4588 Background: Several current ongoing clinical trials have shown promising efficacy and safety of antibody-drug conjugates (ADCs) alone and in combination with immune checkpoint inhibitors (ICIs) as neoadjuvant treatment for patients with MIBC (ASCO 2024). Disitamab vedotin (RC48-ADC) is a novel humanized anti-HER2 ADC. RC48-ADC combined with cadonilimab (AK104), known as the PD-1/CTLA-4 bispecific antibody ICI, may have enhanced synergistic anti-tumor effects attributed to the mechanism of action and achieve more clinical benefit. Here, we report updated results from a phase II study of perioperative RC48-ADC plus AK104 in HER2-expressing MIBC (NCT06074484). Methods: This single-arm, open-label, multicentre study evaluates the efficacy and safety of RC48-ADC plus AK104 as a novel neoadjuvant and adjuvant therapy in patients (pts) with treatment-naïve HER2-expressing (immunohistochemistry, IHC 1+, 2+, 3+) MIBC (T2-T4a, N0-1, M0; ECOG PS score 0-1). Eligible pts received neoadjuvant RC48-ADC (2.0 mg/kg D1 Q2W, 4 cycles) + AK104 (6.0 mg/kg D1 Q2W, 4 cycles) followed by radical cystectomy and pelvic lymph node dissection (RC+PLND), and postoperative adjuvant RC48-ADC (2.0 mg/kg D1 Q3W, 6 cycles) + AK104 (10.0 mg/kg D1 Q3W, 14 cycles). The primary endpoint was pathologic complete response (pCR, pT0N0M0). Secondary endpoints were pathologic downstaging rate (pDS, yp≤T1N0), disease-free survival (DFS), overall survival (OS), objective response rate (ORR), and safety. Results: By January 2025, 43 pts had been successfully enrolled. Of these, 81.4% (35/43) were male and 18.6% (8/43) were female, with a median age of 65 years (range, 44-78). HER2 expression was positive (IHC 2+ or 3+) in 72.1% of pts and PD-L1 positive (CPS ≥ 10) in 34.9%. The pCR rate was 64.71% (22/34, 95% CI, 47.85-78.58) in all evaluable pts, 81.82% (9/11) in HER2 1+ and 56.57% (13/23) in HER2 2+/3+ pts, meanwhile 77.78% (14/18) in cT2, 30.00% (3/10) in cT3, and 83.33% (5/6) in cT4a/N1 pts. The overall pDS rate was 76.47% (26/34). Treatment-related adverse events (TRAEs) of any grade occurred in 90.7% of pts (39/43), with ≥ Grade 3 TRAEs in 18.6% (8/43), including fever, rash, bone marrow hypocellular, alanine aminotransferase increased, and immune-mediated myocarditis or pneumonitis. No Grade 4 or Grade 5 TRAEs occurred. At a median follow-up of 11.3 months (95% CI, 9.0-12.1), 2 pts had died, but the median DFS and OS were not reached which remained stable on study and would be updated. Conclusions: Neoadjuvant and adjuvant RC48-ADC plus AK104 demonstrated favorable efficacy and a manageable safety profile, supporting its potential as a valuable treatment modality for HER2-expressing MIBC. Long-term benefits and further understanding the role of this combination therapy in the perioperative setting of MIBC will be critical to advance treatment strategies. Clinical trial information: NCT06074484 .

