Summary from the NCI clinical trials planning meeting on next generation of clinical trials in non-muscle invasive bladder cancer.

The National Cancer Institute organized a virtual Clinical Trials Planning Meeting (CTPM) on 'Defining the next generation of clinical trials with combination therapies in non-muscle invasive bladder cancer (NMIBC)' led by the Bladder Cancer Task Force of the NCI Genitourinary Cancers Steering Committee. The purpose of this meeting was to accelerate advances in clinical trials for patients with high-risk NMIBC. The meeting delivered a multidisciplinary expert consensus on optimal strategies for next-generation clinical trial designs in NMIBC with prioritization of combination therapies.

Sarcomatoid areas of urothelial carcinoma are enriched for CD163-positive antigen-presenting cells.

Sarcomatoid urothelial carcinoma (SUC) is a rare histologic subtype with poor prognosis. While there is known intra-tumoral heterogeneity between individual SUC tumors, the relationship between sarcomatoid and conventional urothelial carcinoma (CUC) within the same patient is poorly understood. The objective of this study was to identify differences between the sarcomatoid and CUC tumor microenvironment components that may drive this aggressive phenotype.

Metformin intake and risk of metabolic acidosis after radical cystectomy with urinary diversion: A comparative study using data from the TriNetX research network.

Purpose: To investigate the association of diabetes mellitus and metformin use with metabolic acidosis risk after radical cystectomy (RC) and urinary diversion for bladder cancer.

Materials And Methods: This retrospective cohort study used TriNetX Research Network data. Patients undergoing RC with continent diversion or ileal conduit for bladder cancer were identified using International Classification of Diseases, 10th Revision (ICD-10) and ICD-10 Procedure Coding System (ICD-10-PCS) codes.

Pan-tumor analysis to investigate the obesity paradox in immune checkpoint blockade.

Background: Obesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors (ICIs), a phenomenon called the obesity paradox. To interrogate mechanisms of divergent immune responses in obese and non-obese patients, we examined the relationship among obesity status, clinical responses, and immune profiles from a diverse, pan-tumor cohort of patients treated with ICI-based therapy.

Methods: From June 2021 to March 2023, we prospectively collected serial peripheral blood samples from patients with advanced or metastatic solid tumors who received ICI as standard of care at Johns Hopkins.

Nectin-4 Expression in Prostatic Adenocarcinoma: An Immunohistochemical Study.

Background: The Nectin-4 directed antibody drug conjugate enfortumab vedotin (EV) has emerged as frontline systemic therapy in combination with immune checkpoint blockade for urothelial carcinoma (UC), capitalizing on the ubiquitous expression of this protein in UC. There is limited data available regarding expression of Nectin-4 by immunohistochemistry in prostate cancer, but this is of interest as a substantial number of UC patients likely to receive EV have concomitant prostate cancer.

Methods: Nectin-4 protein expression was evaluated by immunohistochemistry in tissue microarrays encompassing a cohort of 302 prostatic adenocarcinomas spanning Grade Groups 1-5.

Phase II Trial of Risk-Enabled Therapy After Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer (RETAIN 1).

Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Mutations in DNA damage repair genes are associated with pathologic downstaging after NAC. We hypothesized that a combination of biomarker selection and clinical staging would identify patients for cystectomy-sparing active surveillance (AS).

Neoadjuvant Cisplatin, Gemcitabine, and Docetaxel in Sarcomatoid Bladder Cancer: Clinical Activity and Whole Transcriptome Analysis.

Background: Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed.

Objective: We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing.

Methods: A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis.

Enfortumab vedotin-related cutaneous toxicity correlates with overall survival in patients with urothelial cancer: a retrospective experience.

Introduction: Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human monoclonal antibody targeting nectin-4. No validated biomarker predictive of or correlated with response exists for EV. Cutaneous toxicity is among the most common EV-related toxicities and typically emerges in early cycles.

Frontline immune checkpoint inhibitors in patients ≥ 90 years with advanced urothelial cancer: a single center experience.

Introduction: Immune checkpoint inhibitors (ICIs) are approved for advanced urothelial cancer alone and as first-line in combination with enfortumab vedotin. Platinum based chemotherapy which is another frontline choice is often not a treatment option for older patients due to comorbidities that increase with age. Despite ICIs being better tolerated compared to traditional chemotherapy little is known about their efficacy and toxicity in patients ≥ 90 years due to the rarity of this population in clinical trials.

Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates.

Purpose: There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer.

Racial Differences in Cutaneous Events Among Patients Receiving Enfortumab Vedotin.

Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate approved alone and in combination with pembrolizumab for advanced urothelial cancer (UC). EV-related-cutaneous-events (EVCEs) are common and rarely life-threatening. Black patients are frequently under-represented in oncology trials, and dermatologic conditions may vary with race.

Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer.

Background: No treatment has surpassed platinum-based chemotherapy in improving overall survival in patients with previously untreated locally advanced or metastatic urothelial carcinoma.

Methods: We conducted a phase 3, global, open-label, randomized trial to compare the efficacy and safety of enfortumab vedotin and pembrolizumab with the efficacy and safety of platinum-based chemotherapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma. Patients were randomly assigned in a 1:1 ratio to receive 3-week cycles of enfortumab vedotin (at a dose of 1.

Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy.

Background And Objective: Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve.

PET/Computed Tomography Transformation of Oncology: Kidney and Urinary Tract Cancers.

Renal cell carcinoma (RCC) and urothelial carcinoma (UC) are two of the most common genitourinary malignancies. 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) can play an important role in the evaluation of patients with RCC and UC. In addition to the clinical utility of 18F-FDG PET to evaluate for metastatic RCC or UC, the shift in molecular imaging to focus on specific ligand-receptor interactions should provide novel diagnostic and therapeutic opportunities in genitourinary malignancies.

The JAVELIN Bladder Medley trial: avelumab-based combinations as first-line maintenance in advanced urothelial carcinoma.

Results from JAVELIN Bladder 100 established avelumab (anti-PD-L1) first-line maintenance as the standard-of-care treatment for patients with advanced urothelial carcinoma (UC) that has not progressed with first-line platinum-based chemotherapy. We describe the design of JAVELIN Bladder Medley (NCT05327530), an ongoing phase II, multicenter, randomized, open-label, parallel-arm, umbrella trial. Overall, 252 patients with advanced UC who are progression-free following first-line platinum-based chemotherapy will be randomized 1:2:2:2 to receive maintenance therapy with avelumab alone (control group) or combined with sacituzumab govitecan (anti-Trop-2/topoisomerase inhibitor conjugate), M6223 (anti-TIGIT) or NKTR-255 (recombinant human IL-15).

Phase II Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations.

Purpose: Poly (ADP-ribose) polymerase (PARP) inhibitors have demonstrated clinical benefit for patients with solid tumors bearing germline or somatic alterations in DNA damage response (DDR) genes. Somatic alterations in DDR genes are common in advanced urothelial cancer, raising the possibility that PARP inhibition may confer therapeutic benefit in a molecularly selected subgroup of patients with metastatic urothelial cancer (mUC).

Methods: This single-arm, open-label, multi-institutional, investigator-initiated phase II study evaluated the antitumor activity of olaparib 300 mg twice a day in participants with mUC harboring somatic DDR alterations.

Enhancing bladder cancer care through the multidisciplinary clinic approach.

Introduction: To report the impact of our 25-year multidisciplinary care delivery model experience on patients with muscle invasive bladder cancer treated at our National Cancer Institute (NCI)-designated Sidney Kimmel Cancer Center at Jefferson University. To our knowledge, our multidisciplinary genitourinary cancer clinic (MDC) is the longest continuously operating center of its kind at an NCI Cancer Center in the United States.

Materials And Methods: We selected a recent group of patients with cT2-4 N0-1 M0 bladder cancer seen in the Sidney Kimmel Cancer Center Genitourinary Oncology MDC from January 2016 to September 2019.

Diagnosis and Management of Non-Metastatic Upper Tract Urothelial Carcinoma: AUA/SUO Guideline.

Purpose: The purpose of this guideline is to provide a useful reference on the effective evidence-based diagnoses and management of non-metastatic upper tract urothelial carcinoma (UTUC).

Materials/methods: The Pacific Northwest Evidence-based Practice Center of Oregon Health & Science University (OHSU) team conducted searches in Ovid MEDLINE (1946 to March 3rd, 2022), Cochrane Central Register of Controlled Trials (through January 2022), and Cochrane Database of Systematic Reviews (through January 2022). The searches were updated August 2022.

Enfortumab Vedotin-related Cutaneous Toxicity and Radiographic Response in Patients with Urothelial Cancer: A Single-center Experience and Review of the Literature.

Unlabelled: Enfortumab vedotin (EV) is an antibody-drug conjugate approved for the treatment of refractory advanced urothelial cancer. Cutaneous toxicity is well described but has not been correlated with response. In this retrospective single-center study, data from patients treated with more than one dose of EV between December 2017 and June 2022 were analyzed.