4505 Background: First-line nivolumab plus ipilimumab (NIVO+IPI) provided substantial long-term survival benefits over sunitinib (SUN) in patients (pts) with advanced renal cell carcinoma (aRCC) in the CheckMate 214 trial. We now report final efficacy and safety data in the intent-to-treat (ITT) population and by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk. Methods: Pts with clear cell aRCC were randomized 1:1 to NIVO 3 mg/kg + IPI 1 mg/kg Q3W×4 then NIVO (3 mg/kg or 240 mg Q2W or 480 mg Q4W); or SUN 50 mg once daily for 4 weeks on, 2 weeks off. Efficacy endpoints included overall survival (OS), and independent radiology review committee (IRRC)-assessed progression-free survival (PFS) and objective response rate (ORR) in intermediate/poor-risk (I/P; primary), ITT (secondary), and favorable-risk (FAV; exploratory) pts. Response was assessed using RECIST v1.1. Results: With 9 years median follow-up, OS was improved with NIVO+IPI vs SUN in ITT (HR 0.71) and I/P (HR 0.69) pts. The probability of OS at 108 months was 31% vs 20% in ITT pts and 30% vs 19% in I/P pts, respectively. In pts with FAV risk, the HR for OS improved from 1.45 at first report (Motzer NEJM 2018) to 0.80 at 9 years, showing a delayed benefit with NIVO+IPI vs SUN. OS probabilities at 108 months were 35% vs 22% in FAV pts, respectively (Table). The probability of PFS at 96 months with NIVO+IPI vs SUN was 23% vs 9% in ITT pts, 25% vs 9% in I/P pts, and 13% vs 11% in FAV pts. The probability of remaining in response through 96 months with NIVO+IPI vs SUN was 48% vs 19% in ITT pts, 50% vs 23% in I/P pts, and 36% vs not available (NA) in FAV pts. No new treatment-related deaths occurred in either arm. Additional subgroup analyses will be presented. Conclusions: In the longest and final phase 3 follow-up (9 years) of a first-line checkpoint inhibitor combination in aRCC, milestone rates of OS and PFS and durable response remained higher with NIVO+IPI vs SUN. No new safety signals emerged. NIVO+IPI remains a standard first-line option in aRCC. Clinical trial information: NCT02231749 . ITT I/P FAV Arm; n NIVO+IPI; 550 SUN; 546 NIVO+IPI; 425 SUN; 422 NIVO+IPI; 125 SUN; 124 mOS (95% CI), mo 53 (46–64) 38 (32–44) 47 (35–56) 26 (22–33) 78 (65–92) 67 (56–80) 108-mo OS probabilities (95% CI), % 31 (27–35) 20 (16–23) 30 (26–35) 19 (15–23) 35 (27–44) 22 (15–30) mPFS (95% CI), mo 12 (10–16) 12 (10–15) 12 (9–17) 9 (7–11) 13 (10–18) 29 (23–43) 96-mo a PFS probabilities (95% CI), % 23 (18–27) 9 (5–15) 25 (20–31) 9 (4–15) 13 (6–22) 11 (3–27) ORR per IRRC (95% CI); CR, % 39 (35–44); 12 33 (29–37); 3 42 (38–47); 12 27 (23–32); 3 30 (22–38); 13 52 (43–61); 6 mDOR (95% CI), mo 76 (59–NE) 25 (20–33) 83 (54–NE) 20 (16–26) 61 (23–NE) 33 (25–51) 96-mo a DOR probabilities (95% CI), % 48 (39–55) 19 (10–31) 50 (41–58) 23 (13–36) 36 (17–56) NA b a 96-mo probabilities reported due to small numbers of pts at risk at 108 mo. b No pts remain at risk. CR, complete response; DOR, duration of response; m, median; NE, not estimable.

