A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.

A Large-Scale Fabrication of Flexible, Ultrathin, and Robust Solid Electrolyte for Solid-State Lithium-Sulfur Batteries.

All-solid-state lithium metal batteries (ASSLMBs) are considered as the most promising candidates for the next-generation high-safety batteries. To achieve high energy density in ASSLMBs, it is essential that the solid-state electrolytes (SSEs) are lightweight, thin, and possess superior electrochemical stability. In this study, a feasible and scalable fabrication approach to construct 3D supporting skeleton using an electro-blown spinning technique is proposed. This skeleton not only enhances the mechanical strength but also hinders the migration of Li-salt anions, improving the lithium-ion transference number of the SSE. This provides a homogeneous distribution of Li-ion flux and local current density, promoting uniform Li deposition. As a result, based on the mechanically robust and thin SSEs, the Li symmetric cells show outstanding Li plating/stripping reversibility. Besides, a stable interface contact between SSE and Li anode has been established with the formation of an F-enriched solid electrolyte interface layer. The solid-state Li|sulfurized polyacrylonitrile (Li|SPAN) cell achieves a capacity retention ratio of 94.0% after 350 cycles at 0.5 C. Also, the high-voltage Li|LCO cell shows a capacity retention of 92.4% at 0.5 C after 500 cycles. This fabrication approach for SSEs is applicable for commercially large-scale production and application in high-energy-density and high-safety ASSLMBs.

Enhanced cellular therapy: revolutionizing adoptive cellular therapy.

Enhanced cellular therapy has emerged as a novel concept following the basis of cellular therapy. This treatment modality applied drugs or biotechnology to directly enhance or genetically modify cells to enhance the efficacy of adoptive cellular therapy (ACT). Drugs or biotechnology that enhance the killing ability of immune cells include immune checkpoint inhibitors (ICIs) / antibody drugs, small molecule inhibitors, immunomodulatory factors, proteolysis targeting chimera (PROTAC), oncolytic virus (OV), etc. Firstly, overcoming the inhibitory tumor microenvironment (TME) can enhance the efficacy of ACT, which can be achieved by blocking the immune checkpoint. Secondly, cytokines or cytokine receptors can be expressed by genetic engineering or added directly to adoptive cells to enhance the migration and infiltration of adoptive cells to tumor cells. Moreover, multi-antigen chimeric antigen receptors (CARs) can be designed to enhance the specific recognition of tumor cell-related antigens, and OVs can also stimulate antigen release. In addition to inserting suicide genes into adoptive cells, PROTAC technology can be used as a safety switch or degradation agent of immunosuppressive factors to enhance the safety and efficacy of adoptive cells. This article comprehensively summarizes the mechanism, current situation, and clinical application of enhanced cellular therapy, describing potential improvements to adoptive cellular therapy.

Unraveling Paradoxical Effects of Large Current Density on Zn Deposition.

Aqueous zinc-based batteries (ZBs) have been widely investigated owing to their intrinsic safety, low cost, and simple assembly. However, the actual behavior of Zn deposition under large current density is still a severe issue associated with obscure mechanism interpretation of ZBs under high loading. Here, differing from the conventional understanding that short circuit is induced by dendrite penetrating under large current density (10-100 mA cm-2), the separator permeation effect is unraveled to illustrate the paradox between smooth deposition and short lifespan. Generally, a dense plating morphology is achieved under large current density because of intensive nuclei and boosted plane growth. Nevertheless, in the scenes applying separators, the multiplied local current density derived from narrow separator channels leads to rapid Zn2+ exhaustion, converting the Zn deposition mode from nucleation control to concentration control, which eventually results in separator permeation and short circuit. This effect is validated in other aqueous metal anodes (Cu, Sn, Fe) and receives similar results. Based on the understanding, a micro-pore (150 µm) sponge foam is proposed as separators for large-current anodes to provide broader Zn2+ path and mitigate the separator permeation effect. This work provides unique perspectives on coordinating fast-charging ability and anode stability of ZBs.

Knowledge mapping of application of image-guided surgery in prostate cancer: a bibliometric analysis (2013-2023).

