The integration of immune checkpoint inhibitors into perioperative management marks a major evolution in curative-intent oncology. This review examines the current evidence for perioperative immunotherapy encompassing neoadjuvant, adjuvant, and combined strategies in melanoma and non-melanoma skin cancers, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), esophageal and gastroesophageal junction cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, gynecological malignancies, and hepatocellular carcinoma. Neoadjuvant immunotherapy demonstrates biological advantages by exposing the immune system to intact tumor antigens, consistently improving event-free survival and pathological response rates across tumor types. Notable successes include CheckMate 816 in NSCLC, KEYNOTE-522 in TNBC, and emerging trials in melanoma that show superior outcomes compared to adjuvant-only approaches. Pathological complete response and major pathological response have emerged as robust surrogate endpoints correlating with long-term survival. In contrast, adjuvant immunotherapy shows more variable results, with demonstrated recurrence-free survival benefits but inconsistent overall survival (OS) advantages-particularly concerning given the risk of overtreatment in patients potentially cured by surgery alone. Critical challenges include the absence of predictive biomarkers in most cancer types, immune-related adverse events occurring in up to 30% of patients, substantial healthcare costs, and insufficient OS follow-up duration in many approved indications. Future priorities include biomarker development, adaptive trial designs incorporating response-guided therapy, and long-term toxicity assessment. Although perioperative immunotherapy is reshaping curative-intent cancer treatment, optimal patient selection, treatment sequencing, and safety optimization remain essential for widespread implementation.

The International Bladder Cancer Group (IBCG) has proposed a prognostic model for intermediate risk (IR) non-muscle invasive bladder cancer (NMIBC) for clinical decision-making. We applied the IBCG IR model in a population-based Swedish setting in patients with primary IR NMIBC diagnosed 2013–2014 in BladderBaSe 2.0. Patients were stratified into low-risk (unifocal and tumour size < 3 cm) and intermediate-risk (multiple and/or tumour size ≥ 3 cm) for estimation of 1- and 3-year recurrence-free survival (RFS). Among 710 patients with IR NMIBC, 329 (46%) and 381 (54%) were categorized as low- and intermediate-risk, respectively. Probabilities of disease recurrence or death at 1 and 3 years in low-risk patients were 19% (95% confidence interval [CI]: 15–23) and 41% (95% CI: 35–46), versus 27% (95% CI: 22–31) and 45% (95% CI: 40–50) in the intermediate-risk group. In a sensitivity analysis including only patients receiving serial adjuvant instillations (n = 152) the corresponding probabilities at 1 and 3 years were 19% (95% CI: 10–28) and 33% (95% CI: 22–43) versus 15% (95% CI: 7–23) and 31% (95% CI: 20–41), respectively. Thus, no clinically meaningful difference in recurrence-free survival was observed between International Bladder Cancer Group low- and intermediate-risk groups in this population-based primary non-muscle invasive bladder cancer setting.

BACKGROUND:Patients receiving neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) have increased risk for venous thromboembolism and bleeding. Leading guidelines acknowledge these risks but provide only weak recommendations on pharmacologic thromboprophylaxis during NAC, potentially contributing to practice variation. We surveyed clinicians to characterize thromboprophylaxis use in this setting. METHODS:We conducted a cross-sectional survey of oncologists and urologists who frequently administer NAC for MIBC in the United Kingdom, Finland, Sweden, Denmark, and Iceland. The survey, distributed by email, asked about clinician characteristics, use of pharmacologic thromboprophylaxis during NAC in MIBC patients, preferred agents, and reasons for withholding therapy. RESULTS:We received 46 responses from 67 invited clinicians (69%), including 44 oncologists and 2 urologists. Respondents had a median of 12 years in specialist practice and treated a median of 15 MIBC patients with NAC annually. More than half (57%) prescribed thromboprophylaxis to none, 15% to 1% to 9% of patients, 22% to 10% to 49%, and 7% to more than 50%. The main reasons for withholding therapy were insufficient evidence of benefit (57%) and concerns about bleeding (28%). CONCLUSION:Our sample of practicing clinicians reported limited and heterogeneous use of thromboprophylaxis during NAC in MIBC patients, largely driven by lack of evidence and perceived risk of bleeding. More trustworthy evidence and practice guidelines are much needed.

