DNA damage repair gene mutations are prevalent in advanced prostate cancer. Among these, mutations in homologous recombination repair genes could impair the ability of cell to restore the DNA double-strand break, which can be exploited by Poly-ADP-ribose polymerase (PARP) inhibitors through synthetic lethality and result in cell death. The phase Ⅲ study " PROfound" showed that the PAPR inhibitor Olaparib could significantly improve the survival of patients with homologous recombination repair gene mutations compared with novel hormone agents, starting the era of targeted, precise and individualized treatment based on genetic profile detection for prostate cancer treatment.

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.

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.

As an emerging cancer treatment modality, immunotherapy has shown promising efficacy in a variety of solid tumors, but it has failed to achieve a breakthrough in the treatment of prostate cancer.This review aims to provide an overview of the current applications of immunotherapy for prostate cancer, including immune-checkpoint inhibitors, cancer vaccines and chimeric antigen receptor T-cell (CAR-T), briefly describe the mechanisms of various immunotherapy modalities, summarize the results of clinical trials, and discuss the challenges and prospects.

OBJECTIVES: To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics. METHODS: Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR⁺ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR⁺MMR^－ group) and patients without DDR gene germline pathogenic mutation (DDR^－ group). RESULTS: Thirteen (1.52%) MMR⁺ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR^－ group, MMR⁺ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR⁺ group, DDR⁺MMR^－ group and DDR^－ group, respectively. The time to castration resistance in MMR⁺ group was significantly shorter than that in DDR⁺MMR^－ group and DDR^－ group (both P<0.01), while there was no significant difference between DDR⁺MMR^－ group and DDR^－ group (P>0.05). CONCLUSIONS MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.
Male ; Humans ; Prostate-Specific Antigen/genetics* ; Germ-Line Mutation ; Retrospective Studies ; DNA Mismatch Repair/genetics* ; DNA-Binding Proteins/metabolism* ; China ; Prostatic Neoplasms/pathology*