BACKGROUND: Image-guided surgery (IGS) refers to surgery navigated by medical imaging technology, helping doctors better clarify tumor boundaries, identify metastatic lymph nodes and preserve surrounding healthy tissue function. Recent studies have provided expectable momentum of the application of IGS in prostate cancer (PCa). The authors aim to comprehensively construct a bibliometric analysis of the application of IGS in PCa. METHOD: The authors searched publications related to application of IGS in PCa from 2013 to 2023 on the web of science core collection (WoSCC) databases. VOSviewer, CiteSpace, and R package 'bibliometrix' were used for bibliometric analysis. RESULTS: Two thousand three eighty-nine articles from 75 countries and 2883 institutions led by the United States were included. The number of publications related to the application of IGS in PCa kept high in the last decade. Johns Hopkins University is the top research institutions. Journal of Nuclear Medicine has the highest popularity as the selection of journal and co-cited journal. Pomper Martin G. had published the most paper. Ali Afshar-Oromieh was co-cited most frequently. The clinical efficacy of PSMA-PET/CT in PCa diagnosis and treatment are main topics in this research field, with emerging focuses on the use of fluorescence imaging guidance technology in PCa. 'PSMA' and 'PET/CT' are the main keywords as long-term research hotspots. CONCLUSION: This study is the first bibliometric analysis of researches on application of IGS in PCa with three recognized bibliometric software, providing an objective description and comprehensive guidance for the future relevant investigations.

Near-room-temperature water-mediated densification of bulk van der Waals materials from their nanosheets.

The conventional fabrication of bulk van der Waals (vdW) materials requires a temperature above 1,000 °C to sinter from the corresponding particulates. Here we report the near-room-temperature densification (for example, ∼45 °C for 10 min) of two-dimensional nanosheets to form strong bulk materials with a porosity of <0.1%, which are mechanically stronger than the conventionally made ones. The mechanistic study shows that the water-mediated activation of van der Waals interactions accounts for the strong and dense bulk materials. Initially, water adsorbed on two-dimensional nanosheets lubricates and promotes alignment. The subsequent extrusion closes the gaps between the aligned nanosheets and densifies them into strong bulk materials. Water extrusion also generates stresses that increase with moulding temperature, and too high a temperature causes intersheet misalignment; therefore, a near-room-temperature moulding process is favoured. This technique provides an energy-efficient alternative to design a wide range of dense bulk van der Waals materials with tailored compositions and properties.

Electrospun nanofibrous mats loaded with gemcitabine and cisplatin suppress bladder tumor growth by improving the tumor immune microenvironment.

The perplexing issues related to positive surgical margins and the considerable negative consequences associated with systemic chemotherapy have posed ongoing challenges for clinicians, especially when it comes to addressing bladder cancer treatment. The current investigation describes the production of nanocomposites loaded with gemcitabine (GEM) and cisplatin (CDDP) through the utilization of electrospinning technology. In vitro and in vivo studies have provided evidence of the strong effectiveness in suppressing tumor advancement while simultaneously reducing the accumulation of chemotherapy drugs within liver and kidney tissues. Mechanically, the GEM and CDDP-loaded electrospun nanocomposites could effectively eliminate myeloid-derived suppressor cells (MDSCs) in tumor tissues, and recruit CD8+ T cells and NKp46+ NK cells to kill tumor cells, which can also effectively inhibit tumor microvascular formation. Our investigation into the impact of localized administration of chemotherapy through GEM and CDDP-loaded electrospun nanocomposites on the tumor microenvironment will offer novel insights for tackling tumors.

Initial Experience with Hybrid Partial Nephrectomy with Ultrasound-guided Balloon Catheter Occlusion of the Renal Artery for Recurrent Renal Tumors.

Repeat partial nephrectomy (PN) is an effective treatment in improving the prognosis for patients with recurrent renal cancer after initial PN. However, salvage PN (sPN) is inevitably associated with a higher rate of complications, largely because of intraperitoneal adhesions and fibrosis. Here we describe three initial cases for which recurrent renal tumors were treated with a novel minimally invasive approach, namely Ultrasound-guided Renal Artery Balloon catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN).With laparoscopic ultrasound (LUS) guiding a Fogarty catheter to occlude the arterial blood supply, dissection of the renal hilum and most of the abdominal cavity can be avoided. UBo-HPN was successfully performed in three patients. One case of postoperative fever (Clavien-Dindo grade II) occurred, with no other complications. The mean operative time was 106 min, with a mean warm ischemia time of 21 min. UBo-HPN may be considered a safe and effective alternative for sPN, with a minimally invasive surgical footprint and better surgical outcomes.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

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.

Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression.

Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.

Ultrasound-guided paravertebral nerve block anesthesia for percutaneous endoscopic laser unroofing treatment of symptomatic simple renal cysts-An innovative ambulatory surgery mode.

Objective: This study was designed to evaluate the feasibility, efficacy, and safety of percutaneous ureteroscopy laser unroofing as an ambulatory surgery for symptomatic simple renal cysts under multilevel paravertebral nerve block anesthesia. Methods: From December 2015 to September 2017, 33 simple renal cyst patients who had surgical indications were enrolled. Under ultrasound guidance, the T10/T11, T11/T12, and T12/L1 paravertebral spaces were identified, and 7-10 mL 0.5% ropivacaine was injected at each segment. Then a puncture needle was placed inside the cyst cavity under ultrasonic monitoring. A guidewire was introduced followed by sequential dilation up to 28/30 Fr. The extra parenchymal portion of the cyst wall was dissociated and incised using a thulium laser, and a pathological examination was performed. Results: Sensory loss to pinprick from T8 to L1 and sensory loss to ice from T6 to L2 were observed in all patients. None of the patients complained of pain during surgery. No serious complications occurred perioperatively. After the surgery, all patients recovered their lower limb muscle strength quickly, got out of bed, resumed oral feeding, and left the hospital within 24 h of admission. The pathologic diagnosis of all cyst walls was a simple renal cyst. The mean follow-up was 35.8 months. At the end of follow-up, the cyst units were reduced in size by more than 50% compared to the preoperative size, and no patient experienced a recurrence. Conclusion: Multi-level paravertebral nerve block for percutaneous ureteroscopy laser unroofing as an ambulatory surgery mode is feasible, safe, and effective for the treatment of simple renal cysts in selected patients.

High fatigue resistance in a titanium alloy via near-void-free 3D printing.

The advantage of 3D printing-that is, additive manufacturing (AM) of structural materials-has been severely compromised by their disappointing fatigue properties1,2. Commonly, poor fatigue properties appear to result from the presence of microvoids induced by current printing process procedures3,4. Accordingly, the question that we pose is whether the elimination of such microvoids can provide a feasible solution for marked enhancement of the fatigue resistance of void-free AM (Net-AM) alloys. Here we successfully rebuild an approximate void-free AM microstructure in Ti-6Al-4V titanium alloy by development of a Net-AM processing technique through an understanding of the asynchronism of phase transformation and grain growth. We identify the fatigue resistance of such AM microstructures and show that they lead to a high fatigue limit of around 1 GPa, exceeding the fatigue resistance of all AM and forged titanium alloys as well as that of other metallic materials. We confirm the high fatigue resistance of Net-AM microstructures and the potential advantages of AM processing in the production of structural components with maximum fatigue strength, which is beneficial for further application of AM technologies in engineering fields.

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials.

BACKGROUND: Sex is an important factor influencing the immune system, and the distribution of tumors, including their types and subtypes, is characterized by sexual dichotomy. The aim of this study was to investigate whether there is an association between sex and the treatment effect of immune checkpoint inhibitors (ICI). METHODS: Four bibliographic databases were searched. Studies of randomized controlled trials (RCTs) assessing the efficacy of ICI were identified and used, and the primary endpoint was the difference in efficacy of ICI between males and females, presented as overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS). The study calculated the pooled HRs and 95% CIs for OS, PFS and RFS for males and females using a random effects model or a fixed effects model, and thereby assessed the effect of sex on the efficacy of ICI treatment. This study is registered with PROSPERO (CRD42022370939). RESULTS: A total of 103 articles, including a total of 63,755 patients with cancer, were retrieved from the bibliographic database, of which approximately 70% were males. In studies with OS as the outcome, the combined hazard ratio (HR) was 0.77 (95% CI 0.74-0.79) for male patients treated with ICI and 0.81 (95% CI 0.78-0.85) for female patients compared to controls, respectively. The difference in efficacy between males and females was significant. CONCLUSIONS: ICI therapy, under suitable conditions for its use, has a positive impact on survival in various types of tumors, and male patients benefit more than females. It may be necessary to develop different tumor immunotherapy strategies for patients of different sexes.

Evaluation of a novel circulation system for ureteroscopic laser lithotripsy in vitro.

