Oncology Decoded

• 14: Elevating Community Oncology Care: Insights From World GU 2025

  Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, traveled to the 2025 World Conference on Genitourinary Cancers (World GU) to speak with different experts about important advances and key takeaways related to the care of patients with genitourinary malignancies. Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers. In this episode, Bupathi and Garmezy sat down with Sam S. Chang MD, MBA, and Jeff Yorio, MD, to exchange knowledge on elevating the efficacy of multidisciplinary care for patients with prostate cancer, kidney cancer, and bladder cancer in a community-based setting. Chang is the chief surgical officer and the Urologic Oncology division chief at the Vanderbilt Ingram Cancer Center. Yorio is a medical oncologist who serves as the Central Texas Research Site Leader for Texas Oncology and SCRI. The conversation partly focused on overcoming challenges associated with prostate cancer management in a community practice. Chang highlighted strategies for risk stratifying disease based on previously published guidelines, noting the importance of surveillance depending on a patient’s observed degree of risk. Additionally, the experts discussed how factors such as Decipher® Prostate scores, MRI scans, and prostate-specific antigen (PSA) levels may factor into the decision to surveil patients with prostate cancer.  Regarding kidney cancer, the group spoke about strategies for deciding between monitoring patients or expediting intervention with modalities like nephrectomy or cryoablation. An observed mass of less than 2 cm, for example, represented a situation where surveillance could be optimal. The experts also detailed appropriate circumstances for offering immunotherapy and tyrosine kinase inhibitor (TKI)–based regimens upfront prior to surgery. As part of the discussion on bladder cancer management, the group emphasized improving systemic therapies and locally assessing the bladder more efficiently. Additionally, with a newfound “embarrassment of riches and possibilities” regarding the development and approval of novel intravesical therapies, the experts discussed how medical oncologists can best collaborate with urologists to monitor patients undergoing this type of treatment.

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• 13: Optimizing Care Planning for Variant Histology Populations at World GU 2025

  In this episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, traveled to the 2025 World Conference on Genitourinary Cancers (World GU) to speak with various experts about key advances in genitourinary oncology. As part of one discussion, Bupathi and Garmezy sat down with Bradley G. Somer, MD, to exchange ideas about the management of genitourinary cancers harboring variant histologies, which included such populations as those with prostate cancer, bladder cancer, and kidney cancer. Regarding prostate cancer, the group highlighted potential treatment strategies for patient subgroups such as those with small cell histology or neuroendocrine differentiation. The discussion explored how modalities such as androgen deprivation therapy, chemotherapy, and radiation may factor into the care of patients with prostate cancer harboring variant histologies, especially in the context of a community oncology setting. Next, the conversation focused on methods for managing papillary, plasmacytoid, small cell, and other disease variants in the context of bladder cancer. Based on previously published data and prior clinical experience, the group discussed the appropriate circumstances for implementing regimens such as enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) or other immunotherapy approaches depending on how a patient presents with bladder cancer. Additionally, the group reviewed strategies for managing clear cell, papillary, and chromophobe variants in kidney cancer along with other disease histologies. The experts considered key factors for deciding on when to administer VEGF inhibitors and other tyrosine kinase inhibitor combinations based on the observed histology. Bupathi is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers. Garmezy is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers. Somer is a medical oncologist, senior partner on the Executive Cancer Council, and president at West Cancer Center & Research Institute.

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• 12: Beyond the BEP: A Deep Dive into Testicular Cancer Management