Abstract Multiplexed imaging approaches of various molecular modalities in tissues are becoming increasingly adopted in discovery and translational studies. For clinical implementation, novel instrumentation, complex analysis workflows and high costs per sample are bottlenecks that hinders broader introduction in the clinical setting. Here, we demonstrate a cost efficient integrated workflow that combines multiplexed immunofluorescence of a handful of protein markers, with in situ proximity ligation assay, to detect direct protein interactions between neighboring cells. As a proof of concept case of relevance for clinical adaptation, we target the major immunotherapy signalling axis of programmed death receptor 1 (PD-1) and its ligand PD-L1, to demonstrate the interaction between immune cells in germinal centers of tonsil tissue and in a tertiary lymphoid structure in bladder cancer tissue, respectively, from a patient treated with immunotherapy.

Abstract Effective predictive biomarkers for immune checkpoint inhibitor (ICI) therapy remain an unmet need across solid tumors. Here, we present an integrated spatial proteomics workflow that combines in situ proximity ligation assay with multiplexed immunofluorescence to directly resolve PD-1/PD-L1 signaling events at the level of defined cellular phenotypes and their spatial organization within intact tumor tissue. Applied as a proof-of-concept to tumor samples from patients with metastatic urothelial carcinoma treated with pembrolizumab, this approach reveals that PD-1/PD-L1 interactions specifically involving cytotoxic CD8⁺ T cells are significantly enriched in complete responders, while such interactions are rare in patients with progressive disease. This interaction-defined T cell subset achieves superior discrimination of clinical response compared to single-marker PD-L1 expression or immune cell abundance alone. By integrating direct detection of protein–protein interactions with high-dimensional single-cell phenotyping, our workflow provides a mechanistically informed, spatially resolved biomarker of functional immune engagement. Beyond urothelial carcinoma, this platform establishes a generalizable framework for translating spatial signaling biology into predictive tools for immunotherapy response across tumor types. One Sentence Summary In situ detection of PD1/PD-L1 interactions between cancer cells and cytotoxic T cells predicts response to immunotherapy in urothelial carcinoma

BACKGROUND:Patients with muscle-invasive bladder cancer who are ineligible for cisplatin-based chemotherapy proceed directly to radical cystectomy with pelvic lymph-node dissection. Perioperative therapy may improve outcomes in this population. METHODS:In this phase 3, open-label trial, participants with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy were randomly assigned to perioperative (neoadjuvant and adjuvant) enfortumab vedotin, an antibody-drug conjugate directed at nectin-4, plus pembrolizumab and surgery (9 total cycles of enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] plus 17 total cycles of pembrolizumab [200 mg on day 1 every 3 weeks], with surgery after 3 cycles) or surgery alone (control). The primary end point was event-free survival. Key secondary end points were overall survival and pathological complete response (absence of viable tumor after surgical resection). Other secondary end points included safety. RESULTS:A total of 344 participants underwent randomization (170 in the enfortumab vedotin-pembrolizumab group and 174 in the control group). At data cutoff, median follow-up was 25.6 months (range, 11.8 to 53.7). Surgery was performed in 87.6% of participants in the enfortumab vedotin-pembrolizumab group and in 89.7% in the control group. At 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin-pembrolizumab group and 39.4% in the control group (hazard ratio for an event or death, 0.40; 95% confidence interval [CI], 0.28 to 0.57; two-sided P<0.001); estimated overall survival was 79.7% and 63.1% (hazard ratio for death, 0.50; 95% CI, 0.33 to 0.74; two-sided P<0.001). A pathological complete response had occurred in 57.1% and 8.6% of the participants (estimated difference, 48.3 percentage points; 95% CI, 39.5 to 56.5; two-sided P<0.001). Adverse events occurred in all participants in the enfortumab vedotin-pembrolizumab group (grade ≥3, 71.3%; grade ≥3 drug-related, 45.5%) and in 64.8% in the control group (grade ≥3, 45.9%). CONCLUSIONS:Perioperative enfortumab vedotin plus pembrolizumab and surgery led to significantly better event-free and overall survival outcomes and a greater percentage of participants with pathological complete response than surgery alone in a predominantly cisplatin-ineligible population with muscle-invasive bladder cancer. Safety was also assessed. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-905 ClinicalTrials.gov number, NCT03924895.).

