Although the use of tyrosine kinase inhibitors (TKIs), such as sunitinib, has led to impressive advancements in the treatment of clear cell renal cell carcinoma (ccRCC), primary or acquired resistance to sunitinib remains elusive. Here, we report that death receptor 5 (DR5) is upregulated in ccRCC tissues and sunitinib-resistant cells, and is associated with poor outcomes and sunitinib resistance. Gain- and loss-of-function experiments revealed that DR5 promotes sunitinib resistance both in vitro and in vivo. Mechanistically, DR5 enhances the activation of NF-κB signalling by reducing the ubiquitin-mediated proteasomal degradation of p65 via competitive binding to the CUL4B-DDB1 E3 ligase complex linker protein WDR12, leading to the transcriptional upregulation of DR5 and BCL2. The positive feedback loop between DR5 and p65 contributes to the upregulation of BCL2 expression, which in turn modulates sunitinib resistance in ccRCC. Notably, targeting the DR5/NF-κB/BCL2 axis sensitizes ccRCC cells to sunitinib both in vitro and in vivo. Clinically, ccRCC patients with high DR5 expression show decreased responsiveness to TKI-based therapy. Collectively, these results highlight the importance of the positive feedback loop involving the DR5/NF-κB axis in sunitinib resistance and provide an effective therapeutic strategy for overcoming resistance.

Metabolic syndrome (MetS) is a recognized risk factor for prostate cancer (PCa), yet the precise biological mechanisms driving this association remain poorly understood. Unraveling these molecular pathways is essential for developing targeted interventions to improve patient outcomes. In this study, we analyzed NHANES (2005-2014) data to examine associations between MetS and PCa outcomes, finding that MetS was significantly associated with higher PCa risk (OR = 1.52), all-cause mortality (HR = 1.53), and cancer-specific mortality (HR = 2.17). Through integrated multi-omics, weighted gene co-expression network analysis, and machine learning, we identified the orphan receptor GPRC5B as a critical hub gene downregulated in both conditions. Single-cell transcriptomic analysis further confirmed that GPRC5B is predominantly expressed in endothelial cells. Mechanistically, GPRC5B loss was found to hyperactivate p38 MAPK signaling through a specific dual mechanism: increasing phosphorylation of upstream MKK3/6 kinases while concurrently suppressing the negative feedback phosphatase DUSP1. This synergistic dysregulation drove enhanced endothelial proliferation, migration, and tube formation in vitro. In vivo, endothelial GPRC5B deficiency significantly accelerated tumor growth and neovascularization, phenotypes that were effectively reversed by the p38 inhibitor SB202190. Clinical specimens corroborated reduced GPRC5B expression and increased microvessel density in MetS-associated PCa. Collectively, our findings establish endothelial GPRC5B downregulation as a key molecular driver promoting pathological angiogenesis via the MKK3/6-DUSP1-p38 axis, suggesting that targeting this signaling cascade offers a promising therapeutic strategy for managing MetS-associated PCa aggression.

Prostate cancer is a highly heterogeneous malignancy, with distinct subtypes displaying unique molecular and metabolic profiles. This study identifies a compensatory shift in α-ketoglutarate (α-KG) metabolism in prostate cancer, where the tumor relies on IDH1 to incorporate citrate into the TCA cycle. IDH1 inhibition, leads to lower α-KG levels. Since α-KG is required for HIF-1α hydroxylation, IDH1 inhibition stabilizes HIF-1α, which subsequently upregulates c-Fos. C-Fos enhances GLUD1 transcription, promoting the conversion of glutamate to α-KG as a compensatory mechanism. Additionally, c-Fos upregulates downstream effectors, including FOXC1 and SOX2, driving neuroendocrine differentiation in prostate cancer. Targeting α-KG-metabolizing enzymes, such as IDH1 or GLUD1, presents promising therapeutic strategies for prostate cancer subtypes by inhibiting tumor proliferation and inducing oxidative stress, thus sensitizing tumors to ferroptosis. Overall, these findings uncover a metabolic adaptation in response to IDH1 inhibition and highlight the pivotal role of c-Fos in mediating this compensatory pathway, offering new insights into potential metabolic targets for prostate cancer treatment and ferroptosis-based therapies.

