Rapidly dissolving microneedle patch embedded with long-acting microspheres for sustained release of goserelin.

Androgen deprivation therapy (ADT) has been a pillar in the management of prostate cancer (PCa) since the 1940s and remains a standard of care across different clinical scenarios of PCa. Gonadotropin-releasing hormone (GnRH) agonists are the most commonly used form of ADT because they have consistently proven to be effective. The arrival of GnRH antagonists, such as degarelix and relugolix, has introduced an alternative to agonists while offering distinct advantages. Antagonists achieve the rapid suppression of testosterone without the initial flare effect observed with agonists. Relugolix, an oral antagonist, has been reported to result in the rapid recovery of normal testosterone levels after treatment discontinuation and may be associated with a potentially lower cardiovascular (CV) risk than agonists. Moreover, antagonists provide an additional therapeutic option that enables an individualised treatment approach, aligning with the growing emphasis on personalised medicine. However, evidence regarding the superiority of antagonists over agonists in terms of clinical outcomes or side effects remains limited and, in some cases, contradictory. The effectiveness of antagonists, particularly in sustaining long-term testosterone suppression, and their safety profile, especially in relation to CV risks, remain debated. Although early studies indicate potential advantages, current clinical evidence is still evolving and requires further validation. This narrative review of the literature aims to provide a comprehensive update on the role of antagonists in PCa management, highlighting their potential benefits and limitations while addressing existing controversies. Despite the apparent advantages of antagonists, long-term prospective studies must be conducted to confirm their efficacy and safety, particularly when combined with other therapies, and to define their role across different disease stages.

Slow zoledronic acid releasing testis prostheses in the treatment of prostate cancer patients with bone metastases

• To assess the rationale, efficacy, and morbidity of various methods of achieving focal prostatic ablation. • To determine the current role of focal therapy in the management of localized prostate cancer. • We performed a literature review of focal therapy in prostate cancer, with an emphasis on more established methods such as cryoablation and high-intensity focused ultrasound. • Focal ablative methods allow targeted destruction of prostatic tissue while limiting the morbidity associated with whole-gland therapy. • Local cancer control after focal therapy appears promising but does not approach that of established whole-gland therapies. • Until we have the ability to identify patients reliably with truly focal disease and predict their natural history, focal therapy cannot be considered to be the definitive therapy for localized prostate cancer.

Transdermal Oestradiol in the Management of Castration-resistant and Corticosteroid-resistant Prostate Cancer — a Dose Escalation Study

Prostate cancer predominantly affects older men, with a median age at diagnosis of 68 years. Due to the increased life expectancy, management of prostate cancer in senior adults (aged >70 years) represents a major public health problem. This patient population may not receive optimal therapy for their disease, if decisions are made based on their chronological age alone. More so than age alone, health status is a major factor affecting individual life expectancy. Comorbidity is the key predictor of health status and should weigh more heavily on the treatment decision than age alone. Other important parameters to consider in senior adults are the degree of dependence in activities of daily living, the nutritional status and the presence or not of a geriatric syndrome. Although clinical trials are rarely designed specifically for senior adults, evidence suggests that healthy senior adults have similar treatment outcomes to their younger counterparts. The urological approach in senior adults with advanced prostate cancer should be fundamentally the same as in younger patients. In hormone-sensitive metastatic prostate cancer, androgen deprivation represents the first-line treatment. In senior adults, care should be given to the increased risk of metabolic syndrome, cardiovascular mortality and bone fracture. In hormone-refractory metastatic prostate cancer, chemotherapy with docetaxel (75 mg/m(2) every 3 weeks) plus low-dose prednisone is the standard and shows the same efficacy in healthy senior adults as in younger patients. The tolerance of docetaxel (3-weekly schedule) has not been specifically studied in vulnerable and frail senior adults. The place of weekly docetaxel in this setting should be further evaluated. Palliative treatments (palliative surgery, radiopharmaceutics, radiotherapy, medical treatments for pain and symptoms, pharmacological palliative therapies) should also be integrated in the global management of these patients. In conclusion, treatment decisions in senior adults should be adapted to health status. Healthy senior adults should be treated the same as younger patients. The development of guidelines for the management of localized and advanced prostate cancer in senior adults is underway.

