Current Opinion in Urology最新文献

Purpose of review: Advanced prostate cancer (PCa) is still dependent on the androgen receptor (AR) pathway, which has led to the development of new compounds - beyond androgen receptor pathway inhibitors (ARPIs) currently used in clinical practice - and that are able to overcome acquired resistance through AR mutations, splice variants or amplifications. With these new drugs, novel toxicities occur with new challenges for both patients and physicians. This narrative review aims to report and discuss emergent and/or related adverse events associated with these new hormonal therapies.

Recent findings: Adrenal insufficiency-like events and cardiac disorders were the main specific adverse events associated with these new hormonal therapies for advanced PCa. Different profiles of toxicities were also related to either combination of these drugs with usual ARPIs or to compounds with multiple effects on AR pathway, mainly AR antagonism.

Summary: As these new treatments are still under development, physicians need to keep up-to-date with potential emerging toxicities and manage acute and long-term toxicities.

Purpose of review: Infertility affects approximately 15% of couples, with male factors implicated in more than 50% of cases. Concerns over declining semen quality - evidenced by a more than 50% drop in sperm concentration over four decades - have triggered investigation into modifiable lifestyle and environmental factors. This review summarizes recent evidence on exposures that negatively impact male fertility.

Recent findings: Smoking increases sperm DNA fragmentation (SDF) by approximately 10% and alters hormonal profiles; e-cigarettes may carry similar risks. Chronic alcohol use raises SDF by a comparable magnitude, disrupts the hypothalamic-pituitary-gonadal axis, and may cause testicular atrophy. Obesity impairs spermatogenesis through aromatase-mediated hormonal imbalance and inflammation; and even modest weight loss improves sperm parameters. Drug use - particularly steroids, cannabis, and opioids - may also suppress fertility. Environmental exposures such as heat waves, fine particulate matter, and endocrine-disrupting chemicals reduce semen quality and can contribute to testicular dysgenesis. Conversely, adherence to certain diets, antioxidant supplementation modestly improves sperm quality and reduce SDF.

Summary: Lifestyle and environmental factors significantly impair male reproductive health through hormonal disruption, oxidative stress, and direct germ cell damage. These risks are common and often reversible. Identifying and modifying such exposures is essential for improving fertility outcomes and reducing long-term health burdens.

Purpose of review: There is an increasing interest in developing bladder sparing therapies (BSTs) for patients with Bacillus Calmette-Guérin unresponsive (U-BCG) nonmuscle invasive bladder cancer (NMIBC) as an alternative to radical cystectomy (RC). We aimed to perform a review of efficacy and safety of intravesical chemotherapy combination treatments for U-BCG NMIBC patients according to the most recent evidence.

Recent findings: The use of intravesical chemotherapy combination treatments for U-BCG patients has shown promising efficacy and tolerability especially in retrospective series. For U-BCG patients, the most used option in this context is intravesical gemcitabine plus docetaxel, with a 2-year recurrence free-survival ranging between 37-62%, and a 2-year progression free-survival rate of 70-95%, with grade 3-5 adverse events (AEs) varying between 3-8% according to the most recent reports. Other studies are investigating the combination of more than two chemotherapy agents, with a recent prospective trial showing encouraging results for the combination of three intravesical drugs (gemcitabine, cabazitaxel, cisplatin) with a cystectomy-free survival rate of 97% at 1-year and no evidence of grade 3-5 AEs at a median follow-up of 20 months.

Summary: Recent evidence on intravesical chemotherapy combination treatment for U-BCG NMIBC is mostly based on retrospective studies, especially those investigating gemcitabine/docetaxel. However, some studies are currently investigating the combination of more than two chemotherapy agents. Overall, studies show good short-term efficacy, acceptable rates of disease progression, and tolerability in patients with U-BCG NMIBC. Nevertheless, prospective studies will be needed to support the widespread use of new BSTs as valid alternatives to RC in patients who failed BCG.

Purpose of review: Gene therapy has emerged as an attractive bladder-sparing strategy for patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC), addressing a therapeutic gap for those ineligible for or declining radical cystectomy. This review aims to describe the recent advances in gene-mediated therapies for BCG-unresponsive NMIBC.

Recent findings: The bladder's unique anatomy with direct intravesical access and capacity for high local exposure with minimal systemic absorption provides an ideal context for gene delivery. Advances in barrier modulation with Syn3 and vector engineering have enabled efficient delivery. Adenoviral vectors as illustrated by the FDA-approved nadofaragene firadenovec (Adstiladrin), and other platforms, such as the conditionally replicating oncolytic adenoviruses (cretostimogene, CG0070), are maturing. Combination regimens of gene therapy and immune checkpoint inhibitors have shown additive or synergistic activity, deepening durability of gene therapy. Novel advancements including urinary and plasma tumor DNA are emerging as predictive biomarkers to guide patient selection, monitor minimal residual disease, and trigger early salvage.

Summary: Gene-mediated therapy is gradually advancing NMIBC care, with expanding indications and potent combinations positing itself to improve bladder preservation and long-term outcomes.

Purpose of review: This review examines the interplay between environmental changes and urology. While there is widespread recognition of the large impacts of climate change on population health, there are specific ways in which climate change will impact urologic cares. In this article, we will review categories and pathways by which climate change will impact care and briefly discuss opportunities for climate change mitigation.