PURPOSE: To evaluate the cooling effect and other advantages of a novel circulation system for ureteroscopic holmium laser lithotripsy (URSL) in a standardized in vitro model. MATERIALS AND METHODS: The novel circulation system was assembled by connecting a 4Fr ureteral catheter and a filter. Trails were divided into a new URSL group and a conventional URSL group. First, different power settings (18-30 W) of the holmium laser and irrigation flow rates (20-50 mL/min) were used to evaluate the thermal effect on the lithotripsy site of all groups. Then, renal pelvic temperature and pressure were assessed during URSL at a power of 1.5 J/20 Hz and irrigation flow rates of (20-50 mL/min). Finally, the whole process of lithotripsy was performed at 1.5 J/20 Hz (operator duty cycle ODC: 50%) with an irrigation flow rate of 30 mL/min. The time required for lithotripsy, visual field clarity, and stone migration were observed. RESULTS: Temperature of the lithotripsy point was significantly lower in the new URSL group than in the conventional group (P < 0.05) with irrigation rates (20, 30 mL/min). The renal pelvic pressure of the new group was significantly lower than that of the conventional group in which intrarenal hypertension developed at an irrigation rate of 50 ml/min. The new group had better visual clarity and lesser stone upward migration when lithotripsy was performed at 1.5 J/20 Hz and 30 ml/min. CONCLUSION: The novel circulation system is more effective in reducing the thermal effects of URSL, pelvic pressure, stone upward migration, and improving the visual clarity of the operative field.

Unraveling the Coupling Effect between Cathode and Anode toward Practical Lithium-Sulfur Batteries.

The localized reaction heterogeneity of the sulfur cathode and the uneven Li deposition on the Li anode are intractable issues for lithium-sulfur (Li-S) batteries under practical operation. Despite impressive progress in separately optimizing the sulfur cathode or Li anode, a comprehensive understanding of the highly coupled relationship between the cathode and anode is still lacking. In this work, inspired by the Butler-Volmer equation, a binary descriptor (IBD ) assisting the rational structural design of sulfur cathode by simultaneously considering the mass-transport index (Imass ) and the charge-transfer index (Icharge ) is identified, and subsequently the relationship between IBD and the morphological evolution of Li anode is established. Guided by the IBD , a scalable electrode providing interpenetrated flow channels for efficient mass/charge transfer, full utilization of active sulfur, and mechanically elastic support for aggressive electrochemical reactions under practical conditions is reported. These characteristics induce a homogenous distribution of local current densities and reduced reaction heterogeneity on both sides of the cathode and anode. Impressive energy density of 318 Wh kg-1 and 473 Wh L-1 in an Ah-level pouch cell can be achieved by the design concept. This work offers a promising paradigm for unlocking the interaction between cathode and anode and designing high-energy practical Li-S batteries.

A Novel Hydrodynamic Design Greatly Improves the Debris Clearance Rate of Flexible Ureteroscopy.

Objectives: To introduce a novel hydrodynamic design for a flexible ureteroscope that can increase stone debris clearance. Methods: Based on hydrodynamics, the new design allowed the ureteroscope to have six water jets. Fluid gushed from the six jets and would ultimately converge into an eddy. The safety and stone debris clearance efficiency were tested in a 3D-printed kidney model. Stone fragments between 0.5 and 1 mm were used to mimic the debris. A ureteroscope already approved for marketing was used as a control. Results: The new design did not change the local renal pressure and did not raise the whole renal pressure under irrigation at 80 or 100 mL/min but slightly raised it under irrigation at 120 mL/min. The pressures in the 2 g stone clearance procedures were 26.0, 33.1, and 37.5 cmH2O for the new design and 25.1, 30.2, and 39.3 cmH2O for the current design; in the 4 g stone clearance procedures, the pressures were 30.1, 37.2, and 40.0 cmH2O for the new design and 26.9, 30.8, and 39.8 cmH2O for the current design, all under conditions of 80, 100, and 120 mL/min irrigation, respectively. The new design significantly improved the stone clearance rate by ∼10-fold. It effectively cleared 2 and 4 g stones within 900 seconds under the three irrigation rates. In contrast, the current design cleared <10% of the stone debris in all tests. Conclusion: The new hydrodynamic design significantly improved the stone debris clearance rate without causing obviously increased renal pressure, and the improvement was maintained under different irrigation pressures and stone burdens.