  In this episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, spoke with Nabil Adra, MD, about testicular cancer care. The discussion gave a comprehensive overview of managing germ cell tumors, offering practical pearls for community oncologists. The conversation opened with the initial approach to a patient presenting with a testicular mass. The doctors emphasize the importance of a thorough workup, including a CT scan of the chest, abdomen, and pelvis, and the use of tumor markers: AFP and hCG. Adra noted that while AFP and hCG are elevated in about 60% of cases, it’s crucial to understand their half-lives—about 5 to 7 days for AFP and 1 to 2 days for hCG—to properly assess their decline post-orchiectomy. He clarified that an AFP level under 25 ng/mL is considered normal and that mild elevations in hCG can be linked to marijuana use or cross-reactivity with luteinizing hormone, which should be investigated before initiating chemotherapy. The panel also touches on the use of lactate dehydrogenase as a prognostic marker, cautioning against using it as the sole basis for starting treatment. A central part of the discussion revolves around the bleomycin, etoposide, cisplatin (BEP) vs etoposide and cisplatin chemotherapy regimens for good-risk disease. Adra explained the rationale behind the preference for BEP for 3 cycles at his institution, arguing that it avoids the long-term toxicities of neuropathy and ototoxicity associated with a fourth cycle of platinum therapy, a concern with the EP for 4 cycles. He stressed that with careful patient selection—avoiding bleomycin in patients over 50, with renal dysfunction, or pre-existing lung disease—the risk of pulmonary toxicity is minimal. He also influenced Garmezy’s practice by highlighting the importance of monitoring tumor markers with every cycle of chemotherapy, noting that a rising marker could signal a need to pivot to second-line therapy. The conversation shifted to the role of surgery in stage II disease. For patients with non-bulky (less than 3 cm) stage II seminoma or non-seminoma, the panel discusses the preference for a retroperitoneal lymph node dissection (RPLND) over upfront chemotherapy or radiation to spare patients from long-term side effects. Adra highlighted that a proper RPLND at an experienced center can be curative in 80% of cases. The doctors stressed the importance of referring patients to surgeons with extensive experience in these complex procedures. Finally, the hosts and guest tackled the management of relapsed/refractory disease. They discussed the 3 main options: salvage surgery, standard-dose chemotherapy, or high-dose chemotherapy with stem cell transplant. Adra shared that his institutional preference is for high-dose chemotherapy due to published data showing high cure rates, mentioning the ongoing phase 3 TIGER trial (NCT02375204), which is directly comparing standard-dose paclitaxel, ifosfamide, and cisplatin with high-dose chemotherapy. The episode concluded with a key pearl on managing patients with a high burden of pulmonary metastases, where a "cycle 0" of EP is sometimes used before starting a full course of vinblastine, ifosfamide, and cisplatin to mitigate the risk of hemoptysis. Bupathi, is executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers; Garmezy, is associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, and Adra is associate professor of Clinical Medicine and Clinical Urology, service line leader in medical oncology, medical director of Indiana University Health Simon Cancer Center, and program leader-genitourinary. 

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• 11: Navigating the Evolving Second-Line Landscape of Metastatic Urothelial Carcinoma

  The latest Oncology Decoded discussion with Manojkumar Bupathi, MD, MS, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Benjamin Garmezy, MD, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, dissects the current management of metastatic urothelial carcinoma, with a focus on treatment strategies beyond standard first-line therapies. The conversation highlights the recent paradigm shift with the approval of enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda). This combination’s efficacy, as demonstrated in the phase 3 EV-302 trial (NCT04223856), has positioned it as a new standard of care for many patients. The alternative, gemcitabine plus cisplatin with nivolumab (Opdivo), supported by the phase 3 CheckMate 901 trial (NCT03036098), remains a crucial first-line option, particularly for patients who are cisplatin-eligible. The hosts delve into the nuances of second-line therapy, which has become a more complex and critical area. For patients who progress on enfortumab vedotin/pembrolizumab, the discussion covers options such as platinum-based chemotherapy with gemcitabine/cisplatin or carboplatin. The importance of biomarker-driven therapy is also emphasized, particularly the role of molecular testing for FGFR gene alterations. The FDA-approved FGFR inhibitor erdafitinib (Balversa) is highlighted as a viable option for patients with susceptible genetic alterations. Furthermore, the discussion touches on the evolving role of HER2-targeted agents and other novel early-phase assets that are being developed to address the unmet need in this patient population. Management of toxicities is also a significant theme. The clinicians share insights on mitigating adverse effects such as peripheral neuropathy from enfortumab vedotin, and the challenges of managing hyperglycemia and skin toxicities. The need for more data-driven guidance on treatment duration and maintenance therapy is also underscored, with the observation that treatment discontinuation is a common clinical challenge lacking clear guidelines. Reference FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer. News release. FDA. December 15, 2023. Accessed August 13, 2025. https://tinyurl.com/45wkm3bd

