Oncology Decoded

In the newest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, spoke about the implementation of artificial intelligence (AI)–based tools and large language models (LLMs) into the study and management of genitourinary malignancies. Leveraging his background in biomedical informatics, Bupathi broke down the specific tools that can assist with documentation, digital pathology, real-time diagnostics, and other relevant clinical applications.

The conversation helped differentiate between modalities like LLMs, which assist with documentation, chart summarization, and clinical trial matching, and multimodal AI, a tool that involves combining genomics, laboratory values, and other data to generate patient-level insights. Given the growing prevalence of LLMs like ChatGPT and Claude for resolving menial tasks, Bupathi emphasized that these platforms will not replace physicians who can share human oversight and expertise with patients.

In the realm of digital pathology, the hosts discussed how AI tools like ArteraAI can help collect tumor grades and prognostic information from Hematoxylin and Eosin slides and potentially mitigate the subjectivity of Gleason scores through consistent patterns that humans may misinterpret over time. Additionally, Bupathi described how AI can remove subjectivity from imaging by generating mathematical calculations for standardized uptake value metrics on PET scans in place of visual estimation.

Regarding the future of the field, the hosts envisioned a type of AI tool that may synthesize years of patient data into a concise synopsis, which may help treat patients with complex histologies like castration-resistant disease. Overall, they predicted a shift in which specialized AI agents could communicate with one another to present synthesized data and recommendations to human clinicians.

Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Bupathi is the president and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.

In this episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, discussed treatment for urothelial carcinoma following updates from the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. With enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) now the frontline standard, the hosts focused on emerging biomarker-driven strategies that show efficacy after progression on first-line care.

Bupathi outlined the current algorithm, with platinum-based chemotherapy—typically gemcitabine plus carboplatin—representing the most common second-line option. Beyond chemotherapy, sacituzumab govitecan-hziy (Trodelvy) retained its NCCN category 2 recommendation despite losing its FDA accelerated approval in urothelial carcinoma after the confirmatory phase 3 TROPiCS-04 trial (NCT04527991) did not yield an overall survival benefit. For biomarker-selected patients, erdafitinib (Balversa) is available for FGFR3-altered disease, and fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) is FDA-approved for HER2 immunohistochemistry (IHC) 3+ solid tumors, including bladder cancer.

Garmezy, an investigator on the phase 1 NEXUS-01 trial (NCT06465069), discussed data on LY4052031, a nectin-4-directed antibody drug conjugate (ADC) carrying a topoisomerase payload, in patients previously treated with enfortumab vedotin, which also targets nectin-4 but delivers a different payload class. The trial showed response rates of 30% to 40% in that population, with some durable responses, suggesting resistance to enfortumab vedotin often reflects payload-specific resistance rather than loss of nectin-4 expression. Garmezy described the data as hypothesis-generating.

Regarding patients who progress on frontline enfortumab vedotin plus pembrolizumab, the hosts said they would prioritize a biomarker-directed option, such as erdafitinib for FGFR3 alterations or T-DXd for HER2 expression, when a trial is not available, while reserving chemotherapy for later lines. Given the lack of comparative data to help guide a choice between erdafitinib and T-DXd when a patient has both an FGFR3 alteration and HER2 expression, the hosts noted that selections come down to shared decision-making around toxicity profile and route of administration.

Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Bupathi is the president and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers. 

In the newest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, discussed takeaways from the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting that may guide clinical practice. Following their initial conversation on the most critical presentations in prostate cancer, Bupathi and Garmezy spoke about additional presentations that may influence decision-making in the clinic for patients with bladder cancer and kidney cancer.

Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Bupathi is president and medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.

They discussed the following presentations:

EV-302

Long-term data from the phase 3 EV-302/KEYNOTE-A39 trial (NCT04223856) showed that enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) demonstrated a sustained overall survival (OS) benefit compared with platinum-based chemotherapy in the first-line treatment of patients with locally advanced or metastatic urothelial carcinoma.

With a median follow-up of 42.8 months, the median OS was 33.6 months (95% CI, 26.6-39.8) in the enfortumab vedotin arm vs 15.9 months (95% CI, 13.6-18.3) in the chemotherapy arm (HR, 0.53; 95% CI, 0.45-0.63). Additionally, the objective response rate (ORR) was 67.5% vs 44.2% in each respective arm.

Overall, the long-term data reinforced enfortumab vedotin plus pembrolizumab as a frontline standard of care for patients with locally advanced or metastatic urothelial carcinoma.