OBJECTIVE:To describe our surgical technique for intracorporeal ureteroileal anastomosis and to assess its safety and short-term outcomes. PATIENTS AND METHODS:We performed a retrospective review of medical records for 90 consecutive patients who received an intracorporeal ileal conduit constructed using the Xing technique at our center from March 2018 to October 2022. In all cases, an intracorporeal ileal conduit was constructed using the Xing technique with a da Vinci Surgical System robot in a four-arm configuration or a Storz 3D laparoscopic system. Intraoperative variables, postoperative complications, and short-term follow-up data were assessed. A descriptive statistical analysis was performed. RESULTS:The median operative time was 244 min. No conversion to open surgery was needed. One patient needed a red blood cell transfusion (800 mL) for hemorrhage during surgery. Five patients (5.5%) experienced renal hydronephrosis after surgery because of a ureteroileal anastomosis stricture. The study is limited by its retrospective nature, lack of a control group, and short follow-up. CONCLUSION:Use of the Xing technique may simplify the ureteroileal anastomosis procedure for an intracorporeal ileal conduit and reduce the incidence of anastomosis stricture. The short-term results are satisfactory.

Overbiopsy is a serious health issue in prostate cancer (PCa) diagnostics. We have developed a urine tumor DNA multidimensional bioinformatic algorithm, utLIFE, to avoid unnecessary biopsy. The objective is to recognize all or clinically significant PCa. Of the 801 participants recruited in our study, 630 are selected for subsequent analysis. In the training cohort (n = 237), utLIFE-PC gets an area under the receiver operating characteristic curve (AUC) of 0.967 and a sensitivity of 85.57% at 95% specificity. In the independent prospective validation cohort (n = 343), utLIFE-PC has an AUC of 0.929, sensitivity of 84.24%, and specificity of 93.26%. Notably, in patients with ≥grade group (GG)2 and ≥GG3, the assay’s sensitivity is still excellent (85.33% and 87.10%, respectively). The model shows better performance than prostate-specific antigen (PSA) (p < 0.001) or the single-dimensional biomarkers (methylation, p < 0.001; copy-number variations [CNVs], p < 0.001; mutation, p < 0.001). The utLIFE-PC model can potentially optimize the PCa diagnostic process and avoid unnecessary biopsies. This study was registered at Chinese Clinical Trial Registry: ChiCTR2300071837.

Prostate cancer is one of the most common solid tumors in men, and its incidence continues to rise in China. Several guidelines have been developed and published to facilitate the standardization of diagnosis and treatment of prostate cancer. However, there are still many challenges and issues in clinical practice that lack high-level evidence. A panel of recognized domestic experts including urologists, medical oncologists, and radiologists was organized and invited to discuss and vote on the key issues of lacking high-level evidence and unified guideline recommendations questions. Following careful selection and voting processes, 19 questions were identified, leading to the establishment of a consensus based on collective agreement regarding these hot issues. The aim of this consensus is to provide a reference for managing the whole patient journey of prostate cancer for Chinese clinicians.

e16591 Background: The current standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy (RC). However, more than 40% patients are ineligible for cisplatin-based chemotherapy. The adverse reactions, comorbidities and high recurrence rate also limited the implementation of neoadjuvant cisplatin-based chemotherapy. The combination application in perioperative of RC48-ADC and PD-1/CTLA-4 antibody may have synergistic anti-tumor effects and achieve more clinical benefit. Methods: This single arm, open-label, multicenter study evaluates the effectiveness and safety of disitamab vedotin (RC48-ADC), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, plus cadonilimab (AK104, PD-1/CTLA-4 bispecific antibody) as a novel neoadjuvant and adjuvant therapy in patients (pts) with treatment-naïve HER2-expressing (Immunohistochemistry, IHC 1+, 2+, 3+) MIBC (T2-T4a, N0-1, M0; ECOG PS score 0-1). Eligible pts received neoadjuvant RC48-ADC (2.0 mg/kg D1 Q2W, 4 cycles) + AK104 (6.0 mg/kg D1 Q2W, 4 cycles) followed by RC and RC48-ADC (2.0 mg/kg D1 Q3W, 6 cycles) + AK104 (10.0 mg/kg D1 Q3W, 14 cycles) of adjuvant treatment post-surgery. The primary end point was pathologic complete response (pCR, pT0N0M0). Secondary end points were pathologic downstaging rate, disease-free survival, overall survival, objective response rate, and safety. Results: As of January 2024, 18 (16 males, 2 Females) out of the planned 36 pts have been enrolled in the study with median age of 65.5 (44-80) years. HER2 expression was positive (IHC 2+ or 3+) in 84.6% pts, and PD-L1 positive (CPS ≥ 10) in 50%. Five pts had completed neoadjuvant therapy, and 2 pts (2/5) achieved partial response (PR), while 3 (3/5) stable disease (SD), with 100% (5/5) disease control rate (DCR). Four pts underwent RC and 1 refused, all 4 pts (100%) were pathologic downstaging to ≤ypT1N0M0, and 2 of them (2/4, 50%) achieved pCR who were both assessed as SD by imaging techniques before. The most common TRAEs in 14 pts who had undergone more than 1 cycle treatment was pruritus (35.7%). Two cases of Grade ≥3 TRAEs were observed (14.3%), a patient bearing background disease of hypertension experienced grade 4 myocarditis, and another patient with underlying renal insufficiency experienced grade 3 diarrhea. Conclusions: This is the first study to evaluate the effectiveness and safety in perioperative of HER2 targeting ADC plus PD-1/CTLA-4 bispecific antibody in HER2-expressing MIBCs. And neoadjuvant RC48-ADC combined with AK104 showed promising anti-tumor activity with high pCR rate and well tolerance in MIBC pts. More specific pathological assessment results and long-term survival data post adjuvant therapy are worth anticipating. Clinical trial information: NCT06074484 .

