Search

Objective: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. Methods: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone

Simple Summary: In prostate cancer patients with low-volume/oligo-metastatic relapse after radical prostatectomy, radioguided surgery against prostate-specific membrane antigen (PSMA-RGS) might be an option. However, patient selection remains difficult. In this study, we analyzed if the EAU risk stratification for biochemical recurrence (BCR) and the PSA development over time predict the oncological success of PSMA-RGS. We found that neither EAU BCR risk groups nor PSA doubling time and velocity are significant predictors for a complete biochemical response or prolonged biochemical recurrence- or subsequent therapy-free survival. Therefore, PSMA-RGS may be offered to suitable patients independently of prior PSA development and EAU BCR risk group after radical prostatectomy. Objective: To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. Methods: We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). Results: Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70–3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46–2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95–1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97–1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99–1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. Conclusions: The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS. [ABSTRACT FROM AUTHOR]

Background and objective: Metastasis-directed therapy is a feasible option for low PSA, recurrent locoregional metastatic prostate cancer. After initial salvage surgery, patients with good response might consider a repeat salvage surgery in case of recurrent, isolated, and PSMA-positive metastases. This analysis aimed to evaluate the oncological outcome and safety of repeat PSMA-targeted radioguided surgery (RGS) after either prior RGS or "standard" salvage lymph node dissection (SLND). Materials and methods: We identified 37 patients undergoing repeat RGS after prior SLND (n = 21) (SLND-RGS) or prior RGS (n = 16) (RGS-RGS) between 2014 and 2021 after initial radical prostatectomy with or without pelvic radiation therapy at two German tertiary referral centers. Kaplan–Meier analyses and uni-/multivariable Cox regression models were used to investigate factors associated with biochemical recurrence-free survival (BRFS) and treatment-free survival (TFS) after repeat salvage surgery. Results and limitations: Complete Biochemical Response (cBR, PSA < 0.2 ng/ml) was observed in 20/32 patients (5 NA). Median overall BRFS [95% confidence interval (CI)] after repeat salvage surgery was 10.8 months (mo) (5.3–22). On multivariable regression, only age (HR 1.09, 95% CI 1.01–1.17) and preoperative PSA (HR 1.23, 95% CI 1.01–1.50) were associated with shorter BRFS, although PSA (HR 1.16, 95% CI 0.99–1.36) did not achieve significant predictor status in univariable analysis before (p value = 0.07). Overall, one year after second salvage surgery, 89% of the patients (number at risk: 19) did not receive additional treatment and median TFS was not reached. Clavien–Dindo grade > 3a complications were observed in 8% (3/37 patients). Limitations are the retrospective evaluation, heterogeneous SLND procedures, lack of long-term follow-up data, and small cohort size. Conclusion: In this study, repeat RGS was safe and provided clinically meaningful biochemical recurrence- and treatment-free intervals for selected cases. Patients having low preoperative PSA seemed to benefit most of repeat RGS, irrespective of prior SLND or RGS or the time from initial RP/first salvage surgery. [ABSTRACT FROM AUTHOR]

Purpose: Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence. Methods: For this narrative comprehensive review, we employed PubMed®, Web of Science™, Embase®, Scopus®, and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials. Results: Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone. Conclusion: Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition. [ABSTRACT FROM AUTHOR]

Purpose: The extent of effectiveness of upfront androgen receptor-axis-targeted therapies (ARAT) versus total an- drogen blockade (TAB) in improving prostate cancer-specific survival (CSS) and progression-free survival (PFS) in a real-world sample of Japanese patients with high-volume mHSPC remains unclear. We, therefore, investigated the efficacy and safety of upfront ARAT versus bicalutamide for de novo high-volume mHSPC in Japanese pa- tients. Material and Methods: This was a multicenter retrospective study that analyzed CSS, clinical PFS, and adverse events (AEs) in 170 patients with newly diagnosed high-volume mHSPC. Fifty-six patients were treated with up- front ARAT, and 114 of them were prescribed bicalutamide in addition to ADT between January 2018 and March 2021. The primary and secondary endpoints were CSS and PFS, respectively. A 1:1 nearest neighbor propensity score matching (PSM) with a caliper of 0.2 was performed to match the ARAT group to TAB patients. Results: During the follow-up for a median of 21.5 months, the median CSS was not reached and 37 months in the upfront ARAT and total androgen blockade (TAB) groups, respectively (log-rank test: P = 0.006) by propensity score matching (PSM). Moreover, while the PFS of ARAT was unreached, the median PFS of TAB was 9 months (log-rank test: P < 0.001). Nine patients discontinued ARAT owing to grade ≥ 3 AEs; one patient who was treated with TAB had a grade 3 AE. Conclusion: Upfront ARAT significantly prolonged the CSS and PFS of patients with high-volume mHSPC better than TAB, although ARAT was associated with a higher rate of grade ≥ 3 AEs. Upfront ARAT can be more ben- eficial for patients with de novo high-volume mHSPC than TAB. [ABSTRACT FROM AUTHOR]