4510 Background: In KEYNOTE-905/EV-303 (NCT03924895), neoadj-adj EV + pembro and radical cystectomy (RC) + pelvic lymph node dissection (PLND) showed significant and meaningful improvements in EFS, OS, and pathologic complete response vs RC + PLND in pts with MIBC who were ineligible for or declined cisplatin (cis) therapy. Prespecified exploratory HRQoL outcomes are reported. Methods: Pts with MIBC who were ineligible/declined cis were randomized 1:1 to neoadj-adj EV + pembro and RC + PLND or RC + PLND (control). HRQoL was analyzed in pts who completed ≥1 PRO assessment. EQ-5D-5L and Functional Assessment of Cancer Therapy (FACT)–Bladder-Cystectomy (Bl-Cys) with FACT-general (FACT-G) and Bladder Cancer Index (BCI) were assessed predose on D1 of neoadjuvant cycles 1 (baseline [BL]), 2, and 3; pre- and post-surgery; and predose on D1 of adjuvant cycles 1, 2, 4, 8, and 12 in the EV + pembro arm. In the control arm, assessments were at pre- (BL) and post-surgery. In both treatment (Tx) arms, assessments were also done at Tx discontinuation, Q12W for ≤2y, and Q24W thereafter. End points included mean (95% CI) change from BL to post-surgery wk 18 in FACT-G score; FACT–Bl-Cys scores (Bl-Cys subscale and Trial Outcome Index [TOI]); BCI urinary, bowel, and sexual scores; and EQ-5D-5L visual analog scale (VAS). Results: At post-surgery wk 18, completion and compliance rates for all assessments were ≥65% in the EV + pembro arm and >86% in the control arm. Mean changes from BL to post-surgery wk 18 were similar between arms for FACT-G total and FACT–Bl-Cys subscale scores; FACT–Bl-Cys TOI score; BCI urinary, bowel, and sexual scores; and EQ-5D-5L VAS score (Table). BCI sexual and bowel score diminution was observed in both arms. For all PRO assessments, mean changes from BL over time were similar between Tx. Conclusions: The addition of neoadj-adj EV + pembro did not decrease HRQoL 18 wk post-surgery relative to RC + PLND alone; BCI bowel and sexual domains worsened in both arms, consistent with prior reports of RC impact. Given the superior efficacy and manageable safety, these results support the benefit/risk profile of EV + pembro and RC + PLND as Tx for pts with MIBC ineligible for or declining cis. Clinical trial information: NCT03924895 . Mean change from BL to post-surgery wk 18, (95% CI), n EV + pembro Control FACT-G total score −2.73 (−6.22 to 0.75)n = 102 −2.84 (−6.11 to 0.43)n = 75 FACT–Bl-Cys (subscale/symptom index) total score 1.31 (−0.70 to 3.32)n = 102 1.85 (−0.59 to 4.29)n = 75 FACT–Bl-Cys TOI −1.89 (−5.61 to 1.84)n = 102 −0.58 (−4.35 to 3.20)n = 75 BCI urinary −2.03 (−6.12 to 2.07)n = 101 −0.05 (−5.90 to 5.80)n = 70 BCI bowel −4.75 (−8.73 to −0.77)n = 101 −4.27 (−7.93 to −0.61)n = 70 BCI sexual −15.46 (−20.53 to −10.39)n = 94 −17.88 (−24.36 to −11.40)n = 61 EQ-5D-5L VAS −2.52 (−7.23 to −2.19)n = 102 −0.39 (−5.14 to 4.36)n = 75

Upper tract urothelial carcinoma is a rare disease entity with complex diagnostic and treatment options. In the Swedish National Quality Register for Bladder and Urinary Tract Cancer (SNRUBC), prospective registration of tumour and treatment characteristics is performed with high coverage, where data including quality indicators are presented online (RODRET). Between 2023 and 2024 regional differences in the majority of quality indicators are observed in the SNRUBC, with target levels only met in a few regions. For some quality indicators, such as proportion of patients referred to multidisciplinary tumour board discussion or proportion receiving curative treatment and perioperative lymphadenectomy, an association with better performance and hospital volume above 10 patients per year was observed. A regional centralization of multidisciplinary tumour boards for these patients might decrease regional inequalities and improve quality metrics.

