1.Introduction Due to the continuous progress in surgical methodologies and the swift evolution of surgical tools,minimally invasive procedures have emerged as the dominant approach in urologic oncology surgeries.Nota...1.Introduction Due to the continuous progress in surgical methodologies and the swift evolution of surgical tools,minimally invasive procedures have emerged as the dominant approach in urologic oncology surgeries.Notably,robot-assisted surgery(RAS)has led to its extensive adoption in the surgical management of urinary system tumors due to its enhanced maneuverability,precision in suturing,and anastomotic capabilities.展开更多
Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of ...Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.展开更多
The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapi...The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.展开更多
Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrenc...Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.展开更多
Objective:To test the diagnostic performance of percent free prostate-specific antigen(%fPSA)in predicting any prostate cancer(PCa)and high-grade prostate cancer(HGPCa)in a retrospective multi-center biopsy cohort wit...Objective:To test the diagnostic performance of percent free prostate-specific antigen(%fPSA)in predicting any prostate cancer(PCa)and high-grade prostate cancer(HGPCa)in a retrospective multi-center biopsy cohort with a PSA level of 4.0e10.0 ng/mL in China.Methods:Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st,2010 to December 31st,2013.Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization(WHO)standard.The diagnostic accuracy of PSA,%fPSA,and %fPSA in combination with PSA(%fPSA t PSA)was determined using the area under the receiver operating characteristic(ROC)curve(AUC).Results:A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included,and the detection rate of PCa was 25.1%.The AUC of%fPSA and %fPSA t PSA in predicting any PCa was superior to PSA alone in men aged≥60 years(0.623 vs.0.534,p<0.0001)but not in men aged 40e59 years(0.517 vs.0.518,p=0.939).Similar result was yield in predicting HGPCa.Conclusion:In a clinical setting of Chinese men with 4.0e10.0 ng/mL PSA undergoing initial prostate biopsy,adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients≥60 but not in patients aged 40-59 years.展开更多
Objective:This double-blind,placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate+prednisone(abiraterone)to prednisone alone in chemotherapy-naı¨ve,asymptomatic or mi...Objective:This double-blind,placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate+prednisone(abiraterone)to prednisone alone in chemotherapy-naı¨ve,asymptomatic or mildly symptomatic metastatic castrationresistant prostate cancer(mCRPC)patients from China,Malaysia,Thailand and Russia.Methods:Adult chemotherapy-naı¨ve patients with confirmed prostate adenocarcinoma,Eastern Cooperative Oncology Group(ECOG)performance status(PS)grade 0e1,ongoing androgen deprivation(serum testosterone<50 ng/dL)with prostate specific antigen(PSA)or radiographic progression were randomized to receive abiraterone acetate(1000 mg,QD)t prednisone(5 mg,BID)or placebo t prednisone(5 mg,BID),until disease progression,unacceptable toxicity or consent withdrawal.Primary endpoint was improvements in time to PSA progression(TTPP).Results:Totally,313 patients were randomized(abiraterone:n Z 157;prednisone:n Z 156);and baseline characteristics were balanced.At clinical cut-off(median follow-up time:3.9 months),80% patients received treatment(abiraterone:n Z 138,prednisone:n Z 112).Median time to PSA progression was not reached with abiraterone versus 3.8 months for prednisone,attaining 58%reduction in PSA progression risk(HR=0.418;p<0.0001).Abirateronetreated patients had higher confirmed PSA response rate(50%vs.21%;relative odds=2.4;p<0.0001)and were 5 times more likely to achieve radiographic response than prednisonetreated patients(22.9%vs.4.8%,p=0.0369).Median survival was not reached.Most common(≥10% abiraterone vs.prednisone-treated)adverse events:bone pain(7%vs.14%),pain in extremity(6%vs.12%),arthralgia(10%vs.8%),back pain(7%vs.11%),and hypertension(15%vs.14%).Conclusion:Interim analysis confirmed favorable benefit-to-risk ratio of abiraterone in chemotherapy-naı¨ve men with mCRPC,consistent with global study,thus supporting use of abiraterone in this patient population.展开更多