Six cycles of docetaxel in addition to androgen deprivation therapy (ADT) are currently one of the treatment options for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Since the outcomes in patients with highvolume (HV) disease remain modest, we aimed to identify patients for more intensified treatment. We report a cohort of 73 consecutive patients with de novo mHSPC treated with early docetaxel at the Department of Oncology and Radiotherapy, University Hospital of Split, Croatia, from October 2015 until March 2020. The outcomes analyzed were the occurrence of castration-resistant disease (CRPC) and death from any cause (OS). The median follow-up was 54 (50-73) months. Forty-six (63%) patients developed CRPC and 34 (47%) died during the follow-up. The median time to CRPC and median OS were 16.2 and 58.4 months, respectively. The risk of CRPC was higher for patients with high (above median) values of serum alkaline phosphatase (ALP) (HR=2.4; 95% CI [1.4-4.5]), lactate dehydrogenase (LDH) (HR=1.98; 95% CI [1.1-3.7]), prostate-specific antigen (PSA) (HR=1.8; 95% CI [1.1-3]), ECOG performance status >1 (HR=2; 95% CI [1.2-3.3]) and HV disease (HR=1.9; 95% CI [1.1-3.1]). The risk of any-cause death was higher in patients with high values of ALP, LDH, and ECOG performance status >1. The predictive value of LDH was independent of disease volume. A set of baseline characteristics could be used in conjunction with disease volume in deciding on the optimal treatment strategy for patients with de novo mHSPC. [ABSTRACT FROM AUTHOR]

Abstract Objective To investigate the efficacy and safety of docetaxel chemotherapy combined with androgen-deprivation therapy for patients with high-volume disease metastatic hormone-sensitive prostate cancer. Methods 153 cases of high-volume disease metastatic hormone-sensitive prostate cancer in Minhang Hospital between January 2018 and December 2019 were analyzed retrospectively, including the number of patients, age, initial PSA level, Gleason score, TNM stage and ECOG score. 90 patients in the endocrine therapy group received continuous ADT, and 63 patients in the combined chemotherapy group received docetaxel plus ADT. The progression-free survival time (time from initiation of prostate cancer treatment to progression to CRPC), PSA response rate, and adverse reactions were compared between the two groups. Results All 153 cases were closely followed up for a period of 12.3–35.3 months, with a median follow-up time of 23.5 months. The median time to reach the lowest point of PSA in the two groups was 6.3 months and 7.9 months (P = 0.018) in the combination chemotherapy group and the ADT group alone, with 27 (42.9%) and 12 (13.3%) cases in the two groups Within 12 months of treatment, PSA decreased to below 0.2 ng/ml (P = 0.02), and progression-free survival was 16.9 months (6.5–28.5 months) and 11.2 months (4.3–22.7 months) in the two groups. (P

Purpose: Evidence in favor of adding docetaxel in treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has led to docetaxel in conjunction with androgen deprivation therapy (ADT) as standard therapy. The aim of this study was to examine the effectiveness of docetaxel with ADT for Korean patients with mHSPC in real-world practice. Materials and Methods: A retrospective cohort study was performed at six Korean hospitals for patients with mHSPC treated with docetaxel plus ADT. Patients were treated every 3 weeks for up to six cycles with 75 mg/m2 of docetaxel. The primary endpoint was time to castration resistant prostate cancer (CRPC). Results: This study included 46 eligible patients from June 2016 to February 2021. Median age was 68.5 years (range, 52-84) and all patients present with de novo M1 with high-volume disease. The median prostate-specific antigen (PSA) level at ADT initiation was 205.4 (7.7-1933) ng/mL, and time from ADT to docetaxel was 2.4 months (0-5.3). All six planned cycles of docetaxel were delivered in 36 patients (78%), 7 patients (15%) discontinued treatment due to adverse events, and 3 patients (7%) discontinued due to progression. At the time of the analysis, CRPC had developed in 34 patients (74%), and the median time to CRPC was 18.0 (95% confidence interval, 14.1-21.9) months. PSA <0.2 ng/mL was achieved in 11 patients (24%) after 6 months of ADT and in 10 patients (22%) after 12 months. At last follow-up, 35 patients (76%) were alive; the median overall survival was not reached. Conclusion: The effect of docetaxel combined with ADT for Korean patients with mHSPC is comparable with prior results in Western studies. [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value.

