PURPOSE:Following completion of the 2025 Update Literature Review (ULR), the American Urological Association (AUA) incorporated new evidence generated since the 2023 publication of this Guideline via the AUA Amendment process. The summary presented herein represents Part II of the two-part series dedicated to addressing updated recommendations to provide a clinical framework for the evaluation and management of metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS:The AUA/SUO Advanced Prostate Cancer Guideline was reviewed via the AUA ULR process, which identified 38 studies for full-text review that were published between March 16, 2022, and August 26, 2025. Relevant studies were incorporated into the Guideline evidence base, and Guideline statements were updated as appropriate. RESULTS:The Panel developed evidence- and consensus-based statements based on an updated review to provide guidance on evaluation and management of advanced prostate cancer. These updates are detailed herein. CONCLUSIONS:Part II of this Amendment provides new guidance on treatment of mCRPC and discusses future directions for the evaluation and management of advanced prostate cancer overall. Additional guidance regarding non-metastatic castration-resistant prostate cancer (nmCRPC) was deemed current following review. This Guideline will require further review as the diagnostic and treatment options in this space continue to evolve.

PURPOSE:Following completion of the 2025 Update Literature Review (ULR), the American Urological Association (AUA) incorporated new evidence generated since the 2023 publication of this Guideline via the AUA Amendment process. The summary presented herein represents Part I of the two-part series dedicated to addressing updated recommendations to provide a clinical framework for the evaluation and management of biochemically recurrent (BCR) and metastatic hormone-sensitive prostate cancer (mHSPC). MATERIALS AND METHODS:The AUA/SUO Advanced Prostate Cancer Guideline was reviewed via the AUA ULR process, which identified 38 studies for full-text review that were published between March 16, 2022 and August 26, 2025. Relevant studies were incorporated into the Guideline evidence base, and Guideline statements were updated as appropriate. RESULTS:The Panel developed evidence- and consensus-based statements based on an updated review to provide guidance on evaluation and management of advanced prostate cancer. These updates are detailed herein. CONCLUSIONS:Part I of this Amendment provides updated guidance on imaging, germline and somatic testing, and evaluation and treatment of BCR following exhaustion of local therapy and mHSPC. This Guideline will require further review as the diagnostic and treatment options in this space continue to evolve.

Recent approval of immunotherapy for urothelial cell carcinoma, including patients with bacillus Calmette-Guerin–unresponsive high-risk nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ, creates the potential for urologic oncologists to manage immunotherapy and any adverse events (AEs). Understanding immunotherapy AEs may reduce barriers to immunotherapy utilization as a part of a multidisciplinary treatment. We have developed a standardized staff training program to improve identification of immunotherapy AEs at the University of Oklahoma Stevenson Cancer Center Urologic Oncology Clinic. This system is part of a multidisciplinary strategy that includes urologists, medical oncologists, pharmacists, and advanced practice providers. Staff are trained to screen and identify potential immunotherapy AEs, implement approved AE management protocols, and monitor AE improvement. The most commonly reported AEs by clinic staff were laboratory abnormalities. Most patients with low-grade AEs were able to remain on treatment. Urologists led AE management included treatment of thyroid dysfunction, renal function decline, and myositis. Comanagement with additional specialists was rarely required. Identification of AEs occurred primarily at regularly scheduled visits, although some patients presented to the emergency room or primary care provider. The implementation and management of an immunotherapy prescribing program in urologic oncology is feasible and safe. Trainees, especially urology residents/fellows will benefit from exposure to these programs because the role of urologists in the management of NMIBC continues to evolve.

Indications for and implications of germline genetic testing (GGT) in patients with prostate cancer have expanded over the past decade, particularly related to precision therapies and management. GGT has become the standard of care for many cancers such as breast, ovarian, colorectal, pancreatic, and metastatic prostate cancer, and it is imperative that patients be offered timely and equitable access to testing as it can inform patient-physician shared decision making for management of the current cancer as well as anticipatory guidance for disease progression. Additionally, GGT guides screening for and prevention of secondary malignancies for the patient and cascade testing for at-risk family members. Here, we present data supporting the notion that clinicians should offer all patients with prostate cancer the opportunity to undergo comprehensive GGT for pathogenic germline variants known to be associated with familial cancer and/or known to have implications for treatment and management.

