Clinical features and prognostic value of TP53 mutation in Chinese prostate cancer patients

Objective: 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.