BACKGROUND:At present, biopsy is essential for the diagnosis of prostate cancer (PCa) before radical prostatectomy (RP). However, with the development of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and multiparametric magnetic resonance imaging (mpMRI), it might be feasible to avoid biopsy before RP. Herein, we aimed to explore the feasibility of avoiding biopsy before RP in patients highly suspected of having PCa after assessment of PSMA PET/CT and mpMRI. METHODS:Between December 2017 and April 2022, 56 patients with maximum standardized uptake value (SUVmax) of ≥4 and Prostate Imaging Reporting and Data System (PI-RADS) ≥4 lesions who received RP without preoperative biopsy were enrolled from two tertiary hospitals. The consistency between clinical and pathological diagnoses was evaluated. Preoperative characteristics were compared among patients with different pathological types, T stages, International Society of Urological Pathology (ISUP) grades, and European Association of Urology (EAU) risk groups. RESULTS:Fifty-five (98%) patients were confirmed with PCa by pathology, including 49 (89%) with clinically significant prostate cancer (csPCa, defined as ISUP grade ≥2 malignancy). One patient was diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN). CsPCa patients, compared with clinically insignificant prostate cancer (cisPCa) and HGPIN patients, were associated with a higher level of prostate-specific antigen (22.9 ng/mL vs . 10.0 ng/mL, P = 0.032), a lower median prostate volume (32.2 mL vs . 65.0 mL, P = 0.001), and a higher median SUVmax (13.3 vs . 5.6, P <0.001). CONCLUSIONS:It might be feasible to avoid biopsy before RP for patients with a high probability of PCa based on PSMA PET/CT and mpMRI. However, the diagnostic efficacy of csPCa with PI-RADS ≥4 and SUVmax of ≥4 is inadequate for performing a procedure such as RP. Further prospective multicenter studies with larger sample sizes are necessary to confirm our perspectives and establish predictive models with PSMA PET/CT and mpMRI.

