OBJECTIVE: Androgen receptor inhibitors (ARIs) have become an effective treatment for advanced prostate cancer (PC). However, it is unknown which ARI is the most helpful and safe for men with advanced PC. Our aim is to help physicians make clinical decisions and provide medication guidelines for patients with advanced PC to avoid potential risks when using ARIs for treatment.
METHODS: We systematically searched the following databases: PubMed, Embase and Cochrane Library, with a literature publication deadline of February 2023. The primary efficacy outcomes were 18-month overall survival (OS), treatment-emergent adverse events (TEAEs), hypertension and fatigue. The network meta-analysis (NMA) was performed by Stata 15.1, and Revman 5.3 was used to assess the included studies\' risk of bias.
RESULTS: The analysis included 26 trials with 26 263 people. The surface under the cumulative ranking curve (SUCRA) concluded that enzalutamide (86.8%) showed the best effect in prolonging the OS of patients. Flutamide led to the highest risk of TEAEs (29.9%) and AEs leading to discontinuation (12.8%). Apalutamide (13.4%) led to the highest risk of grade ≥3 TEAEs. Enzalutamide had the highest risk of hypertension (0.2%), grade ≥3 hypertension (4.5%) and fatigue (5.2%).
CONCLUSIONS: This NMA indicates there is no one ARI to reach both the most effective and safe therapy aims for treating advanced PC and that there is a compromise between the efficacy and safety of ARIs in the treatment of advanced PC. Physicians should weigh the risks to safety against the anticipated benefits when prescribing these drugs to patients with PC.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

OBJECTIVE: The study aimed at investigating prostate cancer patients\' choice of androgen deprivation treatment (ADT) and possible factors that would affect their preferences of ADT.
METHODS: This was a single-centre cross-sectional study investigating the usage and preferences of ADT. Consecutives prostate cancer patients who were receiving injectable luteinizing hormone-releasing hormone (LHRH) agonist or antagonist were recruited from the prostate cancer clinic in a tertiary academic hospital. Patients who received bilateral orchidectomy or those who could not consent to the study were excluded. Disease characteristics, treatment information and patient background were documented. The survey collected information related to their change in ADT regimen, preferences on drug usage (routes and frequency of administration) and their reasons. A hypothetical set of three drug formularies was designed. Questions regarding patient preference and the contributing reasons raised in the format of questionnaire.
RESULTS: 100 patients completed the survey. Most patients started with more frequent injections (3-monthly, 54%; 1-monthly, 38%) and switched to 6-monthly injections (89%) at the time of the survey. Primary reasons for the change were healthcare opinion (72%) and less frequent treatment (51%). Three options of ADT (oral daily, 1-monthly and 6-monthly injection) with the same efficacies and side effect profile were offered: 61% preferred 6-monthly injection, 1% preferred 1-monthly injection and 38% preferred oral regimen. When patients were informed of lower cardiovascular side effects in 1-monthly injection or daily oral drug, patients\' preference was 56% (6-monthly), 6% (1-monthly), and 39% (oral). Patients with polypharmacy (more than 5 regular medications) were more inclined to choose injections (p = 0.025). Patient age, educational background, employment status, marriage status and disease status were not found to be statistically significant contributing factors to patient preference.
CONCLUSIONS: 6-monthly ADT injection was the preferred ADT despite greater cardiovascular risks. Among 1-monthly or daily oral LHRH antagonist, more patients prefer oral option. Convenience factor was highly valued.

UNASSIGNED: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time.
UNASSIGNED: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes.
UNASSIGNED: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Prostate cancer (PCa) is a prevalent malignancy with increasing incidence in middle-aged and older men. Despite various treatment options, advanced metastatic PCa remains challenging with poor prognosis and limited effective therapies. Nanomedicine, with its targeted drug delivery capabilities, has emerged as a promising approach to enhance treatment efficacy and reduce adverse effects. Prostate-specific membrane antigen (PSMA) stands as one of the most distinctive and highly selective biomarkers for PCa, exhibiting robust expression in PCa cells. In this review, we explore the applications of PSMA-targeted nanomedicines in advanced PCa management. Our primary objective is to bridge the gap between cutting-edge nanomedicine research and clinical practice, making it accessible to the medical community. We discuss mainstream treatment strategies for advanced PCa, including chemotherapy, radiotherapy, and immunotherapy, in the context of PSMA-targeted nanomedicines. Additionally, we elucidate novel treatment concepts such as photodynamic and photothermal therapies, along with nano-theragnostics. We present the content in a clear and accessible manner, appealing to general physicians, including those with limited backgrounds in biochemistry and bioengineering. The review emphasizes the potential benefits of PSMA-targeted nanomedicines in enhancing treatment efficiency and improving patient outcomes. While the use of PSMA-targeted nano-drug delivery has demonstrated promising results, further investigation is required to comprehend the precise mechanisms of action, pharmacotoxicity, and long-term outcomes. By meticulous optimization of the combination of nanomedicines and PSMA ligands, a novel horizon of PSMA-targeted nanomedicine-based combination therapy could bring renewed hope for patients with advanced PCa.

