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This is Part 3 of Immunotherapy Approaches in Muscle-Invasive Bladder Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Matthew Galsky, Srikala Sridhar, and Abhishek Tripathi discuss perioperative treatment strategies for a patient with muscle-invasive bladder cancer and borderline renal function. The patient is a 74-year-old man with a history of hypertension who is seen in the ER for lower abdominal discomfort. A CT scan reveals a bladder mass, and labs are notable for a creatinine clearance of 43 mL/min. He undergoes cystoscopy and transurethral resection of the bladder tumor (TURBT). Pathology reveals high-grade urothelial cancer with invasion of the lamina propria but no muscularis propria present in the sample. In the conversation that follows, the faculty discuss the importance of repeat TURBT in patients with high-grade urothelial cancer and no muscularis propria in the pathology specimen, the clinical implications of the NIAGARA study, whether bladder-sparing trimodality approaches could be an option, and more.
This is Part 2 of Immunotherapy Approaches in Muscle-Invasive Bladder Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Matthew Galsky, Srikala Sridhar, and Abhishek Tripathi discuss adjuvant treatment options for a patient with cisplatin-ineligible, pathologic node-positive muscle-invasive bladder cancer. The patient is an 82-year-old woman with a history of non–muscle-invasive bladder cancer who was subsequently treated with intravesical docetaxel plus gemcitabine for high-grade cT1 recurrence. On staging cystoscopy plus transurethral resection of the bladder tumor, she is found to have muscle-invasive bladder cancer. A CT scan reveals bladder wall thickening, and lab work is notable for creatinine clearance of 35 mL/min. She proceeds with radical cystectomy, and pathology reveals pT3N0 urothelial cancer of the bladder, and she has detectable ctDNA. In the conversation that follows, the faculty discuss how to counsel older or frail patients who are not eligible for upfront neoadjuvant chemotherapy, the role of adjuvant immunotherapy, and the impact on ctDNA on outcomes.
This is Part 1 of Immunotherapy Approaches in Muscle-Invasive Bladder Cancer, a three-part video roundtable series. Scroll down to watch the other videos from this roundtable. In this video, Drs. Matthew Galsky, Srikala Sridhar, and Abhishek Tripathi discuss neoadjuvant treatment options for a patient with muscle-invasive bladder cancer and squamous differentiation. The patient is a 65-year-old man with a history of hypertension and type 2 diabetes mellitus who presents with gross hematuria. A CT scan reveals a bladder mass, a single borderline enlarged pelvic lymph node, and mild right-sided hydronephrosis. Lab work is notable for a creatinine clearance of 65 mL/min and urinalysis showing red blood cells. Cystoscopy reveals a bladder tumor, and he undergoes cystoscopy and transurethral resection of the bladder tumor. Pathology reveals muscle-invasive urothelial cancer of the bladder with ~55% squamous differentiation. In the conversation that follows, the faculty discuss the relevance of histology in determining his treatment course, whether immune checkpoint blockade should be considered, the role of local therapy, and more.
Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, and Thomas Powles, MD, PhD, of Barts Cancer Institute and the University of London, discuss phase III findings from two studies: the first, investigating enfortumab vedotin-ejfv and pembrolizumab vs platinum-based chemotherapy in previously untreated patients with locally advanced or metastatic urothelial cancer; and the second, looking at nivolumab plus gemcitabine and cisplatin vs gemcitabine and cisplatin alone in patients with lymph node–only metastatic disease enrolled in the CheckMate 901 trial (Abstracts 4581 and 4565).
Thomas Powles, MD, PhD, of Barts Cancer Institute and the University of London, and Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, discuss clinical outcomes of sacituzumab govitecan-hziy after prior exposure to enfortumab vedotin-ejfv in patients with metastatic urothelial carcinoma, as well as the safety and efficacy of fam-trastuzumab deruxtecan-nxki in patients with HER2-expressing bladder tumors (Abstracts 4502 and 4509).