This study aims to systematically identify and review published economic evaluations related to the treatment of mHSPC and assess their quality. These datas will help to provide a better understanding of these treatments and a better use of healthcare resources. The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion cr iter ia. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≤ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of docetaxel chemotherapy combined with androgen-deprivation therapy for patients with high-volume disease metastatic hormone-sensitive prostate cancer. Methods: 153 cases of high-volume disease metastatic hormone-sensitive prostate cancer in Minhang Hospital between January 2018 and December 2019 were analyzed retrospectively, including the number of patients, age, initial PSA level, Gleason score, TNM stage and ECOG score. 90 patients in the endocrine therapy group received continuous ADT, and 63 patients in the combined chemotherapy group received docetaxel plus ADT. The progression-free survival time (time from initiation of prostate cancer treatment to progression to CRPC), PSA response rate, and adverse reactions were compared between the two groups. Results: All 153 cases were closely followed up for a period of 12.3–35.3 months, with a median follow-up time of 23.5 months. The median time to reach the lowest point of PSA in the two groups was 6.3 months and 7.9 months (P = 0.018) in the combination chemotherapy group and the ADT group alone, with 27 (42.9%) and 12 (13.3%) cases in the two groups Within 12 months of treatment, PSA decreased to below 0.2 ng/ml (P = 0.02), and progression-free survival was 16.9 months (6.5–28.5 months) and 11.2 months (4.3–22.7 months) in the two groups. (P < 0.001). There were 18 cases (28.6%) and 54 cases (60%) in the two groups with disease progression (P < 0.001). There were 6 cases (9.5%) and 15 cases (16.7%) in the combination chemotherapy group and the ADT group died of prostate cancer and related complications, respectively. All 63 cases in the combined chemotherapy group completed 6 cycles of chemotherapy. 39 (61.9%) cases experienced varying degrees of neutropenia, of which 12 (19%) experienced grade 3–4 neutropenia, with 6 cases (9.5%) developed febrile neutropenia. 30 cases (47.6%) had toxic reactions in the digestive system, and 3 case (4.3%) had grade 3 liver dysfunction. 27 cases (42.8%) had skin and mucosal toxicity. 9 cases (14.3%) had mild fluid retention. No blood and digestive toxicity were observed in the ADT group. 33 cases (52.4%) and 48 (53.3%) of the two groups had symptoms of afternoon hot flashes and fatigue, (P = 0.961). Conclusion: Docetaxel chemotherapy combined with endocrine therapy could be one of effective treatments for delaying castration resistance of HVD-mHSPC, which could prolong PFS effectively and obtain a higher PSA response rate, high safety under close monitoring, and controllable adverse reactions. [ABSTRACT FROM AUTHOR]

Background: Docetaxel has emerged as a standard‐of‐care for metastatic hormone‐sensitive prostate cancer (mHSPC). Uptake of docetaxel for mHSPC in Australia has not previously been reported. Aims: To investigate the real‐world uptake of docetaxel in mHSPC and to identify predictors of utilisation of docetaxel in mHSPC. Methods: Men diagnosed from June 2014 to December 2018 and enrolled in the Prostate Cancer Outcomes Registry‐Victoria (PCOR‐Vic) were included. Data collected include demographics, diagnosis method and institution, staging investigations and treatments within 12 months of diagnosis. Wilcoxon rank‐sum, Chi‐squared and trend tests were used to identify predictors of docetaxel utilisation. All predictors were entered as covariates simultaneously into a multivariable logistic regression model. Statistical significance was set at 0.05 (two sided). Results: In all, 1014 men with mHSPC were analysed, 25% of whom received docetaxel with androgen deprivation therapy. Uptake of docetaxel increased from 20% in 2014 to 33% in 2018. Predictors of higher usage of docetaxel were younger age and treatment in a private hospital, with both remaining significant on multivariable analysis. Notably, the proportion of men aged <70 years receiving docetaxel increased from 54% in 2014–2015 to 64% in 2016–2018, while in men aged ≥70 years the comparative figures were 15% and 22% respectively. Conclusions: Although docetaxel was not used in the majority of cases, there was a clear increase in docetaxel uptake, especially in younger men following publication of the CHAARTED and STAMPEDE trials. Identifying barriers to real‐world implementation of pivotal clinical trial data is critical to improving outcomes in mHSPC. [ABSTRACT FROM AUTHOR]

Background: To develop and validate a prognostic risk model for high-risk metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with upfront abiraterone acetate (ABI)., Methods: This retrospective multicenter study involved 233 high-risk mHSPC patients who received upfront ABI, developed by three academic centers. The model was externally validated with an independent cohort of 282 patients. To identify independent prognostic factors for second progression-free survival (PFS2) and develop the best-fitted model, Cox proportional hazards regression, followed by the Akaike information criterion, was used. Patients were categorized into three groups based on their risk scores. PFS2 and overall survival (OS) were evaluated according to the risk groups in the discovery and validation cohorts., Results: The median age was 72 (range 51-89) years, with a median follow-up duration of 27 months. Independent factors linked to PFS2 included an Eastern Cooperative Oncology Group performance status ≥2, a primary Gleason score of 5, an extent of disease score of ≥3 or liver metastasis, and lactate dehydrogenase >220 U/L. Median PFS2 for favorable-, intermediate-, and poor-risk groups were not reached, 43 months, and 16 months, respectively. The median OS was 29 months in the poor-risk group, whereas it was not reached in the favorable- and intermediate-risk groups. The 2-year OS rates in the favorable-, intermediate- and poor-risk groups were 94.5%, 80.1%, and 60.3%, respectively. The validation cohort confirmed the risk model's relationship with PFS2 and OS. The median PFS2 and OS in the high-risk group were 21 months and 32 months, respectively., Conclusions: Our prognostic model, including five clinical factors, is useful for patient care and treatment selection in high-risk mHSPC patients treated with ADT plus ABI. The developed model could provide more accurate information, guide treatment decisions, or classify patients in future clinical trials., (© 2024 Wiley Periodicals LLC.)