BACKGROUND:Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS:Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS:A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS:PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

OBJECTIVE:The aim of our study was to characterize the spectrum of mutations in muscle-invasive bladder cancer (MIBC) in the Chinese population, identifying mutational features and exploring potential therapeutic targets. METHODS:We collected samples from 62 Chinese patients with MIBC. For each patient, tumor tissues or blood samples were collected and sequenced by whole exome sequencing. RESULTS:Our findings revealed the most frequently mutated genes included TP53 (41%), TTN (41%), HYDIN (34%), FRG1 (33%), ZNF717 (23%), AHNAK2 (21%), MUC4 (21%), KMT2D (20%), CDC27 (18%) and IGSF3 (18%). The most frequently mutated DNA damage repair (DDR) genes were TP53 (49%), SMARCA4 (10%), ERCC2 (8%), BRAC2 (6%), HERC2 (6%), HLTF (6%), PALB2 (6%) and POLG (6%). Additionally, our analysis confirmed an association between DDR mutations and high TMB (P = .022). Significant differences in MSI were observed between smokers and nonsmokers (P = .022), drinkers and nondrinkers (P = .018). By analyzing the data of 323 white MIBC samples from TCGA database, we identified frequently mutated driver genes in both our cohort and TCGA white cohort, including TP53, KMT2D, KMT2C, and FGFR3. Our study also revealed genes with distinct mutation frequencies compared to the TCGA white cohort, including FRG1, CDC27, IGSF3, MUC16, and ARID1A. CONCLUSIONS:Our study provided comprehensive insights into genomic alterations in a cohort of Chinese MIBC, which could provide potential clues for clinical applications.

e16572 Background: The first-line regimens for locally advanced or metastatic urothelial carcinoma(la/mUC)remain an unmet need. RC48-ADC has been approved in China for platinum-refractory la/mUC with HER2 overexpression (IHC 2+ or 3+). Cadonilimab (AK104, PD-1/CTLA-4 bsAb) showed encouraging antitumor activity in gynecologic cancer, urological tumors, etc. The aim of this study is to evaluate the efficacy and safety characteristics of RC-48 ADC combined with cadonilimab in the treatment of la/mUC with HER2 expression. Methods: This is an open-label, multicenter, prospective, phase 2 trial to evaluate RC48-ADC combined with cadonilimab in mUC. The study set a safe introduction period, 6 patients were included and received the initial dose of RC48-ADC at 2 mg/kg combined with cadonilimab at 6 mg/kg every two weeks. If no DLT event occurred in the 6 patients, then continued to expand 30 patients, with an expected sample size of 36 cases; If DLT safety event occurred in 6 cases, the RC48-ADC dose reduced to 1.5 mg/kg and cadonilimab dose reduced to 4 mg/kg for Q2W; Treatment continued until disease progression, intolerable toxicity, death, etc. Primary endpoint was ORR and safety, Secondary endpoints included DOR, PFS, OS, and exploration of tumor biomarkers. Results: By the cutoff date of 4 February 2024, Thirteen la/mUC patients were enrolled who have not received systematic treatment or intolerant to cisplatin or refuse chemotherapy {8 males; median age 72 y [61-83]; 77%(10/13) of patients had distant metastasis. HER2 expression IHC 2+ or 3+ was in 85% patients (11/13), and PD-L1 low expression was 100% (6/6)}. Dose-limiting toxicity was observed (Bullous rash, ALT/AST elevated) among first 6 patients, therefore reduced cadonilimab from 6mg/kg to 4mg/kg Q2W, RC48-ADC remained. 8 patients have efficacy evaluation, ORR was 75.0% (6/8), including 12.5% CR (1/8). DCR was 100%. Median progression-free survival (PFS) and overall survival (OS) were not reached. 69.2% (9/13) Pts experienced treatment-related adverse events (TRAEs). The most common TRAEs were AST/ALT increase (30.8%), fever (23.1%), anemia (23.1%), rash (15.4%), and pruritus (15.4%), etc. TRAEs ≥G3 were occurred in 15.4%(2/13) patients, one patient died due to a cerebrovascular event. 30.8% had immune-related AEs(≥G3 irAE 15.4%), including immune-related skin reactions, hepatitis, and colitis. Conclusions: This was the first study to evaluate RC48-ADC in combination with cadonilimab (anti-PD-1/CTLA-4 bispecific antibody) in urothelial carcinoma. Preliminary results showed that the combination have promising efficacy in first-line treatment of la/mUC and a manageable safety profile, it may potentially provide a new option for la/mUC treatment, especially for those who cannot tolerate cisplatin-based chemotherapy. Clinical trial information: NCT06178601 .