The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

To investigate the impact of virtual reality (VR) technologies on urological surgeries, specifically in the management of prostate cancer and renal cancer. A non-systematic review of the literature was performed. Medline, Pubmed, and the Cochrane Database were screened for studies regarding the use of VR technologies in the management of prostate and renal cancer. In the management of prostate cancer, VR technologies have been increasingly applied for diagnosis with magnetic resonance imaging/ultrasound fusion biopsy, surgical training using a simulator, surgical navigation in robot-assisted radical prostatectomy, and targeted focal therapy. In partial nephrectomy, surgical simulation and intra-surgical guidance with three-dimensional VR have been used for better understanding of thehilar vascular information, tumor location,and positional relationships of the tumor-feeding vessel and pyelocaliceal system. VR contributes to the education, training, and simulation of surgical procedures as well as helping the surgeonsto tailor surgical planning oneach patient. Further prospective studies are needed to assess the beneficial impacts of this technology for both the physician and patient by objective parameters.

Decentralized manufacture of thermostable mRNA vaccines in a microneedle patch (MNP) format could enhance vaccine access in low-resource communities by eliminating the need for a cold chain and trained healthcare personnel. Here we describe an automated process for printing MNP Coronavirus Disease 2019 (COVID-19) mRNA vaccines in a standalone device. The vaccine ink is composed of lipid nanoparticles loaded with mRNA and a dissolvable polymer blend that was optimized for high bioactivity by screening formulations in vitro. We demonstrate that the resulting MNPs are shelf stable for at least 6 months at room temperature when assessed using a model mRNA construct. Vaccine loading efficiency and microneedle dissolution suggest that efficacious, microgram-scale doses of mRNA encapsulated in lipid nanoparticles could be delivered with a single patch. Immunizations in mice using manually produced MNPs with mRNA encoding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain stimulate long-term immune responses similar to those of intramuscular administration.

Rapid progress in diagnostics and therapeutics for the management of prostate cancer (PCa) has created areas where high-level evidence to guide practice is lacking. The Genitourinary Research Consortium (GURC) conducted its second Canadian consensus forum to address areas of controversy in the management of PCa and provide recommendations to guide treatment. A panel of PCa specialists discussed topics related to the management of PCa. The core scientific committee finalized the design, questions, and analysis of the consensus results. Attendees then voted to indicate their management choice regarding each statement/topic. Questions for voting were adapted from the 2019 Advanced Prostate Cancer Consensus Conference. The thresholds for agreement were set at ≥75% for "consensus agreement," >50% for "near-consensus," and ≤50% for "no consensus." The panel was comprised of 29 PCa experts, including urologists (n=12), medical oncologists (n=12), and radiation oncologists (n=5). Voting took place for 65 predetermined questions and three ad hoc questions. Consensus was reached for 34 questions, spanning a variety of areas, including biochemical recurrence, treatment of metastatic castration-sensitive PCa, management of non-metastatic and metastatic castration-resistant PCa, bone health, and molecular profiling. The consensus forum identified areas of consensus or near-consensus in more than half of the questions discussed. Areas of consensus typically aligned with available evidence, and areas of variability may indicate a lack of high-quality evidence and point to future opportunities for further research and education.

IntroductionProstate cancer, a major global health issue, necessitates early and precise detection for effective management. Traditional diagnostic methods like DRE, PSA tests, and biopsies have drawbacks in accuracy and safety....

Perindopril Erbumine is a widely used angiotensin-converting enzyme (ACE) inhibitor for managing hypertension and cardiovascular diseases. Its dual action of lowering blood pressure and mitigating inflammation makes it a cornerstone treatment in these conditions. However, its oral administration often results in suboptimal bioavailability and gastrointestinal side effects. This study aimed to develop and characterize a dissolving microneedle (dMN) patch for the transdermal delivery of Perindopril Erbumine to enhance therapeutic efficacy and patient compliance. A Perindopril Erbumine-loaded microneedle patch was fabricated using chitosan and polyvinyl alcohol (PVA) using the solvent casting method. The microneedle patch was evaluated for physical properties, mechanical strength, drug loading, and moisture content. Ex-vivo permeation through rat skin and in-vivo pharmacokinetic studies in rabbits was conducted to compare its performance with a marketed oral Perindopril Erbumine formulation. The developed patch demonstrated effective skin penetration, controlled drug release, and a six-fold enhancement in cumulative drug permeation (82.45% ± 1.54) compared to the oral solution (14.32% ± 1.60). The pharmacokinetic study revealed prolonged drug release, with a 7.9-fold increase in half-life (7.739 ± 0.243h vs. 0.986 ± 0.93h) and a significantly higher area under the curve (AUC) for the microneedle patch. Skin irritation studies confirmed the biocompatibility of the formulation, with no significant adverse effects observed. These findings highlight the potential of Perindopril Erbumine-loaded dissolving microneedles as a promising transdermal delivery system for improved therapeutic outcomes in managing hypertension and inflammation-related vascular conditions, potentially reducing inflammation through enhanced and targeted drug delivery.