RAMPART

In the phase 3 RAMPART trial (NCT03288532), combining durvalumab (Imfinzi) with tremelimumab-actl (Imjudo) showed a statistically significant improvement in disease-free survival (DFS) vs active monitoring among patients with resected primary renal cell carcinoma, although no significant improvement was observed with durvalumab monotherapy. According to the hosts, these findings may introduce some uncertainty surrounding the increased uptake of PD-L1 inhibitors in this patient population.

Data showed that durvalumab monotherapy reduced the risk of disease recurrence or death by 26%, although this improvement did not cross the prespecified threshold for statistical significance (HR, 0.74; 95% CI, 0.53-1.04; 1-sided P = .041). The 3-year DFS rates were 78% with durvalumab alone vs 72% with active monitoring.

References

In the newest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, provided a recap of the most critical presentations and data to emerge from the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. Specifically, they highlighted the late-breaking abstracts that may transform the standard of care for different prostate cancer populations.

Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Bupathi is president and medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.

Together, they dissected updated results from the following trials:

TALAPRO-3

In the phase 3 TALAPRO-3 trial (NCT04821622), combining talazoparib (Talzenna) with enzalutamide (Xtandi) significantly improved radiographic progression-free survival (rPFS) vs standard enzalutamide monotherapy among patients with metastatic castration-sensitive prostate cancer (CSPC) harboring homologous recombination repair (HRR) alterations. Based on investigator assessment, the median rPFS was not reached (NR; 95% CI, NR-NR) with the talazoparib combination vs 45.8 months (95% CI, 37.7-NR) with enzalutamide plus placebo (HR, 0.481; 95% CI, 0.357-0.647; P <.0001).

Overall, the data supported talazoparib plus enzalutamide as a potential treatment option for patients with HRR-altered metastatic CSPC and highlighted the importance of early molecular testing in prostate cancer.

PROTEUS

Findings from the phase 3 PROTEUS trial (NCT03767244) demonstrated a reduced risk of death or metastasis with apalutamide (Erleada) plus androgen deprivation therapy (ADT) vs placebo plus ADT among patients with high-risk localized or locally advanced prostate cancer. With a median follow-up of 61.7 months, 8.9% of patients in the apalutamide group experienced a pathological complete response (pCR) vs 1% of those who received placebo (OR, 10.17; 95% CI, 5.27-19.64; P <.001). The likelihood of metastasis-free survival at 5 years was 78.2% vs 73.5% in each respective arm (HR, 0.80; 95% CI, 0.67-0.96; P = .02).

According to the study investigators, results from PROTEUS may support apalutamide plus ADT and radical prostatectomy as a new standard of care for patient with high-risk localized or locally advanced disease.

References

In the newest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, convened with their colleagues Suzanne B. Merrill, MD, FACS, and Mark D. Tyson, II, MD, MPH. They broke down the current treatment paradigm for those with non–muscle-invasive bladder cancer (NMIBC) by discussing how novel therapeutic modalities, patient selection criteria, and other practical considerations fit into effective clinical strategies. 

The discussion began with an overview of the effectiveness and limitations associated with Bacillus Calmette-Guérin (BCG), and how clinical trials like the phase 3 KEYNOTE-676 (NCT03711032) and phase 3 POTOMAC (NCT03528694) studies may support novel treatment regimens that incorporate checkpoint inhibitors. The group discussed how immunotherapy agents like pembrolizumab (Keytruda) may play important roles in the treatment of patients with NMIBC, especially in the event of BCG-unresponsive disease or BCG shortages. 

Additionally, the experts spoke about forming effective collaborations between urologists and medical oncologists to optimally care for patients. Specifically, Merrill emphasized a dedicated team approach to check symptoms, process referrals, and handle other tasks when treating patients who are receiving immune checkpoint inhibitors for their diseases. The conversation concluded with the group emphasizing the development of novel treatment delivery systems across the NMIBC space, which may improve outcomes and positively impact patients from a quality-of-life perspective.

Drs. Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Dr. Bupathi is president and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Dr. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.

Merill is a board-certified urologic surgeon at Colorado Urology. Tyson is a urologic oncologist with a subspecialty interest in bladder cancer at Mayo Clinic in Arizona.

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, spoke about the clinical utility of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) for those with muscle-invasive bladder cancer (MIBC) and similar patient populations. They highlighted the “transformational” potential of this therapeutic regimen in the context of findings from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124) that investigators presented at the 2026 ASCO Genitourinary Cancers Symposium.