The clinical data of 33 patients who underwent robot-assisted laparoscopic Vattikuti Institute prostatectomy (VIP) in Cancer Hospital of Chinese Academy of Medical Sciences from October 2020 to April 2022 were reviewed and analyzed. Among them, 18 patients received traditional VIP technique and 15 patients received VIP technique with pre-sutured dorsal venous complex (DVC). The ages of the traditional VIP group and the pre-sutured DVC VIP group were (66.1±7.3) and (66.6±5.7) years, respectively. The body mass index (BMI) of the traditional VIP group and the pre-sutured DVC VIP group was (24.3±2.9) and (25.3±2.6) kg/m2, respectively. The medical expenses were (91 797.0±7 029.6) and (87 106.6±7 031.4) yuan, respectively, with no statistical significance (all P>0.05). The operations of all the 33 cases were successfully completed, and no cases were transferred to open surgery. The operation time of traditional VIP group was longer than that of pre-sutured DVC VIP group [(193.0±37.2) vs (171.1±16.1) min]. The amount of intraoperative blood loss was higher than that in the pre-sutured DVC VIP group [(68.3±22.8) vs (44.0±9.1) ml)], all P<0.05. No patients had perioperative blood transfusion, and no patients had complications within 30 days after surgery. All the 33 patients had negative incisal margins. DVC presuture technique can reduce intraoperative bleeding and shorten operative time in robot-assisted laparoscopic VIP radical prostatectomy, and has good curative effect.

Radical cystectomy with urinary diversion is one of the most complicated and important operations in urology. The operation time is long, the operation risk is high, and the complication rate is high. NOSES is technically feasible and safe. Compared with conventional laparoscopic surgery, the most important and intuitive advantage of NOSES is that it avoids the auxiliary incision of extracting samples from the abdominal wall, and there are only a few tiny card scars left in the abdominal wall after operation. It reduces the estimated blood loss and postoperative complications. It is noteworthy to surgeons that serum albumin significantly reduced after LRC, nutrition should be kept balanced after surgery, and the most common complication was hypoproteinemia. NOSES is more minimally invasive and cosmetic without increasing surgical complications and affecting the pelvic floor function. There were no difference between NOSES and conventional laparoscopic surgery in pelvic floor dysfunction. We analyzed that transvaginal specimens extraction needed to cut open the posterior vaginal fornix, but the blood flow of the posterior vaginal wall was good, no tension after continuous suturing, and the vaginal wall had strong extensibility and repair ability, and the patient's postoperative incision healed well. It was recommended that the specimen was removed through the vagina to reduce postoperation complications. To sum up, transvaginal specimen extraction in laparoscopic surgery for bladder cancer is safe and feasible.

Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle‐invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD‐1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients.

Objective:To evaluate the clinical value of Xing's ureteroileal anastomosis technique in radical cystectomy.Methods:The data of 38 patients who underwent radical cystectomy with Xing's ureteroileal anastomosis technique at Cancer Hospital, Chinese Academy of Medical Sciences and Beijing Chaoyang Hospital from July 2013 to June 2021 were retrospectively reviewed. There were 30 males and 8 females. The mean age was 61.6±15.1 years old. The mean body mass index (BMI) was 25.1±2.7 kg/m 2. The American Society of Anesthesiology (ASA) graded 25 cases as grade 1, 10 cases as grade 2 and 3 cases as grade 3. There were 35 cases with stage cT 2N 0M 0 and 3 cases with cT 3N 0M 0. All patients underwent radical cystectomy and ileal conduit, and the ureteroileal anastomosis was performed using the Xing's ureteroileal anastomosis technique. Afferent loop entry was divided equally into two lumens. After 1.5 cm-long lengthwise incisions, each ureter was directly and end-to-end anastomosed to the aforementioned lumens. Postoperative information was recorded, including ureteric stricture, ureteric reflux, hydronephrosis, anastomotic leakage, renal calculus, urinary tract infection, and pyelonephritis. Results:Ureteroileal anastomosis was performed successfully in 38 cases with 76 units. The median follow-up time was 35.6 (17.0, 46.3) months. Three patients developed unilateral anastomotic stenosis after operation. Five patients had unilateral ureteral reflux. Two patients had unilateral hydronephrosis. No anastomotic leakage, urinary tract infection, or pyelonephritis occurred after the operation. Renal calculus appeared in 3 cases, all on the left unit.Conclusions:Xing's ureteroileal anastomosis technique is a simple method with few postoperative and good functional outcomes.