BACKGROUND AND PURPOSE:Clinical tools to optimally select real-world metastatic renal cell carcinoma (mRCC) patients for treatment with ipilimumab-nivolumab remain to be identified. PATIENT AND METHODS:Medical records of the first 100 mRCC patients treated with ipilimumab-nivolumab at three Swedish centers were retrospectively analyzed. Data on International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, baseline levels of routine blood markers, and tumor burden were collected. Outcome variables were progression-free survival (PFS), overall survival (OS), and radiological response (RR) according to clinical routine imaging. RESULTS:At a median follow-up of 22 months, 65% had progressed or died with a median PFS of 7 months and an estimated median OS of 28 months. The RR rate was 45%, including 11% complete responses (CR). 29% had progressive disease as best response. IMDC poor-risk patients had shorter mPFS (4 vs 14 months; HR [hazard ratio] 1.90; P = 0.009), shorter mOS (12.5 months vs not reached; HR 4.27; P < 0.0001), and lower CR rate (3% vs 16%, P = 0.06) than IMDC intermediate/favorable patients. C-reactive protein (aHR 2.67; P = 0.040), albumin (aHR, 2.13; P = 0.039), neutrophil-lymphocyte-ratio (aHR, 2.8; P = 0.009), and > 2 metastatic sites (aHR, 2.13; P = 0.024) were associated with OS after adjusting for IMDC risk. Prior nephrectomy was not (aHR, 0.84; P = 0.62). A normal C-reactive protein was associated with an increased likelihood of CR (OR 7.2; P = 0.017). INTERPRETATION:Baseline blood markers and number of metastatic sites add prognostic value independently of IMDC risk in real-word mRCC patients treated with ipililmumab-nivolumab.

Background:Guidelines recommend neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). Current recommendations do not consider genomic profiles, although the Basal/Squamous (Ba/Sq) subtype is less likely to respond to NAC compared to Urothelial-like (Uro) and Genomically Unstable (GU) subtypes. The aim of this study is to perform cost-effectiveness analyses of a de-escalated use of NAC in patients with Ba/Sq tumors and MIBC. Methods:A cost-effectiveness analysis was performed using a decision analytic Markov model using a healthcare provider perspective. Treatment and prognosis probabilities originated from the Bladder Cancer Data Base, Sweden (BladderBaSe) 2.0. Information on molecular subtype and outcomes was retrieved from published studies, and quality-adjusted life year (QALY) data were obtained from the iROC trial. Costs were collected from the regional healthcare registers in Sweden, utility values were obtained from the literature, and outcomes are presented as incremental cost-effectiveness ratio (ICER). Scenario analyses, along with several one-way and probabilistic sensitivity analyses were performed to capture uncertainties. Results:At a 5-year time horizon, the model predicts that molecular subtype-based treatment has an ICER of 4,964 Euro/QALY (66,766 Swedish Krona/QALY), which is deemed cost-effective in the Swedish setting. At €7,427 (100,000 SEK) willingness-to-pay threshold, the molecular subtype-based treatment has a 65% probability of being cost-effective. The results were not sensitive to uncertainty analyses. Conclusion:Molecular subtype-based treatment of MIBC, i.e., refraining from administering NAC to patients with Ba/Sq tumors, is cost-effective compared to the current treatment practices in Sweden.

Objectives:To investigate the risk of upper urinary tract urothelial carcinoma (UTUC) in patients with non-muscle-invasive bladder cancer (NMIBC), in relation to the primary NMIBC tumour risk categories, calendar time trends and intravesical Bacillus Calmette-Guerin (BCG) treatment. Patient and methods:All patients with primary NMIBC diagnosed 1997-2019 registered in Bladder Cancer Data base Sweden (BladderBaSe) 2.0 were included in the study. Risk of UTUC was calculated by cumulative incidence proportion using competing risk analysis. Associations with risk of UTUC by tumour stage category, calendar time, and intravesical BCG treatment was estimated by hazard ratios from multivariable Cox regression analyses. Results:Of 36 038 NMIBC patients, 537 (1.5%) were diagnosed with UTUC during a mean time of 7 years in follow-up. The risk of UTUC within 10 years from NMIBC diagnosis was 1.7% (95% 1.6-1.9) with highest estimates for TaG3/CIS. Stage T1 and TaG3/CIS, as compared with TaG1-2 was associated to risk, with stronger associations during later calendar times. Within high-risk NMIBC patients (CIS/TaG3/T1), intravesical BCG treatment was associated with higher risk of UTUC. Conclusions:This large study of more than 36 000 patients with NMIBC found 1.7% (95% 1.6-1.9) risk of UTUC within 10 years of diagnosis. Differences by tumour stage category indicate the need for refined studies accounting for tumour characteristics, location in the bladder and given treatment to optimise follow-up routines in NMIBC.