Nivolumab monotherapy has been approved for the adjuvant treatment of adult patients with urothelial carcinoma who are at high risk of recurrence after undergoing radical resection of urothelial carcinoma based on results of the phase 3 CheckMate 274 trial, in which adjuvant nivolumab versus placebo demonstrated improvement in the primary endpoint of disease-free survival (DFS) in high-risk muscle-invasive urothelial carcinoma (MIUC). Identification of biomarkers associated with treatment outcomes can help refine patient selection, and inform on the immunobiology of disease. To assess the relevance of key biomarkers in the adjuvant MIUC setting, extensive exploratory analyses of tumor biomarkers, including associations with DFS, were performed. Differential gene expression and gene signature analysis found that immune-related genes and pathways, in particular a high interferon-γ signature, were predictive of improved DFS in nivolumab-treated patients. Positive predictive and prognostic associations, respectively, were found for CD4 gene expression and measures of CD8 T cell infiltration. A composite predictive model suggested that high tumor cell PD-L1 expression, high CD4 gene expression, high tumor mutational burden score, receipt of neoadjuvant cisplatin and low transforming growth factor-β gene signature score made the greatest contributions to predicting improved outcomes in nivolumab-treated patients. These results reinforce studies establishing the importance of tumor biomarkers of adaptive immunity in influencing response to PD-1-PD-L1 blockade, indicating the potential predictive rather than solely prognostic nature of such findings. ClinicalTrials.gov identifier: NCT02632409 .

The aim of active surveillance (AS) is to avoid overtreatment of clinically insignificant prostate cancer (PCa). It is now strongly recommended for patients diagnosed with localized low-risk PCa. Additionally, it can be considered for selected patients with localized PCa in the International Society of Urological Pathology (ISUP) group 2, provided patients have a favorable risk profile. This profile is histopathologically characterized by the presence of a low percentage of Gleason pattern 4 and the absence of cribriform or intraductal components. The role of magnetic resonance imaging (MRI), including the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations on monitoring is increasing. It is crucial to adhere to defined intervals for prostate-specific antigen (PSA) level checks, repeat biopsies, MRI and further targeted and systematic biopsies under AS. The MRI of the prostate (according to the current recommendations as multiparametric MRI, mpMRI), as a noninvasive diagnostic tool, has the potential to be used as a decision aid for determining the need for repeated biopsies during AS. As the trigger for deciding for an active treatment PSA progression alone is not sufficient but there must be a biopsy-confirmed tumor progression with an upgrading. This continuing medical education (CME) article summarizes the current indications, procedures and discontinuation criteria for AS based on the latest evidence and an adaptation to international guidelines.

Objectives: To evaluate the diagnostic accuracy of AI-assisted biparametric MRI (AI-bpMRI) in detecting prostate cancer (PCa) as a possible replacement for multiparametric MRI (mpMRI) depending on readers’ experience. Methods: This fully crossed, multireader multicase, single-centre, consecutive study retrospectively included men with suspected PCa. Three radiologists with different levels of experience independently scored each participant’s biparametric (bp) MRI, mpMRI, and AI-bpMRI according to the PI-RADS V2.1 classification. The AI-assisted image processing was based on a sequential deep learning network. Histopathological findings were used as a reference. The study evaluated the mean areas under the receiver operating characteristic curves (AUCs) using the jackknife method for covariance. AUCs were tested for non-inferiority of AI-bpMRI to mpMRI (non-inferiority margin: −0.05). Results: A total of 105 men (mean age 66 ± 7 years) were evaluated. AI-bpMRI was non-inferior to mpMRI in detecting both Gleason score (GS) ≥ 3 + 4 PCa (AUC difference: 0.03 [95% CI: −0.03, 0.08], p = 0.37) and GS ≥ 3 + 3 PCa (AUC difference: 0.04 [95% CI: −0.01, 0.09], p = 0.14) and was superior to bpMRI in detecting GS ≥ 3 + 3 PCa (AUC difference: 0.07 [95% CI: 0.02, 0.12], p = 0.004). The benefit of AI-bpMRI was greatest for the readers with low or medium experience (AUC difference in detecting GS ≥ 3 + 4 compared to mpMRI: 0.06 [95% CI: −0.03, 0.14], p = 0.19 and 0.06 [95% CI: −0.03, 0.14], p = 0.19, respectively). Conclusions: This study indicates that AI-bpMRI detects PCa with a diagnostic accuracy comparable to that of mpMRI.