Recent findings: Recent literature highlights how the epidemiology of urological diseases is influenced by climate change, explaining the underlying mechanisms driving these changes. Climate change impacts urological disease through mechanisms that can be classified as first-order, second-order, and third-order effects. Whereas first-order effects are direct impacts of climate change on urologic diseases, second-order effects are situations where climate change affects more proximate risk factors for urologic disease (such as indentation of water supplies with carcinogenic chemicals after hurricanes), third-order impacts are situations where climate change and its effects limit the medical systems' ability to treat patients.

Summary: Although the effects of climate change on urologic care are complex and wide ranging, efforts to identify and categorize these effects will be critical in order to adapt to climate change and to mitigate its effects.

Purpose of review: Antibody-drug conjugates (ADCs) have recently emerged as a promising targeted therapeutic strategy in urothelial carcinoma, and their application in nonmuscle invasive bladder cancer (NMIBC) is an evolving frontier. This review is timely as it synthesizes recent advances in ADC development for NMIBC, addressing critical unmet needs among both Bacillus Calmette-Guérin (BCG) naïve high-risk and BCG-unresponsive patients.

Recent findings: The literature reveals that ADCs that target HER2, Trop-2, Nectin-4 are under active investigation. Several retrospective and prospective studies have reported encouraging complete response rates, durable event-free survival, and manageable safety profiles with these agents. Current clinical trials are evaluating ADCs as monotherapy or in combination with immune checkpoint inhibitors (e.g., durvalumab, tislelizumab) and intravesical therapies, aiming to refine dosing regimens and maximize therapeutic efficacy.

Summary: The findings underscore the potential of ADCs to revolutionize NMIBC management by providing novel bladder-sparing strategies in patients traditionally limited by BCG failure. Future research should concentrate on optimizing patient selection, treatment sequencing, and combination strategies to improve long-term outcomes, enhancing survival and quality of life.

Purpose of review: The purpose of this narrative review is to compile the latest available evidence on targeted therapy in the management of Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC).

Recent findings: Several recent studies have reported promising results for anti-fibroblast growth factor receptor (FGFR) (erdafitinib) in patients with advanced or metastatic urothelial carcinoma with FGFR alterations. These findings support the exploration of targeted therapies, including tyrosine kinase inhibitors (anti-FGFR and anti-vascular endothelial growth factor (VEGF)), mTOR inhibitors, and EpCAM inhibitors at an earlier stage of the disease to avoid or delay radical cystectomy.

Summary: The THOR-2 study demonstrated promising results for oral Erdafitinib in 73 high-risk BCG-unresponsive pTa/pT1 patients, showing 6 and 12-month recurrence-free survival rates of 96 and 77%, respectively. However, it was associated with notable adverse events (100%, including 22% serious). Other targeted therapies, such as Dovitinib (FGFR inhibitor), Sunitinib (VEGF inhibitor), and Everolimus (mTOR inhibitor), were assessed in three phase II studies, yielding disease-free survival rates between 8 and 44% over 3-12 months. Additionally, in a recent phase 3 trial involving 134 patients with BCG-unresponsive NMIBC, Oportuzumab Monatox (an EpCAM inhibitor) demonstrated a complete response rate of 40% at 3 months and a median response duration of 9.4 months.

Purpose of review: This review aims to highlight the often-overlooked environmental impact of medical imaging in urological practice, focusing on energy consumption, associated carbon emissions, and practical strategies for reducing the carbon footprint of imaging modalities.

Recent findings: Medical imaging accounts for a significant proportion of a hospital's total energy use, with MRI, CT, and PET-CT being the most energy-intensive modalities. A recent life cycle assessment found that energy usage accounted for over half of a radiology department's greenhouse gas (GHG) emissions. Imaging systems such as fluoroscopy and ultrasound also contribute meaningfully, particularly when idle power consumption is overlooked. New data reveal that simple interventions, such as shutting down imaging devices during nonoperational hours and reducing unnecessary imaging, can cut nonoperational energy use by 20-70%.

Summary: Given the slow adoption of energy-efficient imaging systems due to long development cycles, immediate emission reductions must come from operational changes. Strategies such as optimizing scheduling, shortening protocols, reduction of low-value imaging and powering down unused equipment can significantly reduce carbon emissions and costs - without compromising diagnostic value. Collaboration between referring clinicians and radiologists is critical to driving this transition.

Purpose of review: Increases in wealth, scientific knowledge, and resources have contributed to unprecedented improvements in overall and urologic health over the past century. However, anthropogenic greenhouse gas emissions driving these advancements are a primary driver of climate change, including a substantial share contributed from the healthcare industry itself. Reducing resource-intensive processes in urologic care has been proposed to support environmental sustainability but these initiatives could conflict with economic forces that drive progress in biomedical innovation. Paradoxically, such strategies may also have unintended consequences for human health by slowing the pipeline or scientific discovery or delivery of treatment. A balanced approach can prioritize the elimination of low-value services in order to enhance care value while simultaneously reducing environmental waste and resource consumption. In this review, we examine strategies that seek to align environmental and economic forces in urologic care delivery within a market-influenced healthcare system.

Recent findings: Strategies to reduce low-value urologic care, including decreased reliance on single-use items, reducing use of the operating room when feasible, and judicious use of resource-intensive research methods, have potentially favorable environmental impacts. A maturing body of research has examined ways in which reductions in low-value services can be incorporated into clinical practice without compromising quality, safety, and patient outcomes.

Summary: Sustainability efforts in urology can be aligned with economic realities to be effective and scalable. Strategies that reduce environmental impact should consider cost, local market, and incentives within existing healthcare systems. Aligning ecological responsibility with economic value ensures that sustainable practices can be adopted without slowing clinical progress.