The combination of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) has improved clinical outcomes in advanced renal cell carcinoma (aRCC), though therapeutic resistance remains a major challenge. We conducted single-cell transcriptomic analysis on 61 tumor samples from 34 aRCC patients treated with TKIs alone or in combination with ICIs. Non-responders exhibited increased neutrophil infiltration and enrichment of SAA+ tumor cells following treatment. We identified a VEGFA+CEACAM1+ neutrophil subset exhibiting immunosuppressive properties that is associated with poor clinical response. In vivo, pharmacologic inhibition of SAA enhanced sensitivity to ICI plus TKI combination therapy, while blockade of the CEACAM1-TIM-3 axis in humanized PD-1 mouse models significantly potentiated anti-PD-1 efficacy. Our study establishes a single-cell atlas of the aRCC tumor microenvironment under treatment pressure and identifies a previously unrecognized SAA-CEACAM1-TIM-3 axis driving drug resistance, highlighting potential targets to improve therapy efficacy.

Neoadjuvant immunotherapy-based combination holds promises in reducing surgical risk and improving survival for renal cell carcinoma (RCC) with venous tumor thrombus (VTT). However, its role in RCC-VTT has been less explored. To evaluate the efficacy and safety of neoadjuvant toripalimab plus axitinib in nonmetastatic RCC-VTT, we conducted a combined analysis of two Phase II trials with similar design. Thirty-four patients with nonmetastatic clear cell RCC (ccRCC) and Mayo Level 0-IV VTT were enrolled. Toripalimab plus axitinib was administered for up to 12 weeks before surgery. The primary endpoint was objective response rate (ORR). In this study, the ORR and disease control rates were 41% (14 out of 34) and 97% (33 out of 34), respectively. 47% (16 out of 34) patients experienced a reduction in VTT levels. Grade 3 treatment-related adverse events (TRAEs) occurred in 24% (eight out of 34) patients, and no Grade 4 or 5 TRAEs were observed. Thirty patients were eligible for surgery, and the surgical strategy was simplified in 53% (16 out of 30) patients. One-year disease-free survival and overall survival were 76.7% (95% CI, 59.1-88.2%) and 91.2% (95% CI, 77.0-97.0%), respectively. Multiomics analysis revealed the nonresponder group exhibited significant tumor heterogeneity and a stroma-characterized tumor microenvironment. In conclusion, neoadjuvant toripalimab plus axitinib was clinically active and safe in patients with nonmetastatic ccRCC-VTT.

Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). Methods: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [68Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [68Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. Results: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [68Ga]Ga, a dual-modality radionuclide-fluorescence probe ([68Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/106 cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [68Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. Conclusions: This preclinical study demonstrates that [68Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery.

ObjectiveTo evaluate the efficacy of neoadjuvant hormonal therapy (NHT) on perioperative and oncological outcomes in patients with oligometastatic prostate cancer (OmPCa) treated with robot-assisted radical prostatectomy (RARP) and adjuvant androgen-deprivation therapy (ADT).MethodsIn this multicenter retrospective study, 160 OmPCa patients treated from five Chinese medical centers between May 2010 and May 2023 were included: 80 received NHT followed by RARP+ADT, and 80 underwent RARP+ADT alone. We evaluated surgical information, pathological findings, biochemical progression-free survival (bPFS), radiological progression-free survival (rPFS), overall survival (OS), subsequent treatments, and ADT-related adverse events.ResultsCompared to the standard therapy (ST) group, the NHT group exhibited shorter operative time (170 vs. 200min; P = 0.030), less blood loss (100 vs. 200 mL; P = 0.022), lower positive surgical margin rate (17.50% vs. 37.50%; P = 0.005), and higher rates of pathological downstaging in T-stage (48.8% vs. 6.3%; P<0.001). More NHT patients achieved undetectable PSA (83.8% vs. 65.0%; P = 0.007) with a shorter time to PSA nadir (2 vs. 3 months; P = 0.002). After a median postoperative follow-up of 52 months, no significant differences were observed in bPFS, rPFS or OS between groups. However, subgroup analysis revealed significant interaction effects between NHT and biopsy Gleason score ≥8, seminal vesicle invasion, and clinical T stage ≥ T3 (all P-interaction<0.05), with these subgroups showing significantly improved bPFS, rPFS and OS. Furthermore, patients in the NHT group received fewer subsequent treatments (32.5% vs. 47.5%, P = 0.031), and the incidence of ADT-related adverse events was comparable between the two groups (all P >0.05).ConclusionNHT improves perioperative outcomes and reduces the need for subsequent salvage therapies in OmPCa patients undergoing RARP. It may offer oncological benefits, particularly those with a biopsy Gleason score ≥8 or clinical T-stage≥T3. It represents a safe and feasible neoadjuvant approach.