BACKGROUND AND OBJECTIVE:Darolutamide + docetaxel + androgen-deprivation therapy (ADT) significantly improved overall survival (OS) and delayed time to disease progression versus docetaxel + ADT in ARASENS (NCT02799602). We report data on subsequent antineoplastic therapies received and associated OS after discontinuation of the study treatment. METHODS:Patients were randomized 1:1 to darolutamide 600 mg orally twice daily or placebo, both with docetaxel + ADT. After treatment discontinuation, patients entered follow-up periods during which information on subsequent therapies and survival was collected. Postprogression OS was estimated using the Kaplan-Meier method as the time from initiation of first subsequent therapy to death and was compared in multivariable Cox regression analyses. KEY FINDINGS AND LIMITATIONS:Of the 1305 patients treated, 315/651 who received darolutamide and 495/654 who received placebo entered follow-up, and 57% and 76% of these patients, respectively, received subsequent therapy. In the darolutamide group, first subsequent therapy was either an androgen receptor pathway inhibitor (ARPI; 63%) or a taxane (29%), and corresponding postprogression median OS was similar (13 vs 11 mo; hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.50-3.09). In the placebo group, first subsequent therapy was an ARPI in 78% and a taxane in 19% of cases, with worse OS for the taxane versus ARPI subgroup (14 vs 23 mo; HR 3.18, 95% CI 1.56-6.50). The main limitation of these analyses is their post hoc nature. CONCLUSIONS AND CLINICAL IMPLICATIONS:For ARPI-naïve patients who did not receive darolutamide in ARASENS, postprogression survival was longer with subsequent ARPI versus taxane treatment, but OS remained shorter in comparison to the darolutamide group. Decisions on postprogression therapy should consider disease volume and drugs with different mechanisms of action.

The aim of this article is to raise awareness among healthcare providers about the adverse events (AEs) associated with the combined treatment with enfortumab vedotin and pembrolizumab. The differential diagnostic allocation of these AEs to the respective agents is discussed, overlaps between the side effect profiles of the two drugs are identified and strategies for an effective management of these AEs are presented. The recommendations are based on the currently valid prescription information for both drugs, the results of pivotal approval studies and the guidelines of recognized specialist organizations as well as the clinical experience of the authors.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes. Frequent loss of heterozygosity in FGFR3 and 17p (affecting TP53) was found in tumors with mutations in FGFR3 and TP53, respectively. Whole-genome doubling (WGD) was observed in 15

Das Ziel dieser Arbeit besteht darin, Behandler für die unter der Kombinationstherapie mit Enfortumab Vedotin und Pembrolizumab auftretenden Nebenwirkungen zu sensibilisieren. Dabei wird die differenzialdiagnostische Zuordnung der Nebenwirkungen zu den jeweiligen Therapeutika erörtert, und es werden Überschneidungen zwischen den Nebenwirkungsprofilen der beiden Substanzen identifiziert und Strategien für ein effektives Management dieser Nebenwirkungen dargestellt. Die Empfehlungen basieren auf den aktuell gültigen Fachinformationen beider Medikamente, auf den Ergebnissen zulassungsrelevanter Studien und den Leitlinien anerkannter Fachorganisationen sowie auf der klinischen Erfahrung der Autoren.