Objective:Primary urethral carcinoma(PUC)is a rare malignant carcinoma but with limited therapeutic options.This review aims to provide an overview of the current strategies on this patient settings.Methods:Recent lit...Objective:Primary urethral carcinoma(PUC)is a rare malignant carcinoma but with limited therapeutic options.This review aims to provide an overview of the current strategies on this patient settings.Methods:Recent literature ranging from January 1987 and December 2021 was assessed through PubMed search to assess the diagnostic and therapeutic principles of PUC.Results:A complete of examination including cystoscopy,imaging,and biopsy should be conducted for these patients.Once diagnosed,the clinical decision of PUC should be made according to the tumor location,pathological pattern,and extent of the tumor.For patients with superficial and distal urethral lesions,organ sparing approaches or radical reconstructive procedures can be utilized.While for more advanced disease or nodal involvement,an optimal multimodal treatment strategy consisted of surgery and radiochemotherapy should be adopted.For patients with urothelial carcinoma of the prostate,the management including transurethral resection of the prostate followed by bacille Calmette-Guerin or radical cysto-prostatectomy should depend on the infiltration depth of PUC.Conclusion:A complete of examination is important for the diagnosis of PUC.The management of PUC should be determined by the location,pathological pattern,and extent of the tumor.More multi-institutional collaborations should be held to investigate better treatment modal-ities for PUC.展开更多
Objective:To evaluate the diagnostic value of fluorescence in situ hybridization(FISH)in bladder cancer.Methods:We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and cond...Objective:To evaluate the diagnostic value of fluorescence in situ hybridization(FISH)in bladder cancer.Methods:We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008.Receiver operating characteristic(ROC)curve analysis was performed and the area under curve(AUC)values were calculated for both the FISH and urine cytology tests.Results:A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population.A total of 4807 patients with hematuria were prospectively,randomly enrolled for the simultaneous analysis of urine cytology,FISH testing,and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen.Overall,the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%,while that of cytology was 33.4%(p<0.001).The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7%and 89.6%,respectively(p=0.004).The sensitivity values of FISH for low and high grade bladder cancer were 82.6%and 90.1%,respectively(p=0.002).Conclusion:FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages.Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.展开更多
Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer...Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer who underwent radical cystectomy(RC)in 13 centers of the Chinese Bladder Cancer Consortium(CBCC).Perioperative outcomes were compared between MIRC and ORC.The influence of surgical approaches on overall survival(OS)and cancer-specific survival(CSS)in the entire study group and subgroups classified according to pathologic stage or lymph node(LN)status was assessed with the log-rank test.Multivariable Cox proportional hazard models were used to evaluate the association among OS,CSS and risk factors of interest.Results:Of 2098 patients who underwent RC,1243 patients underwent MIRC(1087 laparoscopic RC and 156 robotic-assisted RC,respectively),while 855 patients underwent ORC.No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate.MIRC was associated with less estimated blood loss,more LN yield,higher rate of neobladder diversion,longer operative time,and longer length of hospital stay.There was no significant difference in OS and CSS according to surgical approaches(pZ0.653,and 0.816,respectively).Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement.Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS.Conclusions:Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.展开更多
Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family...Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.展开更多
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...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-na?ve 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/d L),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/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.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.展开更多
Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends,and telomere dysfunction may lead to tumorigenesis.Genetic variation in telomere m...Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends,and telomere dysfunction may lead to tumorigenesis.Genetic variation in telomere maintenance genes has been confirmed.Cumulative evidence shows that the difference of telomere length and stability among the individual depends on the genetic variants of telomere maintenance genes.Genetic variants in telomere maintenance genes may affect telomere length and stability,thus the increased cancer risk.This review intends to summarize the association of genetic variants in telomere maintenance genes with bladder cancer risk.展开更多
