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Highlights from the American Society of Radiation Oncology Genitourinary Cancers Symposium |
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| Survey-Based Study of Treatment Sequencing After First Line Enfortumab Vedotin + Pembrolizumab in the Evolving Landscape of Locally Advanced or Metastatic Urothelial Cancer
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| Priyanka V. Chablani, MD
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| Priyanka Chablani presented a survey-based study at ASCO GU 2025, analyzing treatment sequencing after first-line enfortumab vedotin + pembrolizumab for locally advanced or metastatic urothelial cancer. The survey revealed that after progression, most oncologists preferred platinum-based chemotherapy, erdafitinib for FGFR3 alterations, or avoided immune checkpoint inhibitors in the second-line setting. Clinical trial recommendations also favored non-immune checkpoint inhibitor regimens, highlighting the need for more data, especially regarding residual toxicity and HER-2 IHC3+ tumors, to guide treatment choices.
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| Impact of Tumor Burden or Focality in Recurrent Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer on Response to Treatment with UGN-102: A Substudy of the Phase 3 ENVISION Trial
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| Sandip M. Prasad, MD
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| Sandip Prasad presented a substudy from the phase 3 ENVISION trial, evaluating the impact of tumor burden and focality on the response to UGN-102 in recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer. The analysis showed that UGN-102 achieved a high complete response rate at 3 months (79.6%), with no significant difference in response or duration of response based on tumor size or number.
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| Updated Long-Term Follow-up from a Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients with High-Grade Upper Tract Urothelial Carcinoma |
| Viranda Jayalath, MD |
| Viranda Jayalath presented updated long-term follow-up from a phase II clinical trial on gemcitabine and cisplatin as neoadjuvant chemotherapy for high-risk upper tract urothelial carcinoma (UTUC) at ASCO GU 2025. The study involved 57 patients with high-risk localized UTUC, who received 4 cycles of GC before undergoing radical nephroureterectomy (RNU) or distal ureterectomy. |
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| Molecular Subtypes, NECTIN4/HER2 Expression, and Clinical Outcomes in Patients with Advanced Urothelial Carcinoma or Muscle Invasive Bladder Cancer: Exploratory Analyses from JAVELIN Bladder 100 and the Tempus Databases |
| Marcus Eckstein, MD |
| Marcus Eckstein presented an exploratory analysis at ASCO GU 2025 evaluating the relationship between molecular subtypes, NECTIN4, and HER2 expression in advanced urothelial carcinoma (UC) and muscle-invasive bladder cancer (MIBC). The study found heterogeneous expression of both biomarkers across molecular subtypes, with the highest expression in luminal subtypes (LumU, LumP, and LumNS) and the lowest in the NE-like subtype. |
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| Determining an Immunohistochemical Profile to Predict Response to Intravesical Bacillus Calmette–Guérin (BCG) in Patients with High-Grade Non-Muscle Invasive Bladder Cancer |
| Darren Lam, MD |
| Darren Lam presented a study focused on determining an immunohistochemical profile to predict response to intravesical Bacillus Calmette–Guérin (BCG) in high-grade non-muscle invasive bladder cancer (NMIBC). The study found distinct gene expression profiles between BCG responders and non-responders, with non-responders showing higher pro-inflammatory signatures and T-cell exhaustion. |
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| Avelumab First-Line Maintenance in Patients With Advanced Urothelial Carcinoma With or Without Diabetes Mellitus: Long-Term Outcomes From JAVELIN Bladder 100 |
| Shilpa Gupta, MD |