BACKGROUND AND OBJECTIVE:The aim of this study was to evaluate the prognostic value of undetectable circulating tumor DNA (ctDNA) and the dose-response relationship between ctDNA levels and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC). METHODS:We analyzed data for patients enrolled in the ProBio trial up to November 2022 who received an androgen receptor pathway inhibitor or taxane. We compared survival outcomes between patients with undetectable ctDNA and those with detectable ctDNA randomized to physician's choice or investigational arms. Time to no longer clinically benefiting (NLCB) and overall survival (OS) were assessed using Bayesian survival models, with results reported as survival time ratios (STRs). Dose-response relationships were estimated using spike-at-zero models. KEY FINDINGS AND LIMITATIONS:A total of 220 patients were included, of whom 139 had detectable ctDNA (56 in the physician's choice arm, 83 in investigational arms) and 81 had undetectable ctDNA. In comparison to the undetectable ctDNA group, the physician's choice arm had 60% shorter time to NLCB (STR 0.40, 90% credible interval [CrI] 0.31-0.51) and 51% shorter OS (STR 0.49, 90% CrI 0.38-0.61). Similar results were observed in comparison to the investigational arms. Dose-response analysis revealed that the undetectable ctDNA group had twofold longer time to NLCB (STR 2.05, 90% CrI 1.66-2.57) and 1.6-fold longer OS (STR 1.63, 90% CrI 1.33-2.05) in comparison to the subgroup with a ctDNA fraction of 2.5%. Every 10-point increment in the ctDNA fraction corresponded to a 10% reduction in NLCB and OS times. CONCLUSIONS AND CLINICAL IMPLICATIONS:Undetectable ctDNA at baseline predicts superior prognosis in mCRPC, suggesting potential for treatment de-escalation and less intensive monitoring for this subgroup of patients. This trial is registered on ClinicalTrials.gov as NCT03903835.

In the JAVELIN Bladder 100 randomized phase 3 trial (N = 700), avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (aUC) without progression after first-line platinum-based chemotherapy (PBC). Here, we report exploratory analyses of subgroups with nonvisceral metastases at the start of PBC (including bone metastases) or lymph node-only disease at randomization. The median OS with avelumab versus control in patients with nonvisceral metastases (n = 318) was 31.4 versus 17.1 mo (hazard ratio [HR], 0.60 [95% confidence interval {CI}, 0.45-0.79]), and in patients with lymph node-only disease (n = 102), it was 31.9 versus 22.7 mo (HR, 0.86 [95% CI, 0.51-1.47]). In patients with nonvisceral metastases, prolonged OS was observed with avelumab irrespective of the response to PBC or PBC regimen received. PFS analyses favored avelumab over control in all the subgroups. Incidences of avelumab-related adverse events were similar across the subgroups. Limitations include small sample sizes and the exploratory nature of analyses. Overall, exploratory analyses suggest that in first-line PBC-treated patients without progression, avelumab maintenance is effective and has a manageable toxicity profile in patients with aUC who have nonvisceral metastases or lymph node-only disease.

Background and purpose: The Measure of Case-Discussion Complexity (MeDiC) tool was created to gauge case complexity at multidisciplinary team meetings (MDTM) for case selection and prioritization. We aimed to assess applicability and association with MeDiC score and non-compliance with national guideline-recommendations for MDTM referral in a bladder cancer setting. Material and methods: A modified MeDiC scoring system was applied in 8955 subjects with localized (T1-T4N0M0) or metastasized disease as per the Bladder Cancer Data Base Sweden (BladderBaSe) 2.0. Association between MeDiC score and not being discussed at MDTM was investigated by multivariable logistic regression, and further explored in relation to calendar time period, healthcare region, age at diagnosis and hospital volume. Results and interpretation: Median total MeDiC score was lower in individuals not being discussed at an MDTM (7.0 Inter Quartile Range [IQR] 6.0–9.0) compared to those who were (8.0 IQR 6.0–10.0). Adjusted odds ratio for not being discussed at an MDTM was 2.1 (95% confidence interval [CI] 1.8–2.4) for a MeDiC score in the lower quartile, as compared to the highest quartile, with higher estimates when performing stratified analyses in later calendar years and in specific healthcare regions. Our data indicate that the MeDiC score is applicable in bladder cancer patients, and we identified an association between lower MeDiC score and not being discussed at an MDTM.

