March 05, 2025
Author: Zeynep Irem Ozay, MD
The treatment landscape of genitourinary (GU) cancers is rapidly evolving, presenting both new opportunities and challenges. On February 12, during the ASCO Genitourinary Cancers Symposium in San Francisco, a special live event brought together leading experts to discuss these advancements. Hosted by Rahul Gosain, MD, MBA, and Rohit Gosain, MD—widely known as the Oncology Brothers—the event featured three focused discussions with six expert panelists. Drawing from the latest ASCO GU data, the panels explored major updates in bladder, prostate, and kidney cancers, offering practical strategies for integrating these findings into patient care.
Bladder Cancer 
Amanda Nizam, MD, of Cleveland Clinic, and Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center, took the stage to share their perspectives on recent advances in bladder cancer. The discussion first focused on muscle-invasive bladder cancer (MIBC). For cystectomy-eligible patients, Dr. Nizam follows the standard approach of neoadjuvant gemcitabine plus cisplatin, followed by surgery. However, she anticipates a shift with the expected US Food and Drug Administration approval of perioperative durvalumab, based on NIAGARA trial data showing improved event-free and overall survival. She emphasized NIAGARA’s “paradigm-shifting” nature as the first perioperative study in bladder cancer to demonstrate an overall survival advantage. Dr. Rosenberg acknowledged that while many clinicians are eager to adopt this regimen, regulatory approval is pending. He added that split-dose cisplatin can allow a wider range of patients to qualify. Both panelists viewed circulating tumor DNA (ctDNA) as an investigational tool rather than a routine one for guiding neoadjuvant therapy, citing a lack of definitive data on its role in treatment decisions.
For patients ineligible for cystectomy or those who decline surgery, both experts favor chemoradiation, recognizing the challenge of balancing efficacy and tolerability. Dr. Rosenberg emphasized the preference for cisplatin over carboplatin due to its superior efficacy in a curative setting. Since carboplatin is generally considered less effective for MIBC, he recommended using dose modifications and growth factors to support cisplatin administration rather than switching to carboplatin.
When the discussion moved to metastatic disease, Dr. Nizam mentioned enfortumab vedotin (EV) plus pembrolizumab as a new gold standard frontline regimen, referencing the EV-302 trial’s doubling of overall survival. She noted that most patients, except those with severe neuropathy or absolute contraindications to immunotherapy, can tolerate this approach. Both physicians agreed that EV’s adverse effects of neuropathy, hyperglycemia, and skin toxicity require close monitoring and dose adjustments.
The panel concluded with an overview of second-line therapy, highlighting the need for early genomic profiling to identify FGFR3 or HER2 alterations. Dr. Rosenberg routinely performs next-generation sequencing (NGS) at the time of advanced disease diagnosis to proactively guide treatment decisions. He noted that although ertifitinib, an FGFR inhibitor, can extend survival, its long-term use requires careful management due to risks of ocular toxicity and hyperphosphatemia. Meanwhile, trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody–drug conjugate, is generally well tolerated but requires close monitoring for potential interstitial lung disease.
Prostate Cancer 
Rahul Aggarwal, MD, of the University of California, San Francisco, and Tian Zhang, MD, of UT Southwestern, shared their insights on prostate cancer, focusing on treatment decisions in the high-risk, localized setting. Dr. Aggarwal noted the absence of direct randomized trials comparing surgery and radiation, making the choice largely dependent on patient preference, age, and the potential need for salvage therapy. Both panelists emphasized the role of abiraterone for patients with “very high-risk” features—defined as Gleason 8 or higher, T3 disease or above, or prostate-specific antigen (PSA) exceeding 40—favoring radiation over surgery. They also highlighted the increasing use of prostate-specific membrane antigen–positron emission tomography (PSMA-PET) imaging, which frequently reveals micrometastases and often leads to more aggressive up-front systemic treatment strategies.
Both panelists agreed that 2 years of androgen deprivation therapy (ADT) remains the standard. In some cases, they opt for relugolix, an oral gonadotropin-releasing hormone receptor antagonist, as an alternative for patients concerned about cardiac risks or those seeking faster testosterone recovery after treatment. Dr. Aggarwal noted that relugolix can be safely combined with abiraterone or other androgen receptor pathway inhibitors (ARPIs), as supported by later subsets of the HERO trial. However, when used with abiraterone, monitoring of the QT interval is recommended.
The discussion shifted to M0 castration-sensitive prostate cancer (CSPC), with Dr. Aggarwal noting that PSMA PET frequently detects occult metastases in patients initially classified as M0. Given this, he emphasized the importance of treatment intensification, typically combining ADT with an ARPI rather than relying on monotherapy. Dr. Zhang noted that she tailors ARPI selection based on individual patient factors, including adverse effect profiles, comorbidities, and financial considerations such as insurance coverage and co-pays. 
