Prognostic impact of dose reduction in androgen receptor pathway inhibitors for castration-resistant prostate cancer.

Background: Androgen receptor pathway inhibitors (ARPIs) such as abiraterone and enzalutamide have been shown to prolong survival in patients with advanced prostate cancer. However, there is limited evidence on the anticancer effect of a reduced dose of ARPIs. This study compared the prognosis in patients with chemotherapy-naïve castration-resistant prostate cancer (CRPC) between ARPI treatment with standard dose and treatment with reduced dose. Methods: Japanese patients who were treated with ARPI as first-line treatment for CRPC between 2014 and 2018 were included. The associations between dose reduction and clinicopathological factors, progression-free survival, and overall survival were investigated. Results: Of the 162 patients included, 33 (20.4%) patients had their dose reduced during ARPI treatment. In the multivariate analysis, higher PSA, abiraterone treatment, and dose reduction were significant prognostic factors for progression-free survival (PFS); however, dose reduction was not associated with overall survival. In the enzalutamide-treated group, the median PFS was 12.1 months (95% CI, 8.5-21.4 months) in the standard-dose group and 7.2 months (95% CI, 5.0-11.5 months) in the reduced-dose group (P = 0.038). Conclusion: This study suggests inferior oncological outcome when treated with reduced-dose ARPI for CRPC. Full-dose administration of ARPI for CRPC may be appropriate if feasible.

Prognostic significance of risk stratification in CHAARTED and LATITUDE studies among Japanese men with castration-resistant prostate cancer.

BACKGROUND: The CHAARTED and LATITUDE trials demonstrated a survival benefit of docetaxel and abiraterone for hormone-sensitive prostate cancer. In this study, we examined the impact of the risk stratification criteria used in the CHAARTED and LATITUDE trials on the prognosis of castration-resistant prostate cancer (CRPC). We also tested whether these risk stratification criteria could help in selecting effective initial treatment for CRPC. METHOD: Japanese patients with CRPC who were treated with docetaxel or androgen receptor pathway inhibitors such as abiraterone acetate or enzalutamide between 2014 and 2018 were included in this study. Clinicopathological factors, progression-free survival, and overall survival were investigated. RESULTS: Of 215 patients, 110 men (51.2%) and 93 men (43.3%) were grouped as high volume by CHAARTED criteria and high risk by LATITUDE criteria, respectively. Median progression-free survival was 10.3/4.5 months (P < 0.0001) for low/high volume (CHAARTED criteria) and 9.9/4.8 months (P = 0.0032) for low/high risk (LATITUDE criteria). The median overall survival was 44.8/17.4 months (P < 0.0001) for low/high volume (CHAARTED criteria) and 37.4/17.4 months (P = 0.0011) for low/high risk (LATITUDE criteria). The prognostic impact of CHAARTED and LATITUDE criteria was comparable between androgen receptor pathway inhibitors and docetaxel as first-line treatment for CRPC. CONCLUSION: The CHAARTED and LATITUDE criteria were prognostic, but not useful to discriminate the therapeutic outcome between androgen receptor pathway inhibitors and docetaxel for CRPC.

Anticancer Effect of Second-line Treatment for Castration-Resistant Prostate Cancer Following First-line Treatment with Androgen Receptor Pathway Inhibitors.

INTRODUCTION: Studies on the effect of androgen receptor pathway inhibitors (ARPI), docetaxel (DTX), and radium-223 (Ra-223) after first-line treatment with ARPI in patients with castration-resistant prostate cancer (CRPC) are scarce. This study compared the efficacy of treatment after ARPI for CRPC. METHODS: Patients with CRPC who received ARPI as first-line treatment and different second-line treatments were retrospectively reviewed. Clinicopathological backgrounds and treatment outcomes, including maximum prostate-specific antigen (PSA) decrease, progression-free survival (PFS), and overall survival (OS), were compared between second-line treatments. RESULTS: In total, 88 patients were enrolled. Forty-one (46.6%), 37 (42.0%), and 10 (11.4%) patients were treated with ARPI, DTX, and Ra-223, respectively. Patients whose PSA levels were not adequately reduced by first-line treatment with ARPI were eventually enrolled in the DTX treatment (P = 0.030). PSA decrease was not significantly different when comparing treatments. PFS in the DTX group was significantly better than in the other two groups (P = 0.023). In multivariate analysis, DTX was an independent prognostic factor for better PFS compared to ARPI (hazard ratio, 95% confidence interval; 0.44, 0.25-0.79, P = 0.006). Subgroup analysis showed a favorable impact of DTX on PFS in patients with Gleason score >8 (interaction P = 0.027) and a PSA decline >50% (interaction P = 0.019) during first-line treatment with ARPI. However, no significant difference in OS was observed between groups of different second-line treatments. CONCLUSIONS: This study suggests that in patients with CRPC, second-line treatment with DTX following progression in patients who received ARPI as first-line treatment is more beneficial compared with second-line treatment with ARPI or Ra-233.

Lactate Dehydrogenase Is a Serum Prognostic Factor in Clinically Regional Lymph Node-positive Prostate Cancer.

BACKGROUND/AIM: Currently, there is no established prognostic serum parameter except PSA in clinically regional lymph node-positive prostate cancer. The aim of this study was to identify serum prognostic factors in clinically regional lymph node-positive prostate cancer. PATIENTS AND METHODS: Patients diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017 were included. The prognostic value of serum parameters for progression-free survival (PFS) and overall survival (OS) was investigated. RESULTS: Univariate and multivariate analyses showed a statistically significant increased hazard risk for PFS and OS for men with lactate dehydrogenase (LDH) ≥230 IU/l at diagnosis. PFS at 5 years for patients with high and low LDH levels were 69.9% (95% CI=56.8-79.8%) and 18.9% (95% CI=1.23-53.2%), respectively (p=0.003). OS at 5 years for low and high LDH levels were 89.2% (95% CI=78.6-94.7%) and 46.3 (95% CI=11.2-76.2%), respectively (p=0.006). CONCLUSION: This study shows that LDH is an independent predictor of PFS and OS in patients with regional lymph node metastatic prostate cancer.

Predictive factors of biochemical recurrence after radical prostatectomy for high-risk prostate cancer.

OBJECTIVE: To identify risk factors of biochemical recurrence after radical prostatectomy in high-risk patients. METHODS: A total of 191 high-risk prostate cancer patients according to the D'Amico classification treated with radical prostatectomy at a single institution between April 2000 and December 2013 were enrolled. The pathological evaluation including intraductal carcinoma of prostate was reassessed, and the clinical and pathological risk factors of biochemical recurrence were analyzed. RESULTS: The median follow up after radical prostatectomy was 49 months. The 5-year biochemical recurrence-free survival rate after radical prostatectomy in high-risk prostate cancer patients was 41.6%. Initial prostate-specific antigen, pathological Gleason score, seminal vesicle invasion, extraprostatic extension and intraductal carcinoma of the prostate were significantly associated with biochemical recurrence-free survival. The 5-year biochemical recurrence-free survival rates in patients with zero, one, two and three of these risk factors were 92.9%, 70.7%, 38.3% and 28.8%, respectively. In patients with four or more factors, the biochemical recurrence-free survival rate was 6.1% after 18 months. CONCLUSIONS: In D'Amico high-risk patients treated with radical prostatectomy, risk factors for biochemical recurrence can be identified. Patients with fewer risk factors have longer biochemical recurrence-free survival, even among these high-risk cases.