经阴道取标本手术是目前可用于泌尿系统肿瘤手术的一项技术,此项技术可以有效避免开放切口对患者造成的身体和心理创伤,并减少术后并发症.本文结合文献就Tv-NOSES的基本原理、适应证与禁忌证、技术步骤,其在泌尿系统肿瘤手术中的应用、优缺点、并发症及注意事项等进行阐述,旨在为其在泌尿外科的应用提供参考.

Abstract Background Prostate cancer is one of the most common cancers in men with notable interpatient heterogeneity. Implications of the immune microenvironment in predicting the biochemical recurrence-free survival (BCRFS) after radical prostatectomy and the efficacy of systemic therapies in prostate cancer remain ambiguous. Methods The tumor immune contexture score (TICS) involving eight immune contexture-related signatures was developed using seven cohorts of 1120 patients treated with radical prostatectomy (training: GSE46602, GSE54460, GSE70769, and GSE94767; validation: GSE70768, DKFZ2018, and TCGA). The association between the TICS and treatment efficacy was investigated in GSE111177 (androgen deprivation therapy [ADT]) and EGAS00001004050 (ipilimumab). Results A high TICS was associated with prolonged BCRFS after radical prostatectomy in the training (HR = 0.32, 95% CI 0.24–0.45, P < 0.001) and the validation cohorts (HR = 0.45, 95% CI 0.32–0.62, P < 0.001). The TICS showed stable prognostic power independent of tumor stage, surgical margin, pre-treatment prostatic specific antigen (PSA), and Gleason score (multivariable HR = 0.50, 95% CI 0.39–0.63, P < 0.001). Adding the TICS into the prognostic model constructed using clinicopathological features significantly improved its 1/2/3/4/5-year area under curve (P < 0.05). A low TICS was associated with high homologous recombination deficiency scores, abnormally activated pathways concerning DNA replication, cell cycle, steroid hormone biosynthesis, and drug metabolism, and fewer tumor-infiltrating immune cells (P < 0.05). The patients with a high TICS had favorable BCRFS with ADT (HR = 0.25, 95% CI 0.06–0.99, P = 0.034) or ipilimumab monotherapy (HR = 0.23, 95% CI 0.06–0.81, P = 0.012). Conclusions Our study delineates the associations of tumor immune contexture with molecular features, recurrence after radical prostatectomy, and the efficacy of ADT and immunotherapy. The TICS may improve the existing risk stratification systems and serve as a patient-selection tool for ADT and immunotherapy in prostate cancer.

Cuproptosis is a new cell death that depends on copper (Cu) ionophores to transport Cu into cancer cells, which induces cell death. However, existing Cu ionophores are small molecules with a short blood half-life making it hard to transport enough Cu into cancer cells. Herein, a reactive oxygen species (ROS)-sensitive polymer (PHPM) is designed, which is used to co-encapsulate elesclomol (ES) and Cu to form nanoparticles (NP@ESCu). After entering cancer cells, ES and Cu, triggered by excessive intracellular ROS, are readily released. ES and Cu work in a concerted way to not only kill cancer cells by cuproptosis, but also induce immune responses. In vitro, the ability of NP@ESCu to efficiently transport Cu and induce cuproptosis is investigated. In addition, the change in the transcriptomes of cancer cells treated with NP@ESCu is explored by RNA-Seq. In vivo, NP@ESCu is found to induce cuproptosis in the mice model with subcutaneous bladder cancer, reprograming the tumor microenvironment. Additionally, NP@ESCu is further combined with anti-programmed cell death protein ligand-1 antibody (αPD-L1). This study provides the first report of combining nanomedicine that can induce cuproptosis with αPD-L1 for enhanced cancer therapy, thereby providing a novel strategy for future cancer therapy.