In metastatic castration-sensitive disease (M1 CSPC), Dr. Aggarwal noted that in the real world, only about 60% to 65% of patients receive intensified therapy. He typically considers a triplet approach (chemotherapy, ADT, and an ARPI) for younger, fitter patients with de novo high-volume disease, especially if conventional imaging shows visceral metastases or multiple bone lesions. Both panelists stressed the importance of NGS and genomic testing, regardless of volume or metastatic distribution. They usually introduce genetic counseling and testing early in the treatment course so that identified homologous recombination repair (HRR) defects can inform the next lines of therapy.
Turning to castration-resistant prostate cancer (CRPC), Dr. Zhang noted that true “M0 CRPC” has become increasingly rare with the widespread use of advanced imaging. For patients who remain M0 on conventional scans, the choice of ARPI is guided by PSA doubling time, overall health status, and insurance coverage. Both experts emphasized the critical role of genomic profiling in identifying patients who may benefit from targeted therapies, particularly poly (ADP-ribose) polymerase inhibitors, as the disease progresses to metastatic CRPC. Dr. Zhang highlighted the TALAPRO-2 data, which she believes could expand the use of talazoparib in combination with ARPIs for a broader range of HRR mutations.
The panel wrapped up with a discussion on treatment options for patients whose disease progresses beyond novel hormonal therapies. Panelists prioritize lutetium-177–PSMA therapy (Pluvicto) for patients with strong PSMA-PET avidity. However, if the lesions are PSMA negative or the tumor exhibits a more anaplastic phenotype, Dr. Zhang often turns to cabazitaxel. She also reserves pembrolizumab for microsatellite instability–high (MSI-H) disease, which can produce significant responses.
Kidney Cancer 
David Braun, MD, of Yale Cancer Center, and Elizabeth Plimack, MD, of Fox Chase Cancer Center, began the session by highlighting how, due to the approval of adjuvant pembrolizumab, medical oncologists now play a more prominent role in localized renal cell carcinoma (RCC). Dr. Braun typically follows the KEYNOTE-564 eligibility criteria—focusing on intermediate-high or high-risk tumors—and offers a year of adjuvant pembrolizumab after nephrectomy. He acknowledged that overtreatment is inevitable, since the true extent of micrometastatic disease is unknown; however, many of his patients choose to proceed, recognizing the potential to reduce recurrence risk. The panelists briefly discussed the role of ctDNA for surveillance but agreed that its utility in RCC remains limited due to the tumor’s low shedding rate. 
Shifting the focus to advanced or metastatic disease, Dr. Braun noted that for patients with more aggressive disease—particularly those with high-risk features or sarcomatoid histology—he prefers dual immune checkpoint inhibitors (ICIs), such as ipilimumab plus nivolumab, when there is sufficient time to achieve a durable response. For those requiring rapid disease control, he typically opts for an ICI–tyrosine kinase inhibitor (TKI) combination, such as cabozantinib plus nivolumab or lenvatinib plus pembrolizumab. Dr. Plimack emphasized the importance of selecting from established first-line combination regimens as disease burden increases. She highlighted that ipilimumab plus nivolumab has the longest available follow-up data, adding that updated trials with ICI-TKI combinations continue to demonstrate survival benefits. The panelists agreed that no single regimen is definitively superior; each combination has distinct adverse effect profiles, and clinicians should become adept at managing one or two options.
The discussion shifted to toxicity management. Dr. Braun highlighted that immunotherapy can lead to severe immune-related adverse events, such as hepatitis or pneumonitis, which often require steroids and a temporary hold on both agents. When combined with TKIs, adverse effects can overlap, making it crucial to determine the cause. If liver enzyme abnormalities arise, clinicians may pause both treatments briefly to assess improvement before deciding if steroids are necessary. Dr. Plimack emphasized the importance of TKI dose adjustments to optimize tolerability while maintaining efficacy.
For second-line therapy after ICI-based combinations, both panelists consider cabozantinib and tivozanib to be effective TKI options, with belzutifan emerging as a promising alternative. Dr. Braun noted that belzutifan’s most common toxicities—anemia and hypoxia—can often be managed with dose adjustments or erythropoiesis-stimulating agents.
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In summary, the event highlighted how evolving therapies are transforming the treatment of GU cancers. Experts explored shifting treatment paradigms, the expanding role of genomic testing, and strategies for optimizing sequencing and managing toxicity. As research advances, these insights will continue to drive more personalized and effective patient care.