| The JAVELIN Bladder 100 trial demonstrated that avelumab first-line maintenance significantly prolonged overall and progression-free survival in patients with advanced urothelial carcinoma, regardless of diabetes mellitus status. Median overall survival was extended to 20.8 vs. 14.5 months in patients with diabetes and 24.7 vs. 15.8 months in those without, compared to best supportive care alone. |
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| Efficacy and Safety of Disitamab Vedotin plus Tislelizumab Combined with Re-TURBT in the Treatment of HER-2-High Expression (2+-3+) Non-Muscle Invasive Bladder Cancer at High-Risk and Very High-Risk |
| Jianhui Chen, MD |
| Jianhui Chen presented a trial at ASCO GU 2025 evaluating the combination of disitamab vedotin and tislelizumab with re-TURBT in treating HER2-high expression non-muscle invasive bladder cancer (NMIBC) at high and very high risk. The study aims to assess the efficacy and safety of this triplet regimen, with the primary endpoint being 1-year event-free survival, following promising results from a retrospective study. The trial will include 10 patients and explore outcomes such as bladder-intact disease-free survival and overall survival. |
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| ResQ132A: Phase 2 Trial of Intravesical Gemcitabine Plus N-803 Versus Intravesical N-803 and BCG for Intermediate-Risk NMIBC |
| Sandeep Reddy, MD |
| Sandeep Reddy presented ResQ132A, a phase 2 trial comparing intravesical N-803 + gemcitabine versus N-803 + BCG for intermediate-risk non-muscle invasive bladder cancer (NMIBC). The trial aims to evaluate the complete response rate at 3 months in patients with BCG-naïve intermediate-risk Ta/T1 papillary NMIBC, with secondary endpoints focusing on progression-free survival, overall survival, and cystectomy avoidance. |
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| Nectin-4 Targeted ADC, SHR-A2102, in Patients With Advanced or Metastatic Urothelial Carcinoma: A Phase 1 Study
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| Bixia Tang, MD
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| Bixia Tang presented findings from a phase 1 trial of SHR-A2102, a nectin-4 targeted antibody-drug conjugate, in advanced or metastatic urothelial carcinoma at #ASCOGU2025. The study showed a manageable safety profile, with hematologic toxicities being the most common adverse events. Promising anti-tumor activity was observed, with an objective response rate of 41.9% at 6 mg/kg and 50% at 8 mg/kg, leading to 6 mg/kg Q3W being recommended for further evaluation.
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| Evolution of ctDNA Detection with Next Generation Technology |
| Alexander Wyatt, PhD |
| Alexander Wyatt discussed advancements in ctDNA detection, highlighting its evolving role as a biomarker for bladder cancer. Next-generation technologies improve sensitivity for cancer detection, treatment response monitoring, and resistance profiling. Challenges remain, including clonal hematopoiesis interference and standardization across platforms, but novel epigenomic approaches show promise in refining ctDNA-based diagnostics. |
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| Capturing What You Cannot See: How Can ctDNA Be Used to Improve Clinical Staging for Upper Tract Disease? |
| Roger Li, MD |
| Roger Li presented on the role of ctDNA in improving clinical staging for upper tract urothelial carcinoma (UTUC). Preoperative ctDNA was found to be a poor prognostic factor, with nearly 50% of ctDNA-positive patients experiencing disease progression. Plasma ctDNA alterations were more common in advanced disease, reinforcing its potential in risk stratification and treatment selection. |
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| Beneath the Surface: Unleashing the Potential of ctDNA across the Spectrum of Urothelial Carcinoma |
| Gillian Vandekerkhove, PhD, MSc |
| Gillian Vandekerkhove’s presentation highlighted the expanding role of ctDNA and urine tumor DNA (utDNA) as biomarkers across the urothelial carcinoma spectrum. Liquid biopsy applications range from early cancer detection to treatment response monitoring and minimal residual disease assessment. Ongoing trials are evaluating ctDNA-guided therapy decisions in muscle-invasive and metastatic disease, while emerging technologies, such as epigenomic and fragmentomic analysis, offer new avenues for tumor characterization and precision oncology in bladder cancer. |