The incidence and mortality of prostate cancer(PCa)in China have risen sharply in recent years,posing an escalating public health concern.In contrast to Western populations,Chinese patients are more frequently diagnos...The incidence and mortality of prostate cancer(PCa)in China have risen sharply in recent years,posing an escalating public health concern.In contrast to Western populations,Chinese patients are more frequently diagnosed at advanced stages,often with metastatic disease and suboptimal survival outcomes.These disparities reflect in-trinsic differences in epidemiological patterns,molecular landscapes,and healthcare delivery systems unique to the Chinese context.Nevertheless,prevailing PCa management paradigms,largely derived from Western-centric evidence,remain inadequately calibrated to the biological and clinical realities of Chinese patients.This review provides a comprehensive synthesis of the epidemiology,genomic alterations,clinical presentations,and treatment disparities of PCa in China,highlighting the urgent need for population-specific strategies.Priority areas include the development of ethnically optimized screening protocols,the integration of precision medicine approaches,and the implementation of regionally adapted prevention and early detection programs.Furthermore,expanding participation in clinical trials and accelerating translational research efforts,particularly in multi-omics and biomarker discovery,will be critical to bridging current gaps.By aligning emerging scientific innovations with localized healthcare needs,China holds the potential to reshape its prostate cancer care paradigm,improving outcomes,reducing disparities,and contributing to the global advancement of precision oncology.展开更多
The randomized phase 3 CHART trial(NCT03520478)revealed that rezvilutamide(REZ)plus androgen deprivation therapy(ADT)in high-volume,metastatic,hormone-sensitive prostate cancer(mHSPC)significantly enhanced radiographi...The randomized phase 3 CHART trial(NCT03520478)revealed that rezvilutamide(REZ)plus androgen deprivation therapy(ADT)in high-volume,metastatic,hormone-sensitive prostate cancer(mHSPC)significantly enhanced radiographic progression-free and overall survival than bicalutamide(BIC)-ADT.Accordingly,we examined patient-reported outcomes(PROs)results,which were exploratory endpoints in the CHART trial.The patients were randomly allocated to receive REZ-ADT or BIC-ADT in a 1:1 ratio.The PROs were evaluated with the Brief Pain Inventory-Short Form(BPI-SF)and the Functional Assessment of Cancer Therapy-Prostate(FACT-P)questionnaires.Both study groups displayed comparable baseline pain scores and functional status.Patients administered REZ-ADT had an extended time to progression of worst pain intensity in comparison to those treated with BIC-ADT(25th percentile,9.2[95%CI 7.4-16.6]vs.6.4 months[95%CI 5.5-8.3];HR 0.75[95%CI 0.57-0.97];p=0.026).Similarly,patients received REZ-ADT exhibited a delayed time to progression of pain interference in comparison to those receiving BIC-ADT(25th percentile,20.2[95%CI 12.9-31.3]vs.10.2 months[95%CI 7.4-11.1];HR 0.70[95%CI 0.52-0.93];p=0.015).Additionally,the REZ-ADT group demonstrated a prolonged delay in the deterioration of the total score on the FACT-P questionnaire(25th percentile,12.8[95%CI 7.4-20.3]vs.6.0 months[95%CI 4.6-9.2];HR 0.66[95%CI 0.50-0.86];p=0.002),as well as most of the FACT-P subscale scores,in comparison to the BIC-ADT group.In conclusion,REZ-ADT is superior to BIC-ADT regarding the pain alleviation and enhancement of functional scales for high-volume mHSPC.展开更多
The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and ...The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and therapeutic efficacy,this special issue,“Tumor Microen-vironment and Immunotherapy:From Bench to Bedside,”brings forth the latest breakthroughs in these domains.It highlights the interplay be-tween the TME,immune system dynamics,and cancer therapies,with a particular emphasis on precision medicine and the development of targeted treatments.展开更多
Background:Tertiary lymphoid structure(TLS),ectopic lymphoid aggregates formed in response to chronic inflammation,have emerged as potential prognostic biomarkers and mediators of anti-tumor immunity in various cancer...Background:Tertiary lymphoid structure(TLS),ectopic lymphoid aggregates formed in response to chronic inflammation,have emerged as potential prognostic biomarkers and mediators of anti-tumor immunity in various cancers.However,the heterogeneity of TLS spatial distribution,maturity,and their prognostic and immunological significance in prostate cancer(PCa)remain poorly characterized.Methods:We utilized immunohistochemistry,multispectral fluorescence immunohistochemistry(mIHC)and spatial multi-omics analyses to evaluate the heterogeneity of TLS and its relationship with immune components in the tumor microenvironment(TME).Prognostic implications were assessed in 701 PCa patients