Andrea B. Apolo, MD, of the National Cancer Institute, National Institutes of Health, discusses the results of the AMBASSADOR Alliance A031501 study, which showed adjuvant pembrolizumab improved disease-free survival vs observation for patients with high-risk muscle-invasive urothelial carcinoma after radical surgery. According to Dr. Apolo, the findings support adjuvant pembrolizumab as a new treatment option for this population (Abstract LBA531).
Rohit K. Jain, MD, MPH, of the H. Lee Moffitt Cancer Center and Research Institute, discusses a novel phase II trial of pembrolizumab plus cabozantinib. The study showed this combination may be efficacious as first-line therapy for patients with metastatic urothelial carcinoma, including those who are ineligible for cisplatin. Further investigation with a focus on predictive biomarkers is ongoing (Abstract 539).
Bishoy M. Faltas, MD, of Weill Cornell Medicine, discusses the biology of upper tract urothelial carcinoma and how it affects treatment, noting that most of these tumors are luminal papillary with a T-cell–depleted immune contexture driven by FGFR3 activation. Phase III trials have confirmed the predicted differential effects of FGFR3 inhibitors in this type of tumor compared with bladder cancer based on biological differences.
David H. Aggen, MD, PhD, of Memorial Sloan Kettering Cancer Center, discusses reportedly the first data to describe an inverse correlation between HER2 immunohistochemistry expression and PD-L1 combined positive score. According to Dr. Aggen, these and other findings by his team may provide a foundation for further HER2-directed advanced bladder cancer studies (Abstract 538).
Michiel S. Van Der Heijden, MD, PhD, of the Netherlands Cancer Institute, discusses phase III results from the global EV-302 study, showing that enfortumab vedotin-ejfv plus pembrolizumab improves outcomes in patients with previously untreated locally advanced metastatic urothelial carcinoma compared with chemotherapy. Overall survival benefit was observed across select prespecified subgroups. According to Dr. Van Der Heijden, this immunotherapy combination is a potential new standard of care for first-line locally advanced metastatic urothelial carcinoma (Abstract LBA530).
Syed Muneeb Alam, MD, of Memorial Sloan Kettering Cancer Center, discusses study findings evaluating links among microsatellite instability status, tumor mutational burden, and response to immune checkpoint blockade in patients with microsatellite instability–high urothelial carcinoma (Abstract 536).
Amanda Nizam, MD, of the Cleveland Clinic, discusses results from the UNITE study, which shows patients with advanced urothelial cancer who were treated with enfortumab vedotin-ejfv (EV) after switch maintenance avelumab had outcomes consistent with data with EV in platinum- and immune checkpoint inhibitor–refractory disease (Abstract 537).
Mark D. Tyson, MD, MPH, of the Mayo Clinic School of Graduate Medical Education, discusses the first results from BOND-003, a phase III study of intravesical cretostimogene grenadenorepvec monotherapy for patients with high-risk non–muscle-invasive bladder cancer that does not respond to Bacillus Calmette-Guérin (BCG) immunotherapy. Recently, the U.S. Food and Drug Administration granted cretostimogene monotherapy Fast Track status in BCG-unresponsive carcinoma in situ with or without Ta/T1 papillary disease.
Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, discusses the combination of erdafitinib and cetrelimab, which demonstrated clinically meaningful activity and was well tolerated in cisplatin-ineligible patients with metastatic urothelial carcinoma and fibroblast growth factor receptor alterations (Abstract 4504).
Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, discusses phase III findings showing that for patients with advanced or metastatic urothelial carcinoma and FGFR alteration who already had been treated with a PD-(L)1 inhibitor, erdafitinib significantly improved overall and progression-free survival, as well as overall response rate, compared with investigator’s choice of chemotherapy (LBA4619).
Christian Pfister, MD, PhD, of Rouen University Hospital, discusses phase III results from the VESPER trial, which showed that dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin provided a better overall survival rate at 5 years and improved disease-specific survival compared with gemcitabine as perioperative chemotherapy in patients with muscle-invasive bladder cancer (Abstract LBA4507).
