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Background/Objectives: Patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and high-risk features frequently have progression to life-threatening metastasis without second-generation antiandrogens. This study investigated nmCRPC patients for the survival and prognostic factors from a cohort before the approved use of second-generation antiandrogens. Methods: From March 2016 to January 2021, 326 patients treated with second-generation antiandrogens for metastatic castration-resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer were retrieved. Forty-four patients experiencing nmCRPC with no use of second-generation antiandrogens were reviewed. The prognostic factors, at initial diagnosis or at nmCRPC, associated with metastasis-free survival (MFS) and overall survival (OS) were analyzed. Results: The median follow-up time after nmCRPC was 46 months. The median PSA level at nmCRPC was 2.7 ng/mL. Thirty-eight of forty-four patients with nmCRPC had a PSA doubling time (PSADT) of 10 months or shorter, and the median PSADT was 4 months. The median OS from nmCRPC was 53 months, and the median interval for nmCRPC patients progressing to mCRPC was 20 months. Upon univariate analysis, PSADT < 10 months (p = 0.049) and the very-high-risk group at the initial diagnosis (p = 0.043) were associated with significantly shorter post-nmCRPC MFS. The very-high-risk group (p = 0.031) was associated with significantly worse post-nmCRPC OS. In terms of survivals from the initial diagnosis of prostate cancer, Gleason grade ≥ 8 was the only independent factor with MFS and OS. Conclusions: Without second-generation antiandrogens, nmCRPC patients with PSADT <10 months and in the initial very-high-risk group developed subsequent mCRPC in a significantly faster fashion. Patients of the very-high-risk group had shorter survival rates after nmCRPC. [ABSTRACT FROM AUTHOR]

Aim: The aim of the third Asia‐Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia‐Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). Methods: The one‐day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate‐ and high‐risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone‐sensitive prostate cancer; (3) Management of non‐metastatic castration‐resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration‐resistant prostate cancer. Pre‐ and post‐symposium polling gathered APAC‐specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. Results: APAC APCCC highlights APAC‐specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision‐making. Conclusion: The use of next‐generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality‐of‐life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC‐specific issues and considerations in areas of low evidence where clinical experience is growing. [ABSTRACT FROM AUTHOR]

Docetaxel‐based chemotherapy has generally been considered as one of the effective treatments for castration‐resistant prostate cancer (PCa). However, clinical treatment with docetaxel often encounters a number of undesirable effects, including drug resistance. Tubulin isoforms have been previously examined for their resistance to docetaxel in many cancers, but their real mechanisms remained unclear. In this study, a series of docetaxel‐resistant PC/DX cell sublines were established by chronically exposing PC3 to progressively increased concentrations of docetaxel. Western blotting results showed significantly higher expression of acetyl‐tubulin, α‐tubulin, β‐tubulin, γ‐tubulin, and βIII‐tubulin in PC/DX25 than in parental PC3 cells. PC/DX25 with greater resistance to docetaxel had higher levels of acetyl‐tubulin and mitotic centromere‐associated kinesin (MCAK) than PC3 cells. This study found that docetaxel induced the expression of acetyl‐tubulin and MCAK in PC3 cells at a dose‐ and time‐dependent manner. Both mRNA and protein levels of histone deacetylase 6 (HDAC6) were significantly decreased in PC/DX25 compared with PC3 cells. PC3 increased the resistance to docetaxel by HDAC6 knockdown and Tubastatin A (HDAC6 inhibitor). Conversely, PC/DX25 reversed the sensitivity to docetaxel by MCAK knockdown. Notably, flow cytometry analysis revealed that MCAK knockdown induced significantly sub G1 fraction in PC/DX cells. Overexpression of polo‐like kinase‐1 increased the cell survival rate and resistance to docetaxel in PC3 cells. Moreover, epidermal growth factor receptor (EGFR) activation induced the upregulation of acetyl‐tubulin in docetaxel‐resistant PCa cells. These findings demonstrated that the EGFR‐mediated upregulated expression of acetyl‐tubulin played an important role in docetaxel‐resistant PCa. [ABSTRACT FROM AUTHOR]

Purpose: In the management of prostate cancer (PC), outcome prediction using clinical stages determined via magnetic resonance imaging (MRI) or digital rectal examination (DRE) is controversial. Materials and Methods: Patients with PC who received primary total prostate cryoablation (PTPC) at our institution between October 2008 and March 2021 were enrolled in this study. The primary outcome was biochemical recurrence (BCR), which was defined according to the Phoenix criteria. The concordance of clinical stages determined via DRE and MRI was measured using the weighted kappa coefficient. The Cox proportional-hazards models were used to assess the BCR risks. Results: A total of 230 patients with a median age of 70 years were included in the analysis. The consensus rate of clinical T stages between DRE and MRI was 60.9% with fair concordance (? = 0.310). DRE upstaged 25 (10.9%) patients, whereas MRI upstaged 65 (28.3%) patients. During the median follow-up duration of 83.1 months, BCR occurred in 78 patients. The univariate analysis of BCR revealed that initial prostate-specific antigen, Gleason sum, and DRE-determined T stage (T3a-b vs. T1-2c; hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.2-2.94) were statistical predictors of BCR. However, no significant association was observed between MRI-determined T stage and BCR (T3a-b vs. T1-2c; HR 1.30; 95% CI 0.83-2.02). The multivariate models consisting of DRE-determined T stage were better than those consisting of MRI-determined T stage based on the Akaike information criteria. Conclusion: In the patients who underwent PTPC, DRE was a valuable technique for evaluating preoperative tumor status and predicting outcomes. [ABSTRACT FROM AUTHOR]