from the TCGA and Fudan University Shanghai Cancer Center cohorts.The association between TLS heterogeneity and immunoreactivity was assessed through the quantification of immune cell infiltration.CellTreck and robust cell type decomposition deconvolution algorithms were used to decipher the colocalization features of each cell,cell-cell communication and ligand-receptor features within TLS regions.Results:In PCa,TLSs were detected in approximately 20%of patients across both cohorts,with intratumoral TLS(intra-TLS)being twice as prevalent as peritumoral TLS(peri-TLS).Patients harboring intra-TLS exhibited significantly longer disease-free and progression-free survival.Compared to peri-TLS,intra-TLS were more mature,characterized by increased T-effector cell infiltration,activation of interferon pathways,and the presence of follicular dendritic cell centers and B cell aggregates.Notably,compared with immature TLS,mature TLS were markedly associated with reduced PD-L1 expression,lower regulatory T cells(Tregs)infiltration,and increased high endothelial venules(HEVs)density,indicative of an immunologically active microenvironment.Spatial multi-omics analysis revealed that mature TLS exhibited enriched immune cell diversity and HEVs density,suggesting enhanced anti-tumor immunity.Furthermore,cell-cell communication analysis identified significant interactions between CCL5+dendritic cells and ACKR1+activated B cells within mature TLS,reflecting the enhanced capacity of mature TLS to orchestrate robust antigen presentation and B-cell-driven immune responses.Conclusions:In conclusion,this study highlights the prognostic and immunological implications of TLS heterogeneity in PCa,demonstrating that the spatial distribution and maturity of TLSs are closely linked to TME activation and improved clinical outcomes.These findings provide novel insights into the immune landscape of PCa and establish a foundation for immune-based precision stratification and therapeutic development.展开更多
Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and sa...Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.82172741 to Ye D)Shanghai Municipal Health Bureau(No.2020CXJQ03 to Ye D)Xuhui District Hospital Local Cooperation Project(No.23XHYD-14 to Ye D).
文摘1.Introduction Due to the continuous progress in surgical methodologies and the swift evolution of surgical tools,minimally invasive procedures have emerged as the dominant approach in urologic oncology surgeries.Notably,robot-assisted surgery(RAS)has led to its extensive adoption in the surgical management of urinary system tumors due to its enhanced maneuverability,precision in suturing,and anastomotic capabilities.
基金supported by grants from the National Natural Science Foundation of China(No.82172741)Shanghai Municipal Health Bureau(No.2020CXJQ03).
文摘Background:Studies have reported the special value of PANoptosis in cancer,but there is no study on the prognostic and therapeutic effects of PANoptosis in bladder cancer(BLCA).This study aimed to explore the role of PANoptosis in BLCA heterogeneity and its impact on clinical outcomes and immunotherapy response while establishing a robust prognostic model based on PANoptosis-related features.Methods:Gene expression profiles and clinical data were collected from public databases.Spatial heterogeneity of cell death pathways in BLCA was evaluated.Consensus clustering was performed based on identified PANoptosis genes.Cell death pathway scores,molecular,and pathway activation differences between different groups were compared.Protein-protein interaction(PPI)network construction was constructed,and immune-related gene sets,tumor immune dysfunction and exclusion(TIDE)scores,and SubMap analysis were used to evaluate immunomodulator expression and immunotherapy efficacy.Ten machine learning algorithms were utilized to develop the most accurate predictive risk model,and a nomogram was created for clinical application.Results:BLCA demonstrated a spatially heterogeneous distribution of pyroptosis,apoptosis,and necroptosis.Notably,T effector cells significantly colocalized with total apoptosis.Two PANoptosis modes were identified:high PANoptosis(high.PANO)and low PANoptosis(low.PANO).High.PANO was associated with worse clinical outcomes and advanced tumor stage,and increased activation of immune-related and cell death pathways.It also showed increased infiltration of immune cells,elevated expression of immunomodulatory factors,and enhanced responsiveness to the immunotherapy.The PANoptosis-related machine learning prognostic signature(PMLS)exhibited strong predictive power for outcomes in BLCA.CSPG4 was identified as a key gene underlying prognostic and therapeutic differences.Conclusion:PANoptosis shapes distinct prognostic and immunological phenotypes in BLCA.PMLS offers a reliable prognostic tool.CSPG4 may represent a potential therapeutic target in PANoptosis-driven BLCA.