To develop a grading system integrating MRI and clinicopathological features for predicting positive surgical margin (PSM) following robotic-assisted laparoscopic prostatectomy (RALP) among patients with prostate cancer. Patients undergoing RALP were retrospectively included with consecutive MRI examinations collected from two centers (center 1 and center 2). The train cohort included patients at center 1 between January 2020 and December 2021, and the validation cohort comprised those between January 2022 and December 2022. Patients from center 2 were assigned to the test cohort. MRI and clinicopathological features associated with PSM were assessed. A logistic regression model was used to develop the grading system. The prediction and calibration performance were evaluated by area under the receiver operating characteristic curves (AUCs) and Hosmer-Lemeshow goodness-of-fit test. AUC values were compared by Delong test. A total of 396 patients and 29.2

OBJECTIVE:To investigate whether the reliability of telesurgery is non-inferior to that of standard local surgery in patients undergoing urological robotic operations. DESIGN:Multicentre, non-inferiority, randomised controlled trial. SETTING:Five hospitals in China from December 2023 to June 2024. PARTICIPANTS:Patients scheduled to undergo radical prostatectomy or partial nephrectomy. INTERVENTIONS:Patients were randomly assigned 1:1 to undergo telesurgery or local surgery. MAIN OUTCOME MEASURES:The primary outcome was the probability of success of surgery, determined by the medical team on the basis of pre-established criteria. The pre-specified non-inferiority margin was an absolute reduction in probability of 0.1. Thirteen clinical secondary outcomes were associated with the operation and early recovery, and one secondary outcome related to the workload of the medical team. Four technical secondary outcomes for the surgical system were also explored, including network latency, display latency, frame loss during telesurgery, and system malfunction. The participants were followed up at four and six weeks postoperatively for the secondary outcomes of recovery and complications. RESULTS:A total of 72 participants were enrolled in the study and randomised 1:1 to the telesurgery group and the local surgery group for the intention-to-treat set. The median age of patients was 61.0 (interquartile range 57.5-68.0) years in the telesurgery group and 65.0 (56.5-70.0) years in the local surgery group. Telesurgery was not inferior to local surgery in terms of the probability of surgical success in the intention-to-treat population, accounting for clustering by surgeon (success probability difference 0.02 (95% credible interval -0.03 to 0.15) with bayesian posterior probability of 0.99 for non-inferiority). The telesurgery system was stable with a distance from 1000 km to 2800 km, a mean round trip network latency of 20.1-47.5 ms, and frame loss of 0-1.5 per telesurgery. Secondary outcomes, including operative basic data, complications, early recovery, oncological outcome, and medical team workload, did not differ substantially between the two groups. CONCLUSIONS:The reliability of telesurgery was non-inferior to that of local robotic surgery according to the non-inferiority margin of a 0.1 reduction in success probability. TRIAL REGISTRATION:ChiCTR.org ChiCTR2300077721.

Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, yet its response to immunotherapy is notably limited compared to other solid tumors. This resistance stems primarily from a highly immunosuppressive tumor microenvironment (TME), characterized by “cold” tumor features such as low mutational burden, scarce cytotoxic T cell infiltration and extensive regulatory cell populations. Building upon the “tumor ecosystem” concept, we integrate emerging insights from single-cell and spatial transcriptomics to decode the spatiotemporal heterogeneity of the PCa ecosystem. We specifically highlight the underappreciated “neural-immune-microbiome” axis—a triangular regulatory network wherein sympathetic nerves suppress T cell motility, intratumoral microbiota drive chronic inflammation, and metabolic reprogramming creates lipid-mediated immune paralysis. We further dissect how cell-type specific remodeling mechanisms, particularly TREM2+ macrophage-mediated metabolic symbiosis, drive the transition from hormone-sensitive to castration-resistant disease. Furthermore, we critically assess how standard of care (ADT, chemotherapy, radiotherapy) and emerging agents (PARPi, HDACi) reprogram the immune landscape with time-dependent, often paradoxical effects. Finally, we propose a roadmap for precision oncology, emphasizing that future success lies in “ecological editing”—biomarker-driven patient stratification and rational combination strategies to overcome the physical and biological barriers of the TME.

Tumor immunotherapies enhance CD8+ T cell function, yet heterogeneous responses in "cold" and "hot" tumors remain a challenge. Although biomechanical cues modulate T cell cytotoxicity, strategies to harness these forces for broad antitumor potentiation remain elusive. Here, integrating pan-cancer single-cell RNA sequencing data, we identify cofilin 1 (CFL1) as a determinant of immunotherapy response. CFL1 overexpression synergizes with CD8+ T cell-targeted immunotherapy across tumor types, driving intratumoral T cell expansion while rendering tumors physically vulnerable. Mechanistically, CFL1 hyperactivation induces F-actin bundling and actin rod accumulation, elevating cytoskeletal tension to facilitate immunological synapse formation. Conversely, CFL1 inactivation through phosphorylation or our newly identified lactylation correlates with poor outcomes. Combination therapy using adeno-associated virus delivering constitutively active CFL1 and PD-1 blockade achieves near-complete tumor eradication. Together, our findings position CFL1 as a biomechanical checkpoint governing tumor vulnerability to CD8+ T cells through immunological synapse licensing, offering a strategy to overcome immunotherapy resistance.

Objective This study aimed to investigate the characteristics of renal angiomyolipoma (AML) with venous tumor thrombus (VTT), to describe the surgical strategies for AML with VTT, and to compare the surgical methods for AML and renal cell carcinoma (RCC) with VTT, sharing our initial clinical experience. Methods A retrospective analysis was conducted on 17 renal AML patients with VTT and 34 RCC patients with VTT treated at the Senior Department of Urology, The Third Medical Center of PLA General Hospital. Baseline clinical characteristics, imaging findings, surgical methods, and follow-up outcomes were evaluated. Results The baseline characteristics showed no significant difference between the AML group and the RCC group. For the AML group, surgical interventions included partial nephrectomy and thrombectomy in two patients, and radical nephrectomy and thrombectomy in 15 patients. For the RCC group, all patients underwent radical nephrectomy and thrombectomy. Patients in the AML group had significantly less estimated blood loss (p=0.046) and fewer postoperative complications (p=0.029). All the AML patients with VTT survived and had no recurrence or metastasis during the median follow-up of 46 (interquartile range 12–84) months. Patients who underwent nephron-sparing surgery had better renal function preservation. Conclusion VTT originating from AML exhibits unique features, such as an intact capsule, a non-friable consistency, absence of blood thrombosis, and a typically thin structure, which facilitate easy and intact removal from the inferior vena cava. For selected AML patients, robotic partial nephrectomy combined with thrombectomy is a safe and effective option. The management of AML with VTT differs from that of RCC with VTT.

Objective This study aimed to introduce an initial technique of extrafascial Retzius-sparing robot-assisted radical prostatectomy (E-rsRARP) without nerve sparing and evaluate its functional and oncologic results with simple Retzius space preservation for intermediate-to high-risk prostate cancer (PCa) patients who have no sexual function preservation demand. Methods This retrospective study was conducted between January 2021 and December 2022, including 78 cases of E-rsRARP and 152 cases of extrafascial conventional robot-assisted radical prostatectomy (E-cRARP). For E-rsRARP, a triangular tunnel composed of periprostatic fascia, levator ani fascia, and neurovascular bundle (NVB) could be found between the prostate and the pelvic fascia, at the 3 o'clock and 9 o'clock positions above the prostate pedicle, as the correct plane of the extrafascial technique. Neurovascular bundles were isolated thinly enough to be easily ligated with Hem-o-lok clips. Continence was defined as the absence of pad use. The complications and oncological outcomes were analyzed. Results Compared to the E-cRARP group, the E-rsRARP group had shorter mean surgical time (p=0.005), less mean estimated blood loss (p=0.014), and shorter mean catheter time (p=0.005). No significant differences were observed in positive surgical margins or complication rates. The E-rsRARP group showed significantly better recovery of urinary continence at 0, 1, 3, 6, and 12 months postoperatively. Conclusions PCa patients could have better urinary continence recovery with Retzius space preservation during the RARP, even without nerve sparing. For intermediate-to high-risk PCa patients who had no sexual function preservation demand, E-rsRARP could reach a higher early continence rate than E-cRARP.

