scholarly journals The Heterogeneity of Intraductal Carcinoma of the Prostate Is Associated With Different Efficacy of Standard First-Line Therapy for Patients With Metastatic Castration-Resistant Prostate Cancer

2020 ◽  
Author(s):  
Zhipeng Wang ◽  
Sha Zhu ◽  
Jinge Zhao ◽  
Ling Nie ◽  
Xueqin Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Therapeutic Efficacy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
Carcinoma Of The Prostate ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract BackgroundTo explore whether patients with distinct intraductal carcinoma of the prostate (IDC-P) subtypes respond differently to standard first-line therapy among patients with metastatic castration resistant prostate cancer (mCRPC).MethodsWe retrospectively analyzed data of 170 mCRPC patients receiving abiraterone (ABI) or docetaxel (DOC) as first-line therapy between 2014 and 2019. PSA response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed and compared based on the presence of IDC-P and its sub-patterns.ResultsTotally, IDC-P was confirmed in 91/170 (53.5%) patients. Among them, 36/91 (39.6%) and 55/91 (60.4%) harbored IDC-P pattern 1 and pattern 2, respectively. The presence of IDC-P was confirmed to be associated with poor prognosis in the whole cohort. Patients with IDC-P pattern 1 shared similar clinical outcomes to those without IDC-P in both ABI and DOC treatment. However, compared to patients with IDC-P pattern 1 and without IDC-P, IDC-P pattern 2 had markedly poorer prognosis in either ABI (PSA-PFS: P<0.001; rPFS: P<0.001) or DOC (PSA-PFS: P<0.001; rPFS: P<0.001) treatment. For patients without IDC-P, DOC had comparable therapeutic efficacy with ABI. In contrast, the therapeutic efficacy of DOC in patients with either IDCP pattern 1 (PSA-PFS: P=0.021; rPFS: P=0.027) or pattern 2 (PSA-PFS: P=0.003; rPFS: P=0.007) was significantly inferior to ABI.ConclusionCompared to DOC, ABI exhibited better efficacy in patients with IDC-P of either pattern. However, IDC-P pattern 2 still responded unsatisfactorily to either ABI or DOC therapy. Novel therapeutic strategies appropriate for IDC-P pattern 2 need to be further investigated in the future.

Prognostic impact of prior local therapy in castration-resistant prostate cancer

2021 ◽  
Author(s):  
Mikifumi Koura ◽  
Masaki Shiota ◽  
Shohei Ueda ◽  
Takashi Matsumoto ◽  
Satoshi Kobayashi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

High-exosomal AKR1C3 mRNA expression as a marker of poor efficacy of abiraterone in metastatic PCa patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 196-196
Author(s):  
Sha Zhu ◽  
Guangxi Sun ◽  
Xingming Zhang ◽  
Jindong Dai ◽  
Junru Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mrna Expression ◽  
Progression Free Survival ◽  
Study Endpoint ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Line Therapy

196 Background: Aldo-keto reductase family 1 member C3 (AKR1C3) has been proved to be an important part in the androgen biosynthesis process. Previous researches have showed that immunohistochemical (IHC) AKR1C3 expression is a prognosticator in prostate cancer (PCa) patients treated with abiraterone. This study is to find out the relationship between exosomal AKR1C3 mRNA expression and the efficacy of abiraterone in metastatic PCa patients. Methods: Blood samples of metastatic prostate cancer patients during different disease stages were collected. We isolated the exosomes and extracted the RNA for analysis of AKR1C3 by ddPCR. Absolute target mRNA concentration was measured by ddPCR as copies per milliliter (copies/20ul). Clinical data were collected for all patients. Primary study endpoint was progression-free survival (PFS). Statistical analyses were performed with SPSS 25.0. Results: Exosomal AKR1C3 mRNA expression was positive in 71.9% (41/57) patients, and high expression (defined as ≥ 20 copies/20μl) was found in 12.3% (7/57) patients. High exosomal AKR1C3 mRNA expression was not related to positive IHC AKR1C3 expression ( P=0.723). Patients with high exosomal AKR1C3 expression and negative IHC AKR1C3 expression harbored only 4.866 months’ median progression-free survival (PFS) compared with the whole cohort (9.37 months). High exosomal AKR1C3 expression is significantly associated with shorter PFS (median PFS 8.036 months, p<0.001). Multivariate Cox regression analysis revealed that high exosomal AKR1C3 expression was an independent prognosticator of abiraterone treatment efficacy (OR: 8.891, 95%CI: 1.309-61.631, P=0.026). In subsequently subgroup analyses, high exosomal AKR1C3 expression demonstrates particularly high hazard ratio in multiple subgroups (patients with baseline PSA >100 ng/mL, ALP >71 IU/L, HGB >120 g/L, and patients receiving abiraterone as first-line therapy in castration resistant prostate cancer). Conclusions: Exosomal AKR1C3 level is an independent adverse prognosticator in metastatic PCa patients receiving abiraterone treatment, especially when abiraterone was used as first-line therapy in castration resistant prostate cancer.