基金supported by the Program for Changjiang Scholars and Innovative Research Team in University scheme of the Ministry of Education of China(NO.IRT1111)the National Basic Research Program of China(2012CB518300)+2 种基金the National Natural Science Foundation of China(81101946)the Shanghai Pujiang Program(12PJD008)Prostate Cancer Foundation Young Investigator Award,Shanghai Municipal Health and Family Planning Commission Outstanding Young Investigator(XYQ2013077).
文摘The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.
文摘Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.
文摘Objective:To test the diagnostic performance of percent free prostate-specific antigen(%fPSA)in predicting any prostate cancer(PCa)and high-grade prostate cancer(HGPCa)in a retrospective multi-center biopsy cohort with a PSA level of 4.0e10.0 ng/mL in China.Methods:Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st,2010 to December 31st,2013.Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization(WHO)standard.The diagnostic accuracy of PSA,%fPSA,and %fPSA in combination with PSA(%fPSA t PSA)was determined using the area under the receiver operating characteristic(ROC)curve(AUC).Results:A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included,and the detection rate of PCa was 25.1%.The AUC of%fPSA and %fPSA t PSA in predicting any PCa was superior to PSA alone in men aged≥60 years(0.623 vs.0.534,p<0.0001)but not in men aged 40e59 years(0.517 vs.0.518,p=0.939).Similar result was yield in predicting HGPCa.Conclusion:In a clinical setting of Chinese men with 4.0e10.0 ng/mL PSA undergoing initial prostate biopsy,adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients≥60 but not in patients aged 40-59 years.
文摘Objective:This double-blind,placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate+prednisone(abiraterone)to prednisone alone in chemotherapy-naı¨ve,asymptomatic or mildly symptomatic metastatic castrationresistant prostate cancer(mCRPC)patients from China,Malaysia,Thailand and Russia.Methods:Adult chemotherapy-naı¨ve patients with confirmed prostate adenocarcinoma,Eastern Cooperative Oncology Group(ECOG)performance status(PS)grade 0e1,ongoing androgen deprivation(serum testosterone<50 ng/dL)with prostate specific antigen(PSA)or radiographic progression were randomized to receive abiraterone acetate(1000 mg,QD)t prednisone(5 mg,BID)or placebo t prednisone(5 mg,BID),until disease progression,unacceptable toxicity or consent withdrawal.Primary endpoint was improvements in time to PSA progression(TTPP).Results:Totally,313 patients were randomized(abiraterone:n Z 157;prednisone:n Z 156);and baseline characteristics were balanced.At clinical cut-off(median follow-up time:3.9 months),80% patients received treatment(abiraterone:n Z 138,prednisone:n Z 112).Median time to PSA progression was not reached with abiraterone versus 3.8 months for prednisone,attaining 58%reduction in PSA progression risk(HR=0.418;p<0.0001).Abirateronetreated patients had higher confirmed PSA response rate(50%vs.21%;relative odds=2.4;p<0.0001)and were 5 times more likely to achieve radiographic response than prednisonetreated patients(22.9%vs.4.8%,p=0.0369).Median survival was not reached.Most common(≥10% abiraterone vs.prednisone-treated)adverse events:bone pain(7%vs.14%),pain in extremity(6%vs.12%),arthralgia(10%vs.8%),back pain(7%vs.11%),and hypertension(15%vs.14%).Conclusion:Interim analysis confirmed favorable benefit-to-risk ratio of abiraterone in chemotherapy-naı¨ve men with mCRPC,consistent with global study,thus supporting use of abiraterone in this patient population.
文摘Objective:Primary urethral carcinoma(PUC)is a rare malignant carcinoma but with limited therapeutic options.This review aims to provide an overview of the current strategies on this patient settings.Methods:Recent literature ranging from January 1987 and December 2021 was assessed through PubMed search to assess the diagnostic and therapeutic principles of PUC.Results:A complete of examination including cystoscopy,imaging,and biopsy should be conducted for these patients.Once diagnosed,the clinical decision of PUC should be made according to the tumor location,pathological pattern,and extent of the tumor.For patients with superficial and distal urethral lesions,organ sparing approaches or radical reconstructive procedures can be utilized.While for more advanced disease or nodal involvement,an optimal multimodal treatment strategy consisted of surgery and radiochemotherapy should be adopted.For patients with urothelial carcinoma of the prostate,the management including transurethral resection of the prostate followed by bacille Calmette-Guerin or radical cysto-prostatectomy should depend on the infiltration depth of PUC.Conclusion:A complete of examination is important for the diagnosis of PUC.The management of PUC should be determined by the location,pathological pattern,and extent of the tumor.More multi-institutional collaborations should be held to investigate better treatment modal-ities for PUC.