Recent advancements in radiological imaging have raised the possibility of diagnosing prostate cancer (PCa) without biopsy; however, the safety, feasibility, and diagnostic accuracy of this approach require comprehensive evaluation. This study proposes and evaluates an initial decision-making algorithm using PSMA PET/CT and mpMRI for selecting candidates suitable for radical prostatectomy without prior biopsy (RP-WPB). Patient enrollment was conducted strictly according to the prospectively established decision-making algorithm. Candidates for RP-WPB were required to fulfill four essential criteria: PSA > 4 ng/mL, PI-RADS score≥4, miPSMA score≥2, and co-positive lesions identified on mpMRI and PSMA PET/CT. Patients staged as cT3-4, cN1, or cM1 (solitary metastasis) underwent RP-WPB directly. For patients with stage cT2N0M0, PSA levels were further stratified: those with PSA ranging from 4 to 30 ng/mL were invited to participate in the prospective study, whereas individuals with PSA ≥ 30 ng/mL qualified for RP-WPB only if they satisfied additional conditions, including age≥75 years, PSA density (PSAD) ≥ 0.2 ng/mL/cm3, and willingness to undergo non-neurovascular-bundle-sparing surgery. From January 2022 to February 2024, 150 patients were prospectively enrolled following the algorithm; 30 patients withdrew, and 120 underwent RP-WPB. Among the latter, 84 patients were classified as cT2N0M0, 27 as cT3-4, 10 as cN1, and 9 as cM1. The detection rate of clinically significant PCa (csPCa) (ISUP grade ≥2) patients was 100

Background:As treatment for oligometastatic prostate cancer (OmPCa) gains increasing attention, the safety of robot-assisted radical prostatectomy (RARP) in this patient population has sparked growing interest. This study aimed to compare the perioperative outcomes and postoperative functional outcomes of RARP between patients with OmPCa and those with localized prostate cancer (LPCa), and to evaluate the safety and feasibility of RARP in OmPCa patients. Methods:This multicenter, retrospective, case-control study included 100 OmPCa patients (defined as having ≤5 bone and/or lymph node metastases, excluding visceral metastases) who underwent RARP between March 2010 and December 2023 at five hospital centers in China. For comparison, 100 LPCa patients were matched 1:1 to the OmPCa group based on the surgical center and operative date. Perioperative and postoperative functional outcomes were compared between the two groups. Results:The OmPCa group exhibited significantly higher median preoperative prostate-specific antigen (PSA) levels (22.63 vs. 19.09 ng/mL, P=0.006), higher median biopsy Gleason scores (8 vs. 7, P=0.007), and a greater proportion of clinical T stage > T2c (65% vs. 42%, P=0.02) compared to the LPCa group, with no significant differences in other baseline characteristics (all P>0.05). Comparisons of perioperative outcomes revealed no significant differences between the OmPCa and LPCa groups in operative time (154 vs. 150 minutes, P=0.37), estimated blood loss (100 vs. 100 mL, P=0.53), postoperative hospital stay (5 vs. 4 days, P=0.08), positive surgical margin (PSM) rate (19.0% vs. 13.0%, P=0.36), or 30-day complication rate (4.0% vs. 2.0%, P=0.41). Regarding functional outcomes, the Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence (UI) domain scores at 3 and 12 months postoperatively, as well as the UI recovery rates at 1, 3, and 12 months, showed no significant differences between the two groups (all P>0.05). However, the OmPCa group demonstrated significantly poorer EPIC sexual domain scores at 3 and 12 months postoperatively, along with a significantly higher incidence of erectile dysfunction (ED) at 12 months, compared to the LPCa group (all P<0.05). Conclusions:This study demonstrates that compared to LPCa patients, RARP does not increase the risk of perioperative adverse outcomes or postoperative functional decline in patients with OmPCa. This finding provides evidence for expanding the surgical indications for RARP in the treatment of OmPCa.