Abstract Background Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone‐sensitive prostate cancer (mHSPC). Real‐world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC. Methods In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression‐free survival 1 (PFS1), and progression‐free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan–Meier method and log‐rank test. The Cox‐proportional hazards model was used for univariate and multivariate regression analyses. Results Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log‐rank testing (23 vs. 13 mos., p

Introduction: We aimed to evaluate the outcome of treatment with docetaxel plus androgen deprivation therapy (ADT) in newly diagnosed patients with metastatic high tumor burden hormone-sensitive prostate cancer (mHSPC) and correlated the outcome with hemoglobin, albumin, lymphocyte and platelets (HALP) score. Material and methods: Six cycles of docetaxel plus ADT were given to 50 patients with high burden mHSPC. Baseline HALP score was calculated and disease outcome was tabulated; moreover, the prognostic impact of the HALP score in response to treatment and survival was calculated. Results: We found a significant association between high HALP score and response to treatment where a higher rate of complete response occurred in patients with a high HALP score than in patients with a low HALP score (53.8% vs. 5.4% respectively, p-value = 0.001). Patients with = 12-month-duration castration-resistant prostate cancer (CRPC) had a significantly higher HALP score compared to patients with a lower HALP score (84.6% vs. 35.1% respectively, p-value = 0.002); 18-month-duration CRPC-free survival was significantly greater in patients with higher HALP score than patients with a lower HALP score (23.1% and 5.4% respectively, p-value < 0.001). Patients with a high HALP score had insignificantly higher mean overall survival than patients with a low HALP score (mean: 22.91 and 20.66 months respectively, p-value = 0.230). Conclusions: Our results confirmed the benefits of treatment with docetaxel plus ADT in high-burden mHSPC with accepted tolerance. HALP score was found to be an independent predictive factor for benefit from therapy; we can apply it as an easy way to stratify patients for appropriate selection of treatment for better tolerance and outcome. [ABSTRACT FROM AUTHOR]

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value. [ABSTRACT FROM AUTHOR]

Abstract Background Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC. Methods We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin

We report a rare case of ectopic breast tissue situated in a unique location. A 50-year-old female patient came to our institution complaining of a bulge in the inguinal area. CT was unremarkable other than a benign-looking conglomeration of lymph nodes around the inguinal canal. However, excisional biopsy proved otherwise, with strong expression of breast-related immunohistochemical markers on pathology. Based on histological findings, the diagnosis of ectopic breast tissue was made. Since the vast majority of ectopic breast tissue is found around the breast mound, axilla, and along the milk line, this case is peculiar in its location. This report shares our experience and provides indications for excision of incidental ectopic breast tissue.

Background: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System., Methods: In this observational retrospective cohort study, 400 de novo metastatic hormone-sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow-up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan-Meier methods estimated overall survival (OS) and castration-resistant prostate cancer (CRPC)-free survival from mHSPC diagnosis date and a log-rank test compared these outcomes by oligometastatic status., Results: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non-omHSPC had higher median prostate-specific antigen at diagnosis (151.7) than omHSPC (44.1). First-line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non-omHSPC (14%). More omHSPC patients received metastasis-directed therapy/prostate radiation therapy (14%) versus non-omHSPC (2%). Median OS and CRPC-free survival (in months) were higher in omHSPC versus non-omHSPC (44.4; 95% confidence interval [CI], 33.9-not estimated vs. 26.2; 95% CI, 20.5-32.5, p = .0089 and 27.6; 95% CI, 22.1-37.2 vs. 15.3; 95% CI, 12.8-17.9, p = .0049), respectively., Conclusions: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non-omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non-omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies., (© 2024 American Cancer Society.)

This study aims to define optimal sequencing for patients moving from metastatic hormone-sensitive prostate cancer to metastatic castrate-resistant prostate cancer based on their cost and effectiveness through literature publications. The results add useful information to clinicians and patients facing treatment decisions in the real world. Background: The optimal therapeutic strategies for patients with metastatic hormone-sensitive prostate cancer (mHSPC) followed by metastatic castrate-resistant prostate cancer (mCRPC), in terms of cost and effectiveness, remains unknown. This study aims to compare the cost-effectiveness of various potential strategies, from the start of first-line treatment in mHSPC to the death of the patients. Methods: Two Markov decision-analysis models were developed, one for cohort A "asymptomatic/mildly symptomatic patients in mCRPC", and one for cohort B "symptomatic patients in mCRPC". Each strategy reflects daily practice for mHSPC until progression in mCRPC from the start of first treatment regimen with either docetaxel or abiraterone acetate plus prednisone (AA) in mHSPC to the death of the patient. The cost-effectiveness analysis was performed from the French public health care system perspective. Only direct medical costs were included. Survival data were extracted from results of published randomized clinical trials. Results: For cohort A, docetaxel followed by AA is the most cost-effective therapeutic strategy (€96,925 for 4.24 lifeyears). For cohort B, docetaxel followed by docetaxel is the most cost-effective therapeutic strategy (€81,463 for 4.05 life-years). Sensitivity analyses confirmed the robustness of our results except for a price reduction of 70% for AA or enzalutamide. Conclusion: Our approach is innovative to the extent that our analysis considers various potential strategies for metastatic prostate cancer (mPC). Our economic evaluation suggests that a price reduction of AA or enzalutamide impacts on the results. This approach must continue, including new drugs for patients with mPC. [ABSTRACT FROM AUTHOR]