基金This clinical research was funded by the Ministry of Health People’s Republic of China(No.WKJ2007-3-001).
文摘Objective:To evaluate the diagnostic value of fluorescence in situ hybridization(FISH)in bladder cancer.Methods:We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008.Receiver operating characteristic(ROC)curve analysis was performed and the area under curve(AUC)values were calculated for both the FISH and urine cytology tests.Results:A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population.A total of 4807 patients with hematuria were prospectively,randomly enrolled for the simultaneous analysis of urine cytology,FISH testing,and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen.Overall,the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%,while that of cytology was 33.4%(p<0.001).The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7%and 89.6%,respectively(p=0.004).The sensitivity values of FISH for low and high grade bladder cancer were 82.6%and 90.1%,respectively(p=0.002).Conclusion:FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages.Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.
基金supported by the National Natural Science Foundation of China(Grant No.81825016,81772719,81772728,81572514)the Key Areas Research and Development Program of Guangdong(Grant No.2018B010109006)Medical Scientific Research Foundation of Guangdong Province(Grant No.A2018388).
文摘Objective:To investigate oncological outcomes in patients with bladder cancer who underwent minimally invasive radical cystectomy(MIRC)or open radical cystectomy(ORC).Methods:We identified patients with bladder cancer who underwent radical cystectomy(RC)in 13 centers of the Chinese Bladder Cancer Consortium(CBCC).Perioperative outcomes were compared between MIRC and ORC.The influence of surgical approaches on overall survival(OS)and cancer-specific survival(CSS)in the entire study group and subgroups classified according to pathologic stage or lymph node(LN)status was assessed with the log-rank test.Multivariable Cox proportional hazard models were used to evaluate the association among OS,CSS and risk factors of interest.Results:Of 2098 patients who underwent RC,1243 patients underwent MIRC(1087 laparoscopic RC and 156 robotic-assisted RC,respectively),while 855 patients underwent ORC.No significant differences were noted in positive surgical margin rate and 90-day postoperative mortality rate.MIRC was associated with less estimated blood loss,more LN yield,higher rate of neobladder diversion,longer operative time,and longer length of hospital stay.There was no significant difference in OS and CSS according to surgical approaches(pZ0.653,and 0.816,respectively).Subgroup analysis revealed that OS and CSS were not significantly different regardless of the status of extravesical involvement or LN involvement.Multivariable Cox regression analyses showed that the surgical approach was not a significant predictor of OS and CSS.Conclusions:Our study showed that MIRC was comparable to conventional ORC in terms of OS and CSS.
基金This work was in part supported by grants from the Key Project of the National Science Foundation of China to Jianfeng Xu （81130047）, the National Key Basic Research Program Grant 973 of China to Jianfeng Xu （2012CB518301）, the National Natural Science Foundation of China （Grant No. 81402339） to Rong Na, the intramural grants from Huashan Hospital Fudan University to Rong Na. This study is also partially supported by the Ellrodt-Schweighauser Family Chair of Cancer Genomic Research of NorthShore University HealthSystem to JX. Finally, We would like to thank all the subjects included in this study.
文摘Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.
文摘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-na?ve 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/d L),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/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.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.
文摘Telomere maintenance genes play an important role in maintaining the integrity of the telomere structure that protects chromosome ends,and telomere dysfunction may lead to tumorigenesis.Genetic variation in telomere maintenance genes has been confirmed.Cumulative evidence shows that the difference of telomere length and stability among the individual depends on the genetic variants of telomere maintenance genes.Genetic variants in telomere maintenance genes may affect telomere length and stability,thus the increased cancer risk.This review intends to summarize the association of genetic variants in telomere maintenance genes with bladder cancer risk.
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(grant number:2023ZD0510300)National Natural Science Foundation of China(grant numbers:82403377,82473192)+1 种基金China Postdoctoral Science Foundation(grant number:2024M750538)Shanghai Municipal Health Bureau(grant number:2020CXJQ03).