4522 Background: Non-clear cell renal cancers (nccRCC) are a rare and heterogeneous group of >20 histological and molecular defined entities. Due to the rarity of these entities, the clinical data are limited and large randomized trials are missing resulting in uncertainties for optimal treatment recommendations. So far, TKI therapy with or without immune checkpoint inhibitors (ICI) are considered standard of care (SOC) options in these diseases. Here we report the results of the academic prospective randomised European trial in therapy-naïve patients with advanced nccRCC entities, which compared ipilimumab/nivolumab (Ipi/Nivo) vs SOC. Methods: We randomly assigned patients (pts) with nccRCC in a 1:1 ratio to receive either nivolumab 3 mg/kg IV combined with ipilimumab 1 mg/kg IV every 3 weeks for 4 doses followed by a flat dose of 240 mg IV every 2 weeks or 480 mg every 4 weeks versus SOC by investigators choice until disease progression or intolerance occurred. Pts were stratified in papillary vs. non-papillary nccRCC and according to IMDC risk score. Central pathology was mandatory to confirm the correct diagnosis of the nccRCC subtype according to the WHO classification 2022.The primary endpoint was the overall survival (OS) rate at 12 months (mos), secondary endpoints were the OS rate at 6 mos and 18 mos, OS, progression-free survival (PFS) and response rate (RR). Results: 309 pts ( 70.9% male, 29.1% female) out of 316 pts were randomized to receive either Ipi/Nivo or SOC. 173 (56.0%) pts were of papillary subtype (pRCC) and 143 (44.0%) pts of non-papillary subtypes, whereas 59 pts had chromophobe (ccRCC), 20 sarcomatoid/rhabdoid, 10 collecting duct, 11 TFE3-rearranged or TFEB-altered RCC and 37 other histological features. According to the IMDC score, 23.9% were of favorable, 51.8% of intermediate and 24.3% of poor risk. The 12 mos OS rate for Ipi/Nivo of 78.3% (95%-CI 70.9%-83.9%) vs 68.3% (95%-CI 60.0%-75.3%) in the SOC arm was statistically significant (p=0.026). Median OS was 33.2 mos for the Ipi/Nivo arm and 25.2 mos for the SOC arm. The ORR of 32.8% vs. 19.4% and the median PFS of 5.4 mos vs 5.7 mos was not statistically significant different between both arms. The explorative endpoint CPS score differed between the various subentities and was associated with an advantage in OS. Pts with a CPS≥1 had an OS-rate at 12 months of 79.3% in the Ipi/Nivo arm vs. 58.3% and a median OS of 38.6 mos vs. 18.8 mos (p=0.007). Furthermore, pts who did not underwent a tumor nephrectomy (possibly due to high risk) had a survival benefit with 26.3 mos in the Ipi/Nivo arm vs 16.5 mos in the SOC arm (p=0.065) in contrast to nephrectomized pts with 38.9 mos vs 34.0 mos. Conclusions: The OS-Rate at 12 mos was significantly superior for Ipi/Nivo in comparison to SOC and the primary endpoint was met. Additionally, pts in the Ipi/Nivo arm had a longer median OS, especially those with a CPS≥1. Clinical trial information: NCT03075423 .

TPS274 Background: Prostate cancer remains the most common malignancy among men and the fifth leading cause of cancer-related mortality globally. Over the past 15 years, advances in imaging techniques and therapeutic options have significantly transformed the management of recurrent, advanced, and metastatic prostate cancer. However, treatment efficacy and toxicity are highly influenced by prior therapy sequences, highlighting the need for a deeper understanding of the optimal treatment sequence. The prospective real-world evidence registry, PROCARE, addresses this gap by documenting treatment patterns, imaging exams, oncologic outcomes, and safety profiles in routine clinical practice. Methods: This study focuses on four distinct patient cohorts: biochemical recurrence after local treatment with curative intent (e.g. radical prostatectomy, radiotherapy of the prostate or combination thereof), non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic hormone-sensitive prostate cancer (mHSPC), and metastatic castration-resistant prostate cancer (mCRPC). PROCARE is a comprehensive long-term follow-up registry designed to document treatment patterns and outcomes in patients receiving systemic treatment. The study aims to enroll 5,000 patients across 50 sites in Germany. Recruitment is being conducted independently for each cohort, beginning with the mHSPC and mCRPC cohorts. First patient in was in January 2024. Patients will remain in the registry from the time of enrollment until death, withdrawal of consent, or study cohort closure. Throughout the study, additional blood samples will be collected at baseline and with each treatment change, respectively, and at first routine follow-up visit thereafter for exploratory research purposes, such as assessing circulating tumor DNA and RNA, as well as genome-wide single nucleotide polymorphisms (SNPs). This approach will enable a deeper understanding of treatment distribution, sequencing, efficacy, and safety in the real-world setting, contributing valuable insights into the evolving therapeutic landscape. Furthermore, analyses from liquid biopsies might provide important insights potentially guiding future therapeutic strategies for recurrent and metastatic prostate cancer. Clinical trial information: DRKS00033411 .

The recent European Medicines Agency marketing authorisation for belzutifan offers patients with renal cell carcinoma a well-tolerated and effective option for third- and fourth-line treatment. Future studies will assess its efficacy in earlier disease stages.

