摘要目的:探讨中国前列腺癌患者循环肿瘤DNA（ctDNA）中 TP53突变的临床特征及预后价值。 方法:前瞻性纳入2018年5月至2019年6月在复旦大学附属肿瘤医院泌尿外科确诊的239例前列腺癌患者，确诊年龄为（65.4±7.6）岁（范围：45~85岁）。通过目标序列捕获和二代测序检测血浆中ctDNA的 TP53突变。分析接受不同治疗的患者 TP53突变状态与无进展生存时间的相关性。对不同亚组进行Kaplan-Meier分析，绘制生存曲线，并采用Log-rank进行比较。采用Cox回归模型估算多变量校正后的 HR及其与无进展生存时间相关的95% CI。 结果:存在 TP53突变的患者比例为15.9%（38/239）。151例患者初诊时存在转移， TP53突变患者初诊转移比例更高［78.9%（30/38）比60.2%（121/201），χ2=4.829， P=0.028］，处于转移性去势抵抗阶段的比例更高［68.4%（26/38）比42.8%（86/201），χ2=8.434， P=0.004］。 TP53突变患者接受常规雄激素剥夺治疗、阿比特龙治疗、多西他赛治疗的中位无进展生存时间分别为13.0、4.7、3.0个月， TP53野生型患者分别为17.0、11.0、5.0个月。多因素分析结果显示，在接受阿比特龙治疗和多西他赛治疗的患者中， TP53突变是无进展生存时间的独立预后因素（ HR=2.23，95% CI：1.26~3.94， P=0.006； HR=1.92，95% CI：1.01~3.66， P=0.047），在雄激素剥夺治疗患者中未发现这一趋势。 结论:TP53突变与存在转移、患者处于去势抵抗阶段相关，同时也是接受阿比特龙、多西他赛治疗患者的无进展生存时间的独立预后因素。

abstractsObjective:To examine the clinical features and prognostic value of TP53 mutation in circulating tumor DNA(ctDNA) of Chinese prostate cancer patients. Methods:A prospective cohort of 239 prostate cancer patients diagnosed in the Department of Urology, Fudan University Shanghai Cancer Center from May 2018 to June 2019 was included. The age of diagnosis was(65.4±7.6) years(range: 45 to 85 years). Clinical data were collected from patient diagnosis and treatment records as well as follow-up surveys. TP53 mutations in plasma were detected by target sequence capture and second-generation sequencing. The relationship between TP53 mutation status and progression-free survival(PFS) was analyzed in patients who received any treatment lines. Kaplan-Meier analysis was performed in different subgroups, survival curves were drawn, and Log-rank test was used for comparison. Cox regression models were used to estimate multivariate adjusted HR and 95 %CI associated with PFS. Results:In the cohort, 15.9%(38/239) patients had TP53 mutation. Patients with TP53 mutations had a higher rate of metastases initially diagnosed with prostate cancer (78.9% (30/38) vs. 60.2% (121/201), χ2=4.829, P=0.028), as well as a higher rate of castration resistance (68.4% (26/38) vs. 42.8% (86/201), χ2=8.434, P=0.004). Kaplan-Meier analysis revealed a median androgen-deprivation therapy-PFS of 13.0 months in patients with TP53 mutation and 17.0 months in patients with TP53 wild-type. The median abiraterone-PFS was 4.7 months for patients with TP53 mutation and 11.0 months for TP53 wild-type patients. The median docetaxel-PFS was 3.0 months in patients with TP53 mutation and 5.0 months in patients with TP53 wild-type. TP53 mutation was the undependent prognosis factor of PFS in patients treated with abiraterone( HR=2.23, 95 %CI: 1.26 to 3.94, P=0.006) and docetaxel( HR=1.92, 95 %CI: 1.01 to 3.66, P=0.047) had significant differences in PFS. Conclusions:TP53 mutations were associated with the presence of metastasis and castration resistance, and were also an independent prognostic factor for progression-free survival in patients treated with abiraterone and docetaxel.