570 Background: The use of ctDNA-based molecular residual disease detection represents a promising prognostic biomarker in multiple solid tumors, yet limited data exist in RCC. This study aims to prospectively assess the utility of longitudinal ctDNA monitoring in localized and metastatic RCC. Methods: We conducted a retrospective analysis on the use of longitudinal ctDNA testing in a single academic center for patients with RCC from 2022 - 2024. We used a clinically validated, personalized, tumor-informed, multiple PCR-NGS assay (Signatera, Natera, Inc.) to detect and quantify ctDNA. A total of 229 plasma samples from 69 patients were analyzed. Clinical data were collected on pathologic subtype, tumor stage and grade including the presence of sarcomatoid/rhabdoid features and type of treatment. ctDNA dynamics were categorized as follows : clearance, decrease, or increase in ctDNA levels. Treating physicians were not blinded to ctDNA results, no treatment decisions were made based on ctDNA dynamics. Results: A total of 69 patients (mean age=62, 23% female) with RCC were included in the analysis, (median: 3 samples/patient), with 33 (48%) having localized RCC and 36 (52%) having metastatic RCC (mRCC). Clear cell RCC was the predominant subtype, present in 61 (88%) patients. Among 33 patients with localized disease, 8 (24%) patients were on surveillance, and 25 (76%) patients received adjuvant pembrolizumab. Among 36 patients with mRCC, 32 (89%) patients were on systemic therapy and 4 (11%) patients were on surveillance. Among those with localized RCC, 1 (3%) patient was ctDNA positive 12 months after nephrectomy and, subsequently developed metastatic disease 1 month from ctDNA detection. Thirty-two (97%) patients with localized RCC and ctDNA negative results remained relapse-free with a median follow-up of 9 months. Among patients with mRCC, 22 (61%) patients were ctDNA positive, 12 (55%) achieved ctDNA clearance (10 after systemic therapy and 2 spontaneously on surveillance). Of these, 10 (83%) remained progression-free at a median follow-up of 11.5 months, while 2 had rise in ctDNA levels after clearance, correlating with disease progression. At median follow-up of 15 months (range 2 to 70 months), all 4 patients with radiographic progression had rising ctDNA levels (median lead time 4 weeks). One patient had rising ctDNA without evidence of radiographic progression. Conclusions: Our findings highlight the potential of ctDNA detection and dynamics as a valuable prognostic biomarker for patients with both localized and metastatic RCC. These results support further prospective studies to establish the clinical utility of ctDNA clearance as a predictive marker in metastatic RCC.

Preneoplastic and precursor lesions are important to recognize and report, as they can influence clinical management decisions. The International Society of Urological Pathology (ISUP) organized a consensus meeting in Florence, Italy, in September 2024 focused on preneoplastic and precursor lesions of the genitourinary organs. Working group 2 was assigned the topic of bladder and a group of pathologists and clinicians was convened. They developed a 46 question premeeting survey for the ISUP membership assessing flat, papillary, squamous, and glandular entities and clinical issues to determine use of terminology, reporting practices, and areas that needed to be addressed at the consensus meeting. The premeeting survey results showed consistency in the terminology used by pathologists, similarities in reporting practices, and highlighted areas of uncertainty with respect to whether certain entities could be classified as precursors/preneoplastic. The results enabled the working group to conduct focused literature reviews and to develop a presentation and set of in-meeting polling questions to address the problematic topics from the survey results. Overall, 14/18 in-meeting polling questions achieved consensus. The surveys and in-person voting demonstrated a strong preference to use existing terminology such as dysplasia, verrucous squamous, and papillary hyperplasia, to grade glandular and squamous dysplasia and to judiciously use immunohistochemistry to classify lesions. Pathologists expressed highly variable opinions with respect to questions about quantification, management recommendations, and inclusion of newer entities as precursors/preneoplastic lesions.