PURPOSE CheckMate 914 is a two-part, randomized phase III trial evaluating adjuvant nivolumab plus ipilimumab (part A) or adjuvant nivolumab monotherapy (part B) versus placebo in mutually exclusive populations of patients with localized renal cell carcinoma (RCC) at high risk of postnephrectomy recurrence. Part A showed no disease-free survival (DFS) benefit for adjuvant nivolumab plus ipilimumab versus placebo. We report results from part B. METHODS Patients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point. RESULTS Overall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively. CONCLUSION Part B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.

Purpose: To determine accurate organ doses, effective doses, and image quality of computed tomography (CT) compared with cone beam CT (CBCT) for correct identification of prostatic arteries. Method: A dual-energy CT scanner and a flat-panel angiography system were used. Dose measurements (gallbladder (g), intestine (i), bladder (b), prostate (p), testes (t), active bone marrow of pelvis (bmp) and femura (bmf)) were performed using an anthropomorphic phantom with 65 thermoluminescent dosimeters in the pelvis and abdomen region. For the calculation of the contrast-to-noise ratio (CNR) of the pelvic arteries, a patient whose weight and height were almost identical to those of the phantom was selected for each examination type. Results: The effective dose of CT was 2.7 mSv and that of CBCT was 21.8 mSv. Phantom organ doses were lower for CT than for CBCT in all organs except the testes (g: 1.2 mGy vs. 3.3 mGy, i: 5.8 mGy vs. 23.9 mGy, b: 6.9 mGy vs. 19.4 mGy, p: 6.4 mGy vs. 13.2 mGy, t: 4.7 mGy vs. 2.4 mGy, bmp: 5.1 mGy vs. 18.2 mGy, bmf: 3.3 mGy vs. 6.6 mGy). For human pelvic arteries, the CNR of CT was better than that of CBCT, with the exception of one prostate artery that showed stenosis on CT. Evaluation by experienced radiologists also confirmed the better detectability of prostate arteries on CT examination. Conclusions: In our study preprocedural CT had lower organ doses and better image quality comparedd with CBCT and should be considered for the correct identification of prostatic arteries.

AIMS:This retrospective claims data study characterized real-world treatment patterns, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) in Germany. MATERIALS AND METHODS:Continuously insured adults with incident mUC diagnosis (=index; ICD-10: C65-C68/C77-C79) in 2015-2019 were identified from two German claims databases. Patients who received first-line (1 L) treatment within 12 months of index were divided into three mutually exclusive sub-cohorts: platinum-based chemotherapy (PB-CT), non-PB-CT, and immunotherapy (IO). Patient characteristics were assessed during a 24-month baseline period; treatments, HCRU, and costs (of the health insurance fund) per patient-year (ppy) were described during 12-month follow-up. RESULTS:We identified 3,226 patients with mUC (mean age, 73.8 years; male, 70.8%; mean Elixhauser Comorbidity Index, 17.6); 1,286 (39.9%) received 1 L treatment within 12 months of index. Of these, 825 (64.2%) received PB-CT, 322 (25.0%) non-PB-CT, and 139 (10.8%) IO. On average, treated patients had 5.1 hospitalizations ppy. Most UC-related hospitalizations ppy were observed in the PB-CT cohort (5.8), followed by the non-PB-CT (4.2) and IO (2.3) cohorts. Mean UC-related hospitalization costs ppy were €22,218 in the treated cohort, €24,294 in PB-CT, €19,079 in IO, and €18,530 in non-PB-CT cohorts. Cancer-related prescription costs ppy averaged €6,323 in treated patients, and €25,955 in IO, €4,318 in non-PB-CT, and €4,270 in PB-CT cohorts. LIMITATIONS:We recognized limitations in our study's sample selection due to unavailable mUC disease status data. We addressed this through an upstream feasibility study conducted in consultation with clinical experts to determine a suitable proxy. Proxies were also used to delineate treatment lines, switches, and discontinuations due to data absence. Furthermore, due to data restrictions, collective dataset analysis was not possible, prompting a meta-analysis for pooled results. CONCLUSIONS:The study shows that mUC is associated with significant HCRU and costs across different types of 1 L systemic therapy.