The European Association of Urology (EAU) 2021 prognostic model for non-muscle-invasive bladder cancer (NMIBC) is based on the World Health Organization (WHO) 1973 and/or WHO 2004/2022 grading systems for patients who did not receive bacillus Calmette-Guérin (BCG) instillations and is widely used to assess the risk of progression. The estimated risk of progression affects the type of adjuvant intravesical instillation (chemotherapy or BCG), with primary radical cystectomy recommended for patients with the highest risk of progression. We applied the EAU 2021 prognostic model in a population-based setting for 3392 patients with primary NMIBC diagnosed in 2013-2014 according to the BladderBaSe 2.0 database. We assessed the model calibration by comparing the 5-yr progression probability observed in our cohort with the predicted progression probability assigned for the risk groups in the original EAU study, and evaluated the discrimination according to Harrell's C index. At 5-yr follow-up, 394 patients had experienced disease progression. The progression probability observed was 4.9% (95% confidence interval [CI] 3.5-6.3%), 8.6% (95% CI 6.9-10%), 25% (95% CI 22-28%), and 23% (95% CI 14-30%) for the low-, intermediate-, high-, and very high-risk groups, respectively. The discrimination at 5 yr was 0.72 (95% CI 0.69-0.78) for the overall cohort and 0.74 (95% CI 0.70-0.80) in the group excluding the 811 patients who received BCG instillations. Showing moderate predictive ability, the EAU 2021 prognostic model has clinical utility in population-based settings despite underestimation of the observed progression risk in the low- and high-risk groups in the current study. Patient summary:We looked at how well a model predicted the risk of progression of non-muscle-invasive bladder cancer using results for a group of Swedish patients. Approximately one in four patients in the high-risk category progress to more advanced disease within 5 yr. Doctors and patients need to consider the probability of progression in the high-risk category when making shared decisions on which treatment is best for an individual patient.

Objectives:To investigate the association between waiting time and outcomes in patients with upper tract urothelial carcinomas (UTUC). Patients and methods:We studied a population-based cohort of 858 patients in BladderBaSe 2.0 subjected to extirpative surgery for UTUC 2015-2019 in Sweden. Diagnostic waiting time (from referral to diagnosis, reference <1 week), treatment waiting time (from diagnosis to surgery, reference <5 weeks) and total waiting time (reference <10 weeks) were investigated in relation to disease-specific (DSS) and overall survival (OS) by multivariable Cox regression models. To further explore these associations, stage progression from preoperatively recorded clinical tumour stage to pathological tumour stage in the extirpated specimen was assessed by logistic regression. Results:Total waiting time was not associated with DSS, OS or stage progression. A diagnostic waiting time between 1 and 4 weeks was associated with better DSS (HR 0.57 [95% CI 0.35-0.94]) and OS (HR 0.60 [95% CI 0.41-0.87]). In the strata of patients with UTUC in the renal pelvis, a diagnostic waiting time > 4 weeks was associated with stage progression (OR 2.44 [95% CI 1.00-5.95]), and in patients with UTUC in the ureter, a treatment waiting time between 5 and 10 weeks was associated to worse DSS (HR 2.85 (95% CI 1.03-7.89). Conclusions:In general, shorter care pathways were linked to beneficial survival estimates, yet some estimates may be influenced by selection bias due to prioritizing short waiting times for patients with advanced and/or overt symptomatic tumours. Stage progression with increased waiting time may indicate an underlying causal mechanism.