Preneoplastic and precursor lesions are important to recognize and report, as they can influence clinical management decisions. The International Society of Urological Pathology (ISUP) organized a consensus meeting in Florence, Italy, in September 2024 focused on preneoplastic and precursor lesions of the genitourinary organs. Working group 2 was assigned the topic of bladder and a group of pathologists and clinicians was convened. They developed a 46 question premeeting survey for the ISUP membership assessing flat, papillary, squamous, and glandular entities and clinical issues to determine use of terminology, reporting practices, and areas that needed to be addressed at the consensus meeting. The premeeting survey results showed consistency in the terminology used by pathologists, similarities in reporting practices, and highlighted areas of uncertainty with respect to whether certain entities could be classified as precursors/preneoplastic. The results enabled the working group to conduct focused literature reviews and to develop a presentation and set of in-meeting polling questions to address the problematic topics from the survey results. Overall, 14/18 in-meeting polling questions achieved consensus. The surveys and in-person voting demonstrated a strong preference to use existing terminology such as dysplasia, verrucous squamous, and papillary hyperplasia, to grade glandular and squamous dysplasia and to judiciously use immunohistochemistry to classify lesions. Pathologists expressed highly variable opinions with respect to questions about quantification, management recommendations, and inclusion of newer entities as precursors/preneoplastic lesions.

The optimal management of Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC) remains unclear. This study evaluated the safety and tolerability of a novel intense immunotherapy dosing regimen of avelumab for patients with BCG-unresponsive NMIBC during BCG induction. This phase 1b trial, with a 3 + 3 dose escalation design, included 18 patients with a histologically or cytologically documented NMIBC that was unresponsive to BCG treatment. Patients received weekly avelumab (10 mg/kg, intravenous) during BCG (50 mg, intravesical) induction followed by maintenance avelumab and BCG for up to 1 year of treatment (maintenance phase). The primary end point was completion of a full induction course (at least 5 of 6 treatments of BCG + avelumab within 8 weeks of treatment initiation). The secondary end point was completion of 6 months of maintenance treatment. Eighteen patients were enrolled; 15 of 18 (83%) patients completed 5 of 6 courses of planned induction treatment. At the 3-month cystoscopy, 13 of 15 (87%) patients remained on treatment, 10 without evidence of cancer and 3 with persistent disease (2 carcinoma in situ, 1 Ta). No drug-attributable grade 4 or 5 adverse events (AEs) were observed. All patients who discontinued treatment were included in the safety analysis. During induction therapy, 2 (11%) patients had probable drug-related grade 3 AEs, including infusion-related reaction (avelumab) and sepsis (BCG). The combination of BCG and avelumab was safe and well tolerated among patients with BCG-unresponsive NMIBC. This study supports continued efforts to evaluate the optimal dosing regimen to synergize BCG and immunotherapy.