Although certain data from the EV-304 trial, including the improvements in pathologic complete responses (pCRs) with the enfortumab vedotin combination over gemcitabine/cisplatin, represent “historical gamechangers”, the hosts pointed towards some uncertainty related to outcomes for those with varying or mixed histologies. According to Bupathi, it may still make sense to administer chemotherapy with immunotherapy in some of these subgroups. 

The hosts also considered how many cycles of enfortumab vedotin plus pembrolizumab should be administered across the neoadjuvant and adjuvant settings, noting how markers like circulating tumor DNA may help inform treatment schedules. Additionally, they highlighted a need for additional research to clarify whether cystectomy could be spared for patients receiving this combination regimen while translating the benefits observed in trials like EV-304 to the real world.

The discussion also touched upon the treatment of those with metastatic disease, as the hosts considered how dosing cycles, consolidated radiotherapy, and cystectomy with nodal dissection fit into the treatment algorithm for these patients. Garmezy and Bupathi also discussed how the efficacy and safety of the enfortumab vedotin combination compared with gemcitabine plus nivolumab (Opdivo), noting how the EV-304 regimen may be simpler to administer and manage.

Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Bupathi is president of and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.

Reference

Galsky MD, Valderrama BP, Maruzzo M, et al. Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study. J Clin Oncol. 2026;44(suppl 7):LBA630. doi: 10.1200/JCO.2026.44.7_suppl.LBA630

Following the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, Oncology Decoded hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, met to break down the key trials and presentations that may help move the needle in genitourinary oncology. Together, they reviewed findings and clinical implications across various bladder cancer, kidney cancer, and prostate cancer populations.

Among several sessions highlighted during their discussion, the experts covered the following presentations:

1.        Phase 3 KEYNOTE-B15 Trial (NCT04700124)

a.        Enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) significantly prolonged event-free survival (EFS) outcomes vs gemcitabine plus cisplatin among patients with muscle-invasive bladder cancer (MIBC; HR, 0.53; 95% CI, 0.41-0.70; P <.001).

b.       The rate of pathological complete response also improved by an estimated difference of 23.4% (95% CI, 16.7%-29.8%; P <.001) with the enfortumab vedotin combination.

c.        Data from this trial point towards the potential removal of chemotherapy in the perioperative therapy landscape.

2.        Phase 3 LITESPARK-011 Trial (NCT04586231)

a.        Belzutifan (Welireg) plus lenvatinib (Lenvima) improved progression-free survival (PFS; HR, 0.70; 95% CI, 0.59-0.84; P = .00007) and responses vs cabozantinib (Cabometyx) monotherapy among those with advanced clear cell renal cell carcinoma.

b.       Data showed a median duration of response (DOR) of 23.0 months with the belzutifan combination vs 12.3 months with cabozantinib.

c.        Findings may support an eventual FDA approval of belzutifan/lenvatinib in this patient population.

3.        Phase 3 PEACE-3 Trial (NCT02194842)

a.        Combining enzalutamide (Xtandi) with radium-223 (Xofigo) boosted overall survival (OS) compared with enzalutamide alone among patients with metastatic castration-resistant prostate cancer (HR, 0.75; 95% CI, 0.60-0.95; P = .0078).

b.       Previously reported rPFS improvements with the combination were sustained with longer follow-up, as data showed a median rPFS of 19.2 months vs 16.4 months in the experimental and comparator arms, respectively.

Drs. Bupathi and Garmezy are executive cochairs of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI). Additionally, Dr. Bupathi is president and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Dr. Garmezy is the associate director of genitourinary research for SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.

References

As part of honoring National Cancer Prevention Month in February, RadOnc on the Run host Brandon Mancini MD, MBA, spoke with Jenni Beamer about a broad range of topics dedicated to proactively treating patients who are at risk of developing cancer. 

Beamer, senior executive director for the state of Michigan at the American Cancer Society (ACS), emphasized the importance of having a designated month to educate the public regarding lifestyle choices, regular screenings, and other modifiable risk factors that may influence the likelihood of a cancer diagnosis. Regarding specific campaigns focused on cancer prevention, she brought attention to ACS CancerRisk360, a free digital tool that provides a comprehensive cancer risk evaluation based on key areas like genetic risk, family history, screening adherence, and daily life factors. 

Mancini highlighted how the challenges surrounding cancer prevention have evolved as environmental and exposure-related risk factors have transformed over time. For example, while rates of smoking—a common risk factor for lung cancer—have decreased, vaping has appeared to pick up, which may cause long-term complications in terms of cancer risk. Beamer and colleagues stay up to date on strategies for managing these modifiable risk factors via national roundtables, which also cover areas like breast cancer screening and HPV vaccination.