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• 10: Navigating Second-Line Treatment Options in Urothelial Carcinoma

  This episode of Oncology Decoded focuses on a discussion between hosts Manojkumar Bupathi, MD, MS, executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist with Rocky Mountain Cancer Centers specializing in solid tumors and genitourinary cancers, and Benjamin Garmezy, MD, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, in a recent live session with US Oncology Network and the Pathways Task Force, discussing the evolving landscape of second-line and beyond therapy for urothelial carcinoma, particularly in the context of recent advancements in first-line treatment. First Line Strategies The current standard of care for frontline metastatic urothelial carcinoma is enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda). Recent data from the phase EV-302 trial (NCT04223856) presented at the 2025 American Society of Clinical Oncology (ASCO) highlighted the remarkable durability of responses with this combination, showing a 2-year durability in a significant proportion of responders, including 75% of complete responders.1 While this combination is favored for most patients, the hosts acknowledged a subgroup for whom it may not be suitable due to unique toxicities such as neuropathy, skin toxicity, and hyperglycemia.  The phase 3 Checkmate901 trial (NCT03036098), evaluating cisplatin/gemcitabine with nivolumab (Opdivo), is also mentioned as a prior standard of care, though generally superseded by enfortumab vedotin/pembrolizumab. For patients with lymph-node-only disease, both cisplatin/gemcitabine and nivolumab or enfortumab vedotin/pembrolizumab show comparable high response rates, necessitating shared decision-making. Second Line Strategies For patients progressing on enfortumab vedotin/pembrolizumab, the subsequent treatment landscape becomes more complex. Platinum-based chemotherapy doublets (cisplatin/gemcitabine or carboplatin/gemcitabine) are considered, though their efficacy in this heavily pretreated setting is limited and associated with significant toxicity. Molecular testing for FGFR alterations is crucial, as erdafitinib (Balversa) offers a targeted option with a 40% response rate in patients who are FGFR-positive. Managing erdafitinib toxicities, including nail changes, skin reactions, and phosphate level elevations, requires close monitoring and patient education. The potential role of HER2-targeted antibody-drug conjugates is also discussed, particularly for HER2 3+ expression, though data in urothelial carcinoma are limited. For patients without actionable biomarkers, single-agent taxanes (docetaxel, paclitaxel) have historically shown dismal response rates (~15-17%). Sacituzumab govitecan-hziy (Trodelvy), despite its accelerated approval withdrawal due to the confirmatory phase 2 TROPHY-U-01 trial (NCT03547973) not meeting statistical significance against single-agent chemotherapy, is still utilized by the speakers. They emphasize that with appropriate growth factor support, sacituzumab govitecan can be less toxic and equally efficacious as carboplatin/gemcitabine in select patients. References 1.        Bedke J, Powles TB, Valderrama BP, et al. EV-302: long-term subgroup 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). J Clin Oncol. 2025;43(suppl 16):4571. doi:10.1200/JCO.2025.43.16_suppl.4571 2.        Van der Heijden M, Galsky M, Powles T, et al. Nivolumab plus ipilimumab (NIVO+IPI) vs gemcitabine-carboplatin (gem-carbo) chemotherapy for previously untreated unresectable or metastatic urothelial carcinoma (mUC): Final results for cisplatin-ineligible patients from the CheckMate 901 trial. J Clin Oncol. 2025;43(suppl 17):4500. doi:10.1200/JCO.2025.43.16_suppl.4500 3.        Gilead provides update on U.S. Indication for Trodelvy in metastatic urothelial cancer. News release. Gilead Sciences, Inc. October 18, 2024. Accessed July 30, 2025. https://tinyurl.com/2aku377j

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