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD48)1 May 2024PD48-01 EFFICACY OF NADOFARAGENE FIRADENOVEC-VNCG FOR PATIENTS WITH BACILLUS CALMETTE-GUÉRIN-UNRESPONSIVE NON-MUSCLE-INVASIVE BLADDER CANCER: FINAL RESULTS FROM A PHASE 3 TRIAL Stephen A. Boorjian, Vikram M. Narayan, Badrinath R. Konety, Viraj A. Master, Neal D. Shore, Ashish M. Kamat, Trinity J. Bivalacqua, Max R. Kates, Jeffrey S. Montgomery, Seth P. Lerner, Paul L. Crispen, Gary D. Steinberg, Piyush K. Agarwal, Anne K. Schuckman, Robert S. Svatek, Brian R. Lane, Lawrence I. Karsh, Marc A. Bjurlin, Gordon A. Brown, Yair Lotan, Brant A. Inman, Michael B. Williams, Michael S. Cookson, Sam S. Chang, Eric H. Kim, Alexander I. Sankin, Dorte Rehm, Jørn S. Jakobsen, Kristian Juul, and Colin P. N. Dinney Stephen A. BoorjianStephen A. Boorjian , Vikram M. NarayanVikram M. Narayan , Badrinath R. KonetyBadrinath R. Konety , Viraj A. MasterViraj A. Master , Neal D. ShoreNeal D. Shore , Ashish M. KamatAshish M. Kamat , Trinity J. BivalacquaTrinity J. Bivalacqua , Max R. KatesMax R. Kates , Jeffrey S. MontgomeryJeffrey S. Montgomery , Seth P. LernerSeth P. Lerner , Paul L. CrispenPaul L. Crispen , Gary D. SteinbergGary D. Steinberg , Piyush K. AgarwalPiyush K. Agarwal , Anne K. SchuckmanAnne K. Schuckman , Robert S. SvatekRobert S. Svatek , Brian R. LaneBrian R. Lane , Lawrence I. KarshLawrence I. Karsh , Marc A. BjurlinMarc A. Bjurlin , Gordon A. BrownGordon A. Brown , Yair LotanYair Lotan , Brant A. InmanBrant A. Inman , Michael B. WilliamsMichael B. Williams , Michael S. CooksonMichael S. Cookson , Sam S. ChangSam S. Chang , Eric H. KimEric H. Kim , Alexander I. SankinAlexander I. Sankin , Dorte RehmDorte Rehm , Jørn S. JakobsenJørn S. Jakobsen , Kristian JuulKristian Juul , and Colin P. N. DinneyColin P. N. Dinney View All Author Informationhttps://doi.org/10.1097/01.JU.0001008712.53259.7d.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prospective clinical trials to evaluate long-term durability of bladder-preserving therapies for patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) are limited. Nadofaragene firadenovec-vncg (ADSTILADRIN®) is a novel replication-deficient recombinant adenovirus vector-based gene therapy for high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with/without papillary tumors (± Ta/T1). The phase 3 trial met its primary endpoint as 53.4% (95% confidence interval [CI]: 43.3, 63.3) of patients achieved a complete response by 3 months. Final outcomes from the 60-month follow-up are reported. METHODS: This open-label, multicenter phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive NMIBC in 2 cohorts: CIS±Ta/T1 (CIS; n=107) and Ta/T1 without CIS (papillary disease [PD]; n=50). Patients received nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology efficacy assessments. Mandatory biopsies were taken at 12 months, after which patients entered a 4-year follow-up and those remaining high-grade recurrence free (HGRF) were offered continued treatment at the investigator's discretion. RESULTS: For all treated patients, median follow-up was 50.8 months (interquartile range: 39.1, 60.0) with 26.8% of patients receiving 5 or more instillations and 7.6% of patients receiving treatment for at least 57 months. In the efficacy analysis set, 5.8% of patients with CIS and 14.6% of patients with PD were HGRF at month 57. Kaplan-Meier (KM)-estimated HGRF survival rate at 57 months was 13.2% (95% CI: 6.9, 21.5) and 32.7% (19.5, 46.6) in the CIS and PD cohorts, respectively. Within 5 years after the first dose of nadofaragene firadenovec, 40.8% and 29.2% of patients in the CIS and PD cohorts underwent radical cystectomy, respectively. KM-estimated overall survival at 60 months was 76.3% (64.6, 84.5) and 85.9% (70.9, 93.5) in the CIS and PD cohorts, respectively. Four patients with CIS and 1 patient with PD experienced progression to muscle-invasive disease documented by transurethral resection of bladder tumor at the time of high-grade recurrence as collected in the electronic case report form. No new safety signals were identified on long-term follow-up. CONCLUSIONS: Nadofaragene firadenovec provided nearly half of participants with bladder preservation at 60 months and represents a safe intravesical treatment option for patients with BCG-unresponsive CIS±Ta/T1 and Ta/T1 without CIS. Source of Funding: The ongoing follow-up of the phase 3 study is sponsored by Ferring Pharmaceuticals Ltd. The original study was funded by FKD Therapies Oy © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e987 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Stephen A. Boorjian More articles by this author Vikram M. Narayan More articles by this author Badrinath R. Konety More articles by this author Viraj A. Master More articles by this author Neal D. Shore More articles by this author Ashish M. Kamat More articles by this author Trinity J. Bivalacqua More articles by this author Max R. Kates More articles by this author Jeffrey S. Montgomery More articles by this author Seth P. Lerner More articles by this author Paul L. Crispen More articles by this author Gary D. Steinberg More articles by this author Piyush K. Agarwal More articles by this author Anne K. Schuckman More articles by this author Robert S. Svatek More articles by this author Brian R. Lane More articles by this author Lawrence I. Karsh More articles by this author Marc A. Bjurlin More articles by this author Gordon A. Brown More articles by this author Yair Lotan More articles by this author Brant A. Inman More articles by this author Michael B. Williams More articles by this author Michael S. Cookson More articles by this author Sam S. Chang More articles by this author Eric H. Kim More articles by this author Alexander I. Sankin More articles by this author Dorte Rehm More articles by this author Jørn S. Jakobsen More articles by this author Kristian Juul More articles by this author Colin P. N. Dinney More articles by this author Expand All Advertisement PDF downloadLoading ...