Background:Rezvilutamide has demonstrated significant clinical benefits in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) in the phase III CHART study. However, patients enrolled in clinical trials may not fully represent those encountered in routine clinical practice, and real-world evidence in this population remains limited. This study aimed to evaluate the real-world effectiveness of rezvilutamide in combination with androgen deprivation therapy (ADT) in patients with high-volume mHSPC. Methods:This multicenter retrospective cohort study included patients with high-volume mHSPC who received rezvilutamide plus ADT between August 29, 2023, and April 1, 2026 across 21 offline centers and one online center in China. Outcomes included prostate-specific antigen (PSA) 50 (defined as a ≥50% decline from baseline), PSA90 (defined as a ≥90% decline from baseline), and undetectable PSA (PSA <0.2 ng/mL) rates at 3, 6, 9, and 12 months, as well as the 12-month PSA progression-free rate. Prespecified subgroup analyses were performed according to age, Eastern Cooperative Oncology Group performance status, and Gleason score. Results:A total of 1,888 patients were included, with a median age of 73 years [interquartile range (IQR), 68-79 years]. The median baseline PSA was 70.9 ng/mL (IQR, 5.9-146.0 ng/mL). At 3 months, the PSA50, PSA90, and undetectable PSA rates were 83.3% [1,572/1,888, 95% exact confidence interval (CI): 81.5-84.9%], 71.7% (1,353/1,888, 95% exact CI: 69.6-73.7%), and 44.8% (845/1,888, 95% exact CI: 42.5-47.1%), respectively. Overall, the PSA response rates showed a gradual increasing trend over time. By month 12, the PSA50, PSA90, and undetectable PSA rates had reached 86.0% (282/328, 95% exact CI: 81.7-89.6%), 78.7% (258/328, 95% exact CI: 73.8-83.0%), and 72.0% (236/328, 95% exact CI: 66.8-76.8%), respectively. The PSA progression-free rate at 12 months was 93.4%. Conclusions:These real-world findings support the clinical utility of rezvilutamide combined with ADT in achieving durable PSA suppression in patients with high-volume mHSPC. However, the absence of comprehensive safety data and the retrospective nature of the study warrant cautious interpretation, and further prospective validation is needed.

BACKGROUND:Pelvic lymph node dissection (PLND) is integral to prostate cancer staging, but its therapeutic value remains debated. PSMA PET/CT has shown high accuracy in detecting lymph node metastasis (LNM). This study evaluates the feasibility of performing PLND based on PSMA PET/CT findings during robotic-assisted radical prostatectomy (RARP). METHODS:In this prospective, randomized study, biopsy-confirmed prostate cancer (PCa) patients with intermediate or high risk were enrolled. Patients with distant metastasis or prior endocrine therapy were excluded. All underwent 18F-PSMA PET/CT imaging, and those with LNM were assigned to Group A. Patients without LNM were randomized in a 1:1 ratio into Groups B and C. All patients underwent RARP and Groups A and B with PLND while Group C without. The primary outcomes were PSMA PET/CT accuracy in detecting LNM and oncological results. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2200063256). RESULTS:Between September 2022 and August 2023, 120 PCa patients were enrolled. The sensitivity, specificity, accuracy, positive predictive value (PPV), and NPV of PSMA PET/CT were 76.5%, 86.8%, 65.0%, 92.0%, and 84.3%. There were no significant differences in clinical parameters, progression-free survival (PFS) or PSA persistence between Groups B and C. However, PLND patients had longer surgical times, hospital stays, and higher complication rates. CONCLUSIONS:PSMA PET/CT offers high specificity and NPV in detecting LNM.LND may be unnecessary for node-negative patients identified by PSMA PET/CT, with close follow-up recommended for those not undergoing LND.