Background: Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone‐sensitive prostate cancer (mHSPC). Real‐world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC. Methods: In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression‐free survival 1 (PFS1), and progression‐free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan–Meier method and log‐rank test. The Cox‐proportional hazards model was used for univariate and multivariate regression analyses. Results: Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log‐rank testing (23 vs. 13 mos., p < 0.001), a longer PFS2 (48 vs. 33 mos., p = 0.006), and longer OS (80 vs. 61 mos., p = 0.040). In the multivariate analyses AA+ADT outperformed D+ADT in terms of PFS1 (HR = 0.34, 95% CI = 0.183–0.623; p = 0.001) and PFS2 (HR = 0.33 95% CI = 0.128–0.827; p = 0.018), respectively, while OS and toxicity rate were similar between both groups. Conclusions: AA+ADT is mainly associated with a similar efficacy and overall toxicity rate as D+ADT. Further prospective research is required for validation of the clinical value of the observed benefit of AA+ADT for progression‐free end‐points. [ABSTRACT FROM AUTHOR]

Background: Anemia has been a known prognostic factor in metastatic hormone-sensitive prostate cancer (mHSPC). We therefore examined the effect of anemia on the efficacy of upfront abiraterone acetate (ABI) in patients with mHSPC.Methods: We retrospectively evaluated 66 mHSPC patients with high tumor burden who received upfront ABI between 2018 and 2020 (upfront ABI group). We divided these patients into two groups: the anemia-ABI group (hemoglobin < 13.0 g/dL, n = 20) and the non-anemia-ABI group (n = 46). The primary objective was to examine the impact of anemia on the progression-free survival (PFS; clinical progression or PC death before development of castration resistant PC) of patients in the upfront ABI group. Secondary objectives included an evaluation of the prognostic significance of upfront ABI and a comparison with a historical cohort (131 mHSPC patients with high tumor burden who received androgen deprivation therapy (ADT/complete androgen blockade [CAB] group) between 2014 and 2019).Results: We found that the anemia-ABI group had a significantly shorter PFS than the non-anemia-ABI group. A multivariate Cox regression analysis showed that anemia was an independent prognostic factor of PFS in the upfront ABI group (hazard ratio, 4.66; P = 0.014). Patients in the non-anemia-ABI group were determined to have a significantly longer PFS than those in the non-anemia-ADT/CAB group (n = 68) (P < 0.001). However, no significant difference was observed in the PFS between patients in the anemia-ABI and the anemia-ADT/CAB groups (n = 63). Multivariate analyses showed that upfront ABI could significantly prolong the PFS of patients without anemia (hazard ratio, 0.17; P < 0.001), whereas ABI did not prolong the PFS of patients with anemia.Conclusion: Pretreatment anemia was a prognostic factor among mHSPC patients who received upfront ABI. Although the upfront ABI significantly improved the PFS of mHSPC patients without anemia, its efficacy in patients with anemia might be limited. [ABSTRACT FROM AUTHOR]

Introduction: Important changes in the treatment of prostate cancer have taken place in recent years. Non-metastatic castration-resistant prostate cancer (nmCRPC) has been clinically delineated. In this setting, three drugs have been approved in high-risk disease: apalutamide, enzalutamide and darolutamide. Areas covered:This manuscript aims to profile darolutamide, its clinical development, pharmacologic properties, efficacy and safety. We presented the results of published clinical studies, but we also investigated ongoing ones. Expert opinion: An indirect comparison with the other two aforementioned drugs emerged. While the clinical efficacy is comparable, the toxicity profile is different for darolutamide, resulting in greater tolerance. We must wait for the results of the trials that study darolutamide in hormone-sensitive disease, both in the metastatic phase and in the localized phase. Clinical experience will also be important to determine ever more personalized treatments for patients. [ABSTRACT FROM AUTHOR]

Introduction: The last decade has seen a remarkable shift in the treatment landscape of advanced prostate cancer, none more so than in the management of metastatic castration-naïve disease. Methods: This narrative review will examine existing and emerging evidence supporting systemic therapy use for metastatic castration-naïve prostate cancer (mCNPC) and provide guidance on the selection of these agents with respect to optimising patient outcomes. Results: The addition of either docetaxel (chemohormonal approach) or an AR pathway inhibitor (abiraterone, enzalutamide or apalutamide) is a reasonable standard of care option for men commencing long-term ADT for mCNPC. While the issue of disease volume as a predictive biomarker for docetaxel benefit has previously been debated, recent data support consideration of upfront docetaxel in all patients, regardless of metastatic burden. Decisions regarding systemic treatment for men with mCNPC should be based on comprehensive consideration of disease, patient and logistical factors. Multiple novel therapeutics for mCNPC are currently under active investigation. Conclusion: The introduction of potent systemic therapy earlier in the mCNPC disease course has resulted in dramatic improvements in clinical outcomes for patients. As the management of mCNPC continues to evolve, the future remains promising, with the expectation of ongoing improvements to patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Objective: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients., Methods: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive., Results: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone ( n = 99) and PSA ( n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA., Conclusions: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer., Competing Interests: This study was funded by AstraZeneca China. The sponsor was involved in study design, data analysis and interpretation, and writing the report. The manuscript was written with editorial support from medical writers. No other potential conflicts of interests are disclosed by authors., (Copyright © 2023 Cancer Biology & Medicine.)