A Critical Review of Clinical Practice Guidelines for the Management of Clinically Localized Prostate Cancer

Until recently, open radical prostatectomy was the only approach for the surgical management of prostate cancer. Laparoscopy is now increasingly used as an alternative approach. The procedure can be performed directly or with robot assistance. We review the relevant literature regarding oncologic and functional outcomes with laparoscopic surgery in the management of localized prostate cancer. Oncologic and functional outcomes are similar between open and laparoscopic radical prostatectomy. Pure laparoscopic prostatectomy and robotic assisted laparoscopic prostatectomy result in less blood loss and shorter convalescence. Costs associated with the initial investment, disposables, and maintenance of the robot system are higher than for pure laparoscopic prostatectomy. Laparoscopic radical prostatectomy, either pure or robotic, is becoming the preferred approach for the surgical management of localized prostate cancer. Oncologic and functional outcomes are similar to the open approach.

Data are limited on prostate cancer (PC) management in patients with haemophilia (PWH). To describe PC screening and diagnosis, treatment modalities and bleeding complications in a group of unselected PWH followed at French Haemophilia Treatment Centres (HTCs) PATIENTS AND METHODS: PC screening, management and bleeding complications were retrospectively investigated at 14 French HTCs between 2003 and 2018. Among> 1549>50-year-old PWHs, 73 (4.7%) underwent PC screening (median age 71.1 years; 67/6 HA/HB, 17/56 severe-moderate/mild). At diagnosis, haematuria was infrequent. Prophylaxis was administered during 76/86 (88%) prostate biopsies (PB) (n=67 clotting factor concentrates, CFC; n=9 desmopressin; n=17 associated with tranexamic acid, TA). Bleeding (11/86, 12.8%) occurred mainly post-prophylaxis (median delay: 7 days): haematuria (9/11, 81.8%), and rectal bleeding (2/11, 18.2%) including one major (1.2%). PC was confirmed in 50/86PB and in two prostatectomy specimens (total n=50 patients, n=6 with only active surveillance). Surgery (n=28/44 patients) was managed with CFC. Fifteen patients had radiotherapy/brachytherapy, 10 had hormone therapy; CFC-based prophylaxis was only prescribed for brachytherapy (n=2). Major bleedings occurred in 3/28 (10.7%) and 2/15 (13.3%) patients who underwent surgery and radio/brachytherapy, respectively. No bleeding risk factor was found. Our data indicate that PB requires prophylaxis for atleast 7 days, using CFC, desmopressin or TA in function of haemophilia severity. PC surgery should be considered at high bleeding risk. Long-term post-procedural CFC or oral TA could be discussed. Radiotherapy/brachytherapy also should be managed with prophylaxis (CFC orTA).

Multiparametric MRI (mpMRI) of the prostate is an evolving technology that provides functional information of the prostate that helps distinguish benign from malignant lesions. We hypothesized that mpMRI is rapidly adopted in the US to fill the unmet need for a non-invasive, accurate screening tool. The aim of this study is to assess the increasing utilization of mpMRI for the diagnosis and management of prostate cancer. We conducted a retrospective review of an institutional clinical data repository of four million patients. Clinical information from all men undergoing mpMRI from October 2013 to December 2015 was collected in a prospectively designed database. Individual chart reviews were performed for each patient. 1521 mpMRI of the prostate were performed with an increase in the use of 486% over 26months. The most common indication for mpMRI was abnormal screening (64%) and 47% of these men went on to prostate biopsy, either by cognitive mapping (65%) or MRI-US fusion targeting (35%). 261 men elected to defer prostate needle biopsy after informative decision-making with their urologist. 12.7% of mpMRI were performed for active surveillance, 7.5% for clinical staging, and 3.2% by radiation oncologists planning radiotherapy. 7% of mpMRI were performed to evaluate the pelvis for biochemical recurrence, a third of which identified a region of suspicion for targeted. Prostate mpMRI is increasingly performed for both the diagnosis and management of prostate cancer. As clinical utilization increases along with the diffusion of technology and radiologic expertise, MpMRI has the potential to influence clinical decision-making and fulfill the need for a non-invasive, accurate tool for the diagnosis and management of prostate cancer.