The effect of AKR1C3 on the switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients receiving abiraterone.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 133-133
Author(s):  
Yuchao Ni ◽  
Jinge Zhao ◽  
Junru Chen ◽  
Guangxi Sun ◽  
Sha Zhu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Psa Progression ◽  
Biochemical Progression ◽  
First Line Treatment

133 Background: Abiraterone is the first-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) and is recommended to be used with prednisone. Previous studies had demonstrated that the switch from prednisone to dexamethasone in some mCRPC patients can reverse abiraterone-resistance. However, it remains uncertain which group of patients will benefit from such switching. AKR1C3 is a critical enzyme contributing to the drug-resistance of abiraterone. Here, we aim to explore the significance of AKR1C3 in predicting the therapeutic efficacy of the corticosteroid switching in mCRPC patients receiving abiraterone. Methods: In total, 43 PCa patients treated with abiraterone after mCRPC between 2016 and 2018 in our institution were included. After biochemical progression in abiraterone plus prednisone, all cases received a corticosteroid switch to abiraterone plus dexamethasone. The expression of AKR1C3 was detected by immunohistochemical staining from re-biopsy (re‐Bx) of primary prostate lesions at the time of mCRPC. Kaplan‐Meier curves were used to analyze the association between AKR1C3 and treatment outcomes. Results: Totally, AKR1C3 was positive in 19 of 43 (44.19%) cases. In the corticosteroid switch treatment, 30% PSA decline was confirmed in 18/43 (41.86%) patients, while the median PSA progression‐free survival (PSA-PFS) and overall survival (OS) was 4.93 Mo and 31.57 Mo, respectively in the whole cohort. AKR1C3 expression was associated with statistically shorter median PSA-PFS (4.50 Mo vs 7.73 Mo; p =0.010) and numerically lower median OS (25.43 Mo vs 39.37 Mo, p =0.274). While the 30% PSA decline rate was numerically comparable between those with and without AKR1C3 expression (31.6% vs 50.0%, p =0.224). Conclusions: This study showed AKR1C3 detection in tissues from prostate re‐Bx at mCRPC was associated with poor PSA-PFS in the corticosteroid switch from abiraterone plus prednisone to abiraterone plus dexamethasone. These results would be helpful in making optimal personalized treatment decisions for patients with mCRPC, facilitating physicians predicting the effectiveness of corticosteroid switch treatment.

Efficacy of docetaxel and androgen receptor axis-targeted agents in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 150-150
Author(s):  
Akiyuki Yamamoto ◽  
Masashi Kato ◽  
Toyonori Tsuzuki ◽  
Momokazu Gotoh
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Primary Outcome ◽  
Progression Free Survival ◽  
Intraductal Carcinoma ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Carcinoma Of The Prostate ◽  
Castration Resistant ◽  
Time Of Administration

150 Background: This study aimed to investigate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in castration-resistant prostate cancer (CRPC) patients with intraductal carcinoma of the prostate (IDC-P). Methods: We retrospectively identified 311 CRPC patients from June 2002 to February 2016. All patients were initially administered with androgen deprivation therapy (ADT), followed by docetaxel or ARAT (abiraterone or enzalutamide) after progressing to CRPC. The primary outcome of interest was overall survival (OS) from the time of CRPC diagnosis and progression-free survival (PFS) from the time of administration of docetaxel or ARAT. Results: IDC-P was found in 180 of 311 patients. The median OS was 33.4 and 64.0 months with and without IDC-P, respectively (hazards ratio [HR], 2.14; P < 0.001). For the first treatment for CRPC, docetaxel was administered to 71 and 50 patients with and without IDC-P, respectively, with a median OS of 30.4 and 64.0 months, respectively (HR, 2.62; P < 0.001). ARAT was administered to 109 and 81 patients with and without IDC-P, respectively, with a median OS of 45.0 and 69.9 months, respectively (HR, 1.84; P = 0.017). Regarding patients with IDC-P, the OS in patients who were administered with ARAT was longer than that in those administered with docetaxel (HR, 0.58; P = 0.008). The median PFS was 7.5 and 12.1 months with and without IDC-P, respectively (HR, 1.36; P = 0.03). Multivariate analysis showed that the prognostic factors for OS were the presence of IDC-P (HR, 1.91; P < 0.001), and administration of ARAT (HR, 0.66; P = 0.02). Conclusions: The presence of IDC-P is an independent prognostic factor for OS and PFS in CRPC patients. ARAT may prolong OS in CRPC patients with IDC-P.

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