Context: Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical trials that demonstrated significant clinical benefits with docetaxel chemotherapy or novel hormone therapy (NHT) in addition to androgen deprivation therapy (ADT). Despite these advances, there is evidence to show that these treatments are not being utilised for mHSPC in clinical practice., Objective: To determine the utilisation of docetaxel and NHT in mHSPC in routine practice and the determinants of variation in their use., Evidence Acquisition: MEDLINE and Embase were searched systematically for studies on utilisation of treatments for primary mHSPC that were based on regional or national data sets and published after January 2005. Study results were summarised using a narrative synthesis., Evidence Synthesis: Thirteen papers were included in the analysis, six full-text articles and seven abstracts, on studies that included a total of 166 876 patients. The utilisation rate of treatment intensification with either docetaxel or NHT (enzalutamide, apalutamide, or abiraterone) in addition to ADT ranged from 9.3% to 38.1% across the studies. Younger, White patients with fewer comorbidities and living in more urban settings were more likely to be prescribed treatment intensification. Patients treated in private academic institutions by oncologists were more likely to receive docetaxel or NHT. Socioeconomic status did not impact receipt of systemic therapy. NHT utilisation rates appear to have increased over time., Conclusions: These results highlight the need to change the approach to the treatment of primary mHSPC in the real world by harnessing the practice-changing results from recent trials in this setting to optimise upfront systemic therapy for this patient population., Patient Summary: We reviewed the use of treatments for primary metastatic hormone-sensitive prostate cancer that showed a benefit in key clinical trials. We found that these treatments are underused, particularly among certain patient groups., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTChigh) than in low-volume (LV) patients (23% CTChigh; * p = 0.03). HV disease (p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation (p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients.

Purpose: Clinical outcomes of patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC) and initially treated with androgen deprivation therapy (ADT) were evaluated. Methods: The medical records of 605 consecutive mHNPC patients with initial ADT or combined androgen blockade (CAB) at nine study centers between 2008 and 2016 were retrospectively reviewed. Castration-resistant prostate cancer (CRPC)-free and overall survival (OS) were estimated by the Kaplan–Meier method. The association of pretreatment risk factors with CRPC-free survival and OS was evaluated by Cox proportional hazard models and differences in survival were classified by the number of risk factors. Results: Median follow-up was 2.95 years, median CRPC-free survival was 21.9 months and median OS was 5.37 years. Multivariable analysis found that four risk factors, a Gleason score ≥ 9, lymph node metastasis, an extent of disease score ≥ 2, and serum LDH of > 220 IU were independently associated with both CRPC-free survival and OS. Median CRPC-free survival of low-risk patients with no or one factor was 86.5 months, 17.9 months in intermediate-risk patients with two or three factors, and 11.0 months in high-risk patients with four factors. Median OS was 4.72 years in intermediate- and 2.44 years in high-risk patients. It was not reached in low-risk patients. Conclusion: In this series, CRPC-free and OS of a subset of mHNPC patients in Japan who were treated with ADT or CAB had better CRPC-free and overall survivals in Japan. Risk-adapted treatment based on the presence of novel prognostic factors may be beneficial for selected mHNPC patients. [ABSTRACT FROM AUTHOR]

Objective: To compare toxicity and response of docetaxel chemotherapy between metastatic hormone-sensitive prostate cancer (mHSPC) and castration-resistant metastatic prostate cancer (mCRPC) patients of the same therapeutic era for assessing of upfront docetaxel against the benchmark of docetaxel in the castrate resistant stage in the setting outside of clinical trials.Methods: A prospectively collected database of real-world prostate cancer patients receiving docetaxel was divided in mHSPC and mCRPC cases and retrospectively analyzed. Principal objectives were toxicity measured by the common criteria of adverse events terminology and response characterized by Prostate specific antigen decline and radiographic progression-free disease at restaging. The prognostic value of suspected variables for grade 3 to 5 toxicity and response was investigated by logistic regression analysis.Results: Of 72 patients 34 (47%) were treated for mHSPC and 38 (53%) for mCRPC. Patients with mCRPC were older and had worse performance status (P< 0.01). In mHSPC total number of grade 3 to 5 adverse events (24, median 0, interquartile range 0-1) was significantly less than in mCRPC (46, median 1, interquartile range 1-2) (P = 0.01). Multivariable analysis revealed age as independent predictive variable for grade 3 to 5 toxicity (P = 0.03) but not disease stage, Prostate specific antigen predocetaxel, volume of disease, and Eastern Cooperative Oncology Group performance status (P > 0.05). Objective response was significantly higher in mHSPC compared to mCRPC patients (P < 0.01). Multivariable analysis confirmed mHSPC stage as independent prognostic factor for radiographic progression free disease at restaging (P < 0.01).Conclusions: The association of age with toxicity and of mHSPC stage with response resulted in significantly fewer grade 3 to 5 adverse events but higher response rates for upfront docetaxel in mHSPC compared with docetaxel in the later mCRPC stage. [ABSTRACT FROM AUTHOR]