To evaluate interreader agreement on pelvic multiparametric magnetic resonance imaging (mpMRI) interpretation among radiologists using a structured reporting tool based on the METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P) guidelines.
A structured report for follow-up pelvic mpMRI for advanced prostate cancer (APC) patients was formulated based on MET-RADS-P guidelines. In total, 163 paired pelvic mpMRI examinations were performed from December 2017 to February 2021 on 105 patients with APC. These were retrospectively reviewed by two senior and two junior radiologists for metastatic lesion detection and were categorized by these readers using primary/secondary response assessment categories (RACs), with and without the structured report. Interreader agreement regarding metastasis detection and RAC scores was evaluated with Cohen\'s kappa and weighted Cohen\'s kappa statistics (K), respectively.
The two senior radiologists showed higher agreement with the reference standard for metastasis detection using the structured report (S1: K = 0.83; S2: K = 0.73) compared with the conventional report (S1: K = 0.72; S2: K = 0.61). Junior radiologists showed similar results (J1: 0.66 vs. 0.59; J2: 0.65 vs. 0.57). The overall agreement between the two senior radiologists was excellent for the primary RAC pattern using the structured reports (K = 0.81) and was substantial for secondary RAC categorization (K = 0.75). The interreader agreement of the two junior radiologists was substantial for both primary and secondary RAC values (K = 0.76, 0.68).
Good interreader agreement was found for the follow-up assessment of APC patients between radiologists, where the pelvic mpMRI was reported using MET-RADS-P guidelines. This improvement applied to both metastatic lesion detection and qualitative RAC assessment.

UNASSIGNED: Prostatic arterial embolization (PAE) is an effective minimally invasive treatment for lower urinary tract obstruction and hematuria in patients with benign prostatic hyperplasia (BPH). This study was aim to evaluate the safety and short-term efficacy of drug epirubicin-loaded beads transarterial prostatic arterial chemoembolization (DEB-PACE) for the treatment of advanced prostate cancer (PC) with lower urinary tract obstruction or hematuria.
UNASSIGNED: A total of 8 patients with advanced PC undergoing DEB-PACE from August 2020 to February 2022 were retrospectively enrolled. The patients were followed up at 1 week, 1, 3, 6 and 12 months after DEB-PACE. The origin of prostatic arteries, technical success, clinical success rate, duration of the indwelling urinary catheter, International Prostate Symptom Score (IPSS), QoL score (quality of life), prostate volume (PV), prostate-specific antigen (PSA) level and complications were recorded. The short-term efficacy (changes in IPSS, PV and QoL value from baseline to 3 months) were analysed.
UNASSIGNED: There were 17 prostatic arteries in 8 patients, which mainly originated from internal pudendal artery (11/17, 64.7%), the technical success rate is 100%. After treatment, the symptoms of lower urethral obstruction in 8 patients were significantly improved that PSA, PV, IPSS and QoL level were significantly reduced. The catheter was successfully removed within 1 week on average, and 2 patients with hematuria disappeared within 5 days. The clinical success rate is 100%. At 1 month postoperatively, mean PV reduction was 30.28±6.963 cm3 (P=0.0457), mean IPSS reduction was 21.13±2.887 points (P=0.0042), mean QoL reduction was 3.75±0.366 points (P=0.006). At 3 months postoperatively, mean PV reduction was 46.14±8.906 cm3 (P=0.0112), mean IPSS reduction was 24.5±2.398 points (P=0.0003), mean QoL reduction was 4.25±0.25 points (P=0.0003). There were no serious complications occurred in all patients.
UNASSIGNED: DEB-PACE is a promising treatment for advanced PC with lower urinary tract obstruction or hematuria. However, the efficacy and safety of DEB-PACE for advanced PC is needed to validated by prospective large sample randomized controlled study.

Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but various areas of management still lack high-level evidence to inform clinical practice. The 2021 Advanced Prostate Cancer Consensus Conference (APCCC) addressed some of these questions to supplement guidelines that are based on level 1 evidence.
To present the voting results from APCCC 2021.
The experts identified three major areas of controversy related to management of advanced prostate cancer: newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), the use of prostate-specific membrane antigen ligands in diagnostics and therapy, and molecular characterisation of tissue and blood. A panel of 86 international prostate cancer experts developed the programme and the consensus questions.
The panel voted publicly but anonymously on 107 pre-defined questions, which were developed by both voting and non-voting panel members prior to the conference following a modified Delphi process.
The voting reflected the opinions of panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results reported in the Supplementary material.
These voting results from a panel of experts in advanced prostate cancer can help clinicians and patients to navigate controversial areas of management for which high-level evidence is scant. However, diagnostic and treatment decisions should always be individualised according to patient characteristics, such as the extent and location of disease, prior treatment(s), comorbidities, patient preferences, and treatment recommendations, and should also incorporate current and emerging clinical evidence and logistic and economic constraints. Enrolment in clinical trials should be strongly encouraged. Importantly, APCCC 2021 once again identified salient questions that merit evaluation in specifically designed trials.
The Advanced Prostate Cancer Consensus Conference is a forum for discussing current diagnosis and treatment options for patients with advanced prostate cancer. An expert panel votes on predefined questions focused on the most clinically relevant areas for treatment of advanced prostate cancer for which there are gaps in knowledge. The voting results provide a practical guide to help clinicians in discussing treatment options with patients as part of shared decision-making.

Advanced prostate cancer, harboring multiple mutations of tumor suppressor genes, is refractory to conventional therapies. Knockout of the Skp2 gene blocks pRb/p53 doubly deficient prostate cancer in mice, which inspired the authors to develop an approach for delivering siRNA that would efficiently silence Skp2 (siSkp2) in vivo. Here, a facile strategy is reported to directly assemble siSkp2 with the natural compound quercetin (Que) into supramolecular nanoparticles (NPs). This carrier-free siSkp2 delivery system could effectively protect siSkp2 from degradation in serum and enhance its cellular internalization. Furthermore, the siSkp2/Que NPs exhibit synergistic effects in Skp2 silencing, because they can degrade the mRNA and protein of Skp2 simultaneously. Indeed, siSkp2/Que NPs remarkably diminish the Skp2 abundance and further inhibit the proliferation and migration of TMU cells (RB1/TP53/KRAS triple mutations) in vitro. The in vivo results further show that i.v. administration of siSkp2/Que NPs efficiently accumulates in tumor sites and strongly inhibits the growth of TMU tumors in nude mice. Importantly, the siSkp2/Que NPs do not induce any abnormality in the treated mice, which suggests satisfactory biocompatibility. Collectively, this study describes a tractable siRNA self-assembled strategy for Skp2 silencing, which might be a promising nanodrug to cure multitherapy-resistant advanced prostate cancer.

OBJECTIVE: The aim of this study was to explore the diagnostic value of different fluorine-18 (18F)-labeled tracers for lymph node/bone metastasis and biochemical recurrence detection in advanced prostate cancer (PCa).
METHODS: PubMed, Embase, Web of Science, Cochrane databases, and the WHO International Clinical Trial Center were searched. The inclusion criteria were determined based on the Preferred Report Items of the Systematic Review and Meta-Analysis Guidelines. The Quality Assessment of Diagnostic Accuracy Studies-2 was used to assess the quality assessment of the included studies. The quantitative analysis of the included literature was performed on the patient and lesion basis, and the equivocal findings were considered negative or positive results, respectively.
RESULTS: Thirty-seven articles were included. On the patient basis, the pooled sensitivity and specificity of [18F]-labeled tracers were 0.80 (95% confidence interval [CI]: 0.78-0.83) and 0.89 (95% CI: 0.87-0.90) when equivocal results were considered to be positive and 0.80 (95% CI: 0.77-0.82) and 0.87 (95% CI: 0.85-0.89) when equivocal results were considered to be negative. On the lesion basis, the pooled sensitivity and specificity of [18F]-labeled tracers were 0.82 (95% CI: 0.80-0.83) and 0.91 (95% CI: 0.90-0.92) when equivocal lesions were regarded as positive and 0.81 (95% CI: 0.80-0.82) and 0.91 (95% CI: 0.90-0.92) when equivocal lesions were considered to be negative.
CONCLUSIONS: [18F]-labeled tracers have high diagnostic efficacy for lymph node/bone metastasis and biochemical recurrence in advanced PCa.