文摘The incidence and mortality of prostate cancer(PCa)in China have risen sharply in recent years,posing an escalating public health concern.In contrast to Western populations,Chinese patients are more frequently diagnosed at advanced stages,often with metastatic disease and suboptimal survival outcomes.These disparities reflect in-trinsic differences in epidemiological patterns,molecular landscapes,and healthcare delivery systems unique to the Chinese context.Nevertheless,prevailing PCa management paradigms,largely derived from Western-centric evidence,remain inadequately calibrated to the biological and clinical realities of Chinese patients.This review provides a comprehensive synthesis of the epidemiology,genomic alterations,clinical presentations,and treatment disparities of PCa in China,highlighting the urgent need for population-specific strategies.Priority areas include the development of ethnically optimized screening protocols,the integration of precision medicine approaches,and the implementation of regionally adapted prevention and early detection programs.Furthermore,expanding participation in clinical trials and accelerating translational research efforts,particularly in multi-omics and biomarker discovery,will be critical to bridging current gaps.By aligning emerging scientific innovations with localized healthcare needs,China holds the potential to reshape its prostate cancer care paradigm,improving outcomes,reducing disparities,and contributing to the global advancement of precision oncology.
文摘The randomized phase 3 CHART trial(NCT03520478)revealed that rezvilutamide(REZ)plus androgen deprivation therapy(ADT)in high-volume,metastatic,hormone-sensitive prostate cancer(mHSPC)significantly enhanced radiographic progression-free and overall survival than bicalutamide(BIC)-ADT.Accordingly,we examined patient-reported outcomes(PROs)results,which were exploratory endpoints in the CHART trial.The patients were randomly allocated to receive REZ-ADT or BIC-ADT in a 1:1 ratio.The PROs were evaluated with the Brief Pain Inventory-Short Form(BPI-SF)and the Functional Assessment of Cancer Therapy-Prostate(FACT-P)questionnaires.Both study groups displayed comparable baseline pain scores and functional status.Patients administered REZ-ADT had an extended time to progression of worst pain intensity in comparison to those treated with BIC-ADT(25th percentile,9.2[95%CI 7.4-16.6]vs.6.4 months[95%CI 5.5-8.3];HR 0.75[95%CI 0.57-0.97];p=0.026).Similarly,patients received REZ-ADT exhibited a delayed time to progression of pain interference in comparison to those receiving BIC-ADT(25th percentile,20.2[95%CI 12.9-31.3]vs.10.2 months[95%CI 7.4-11.1];HR 0.70[95%CI 0.52-0.93];p=0.015).Additionally,the REZ-ADT group demonstrated a prolonged delay in the deterioration of the total score on the FACT-P questionnaire(25th percentile,12.8[95%CI 7.4-20.3]vs.6.0 months[95%CI 4.6-9.2];HR 0.66[95%CI 0.50-0.86];p=0.002),as well as most of the FACT-P subscale scores,in comparison to the BIC-ADT group.In conclusion,REZ-ADT is superior to BIC-ADT regarding the pain alleviation and enhancement of functional scales for high-volume mHSPC.
基金partially supported by grants from the Non-communicable Chronic Diseases-National Science and Technology Major Project(grant num-ber:2023ZD0510300)the National Natural Science Foundation of China(grant numbers:82403377,82473192).
文摘The landscape of tumor microenvironment(TME)research has un-dergone rapid transformation over the past decade.1,2 As we deepen our understanding of the TME’s role in cancer progression,immune response modulation,and therapeutic efficacy,this special issue,“Tumor Microen-vironment and Immunotherapy:From Bench to Bedside,”brings forth the latest breakthroughs in these domains.It highlights the interplay be-tween the TME,immune system dynamics,and cancer therapies,with a particular emphasis on precision medicine and the development of targeted treatments.