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| A First-in-Human Phase 1 Study of LY3866288 (LOXO-435), a Potent, Highly Isoform-Selective FGFR3 Inhibitor (FGFR3i) in Advanced Solid Tumors with FGFR3 Alterations: Initial Results from FORAGER-1 |
| Gopa Iyer, MD |
| The phase 1 FORAGER-1 trial of LY3866288 (LOXO-435), a highly selective FGFR3 inhibitor, showed promising efficacy in FGFR3-altered metastatic urothelial carcinoma, with a 41% objective response rate (ORR) and 90% disease control rate (DCR), including 50% ORR in prior FGFR inhibitor-treated patients. The drug demonstrated a favorable safety profile, avoiding high-grade FGFR1-4-related toxicities common with pan-FGFR inhibitors like erdafitinib. |
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| Datopotamab Deruxtecan (Dato-DXd) in Locally Advanced/Metastatic Urothelial Cancer: Updated Results from the Phase 1 TROPION PanTumor01 Study
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| Funda Meric-Bernstam, MD
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| The phase 1 TROPION-PanTumor01 study of datopotamab deruxtecan in heavily pretreated metastatic urothelial cancer showed an objective response rate of 25% and a median progression-free survival of 6.9 months, with 76% of responders maintaining response at 6 months. The drug demonstrated a manageable safety profile, though grade ≥3 treatment-emergent adverse events occurred in 55% of patients, with two treatment-related deaths.
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| EV-302: Updated Analysis from the Phase 3 Global Study of Enfortumab Vedotin in Combination with Pembrolizumab (EV+P) vs Chemotherapy (Chemo) in Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC) |
| Thomas Powles, MBBS, MRCP, MD |
| The updated analysis of the phase 3 EV-302 (KEYNOTE-A39) trial confirmed the sustained benefit of enfortumab vedotin + pembrolizumab over chemotherapy in previously untreated metastatic urothelial carcinoma. With a median follow-up of ~2.5 years, median overall survival was extended to 33.8 months with EV+P versus 15.9 months with chemotherapy, and median progression-free survival remained 12.5 vs. 6.3 months. |
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| Clinically Advanced Urothelial Bladder Cancer in Young Onset Bladder Cancer (YOUC) Patients: A Genomic Landscape Study |
| Alina Basnet, MD |
| Alina Basnet presented a genomic landscape study of young onset urothelial bladder cancer (diagnosed before age 50). The study compared genomic alterations and biomarkers in 291 young onset cases with 9,120 older cases of clinically advanced urothelial bladder cancer. Key findings included higher levels of HRAS, CCND1, and PTEN mutations in younger patients, but no significant differences in targetable alterations like ERBB2 or FGFR3 between the two groups. |
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| A Phase 1/2 Trial of Durvalumab plus Intravesical Gemcitabine and Docetaxel in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer Patients (HCRN GU16-243: ADAPT-BLADDER Cohort 4) |
| Noah Hahn, MD |
| Noah Hahn presented results from the HCRN GU16-243: ADAPT-BLADDER Cohort 4, a phase 1/2 trial assessing durvalumab plus intravesical gemcitabine and docetaxel in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients. The combination achieved an 89% complete response rate, with 70% of responses ongoing at 12 months. The treatment demonstrated a favorable safety profile, with low rates of Grade 3 adverse events and no new toxicity signals, positioning this regimen as a promising option for BCG-unresponsive NMIBC. |
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| A Phase 2 Trial of Risk Enabled Therapy After Neoadjuvant Chemo-Immunotherapy for Muscle-Invasive Bladder Cancer (RETAIN-2) |
| Pooja Ghatalia, MD |
| Pooja Ghatalia presented RETAIN-2, a phase II trial evaluating ddMVAC chemotherapy plus nivolumab as neoadjuvant chemo-immunotherapy for muscle-invasive bladder cancer (MIBC). Early results show 84.2% metastasis-free survival in the intent-to-treat population and 82% MFS for those undergoing active surveillance, with 60% of AS patients remaining metastasis-free and with an intact, unirradiated bladder. |
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