Objectives: Perioperative blood transfusion (PBT) has been associated with worse survival after radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC). Here, we evaluated the association between PBT and survival after RC that was preceded by neoadjuvant chemotherapy (NAC). Methods: A retrospective analysis was performed on 949 patients with cT2-4aN0M0 bladder cancer who received NAC prior to RC between 2000 and 2013 at 19 centers. Kaplan–Meier estimates of overall survival (OS) were made. Presumed risk factors for OS were analyzed using Cox regression analysis. PBT was defined by the administration of any packed red blood cells during surgery or during the post-operative hospital stay. Results: A transfusion was given to 608 patients (64%). Transfused patients were more likely to have adverse clinical and pathologic parameters, including clinical stage and performance status. Transfused patients had worse OS (p = 0.01). On multivariable Cox regression, PBT was found to be independently associated with worse OS (HR 1.53 (95% CI 1.13–2.08), p = 0.007). Conclusions: PBT is common after NAC and RC, which may be linked, in part, to the anemia induced by NAC. PBT was associated with several adverse risk factors that correlate with poor outcomes after NAC and RC, and it was an independent predictor of adverse OS on multivariable analysis. Further study should determine if measures to avoid blood loss can reduce the need for PBT and thereby improve patient outcomes.

BACKGROUND:Prostate cancer is the most diagnosed cancer in Black/African American men (AA) and the second‑leading cause of cancer-related deaths. A prostate-specific antigen (PSA) blood test is an early detection screening tool for prostate cancer, but uptake of PSA screening remains low among AA men. Greater PSA screening rates among AA men, coupled with earlier treatment, may reduce disparities in prostate cancer outcomes, including mortality. The current pilot study will test the first-of-its-kind mobile health (mHealth) app to improve prostate cancer knowledge and increase PSA screening uptake among AA men using home-based screening methods. METHODS:AA men aged 55 to 69 and are not up to date with PSA screening will be randomly assigned 1:1 to receive a prostate cancer screening app: Prevention Taskforce App (Taskforce App; control condition) or the Prostate Cancer Genius App (Genius App; intervention condition), which was developed specifically for AA men. RESULTS:We will evaluate the preliminary efficacy of the apps via post-intervention group differences on the validated 18-item Prostate Cancer Knowledge Scale (primary outcome). We will also explore post-intervention group differences in perceived engagement, accessibility, and acceptability between the apps. Finally, we will derive preliminary estimates of PSA screening rates between study conditions and identify mechanisms of screening adherence. DISCUSSION:mHealth apps offer promise to improve prostate cancer knowledge and screening rates among AA men. Demonstrating the preliminary efficacy of the Genius App will support future fully-powered mHealth interventions to address health disparities.