基金supported by grants from Non-communicable Chronic Diseases-National Science and Technology Major Project(grant number:2023ZD0510300)National Natural Science Foundation of China(grant numbers:82403377,82473192,82474506,81760463)+4 种基金China Postdoctoral Science Foundation(grant number:2024M750538)Shanghai Anticancer Association EYAS PROJECT(grant numbers:SACA-CY23A02,SACA-CY23C04)Beijing Xisike Clinical Oncology Research Foundation(grant numbers:Y-Young2024-0138,Y-HR2020MS-0948)Central Government Funds for Guiding Local Scientific and Technological Development(grant number:2021ZY0037)Natural Science Found of In-ner Mongolia(grant number:2023MS08015).
文摘Background:Tertiary lymphoid structure(TLS),ectopic lymphoid aggregates formed in response to chronic inflammation,have emerged as potential prognostic biomarkers and mediators of anti-tumor immunity in various cancers.However,the heterogeneity of TLS spatial distribution,maturity,and their prognostic and immunological significance in prostate cancer(PCa)remain poorly characterized.Methods:We utilized immunohistochemistry,multispectral fluorescence immunohistochemistry(mIHC)and spatial multi-omics analyses to evaluate the heterogeneity of TLS and its relationship with immune components in the tumor microenvironment(TME).Prognostic implications were assessed in 701 PCa patients from the TCGA and Fudan University Shanghai Cancer Center cohorts.The association between TLS heterogeneity and immunoreactivity was assessed through the quantification of immune cell infiltration.CellTreck and robust cell type decomposition deconvolution algorithms were used to decipher the colocalization features of each cell,cell-cell communication and ligand-receptor features within TLS regions.Results:In PCa,TLSs were detected in approximately 20%of patients across both cohorts,with intratumoral TLS(intra-TLS)being twice as prevalent as peritumoral TLS(peri-TLS).Patients harboring intra-TLS exhibited significantly longer disease-free and progression-free survival.Compared to peri-TLS,intra-TLS were more mature,characterized by increased T-effector cell infiltration,activation of interferon pathways,and the presence of follicular dendritic cell centers and B cell aggregates.Notably,compared with immature TLS,mature TLS were markedly associated with reduced PD-L1 expression,lower regulatory T cells(Tregs)infiltration,and increased high endothelial venules(HEVs)density,indicative of an immunologically active microenvironment.Spatial multi-omics analysis revealed that mature TLS exhibited enriched immune cell diversity and HEVs density,suggesting enhanced anti-tumor immunity.Furthermore,cell-cell communication analysis identified significant interactions between CCL5+dendritic cells and ACKR1+activated B cells within mature TLS,reflecting the enhanced capacity of mature TLS to orchestrate robust antigen presentation and B-cell-driven immune responses.Conclusions:In conclusion,this study highlights the prognostic and immunological implications of TLS heterogeneity in PCa,demonstrating that the spatial distribution and maturity of TLSs are closely linked to TME activation and improved clinical outcomes.These findings provide novel insights into the immune landscape of PCa and establish a foundation for immune-based precision stratification and therapeutic development.
文摘Background:LY01005(Goserelin acetate sustained-release microsphere injection)is a modified gonadotropin-releasing hormone(GnRH)agonist injected monthly.This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.Methods:We conducted a randomized controlled,open-label,non-inferiority trial across 49 sites in China.This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections.The primary efficacy endpoints were the percentage of patients with testosterone suppression≤50 ng/dL at day 29 and the cumulative probability of testosterone≤50 ng/dL from day 29 to 85.Non-inferiority was prespecified at a margin of-10%.Secondary endpoints included significant castration(≤20 ng/dL),testosterone surge within 72 h following repeated dosing,and changes in luteinizing hormone,follicle-stimulating hormone,and prostate specific antigen levels.Results:On day 29,in the LY01005 and goserelin implant groups,testosterone concentrations fell below medical-castration levels in 99.3%(142/143)and 100%(140/140)of patients,respectively,with a difference of-0.7%(95%confidence interval[CI],-3.9%to 2.0%)between the two groups.The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3%and 97.8%,respectively,with a between-group difference of 1.5%(95%CI,-1.3%to 4.4%).Both results met the criterion for non-inferiority.Secondary endpoints were similar between groups.Both treatments were well-tolerated.LY01005 was associated with fewer injection-site reactions than the goserelin implant(0%vs.1.4%[2/145]).Conclusion:LY01005 is as effective as goserelin implants in reducing testosterone to castration levels,with a similar safety profile.Trial registration:ClinicalTrials.gov,NCT04563936.