Purpose: To explore the prognostic importance of metastatic volume in a contemporary daily practice cohort of patients with newly diagnosed metastatic hormone-naive prostate cancer (mHNPC) and to develop a pragmatic prognostic model to predict survival for these patients. Methods: Since 2014, 113 patients with newly diagnosed mHNPC were prospectively registered. Statistical analysis was performed using SPSS 25.0™ with two-sided p value < 0.05 indicating statistical significance. Univariate and multivariate cox regression analyses were performed to identify prognostic risk factors. Kaplan–Meier method with log-rank statistics was constructed to analyze difference in survival in the prognostic groups. Model performance was assessed using the Concordance-index (C-index) and cross-validated in R v3.4.1. High-volume mHNPC (HVD) was defined as the presence of visceral metastasis or ≥ 4 bone metastases with ≥ 1 appendicular lesion. Results: Multivariate analysis identified HVD (p = 0.047) and elevated alkaline phosphatase (ALP) (p = 0.018) as independent prognostic risk factors for overall survival (OS). Consequently, three prognostic groups were created: a good (no risk factors), intermediate (1 risk factor) and poor prognosis group (2 risk factors). Median OS for the good, intermediate and poor prognosis group was not reached, 73 and 20 months (95% CI 9–31 months with p < 0.001 and Correspondence-index of 0.78), respectively. Conclusions: We developed a pragmatic and qualitative prognostic model consisting of three prognostic risk groups for OS in a daily practice cohort of patients with newly diagnosed mHNPC. Independent prognostic risk factors included in the model were HVD and abnormal ALP. [ABSTRACT FROM AUTHOR]

When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy. We perform a longitudinal, protein activity-based analysis of TME subpopulations, revealing immune subpopulations conserved across multiple metastatic sites. We also observe dynamic changes in these immune subpopulations in response to treatment and a correlation with clinical outcomes. Our study uncovers a therapy-resistant, transcriptionally distinct tumor subpopulation that expands in cell number in treatment-refractory patients. [Display omitted] • Protein-inferred activity clustering shows complex immune cells in CSPC metastases • ADT and aPD-1 treatment induces robust infiltrates of CD8+, CD4+ T cells, and Tregs • T cell infiltration determined by scRNA-seq correlated with T cells shown by qmIF • Baseline tumor and immune clusters associated with clinical outcomes TME composition of metastatic castration-sensitive prostate cancer (mCSPC) remains elusive. Hawley et al. perform scRNA-seq analysis of metastatic sites from mCSPC patients with ADT and anti-PD-1 treatment, identify tumor and immune subpopulations conserved across multiple metastatic sites, and reveal treatment-induced dynamic changes in these subpopulations and their correlation with clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: This study investigated how differences in the method of the first‐line androgen deprivation therapy (ADT) affected the time to castration‐resistant prostate cancer. Methods: The Japan Study Group of Prostate Cancer compiled a nationwide community‐based database on prostate cancer patients who underwent ADT. That database included 13 774 patients who were started on ADT by surgical or medical castration alone (monotherapy group, 5395 cases) or ADT in combination with a nonsteroidal anti‐androgen (combined androgen blockade (CAB) group, 8379 cases). We used logistic regression analysis with background factors as independent factors to calculate propensity scores in regard to selection of CAB. Next, for 8826 cases of propensity score‐matched patients, we compared the survival rates in the two groups. Results: The CAB group showed a significantly better progression‐free survival (PFS) rate (65.6% vs 59.6% at 5 years; median time to progression, 11.6 vs 7.1 years; hazard ratio in the CAB group: 0.78, with a 95% confidence interval of 0.72 to 0.84; P < 0.001). In subgroup analysis based on the background factors, the PFS rate was generally better in the CAB group in all risk subgroups except for those having significant risk factors. Conclusion: Propensity score matching analysis revealed the prolongation of PFS by CAB in prostate cancer patients without significant risk factors. It would possible to decide the type of the first‐line ADT according to the prostate cancer risk. Propensity score matching analysis using community‐based multi‐institutional database across Japan revealed that combined androgen blockade achieved better oncological outcome in androgen deprivation therapy for prostate cancer. [ABSTRACT FROM AUTHOR]

In recent years, microRNAs (miRNAs) have emerged as promising biomarkers for PCa diagnosis and prognosis. miR-2909 is a novel miRNA that can regulate immunogenomics and oncogenomics. The present study investigated the role of miR-2909 in the pathogenesis of PCa and the potential signalling pathways through which it operates. We have identified miR-2909 as a novel mediator of androgen/androgen receptor (AR) signalling that enhances the proliferation potential of PCa cells and assists in cancer survival under reduced androgen levels. Our results revealed that miR-2909 down regulates TGFBR2 by targeting its 3′-UTR sequence. We also observed that miR-2909 over-expression attenuated TGFβ-mediated SMAD3 activation, cell growth inhibition and apoptosis. Moreover, miR-2909 modulated the expression of p21CIP, c-MYC and CCND1 through TGFβ signalling. Importantly, we also demonstrated that miR-2909 and AR regulates each other's expression resulting in a positive feedback loop. In conclusion, our study suggests that miR-2909 is an androgen-inducible miRNA that exerts its oncogenic effects by attenuating the tumor-suppressive effects of TGFβ signalling. [ABSTRACT FROM AUTHOR]

