.4, 95% CI 5.7-12.3%) but almost similar IRs when compared with the group ≥ 8 to <10 ng/mL (14.8, 95% CI 8.4-26.1%). The adjusted predicted IRs of reclassification showed a similar non-linear increase in IRs, whereby the rates around 4 ng/mL were similar to the rates around 10 ng/mL.
Risk for biopsy reclassification increased non-linearly across PSA concentration in men with low PSAD, whereby no obvious clinically meaningful threshold could be identified. This information could be incorporated into decision-making for AS. However, longer follow-up times are needed to warrant final conclusions.
探讨低 PSA 密度（PSAD）患者主动监测（AS）入组时的血清前列腺特异性抗原（PSA）浓度与随后 AS 活检中的疾病再分类（活检再分类）之间的关系。探讨是否可以根据随后活检再分类的风险，为低 PSAD 男性确定一个有临床意义的 AS 入选/排除的 PSA 临界值。
我们纳入了参加约翰霍普金斯 AS 研究（JHAS）且 PSAD＜0.15ng/mL/g 的男性（640 人）。我们估计了入组 AS 时血清 PSA 浓度分类的活检再分类（Gleason 评分≥7、任何 Gleason 模式 4 或 5、≥3 个阳性核心或≥50%的癌组织/活检核心）的发生率（IR，每 100 人年）和风险比（HR）。我们使用泊松回归生成预测 IRs，以调整年龄和前列腺体积、游离 PSA 的平均百分比（游离 PSA 与总 PSA 的比值）和最大活检核心癌组织参与百分比。
入组 JHAS 时血清 PSA 浓度的未调整 IRs（每 100 人年）总体上呈上升趋势；然而，这种模式并非线性，与≥4 至＜6ng/mL 组（14.2，95%置信区间 [CI] 11.8-17.2%）相比，≥6 至＜8ng/mL 组（8.4，95%CI 5.7-12.3%）的 IR 更高，但与≥8 至＜10ng/mL 组（14.8，95%CI 8.4-26.1%）的 IR 几乎相同。调整后的再分类预测 IRs 显示 IR 呈相似的非线性增加，因此，4ng/mL 左右的比率与 10ng/mL 左右的比率相似。
在低 PSAD 男性中，PSA 浓度与活检再分类的风险呈非线性增加，因此无法确定明显有临床意义的临界值。该信息可以纳入 AS 的决策中。然而，需要更长的随访时间来保证最终结论。