Real-world studies have shown that many pts with mUC do not receive first-line (1L) systemic anticancer tx. With the expanding therapeutic landscape for mUC, identifying factors associated with undertreatment to mitigate outcome disparities is essential. This study identified adults with an incident mUC diagnosis (dx; ICD-10 codes C65-68 + C77-79) in 2015-2019 using 2 German statutory health insurance (SHI) claims databases (2013-2020, ≈8 mil. insured). Baseline (BL) characteristics within 24 mo before dx were analyzed. After dx, pts were followed for ≥12 mo or until death. Overall survival (OS) was calculated by Kaplan-Meier estimation. Multivariable logistic regression was performed to determine variables associated with receiving 1L systemic tx. Overall, 3,226 pts with mUC (mean age, 73.8 y; male, 70.8%; mean Charlson Comorbidity Index [CCI] score, 6.3) were identified. Mean follow-up was 13.8 mo. A large portion of pts with mUC (1,892 [58.6%]) did not receive systemic tx within 12 mo of dx. Median OS after dx was notably shorter in untreated vs treated pts: 3.0 vs 13.7 mo for pts in SHI 1 and 3.6 vs 13.8 mo for pts in SHI 2, respectively. Untreated pts were significantly older (age ≥80 y: untreated, 48.2%; treated, 13.5%); had considerably more comorbidities (mean CCI: untreated, 6.8; treated, 5.5); and had a higher care level (untreated, 37.5%; treated, 11.0%). In regression analysis, older age, no prior UC-related surgery/tx, and earlier dx in the study period were associated with a higher likelihood of not receiving tx (Table). Untreated pts with mUC seem to have a shorter OS than treated pts. Identified factors associated with undertreatment, such as older age and increased comorbidity, need to be addressed by offering better tolerated mUC tx and educating pts on the benefits of systemic tx.Table: 2386PFactors associated with receiving mUC tx within 12 mo of mUC dx (multivariable logistic regression using receiving tx as dependent variable)VariableOdds ratio (95% Cl)p valueAge at index (continuous)0.93 (0.92-0.94)<0.001Diagnosis year (reference year, 2015; categorical)1.11 (1.05-1.17)<0.001Previous UC-related tx, surgeries, and interventions (24-mo BL; dummy*)1.65 (1.37-2.00)<0.001CCI (24-mo BL; continuous)0.97 (0.93-1.00)0.011Outpatient diagnosis setting (dummy*)1.28 (1.05-1.54)0.013No. of previous all-cause hospitalizations (24-mo BL; continuous)0.97 (0.94-1.00)0.027Female (dummy*)0.83 (0.69-0.98)0.032*Binary variable with the expressions 0 and 1. Open table in a new tab

A plethora of urine markers for the management of patients with bladder cancer has been developed and studied in the past. However, the clinical impact of urine testing on patient management remains obscure. The goal of this manuscript is to identify scenarios for the potential use of molecular urine markers in the follow-up of patients with high-risk non-muscle-invasive BC (NMIBC) and estimate potential risks and benefits. Information on the course of disease of patients with high-risk NMIBC and performance data of a point-of-care test (UBC rapid™), an MCM-5 directed ELISA (ADXBLADDER™), and 2 additional novel assays targeting alterations of mRNA expression and DNA methylation (Xpert bladder cancer monitor™, Epicheck™) were retrieved from high-quality trials and/or meta-analyses. In addition, the sensitivity of white light cystoscopy (WLC) and the impact of a urine marker result on the performance of WLC were estimated based on fluorescence cystoscopy data and information from the CeFub trial. This information was applied to different scenarios in patient follow-up and sensitivity, estimated number of cystoscopies, and the numbers needed to diagnose were calculated. The sensitivity of guideline-based regular follow-up (SOC) at 1 year was calculated at 96%. For different marker-supported strategies sensitivities ranging from 77% to 97.9% were estimated. Calculations suggest that several strategies are effective for the SOC. While for the SOC 24.6 WLCs were required to diagnose 1 tumor recurrence (NND), this NND dropped below 5 in some marker-supported strategies. Based on the results of this simulation, a marker-supported follow-up of patients with HR NMIBC is safe and offers the option to significantly reduce the number of WLCs. Further research focusing on prospective randomized trials is needed to finally find a way to implement urine markers into clinical decision-making.