The increasing knowledge of prostate cancer is leading to many questions about its natural history and to reconsider conventional therapeutic strategies. Androgen ablation therapy has been the standard therapy in the advanced setting. Although docetaxel has demonstrated increased survival in patients with metastatic prostate cancer who had progressed to hormone treatments, due to its potential toxicity the role of chemotherapy has been relegated to patients who were symptomatic or who had high tumor burden. Several studies have assessed whether docetaxel could have a role in hormone-sensitive disease or even in earlier stages with no distant metastases. In the CHAARTED and STAMPEDE studies, docetaxel provides an unprecedented increase in overall survival (OS). This review summarizes the evidence behind the paradigm shift to strengthening docetaxel as a new standard of treatment that prolongs survival in earlier stages of prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Evidence in favor of adding docetaxel in treatment of metastatic hormone-sensitive prostate cancer (mHSPC) has led to docetaxel in conjunction with androgen deprivation therapy (ADT) as standard therapy. The aim of this study was to examine the effectiveness of docetaxel with ADT for Korean patients with mHSPC in real-world practice., Materials and Methods: A retrospective cohort study was performed at six Korean hospitals for patients with mHSPC treated with docetaxel plus ADT. Patients were treated every 3 weeks for up to six cycles with 75 mg/m² of docetaxel. The primary endpoint was time to castration resistant prostate cancer (CRPC)., Results: This study included 46 eligible patients from June 2016 to February 2021. Median age was 68.5 years (range, 52-84) and all patients present with de novo M1 with high-volume disease. The median prostate-specific antigen (PSA) level at ADT initiation was 205.4 (7.7-1933) ng/mL, and time from ADT to docetaxel was 2.4 months (0-5.3). All six planned cycles of docetaxel were delivered in 36 patients (78%), 7 patients (15%) discontinued treatment due to adverse events, and 3 patients (7%) discontinued due to progression. At the time of the analysis, CRPC had developed in 34 patients (74%), and the median time to CRPC was 18.0 (95% confidence interval, 14.1-21.9) months. PSA <0.2 ng/mL was achieved in 11 patients (24%) after 6 months of ADT and in 10 patients (22%) after 12 months. At last follow-up, 35 patients (76%) were alive; the median overall survival was not reached., Conclusion: The effect of docetaxel combined with ADT for Korean patients with mHSPC is comparable with prior results in Western studies., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

There have been numerous new findings from clinical trials in recent years regarding the treatment of metastatic hormone-sensitive or castration-resistant prostate cancer. The newly approved treatment options make therapy planning and therapy sequencing more challenging. In addition, local therapy of metastatic prostate cancer is becoming increasingly important. In the new German guidelines on prostate cancer (version 6.2, October 2021), new developments in the recommendations for the treatment of mHSPC and mCRPC were implemented, and their most important resulting recommendations for the clinical practice are presented in this review., (© 2022. The Author(s).)

Ever since the critical role of androgen deprivation therapy for the treatment of metastatic prostate cancer was established, several trials aimed to show an improved outcome with the early introduction of chemotherapy in metastatic disease. Until recently, all these trials-including the GETUG-AFU 15 trial-failed to confirm an improvement in survival. The recently published CHAARTED and STAMPEDE trials showed a striking benefit and changed the standard of care for patients with newly diagnosed metastatic prostate cancer. We summarize the evidence that emerged from these trials that support the use of combined chemohormonal therapy in metastatic hormone-sensitive prostate cancer. [ABSTRACT FROM AUTHOR]

Docetaxel plus androgen deprivation therapy (ADT) offers a survival benefit in metastatic hormone-sensitive prostate cancer (mHSPC). However, one trial evaluating docetaxel in mHSPC (GETUG-AFU15) showed unexpected toxicity; raising concerns that docetaxel may carry increased toxicity when used to treat mHSPC compared to metastatic castration-resistant prostate cancer (mCRPC). We conducted a retrospective analysis evaluating differences in toxicity based on the clinical state (i.e., mHSPC vs. mCRPC) that docetaxel was used. Patients initiating docetaxel between 1/1/2014 and 7/15/2015 were included, with the former date chosen to coincide with the press release for the first mHSPC study that showed a survival benefit with early docetaxel; ensuring contemporary docetaxel-treated cohorts. Thirty-nine mCRPC and 22 mHSPC patients were included. Compared to mCRPC, mHSPC patients were younger (median years: 66.3 vs. 71.8, P = 0.007); had better performance status (ECOG 0-1: 100 vs. 62 %, P < 0.0001); and used opiates less frequently (29 vs. 66 %, P = 0.04). Neutropenic fevers occurred in 9 and 5 % ( P = 0.95) of men with mHSPC and mCRPC, respectively. Other toxicities also occurred at similar rates between cohorts. The incidence of any toxic event was 73 and 67 % ( P = 0.84) for men with mHSPC and mCRPC, respectively. Within the mHSPC cohort, neutropenic fevers occurred at a similar rate regardless of the time interval between initiating ADT and the start of docetaxel. We did not observe a significant difference in toxicity between mHSPC and mCRPC patients receiving docetaxel. However, the small sample size and retrospective nature of this study limit our ability to draw definitive conclusions. [ABSTRACT FROM AUTHOR]