4587 Background: Circulating tumor DNA (ctDNA)-based minimal residual disease has been established as a prognostic biomarker in advanced urothelial carcinoma (UC). Despite the confirmed utility of ctDNA in muscle-invasive non-metastatic UC (nmUC), validation in patients with metastatic UC (mUC) remains unexplored. This study aims to prospectively assess the utility of ctDNA in nmUC and mUC Methods: This prospective study analyzed the results of longitudinal ctDNA testing in a single academic center of patients with UC. A personalized, tumor-informed, multiple PCR-NGS assay (Signatera, Natera, Inc) was used for the detection and quantification of ctDNA. A total of 203 samples were analyzed (median: 3 samples/patient) with a median follow up (mFU) from first ctDNA of 12months. nmUC and mUC patients with >1 ctDNA sample were included for analysis. Disease progression was assessed by clinical/radiographic exams. ctDNA dynamics were categorized based on clearance (ctDNA-), residual (ctDNA+), ≥50% quantitative reduction (≥50%ctDNAr), and <50% quantitative reduction (<50%ctDNAr), at any time point after treatment. We used Cox regression analysis to examine associations between ctDNA and the median time to progression (mTTP). Results: 67 patients (77% male, median age: 70 years,) with nmUC (n=31,46%) and mUC (n=36,54%) were included for analysis. Quantitative reduction in ctDNA samples aligned with radiographic responses in 98.5% (n=200) of samples analyzed. nmUC patients were treated with chemotherapy, immune checkpoint inhibitors (ICPI), and radiation. In nmUC, 74% (n=23) were ctDNA-, and all these patients remained progression free at the time of data analysis (mFU:13 months). Conversely, all ctDNA+ patients (n=8) experienced progression (mTTP:3 months). Among the 38.7% (n=12) of patients who pursued bladder preservation strategies, all ctDNA- patients (n=9) remained progression free (mFU:16 months), while all ctDNA+ patients (n=3) experienced progression (mTTP 3months). In mUC, patients were treated with chemotherapy, ICPI, and enfortumab vedotin. In mUC 86% (n=31) achieved ≥50%ctDNAr and 56% (n=20) achieved ctDNA- status. 23/31 (74%) patients with >50%ctDNAr remained progression free at analysis (mFU:11mo) and mTTP in 8/31 patients was 9.5months. Notably, 5/9 patients with ≥50%ctDNAr who underwent treatment breaks due to adverse events remained progression free (median treatment break: 7 months, mFU:19 months). Patients with ≥50%ctDNAr and ctDNA-had significantly improved mTTP when compared to patients with <50%ctDNAr (HR 0.18, p=0.02 and HR 0.11, p=0.009 respectively). Conclusions: Our findings underscore the potential for personalized assessment of tumor-informed ctDNA dynamics as a promising prognostic biomarker in patients with both localized and metastatic UC. Further prospective studies are necessary to validate utility for ctDNA guided treatment de-escalation in mUC.

Introduction Patients with Bacillus Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) are at significant risk for recurrence and progression and there is an unmet need for local, effective, bladder-preserving treatment options. Nadofaragene firadenovec, a non-replicating recombinant adenovirus vector-based gene therapy that delivers a copy of the human interferon alfa-2b gene into the bladder epithelium, is approved by the FDA for treatment of adult patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with/without papillary tumors (±Ta/T1). The Phase 3 study of nadofaragene firadenovec met its primary endpoint;;53.4% of patients with CIS±Ta/T1 achieved;complete response (CR) at three months. The 24-month follow-up results showed that nadofaragene firadenovec was well tolerated, and 36.4% of the patients with CIS±Ta/T1 who achieved a CR remained high-grade recurrence free (HGRF) at 24 months. Herein, we report 36-month follow-up results from the Phase 3 study for the CIS±Ta/T1 cohort. Methods The open-label Phase 3 study enrolled 107 patients with BCG-unresponsive NMIBC with CIS±Ta/T1 (NCT02773849). The efficacy analysis for this cohort included 103 patients who met the protocol definition of BCG-unresponsive NMIBC. Patients received 75 mL of nadofaragene firadenovec (3×1011 viral particles/mL) once every 3 months for up to 4 doses. The protocol mandated a 5-site biopsy (dome, trigone, right and left lateral walls, posterior wall) at 12 months and patients who were HGRF were offered continued treatment once every 3 months at the investigator's discretion. Assessments beyond 24 months were performed in accordance with usual clinical practice. The study is ongoing, with a planned 5-year treatment and monitoring phase; the follow-up results reported here are based on the 36-month interim data for the CIS±Ta/T1 cohort. Results Mean (standard deviation) duration of follow-up for the entire cohort was 42.1 (12.6) months*, with a total of 13/107 (12.1%) patients having received 36 months of treatment.At 36 months, 14/55 (25.5%) patients who had achieved a CR at 3 months remained HGRF. For these patients, the Kaplan–Meier (KM)-estimated probability of duration of CR for at least 12, 24 and 36 months was 46.5%, 36.6% and 34.2%, respectively (Figure).In the overall CIS±Ta/T1 cohort (N=103), the KM-estimated median (95% confidence interval [CI]) duration of HGRF survival was 6.0 (3.4, 8.3) months, and probability;(95% CI) of HGRF survival for at least 12 months was 30.1% (21.5, 39.2). Two patients (1.9%) discontinued due to adverse events, while four (3.9%) experienced progression to muscle-invasive disease. The KM-estimated cystectomy-free survival (95% CI) at 36 months was 53.8% (43.3, 63.1), and the three-year overall survival was 90.4% (82.3, 94.9). Conclusions Intravesical nadofaragene firadenovec, administered once every three months, demonstrated a sustained durability of response in patients with BCG-unresponsive CIS±Ta/T1 papillary disease. Nadofaragene firadenovec represents a novel treatment option for BCG-unresponsive NMIBC with a favorable benefit-to-risk ratio.*All patients had passed 36 months at data cutoff on 09 September 2021.Figure. Kaplan–Meier estimated durability of complete response in patients with CIS±Ta/T1 papillary disease.

WHAT IS THIS SUMMARY ABOUT?:Advanced prostate cancer is a cancer that began in the prostate (a part of the male body) and has spread to other parts of the body. This is a review of two clinical research studies of patients with advanced prostate cancer who were treated with relugolix combination therapy. Relugolix is a medicine taken by mouth that lowers a male sex hormone, called testosterone. Relugolix is sometimes combined with other medicines such as novel hormonal therapies (NHTs) or chemotherapy to treat advanced prostate cancer. In one study, patients were treated with relugolix combined with an NHT (abiraterone or apalutamide). In a second study, patients were treated with relugolix combined with an NHT (enzalutamide) or chemotherapy (docetaxel). Researchers wanted to understand what possible side effects may happen due to taking these medicines together as prescribed. They also wanted to see if relugolix combination therapy worked to lower testosterone in the same way as relugolix taken alone. WHAT ARE THE KEY TAKEAWAYS?:Researchers found that most of the side effects of relugolix combined with an NHT or chemotherapy were mild or moderate. Side effects of relugolix combination therapy were similar to the side effects of the medicines when taken alone. However, patients who received relugolix with enzalutamide or docetaxel were more likely to have a serious side effect compared with patients who received relugolix taken alone. Testosterone stayed below 50 nanograms per deciliter (known as castration levels) for patients who received relugolix with NHT or chemotherapy. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?:Patients who receive relugolix combination therapy generally experience mild or moderate side effects, rather than serious side effects. No new safety issues were found during these studies. Patients maintained low testosterone levels. Patients and their doctors should discuss the benefits and possible harms of relugolix combination therapy to treat advanced prostate cancer.

Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.