Unveiling the Association between HPV and Pan-Cancers: A Bidirectional Two-Sample Mendelian Randomization Study.

INTRODUCTION: More and more studies have focused on the associations between human papillomavirus (HPV) infection and pan-cancers. However, current evidence is largely based on retrospective studies, which are susceptible to confounding factors and do not enable the establishment of causal relationships. METHODS: A bidirectional two-sample Mendelian randomization (MR) design was employed to thoroughly evaluate the causal relationships between HPV and 12 site-specific cancers except cervical cancer. Single nucleoside polymers (SNPs) with strong evidence from genome-wide association studies (GWAS) were selected from HPV exposure datasets and used as instrumental variables (IVs) in this study. For the MR analysis results, MR-Egger's intercept P test, MR-PRESSO global test, Cochran's Q test and a leave-one-out test were applied for sensitivity analysis. Using HPVTIMER, we also performed immune infiltration analyses in head and neck squamous cell carcinoma (HNSCC), oropharyngeal squamous cell carcinoma (OPSCC) and vulval squamous cell carcinoma (VSCC) to evaluate the tumor-immune microenvironment. RESULTS: Based on the evidence of MR analysis, our study conclusively identified HPV16 as a risk factor implicated in the development of bladder cancer, colorectal cancer, and breast cancer, while HPV18 was identified as a risk factor for prostate cancer, ovarian cancer, lung cancer and breast cancer. The MR results also showed that HPV16 may be a protective factor for prostate cancer, anal cancer, lung cancer and oropharyngeal cancer, while HPV18 may be a protective factor for vaginal cancer. CONCLUSION: An HPV infection may modulate the immune microenvironment and therefore has a potential inhibitory effect on the development of certain cancers. These conclusions provided new insights into the potential mechanisms of carcinogenesis and needed further research for validation.

Management Strategy for Prostate Imaging Reporting and Data System Category 3 Lesions.

PURPOSE OF REVIEW: Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions present a clinical dilemma due to their uncertain nature, which complicates the development of a definitive management strategy. These lesions have an incidence rate of approximately 22-32%, with clinically significant prostate cancer (csPCa) accounting for about 10-30%. Therefore, a thorough evaluation is warranted. RECENT FINDINGS: This review highlights the need for radiology peer review, including the confirmation of dynamic contrast-enhanced (DCE) compliance, as the initial step. Additional MRI models such as VERDICT or Tofts need to be verified. Current evidence shows that imaging and clinical indicators can be used for risk stratification of PI-RADS 3 lesions. For low-risk lesions, a safety net monitoring approach involving annual repeat MRI can be employed. In contrast, lesions deemed potentially risky based on prostate-specific antigen density (PSAD), 68 Ga-PSMA PET/CT, MPS, Proclarix, or AI/machine learning models should undergo biopsy. It is recommended to establish a multidisciplinary team that takes into account factors such as age, PSAD, prostate, and lesion size, as well as previous biopsy pathological findings. Combining expert opinions, clinical-imaging indicators, and emerging methods will contribute to the development of management strategies for PI-RADS 3 lesions.

Novel androgen receptor inhibitors for metastatic hormone-sensitive prostate cancer: Current application and future perspectives.

Androgen receptor (AR) signaling is essential in prostate cancer treatment. For many years, androgen deprivation therapy (ADT) has been primarily applied to manage advanced prostate cancer. However, most individuals with metastatic hormone-sensitive prostate cancer (mHSPC) administered ADT alone are at risk of developing metastatic castration-resistant prostate cancer (mCRPC) in less than two years. New approaches employing novel AR inhibitors (ARi) as intensified upfront systemic treatment in mHSPC have recently demonstrated substantial benefits in delaying disease progression and prolonging overall survival. Administration of novel ARi has become the new standard of care in mHSPC. The new landscape simultaneously makes treatment choice more challenging. This review provides comprehensive data on molecular structure, pharmaceutical properties, and efficacy and safety profiles reported by pivotal clinical trials. We also discuss future directions with ongoing Phase III trials of novel ARi in mHSPC. Considering these biological and clinical insights, this review aimed to provide a comprehensive understanding of differences in the development and applications of novel ARi for mHSPC, which may be helpful in designing strategies for first-line treatment choices.