Background: Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle--invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD--1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. Methods: This was a multi-center, single--arm study that enrolled MIBC patients with a clinical stage of T2-4aN0-1M0, and scheduled for RC. Patients received three 21-day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m(2) on day 1 and 8, and cisplatin 70 mg/m(2) on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). Results: From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune-related AEs were all grade 1 or 2. Pathologic response was not correlated with PD-L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. Conclusions: Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti--tumor activity for MIBC patients with manageable

Advanced MaterialsVolume 35, Issue 22 2370152 Inside Front CoverFree Access Cuproptosis Induced by ROS Responsive Nanoparticles with Elesclomol and Copper Combined with αPD-L1 for Enhanced Cancer Immunotherapy (Adv. Mater. 22/2023) Boda Guo, Boda Guo Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorFeiya Yang, Feiya Yang Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorLingpu Zhang, Lingpu Zhang Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 ChinaSearch for more papers by this authorQinxin Zhao, Qinxin Zhao Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorWenkuan Wang, Wenkuan Wang Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorLu Yin, Lu Yin Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorDong Chen, Dong Chen Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorMingshuai Wang, Mingshuai Wang Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorSujun Han, Sujun Han Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorHaihua Xiao, Haihua Xiao Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 ChinaSearch for more papers by this authorNianzeng Xing, Nianzeng Xing Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China Department of Urology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013 ChinaSearch for more papers by this author Boda Guo, Boda Guo Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorFeiya Yang, Feiya Yang Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorLingpu Zhang, Lingpu Zhang Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 ChinaSearch for more papers by this authorQinxin Zhao, Qinxin Zhao Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorWenkuan Wang, Wenkuan Wang Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorLu Yin, Lu Yin Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorDong Chen, Dong Chen Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorMingshuai Wang, Mingshuai Wang Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorSujun Han, Sujun Han Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 ChinaSearch for more papers by this authorHaihua Xiao, Haihua Xiao Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 ChinaSearch for more papers by this authorNianzeng Xing, Nianzeng Xing Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021 China Department of Urology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, 030013 ChinaSearch for more papers by this author First published: 01 June 2023 https://doi.org/10.1002/adma.202370152AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Graphical Abstract Immunotherapy In article 2212267, Haihua Xiao, Nianzeng Xing, and co-workers present a novel therapeutic strategy to achieve synergistic cancer immunotherapy via cuproptosis induced by reactive oxygen species (ROS)-responsive nanomedicine loaded with elesclomol and copper ([email protected]). With this approach, the tumor microenvironment is reprogrammed, and the expression of PD-L1 is increased, which consequently improves responsiveness of immunotherapy. Volume35, Issue22June 1, 20232370152 RelatedInformation

The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) reported several advancements in the field of urothelial carcinoma. Multiple new treatment options for non-muscle invasive bladder cancer (NMIBC) were introduced, providing more choices for bladder preservation in BCG-resistant/failed NMIBC cases. In muscle invasive bladder cancer (MIBC) perioperative treatment, the updated 3-year follow-up data from the CheckMate 274 study demonstrated a clear advantage in disease-free survival for the nivolumab monotherapy adjuvant treatment group. For metastatic urothelial carcinoma (mUC), the final overall survival (OS) report from the IMvigor130 study was published, prompting further considerations for future first-line treatment options in mUC. Additionally, the conference highlighted research progress in upper tract urothelial carcinoma (UTUC).