Shilpa Gupta, MD, of Cleveland Clinic, discusses the results from the EV-103 study and the unmet need for effective first-line therapies in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma. After nearly 4 years of follow-up, the trial findings showed that enfortumab vedotin-ejfv plus pembrolizumab continues to demonstrate promising survival trends with rapid and durable responses in this population (Abstract 4505).
Enrique Grande, MD, of The University of Texas MD Anderson Cancer Center, discusses new findings that show initial responses to induction therapy with atezolizumab plus platinum and gemcitabine did not seem to impact overall survival for patients with metastatic urothelial carcinoma. Cisplatin-treated patients appeared to derive a greater benefit with atezolizumab than did carboplatin-treated patients (Abstract 4503).
Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, provides an overview of the emerging treatments for urothelial cancer, including several new agents in the antibody-drug conjugate and tyrosine kinase inhibitor classes. She describes the clinical activity and toxicities of enfortumab vedotin-ejfv, erdafitinib, and sacituzumab govitecan-hziy.
Vadim S. Koshkin, MD, and Tanya Jindal, BS, BA, both of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discuss results from the retrospective UNITE study of biomarkers of response to the antibody-drug conjugate enfortumab vedotin-ejfv in patients with advanced urothelial carcinoma. Enfortumab vedotin is used widely in treatment-refractory disease, but there have been limited data available on biomarkers that may predict outcomes with this treatment. The UNITE study has now identified several potential biomarkers that need to be validated to help inform clinical decision-making and therapy sequencing. (Abstract 450).
Sumanta K. Pal, MD, introduces his City of Hope colleagues, Hedyeh Ebrahimi, MD, MPH, who discusses the prevalence of dietary modification and supplement use in patients with metastatic renal cell carcinoma, and Daniela Castro, MSc, who discusses expanding eligibility criteria in kidney, prostate, and urothelial cancer trials to more accurately reflect the real-world population and reducing exclusion criteria. (Abstract 662, 612, 34, 453)
Daniel P. Petrylak, MD, of the Yale Cancer Center, discusses a primary phase II analysis of the TROPHY-U-01 study, cohort 2, which evaluated sacituzumab govitecan-hziy in platinum-ineligible patients with metastatic urothelial cancer that progressed after prior checkpoint inhibitor therapy. (Abstract 520).
Matt D. Galsky, MD, of the Icahn School of Medicine at Mount Sinai and Tisch Cancer Institute, discusses results from CheckMate 274, which investigated nivolumab compared with placebo in patients with bladder or upper urinary tract cancer, following radical surgery to remove invasive disease. (Abstract LBA443).
Matt D. Galsky, MD, of the Icahn School of Medicine at Mount Sinai and Tisch Cancer Institute, discusses final overall survival data from the phase III IMvigor130 study, which compared atezolizumab versus placebo, both of which were paired with platinum and gemcitabine in the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma. (Abstract LBA440).
Andrea Necchi, MD, of Italy’s Vita-Salute San Raffaele University and the IRCCS San Raffaele Hospital and Scientific Institute, discusses new data from the KEYNOTE-057 trial on a novel systemic therapy for papillary high-risk non–muscle-invasive bladder cancer. The findings suggest that patients whose disease does not respond to bacillus Calmette-Guérin or who declined or were ineligible for a radical cystectomy may benefit from pembrolizumab monotherapy. (Abstract LBA442).
Aristotelis Bamias, MD, of the National and Kapodistrian University of Athens, discusses results from the phase III IMvigor130 study, which suggest that atezolizumab monotherapy continues to show better tolerability vs chemotherapy for patients with untreated locally advanced or metastatic urothelial carcinoma. (Abstract LBA441).
Roger Li, MD, of the H. Lee Moffitt Cancer Center, discusses results from a phase II single-arm study of CG0070, a cancer-selective oncolytic adenovirus that creates mechanistic synergy with immune checkpoint blockade. In this trial, the virus was combined with pembrolizumab in patients with non–muscle-invasive bladder cancer that is unresponsive to bacillus Calmette-Guérin. At 3 months, 88% of the 35 patients enrolled achieved a complete response (Abstract 666).
Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, discusses recent findings on the safety and antitumor activity of enfortumab vedotin-ejfv given intravenously as monotherapy or in combination with pembrolizumab to previously untreated cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer (Abstract LBA73).
Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, and Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, discuss the 24-month findings from the phase III EV-301 trial, which suggest that enfortumab vedotin-ejfv continues to show a significant and consistent survival advantage over standard chemotherapy in patients with previously treated advanced urothelial carcinoma (Abstract 4516).
Sumanta K. Pal, MD, of City of Hope National Medical Center, discusses findings from the COSMIC-021 study, which showed that cabozantinib plus atezolizumab demonstrated encouraging clinical activity with manageable toxicity in patients with inoperable locally advanced or metastatic urothelial carcinoma. The combination was administered as first-line therapy in cisplatin-based chemotherapy–eligible and –ineligible patients and as second- or later-line treatment in those who received prior immune checkpoint inhibitors (Abstract 4504).
Shilpa Gupta, MD, of the Cleveland Clinic Foundation, discusses an updated consensus definition for standard therapy and clinical trial eligibility for patients with metastatic urothelial cancer who are platinum-ineligible, criteria that are proposed to guide treatment recommendations for this population. This may be especially important now that the U.S. Food and Drug Administration has restricted the use of first-line pembrolizumab to those who are considered platinum-ineligible (Abstract 4577).
Karim Chamie, MD, of the University of California, Los Angeles, discusses final clinical results on combining the superagonist N-803 with bacillus Calmette-Guérin (BCG) in patients whose carcinoma in situ and high-grade non–muscle-invasive bladder cancers are unresponsive to BCG alone. Of note, cystectomy was avoided in more than 90% of patients with 2 years of follow-up (Abstract 4508).
Thomas W. Flaig, MD, of the University of Colorado Cancer Center, discusses the rapidly changing treatment landscape for patients with bladder cancer, including PD-1 and PD-L1 inhibitors now approved for urothelial carcinoma; a category 1 indication for pembrolizumab in metastatic disease, post-platinum treatment and for non–muscle-invasive bladder cancer; enfortumab vedotin-ejfv for subsequent-line use; and erdafitinib for those with select FGFR mutations.
Sumanta K. Pal, MD, of City of Hope National Medical Center, discusses some key research developments in kidney cancer, including data on nivolumab and ipilimumab with or without CBM588 in metastatic renal cell carcinoma; intestinal microbiome associated with the development of grade 3 or 4 adverse events in patients with metastatic disease who have been treated with nivolumab plus ipilimumab and probiotic support; the link between TERT promoter mutations and clinical outcome with immune checkpoint inhibitor therapy for advanced urothelial cancer; mutations in the androgen receptor gene in patients with prostate cancer receiving novel androgen deprivation treatments; and findings on waning antibody titers in patients who have received COVID-19 vaccinations (Roundup of Abstracts 371, 561, 374, Posters 38 and 48).
Petros Grivas, MD, PhD, of the University of Washington and Fred Hutchinson Cancer Research Center, discusses results from Cohort 3 of the TROPHY-U-01 study, which assessed sacituzumab govitecan-hziy in combination with pembrolizumab in patients with metastatic urothelial cancer who experienced disease progression after platinum-based regimens (Abstract 434).
Massimo Di Maio, MD, of the University of Turin, discusses the Meet-URO12 study, which showed that maintenance niraparib plus best supportive care (BSC) did not prolong progression-free survival, compared with BSC alone, among patients with urothelial cancer that did not progress after first-line platinum-based chemotherapy.
Jonathan E. Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, discusses phase II findings from the BAYOU trial, which studied durvalumab in combination with olaparib for first-line treatment of platinum-ineligible patients with unresectable, stage IV urothelial carcinoma. Because secondary analyses indicated a potential progression-free survival benefit with this combination, there may be a role for PARP inhibitors in the treatment of advanced disease with homologous recombination repair mutation (Abstract 437).