Objective: To overview and summarise the Swedish National Guidelines on Urothelial Carcinoma 2024. Methods: A narrative review of the updated guidelines was performed, highlighting new treatment recommendations for advanced and metastasized disease. Results: Compared to the previous guideline version, the current update includes recommendations for standardised radiological reporting when urothelial carcinomas are detected at CT-urography (CTU), to early identify locally advanced patients and accelerate the care pathway for these patients. The Swedish guidelines apply a more structured and liberal recommendation for the use of 18F-fluorodeoxyglucose-positron emission tomography/computed tomography in patients with locally advanced urothelial carcinomas compared to the EAU-guidelines and recommend such examinations prior to transurethral resection. Improved outcomes for radical cystectomy in Sweden after centralised cystectomy care have led to a recommendation for performing more than six nephroureterectomies (NUs) per year for upper tract urothelial carcinomas (UTUC)-based associations with decreased use of invasive diagnostic modalities and better survival outcomes. Additionally, updated recommendations regarding adjuvant systemic therapies for muscle-invasive disease have been included. Whilst awaiting national regulatory approval for enfortumab vedotin/pembrolizumab, the present guideline version aligns with EAU-guidelines by endorsing cisplatin-gemcitabine-nivolumab as a new first-line treatment option in cisplatin-fit patients with unresectable or metastatic urothelial carcinoma. Conclusions: The current version of the Swedish national guidelines on urothelial carcinoma introduces standardised reporting at CTU to facilitate early identification of advanced disease, includes recommendations for centralisation of NU for UTUC and updated recommendations for adjuvant systemic treatment of muscle-invasive disease and endorses cisplatin-gemcitabine-nivolumab as a new first-line treatment option for non-resectable locally advanced and metastatic disease.

BACKGROUND:Immune checkpoint inhibitors have become a cornerstone in treatment of metastatic urothelial cancer (mUC), but reliable prognostic and treatment predictive factors remain to be defined. Glucocorticoids (GC) are used to manage immune-related adverse events (irAE), and the potential impact on treatment outcome is still unclear. OBJECTIVES:The aim of this study was to explore the impact of GC treatment alongside clinical parameters on outcome in pembrolizumab-treated mUC patients. MATERIALS AND METHOD:A single-center retrospective real-world study was performed including all consecutive mUC patients in first- or second-line treated with pembrolizumab. Multivariate analyses were used to explore the impact of baseline characteristics on response-rate and overall survival (OS). Landmark analysis was applied to adjust for immortal time bias in survival analyzes. RESULTS:107 patients were included. Patients developing irAE requiring GC treatment had superior OS compared to those who did not (17.6 months vs. 8.8 months, P = 0.003). Ongoing treatment with GC prior to the initiation of pembrolizumab, ECOG PS >1 and liver metastases were independently associated with worse OS. We constructed a risk-score model where the number of zero, 1, 2 or 3 risk factors correlated to an OS of 11.7 months, 3.8 months, and 3.0 months respectively (P < 0.001). CONCLUSION:The development of irAE requiring GC treatment was associated with favorable survial outcomes. Ongoing GC treatment before the commencement of pembrolizumab, ECOG PS >1, and presence of liver metastases were associated with worse OS. We propose a risk-score model to assist clinicians in selecting patients for treatment with pembrolizumab.

Background and objective: It has been suggested that urinary tract infections (UTIs) are associated with delayed diagnosis of bladder cancer (BC). Our aim was to investigate prediagnostic treatments related to UTI and the relation to BC diagnostic delay, reflected by advanced disease at diagnosis. Methods: We used data from the BladderBaSe 2.0 with data of treatments related to UTI up to 3 yr before BC diagnosis (2008-2019) for BC patients in comparison to a matched reference population. We investigated the association between UTI treatments and more advanced disease at diagnosis in the BC cohort. We used generalized ordered logistic regression to calculate odds ratios (ORs) for more advanced disease as an ordered outcome: non-muscle-invasive BC (NMIBC), muscle-invasive BC (MIBC), and metastatic BC (MBC). Key findings and limitations: The study population included 29 921 BC patients and 149 467 matched reference subjects. The proportions of individuals receiving UTI treatment were higher in the patient groups than in the corresponding reference groups, with the greatest differences observed for the MIBC and MBC subgroups. The OR for the risk of more advanced disease (MIBC or MBC) with at least one UTI treatment versus none was 1.28 (95% confidence interval [CI] 1.19-1.37) for men and 1.42 (95 % CI 1.27- 1.58) for women. The association to risk of more advanced disease increased with the number of UTI treatments for both sexes. Conclusions and clinical implications: Further studies on the effects of treatments related to UTI in combination with other factors are needed to identify reasons for possible delays in the BC diagnostic pathway. Patient summary: We found that for patients with bladder cancer, previous antibiotic treatment for a urinary tract infection was linked to more advanced disease at diagnosis. Further studies are needed to identify reasons for possible delays in the diagnosis of bladder cancer. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons.