局限性前列腺癌患者前列腺特异性抗原动力学与癌症特异性死亡率之间的关联：SPCG-6研究安慰剂组分析

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study.

作者信息

Thomsen F B, Brasso K, Berg K D, Gerds T A, Johansson J-E, Angelsen A, Tammela T L J, Iversen P

机构信息

Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen

Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen.

出版信息

Ann Oncol. 2016 Mar;27(3):460-6. doi: 10.1093/annonc/mdv607. Epub 2015 Dec 17.

DOI:10.1093/annonc/mdv607

PMID:26681677

Abstract

BACKGROUND

The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting.

PATIENTS AND METHODS

Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method.

RESULTS

Two hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1-25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0-1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml.

CONCLUSION

We found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values.

CLINICAL TRIAL NUMBER

NCT00672282.

摘要

背景

前列腺特异性抗原（PSA）动力学在未经治疗的前列腺癌（PCa）患者中的预后价值存在争议。我们在一组接受观察等待治疗的局限性PCa患者中，研究了PSA倍增时间（PSAdt）、PSA速率（PSAvel）和PSA速率风险计数（PSAvRC）与PCa死亡率之间的关联。

患者与方法

纳入在SPCG-6研究中接受观察性治疗的临床局限性PCa患者，这些患者被随机分配至安慰剂组并至少服用18个月。所有患者存活至少2年且至少有三次PSA测定值。分析PSA动力学的预后价值，并根据患者入组时的PSA水平进行分层：≤10、10.1 - 25和>25 ng/ml。采用Aalen-Johansen方法估计PCa特异性死亡率的累积发生率。

结果

共纳入263例患者，其中116例、76例和71例患者入组时的PSA水平分别≤10、10.1 - 25和>25 ng/ml。中位随访时间为13.6年。对于入组时PSA水平在10.1至25 ng/ml之间的患者，13年PCa死亡风险与PSA动力学相关：PSAdt≤3年：62.0%，而PSAdt>3年：16.3%（Gray检验：P<0.0001）；PSAvel≥2 ng/ml/年：48.0%，而PSAvel<2 ng/ml/年：11.0%（Gray检验：P = 0.0008）；PSAvRC为2：45.0%，而0 - 1：3.8%（Gray检验：P = 0.00）。相比之下，对于入组时PSA水平≤10或>25 ng/ml的患者，PSA动力学与13年PCa死亡风险的变化均无显著关联。