Karen E. Knudsen, PhD, MBA, Chief Executive Officer of the American Cancer Society, discusses ways to address the inequities in genitourinary screening, treatment, and outcomes. Her suggestions focus on increasing awareness of screening, identifying risk factors, the dramatic rise in incidence among Hispanic individuals, and the basis for increased mortality in Black men.
Wesley Yip, MD, of Memorial Sloan Kettering Cancer Center, discusses phase II results on neoadjuvant gemcitabine and cisplatin for high-grade upper tract urothelial carcinoma, which was well tolerated and demonstrated a favorable pathologic response rate. Dr. Yip notes that this treatment, given prior to nephroureterectomy, did not significantly delay surgery or increase perioperative complication rates.
Simon J. Crabb, PhD, MBBS, of the Southampton Experimental Cancer Medicine Centre, discusses data from the ATLANTIS trial, in which the authors hypothesized that switch maintenance therapy with the PARP inhibitor rucaparib, in patients who have derived clinical benefit from first-line chemotherapy, may improve outcomes for those with metastatic urothelial carcinoma that harbored a composite biomarker for DNA repair deficiency (Abstract 436).
Daniel P. Petrylak, MD, of Yale Cancer Center, discusses new data on the antitumor activity of neoadjuvant treatment with enfortumab vedotin-ejfv monotherapy in patients with muscle-invasive bladder cancer who are not eligible for cisplatin.
Thomas Powles, MD, PhD, of Queen Mary University of London, discusses phase II results from the NORSE study, which showed that the kinase inhibitor erdafitinib plus the monoclonal antibody cetrelimab produced meaningful responses in cisplatin-ineligible patients with first-line metastatic or locally advanced urothelial carcinoma and fibroblast growth factor receptor (FGFR) alterations (Abstract LBA27).
Peter H. O’Donnell, MD, of The University of Chicago, discusses response and survival results from the phase II KEYNOTE-052 study, which showed that after up to 5 years of follow-up, pembrolizumab continued to elicit clinically meaningful, durable antitumor activity in cisplatin-ineligible patients with advanced urothelial cancer (Abstract 4508).
Matt D. Galsky, MD, of the Tisch Cancer Institute at Icahn School of Medicine at Mount Sinai, discusses results from a phase II trial designed to test gemcitabine and cisplatin plus nivolumab as neoadjuvant therapy in patients with muscle-invasive bladder cancer and to better predict benefit in those who opted out of cystectomy (Abstract 4503).
Sumanta K. Pal, MD, of City of Hope, discusses results from a phase II study that sought to determine whether adding berzosertib, a selective ATR inhibitor, to the standard upfront chemotherapy regimen of cisplatin with gemcitabine may improve outcomes in patients with metastatic urothelial carcinoma (Abstract 4507).
Enrique Grande, MD, PhD, of The University of Texas MD Anderson Cancer Center, Madrid, discusses phase III overall survival results from the IMvigor130 study of atezolizumab plus platinum and gemcitabine vs placebo plus platinum and gemcitabine in patients with previously untreated metastatic urothelial carcinoma (Abstract CT187).
Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, discusses the changing therapeutic landscape in which atezolizumab, avelumab, and pembrolizumab have either been approved or are under review for treating urothelial bladder cancer in the metastatic, superficial, and adjuvant settings.
Tracy L. Rose, MD, of the University of North Carolina at Chapel Hill, discusses phase II results of gemcitabine and split-dose cisplatin plus pembrolizumab as neoadjuvant therapy prior to radical cystectomy for patients with muscle-invasive bladder cancer. The trial showed this combination treatment is generally safe and may improve pathologic downstaging, but further study is warranted (Abstract 396).
Elizabeth R. Plimack, MD, of Fox Chase Cancer Center, discusses key abstracts discussed at this year’s meeting on bladder cancer and offers her views on the latest trends and findings (Abstracts 391, 393, 434).
A spirited discussion ensued when we asked Christopher Sweeney, MBBS, of Dana-Farber Cancer Institute, and Thomas Powles, MD, PhD, of Cancer Research UK Barts Centre, to compare notes on how they treat bladder, prostate, and kidney cancers.