“Just yesterday, we reported out a 27% decline in cervical cancer incidence rates that are directly related to the implementation of the vaccine. That just gives me chills to know,” Beamer stated. “That’s why my 3 kids have that cancer vaccine. Progress is happening, and it’s in the stories of the everyday people that want to make a difference. I’m so motivated and proud of everyone’s collective energy and work around this.”

Mancini is director at Bold Advanced Medical Future (BAMF) Health, clinical associate professor in the Department of Radiology at Michigan State University College of Human Medicine, and editor-at-large for the RadOnc Review, a supplement of the journal ONCOLOGY®.

Reference

Declines in cervical cancer incidence in U.S. varied substantially by state, aligning with HPV vaccination rates, new ACS study finds. News release. American Cancer Society. February 23, 2026. Accessed February 25, 2026. https://tinyurl.com/57rykdvk

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS; and Benjamin Garmezy, MD, convened with Meredith Pelster, MD, MSCI; and Jason Henry, MD. Together, they looked back at the presentations and data shared at the 2026 ASCO Gastrointestinal Cancers Symposium that may have long-term impacts on community oncology practice across different gastrointestinal (GI) malignancies, including pancreatic cancer and colorectal cancer (CRC).

Trials and sessions of interest included the following:

Phase 1 Trial (NCT06179160) of INCB161734

o   INCB161734, an investigational KRAS G12D small molecule inhibitor, displayed a manageable safety profile among patients with advanced or metastatic pancreatic ductal adenocarcinoma.

o   The agent produced a disease control rate of 73% (n = 16/22) given at 600 mg once daily and 86% (n = 25/29) when given at 1200 mg once daily.

Phase 3 BREAKWATER Trial (NCT04607421)

o   Among those with BRAF V600E-mutated metastatic CRC, encorafenib (Braftovi) plus cetuximab (Erbitux) and chemotherapy improved the overall response rate (ORR) at 64.4% vs 39.2% with chemotherapy with or without bevacizumab (Avastin) in the control arm (OR, 2.76; 95% CI, 1.42-5.35; P = .001).

o   Overall, the data supported the encorafenib-based combination as a new potential standard of care in BRAF V600E-mutated metastatic CRC.

o   The FDA recently granted traditional approval to the encorafenib regimen based on data from the BREAKWATER trial.

Phase 3 COMMIT Trial (NCT02997228)

o   Chemotherapy in combination with bevacizumab and atezolizumab (Tecentriq) improved outcomes among patients with mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H) metastatic CRC vs atezolizumab alone.

o   Data showed a median progression-free survival (PFS) of 30.0 months vs 4.3 months in the combination and monotherapy arms, respectively.

Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers.

Pelster is associate director of GI Cancer Research at SCRI Oncology Partners and specializes in treating GI cancers as well as head and neck cancers. Henry is associate director of Drug Development at Sarah Cannon.

References

In a special episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, spoke with their colleague Debapriya Mondal, MBBS, MD, DrNB, who connected to the conversation from India. Collectively, the trio reviewed how clinical practice may differ in US- and India-based institutions, specifically as it relates to the treatment of patients with prostate cancer. 

According to Mondal, while prostate cancer does not represent one of the top 5 most diagnosed cancer types in India overall, patients appear to present with disease more often in cities like New Delhi, Kolkata, and Bangalore. Additionally, many patients in India appear to be diagnosed with more advanced stages of disease compared with reports in the US. 

Regarding medical practices in the US and India, the group discussed potential differences in treatment pathways and specialties that are initially involved in care. Additionally, they highlighted how urologists decide on sequencing androgen deprivation therapy, androgen receptor pathway inhibitors, and other modalities based on region-specific considerations.

The conversation also touched upon the costs of various therapies between regions, as Mondal outlined how patients in India may have access to cheaper generic products for reference drugs like olaparib (Lynparza) and rucaparib (Rubraca). Despite other differences in terms of insurance coverage and barriers to treatment access between regions, the group noted certain international similarities in their respective treatment models, including strategies for the management of advanced or localized disease. 

Bupathi is the executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and a medical oncologist with Rocky Mountain Cancer Centers, specializing in solid tumors and genitourinary cancers. Garmezy is the associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI and a medical oncologist at SCRI Oncology Partners, specializing in genitourinary cancers. Mondal is a consultant medical oncologist from Foris Healthcare in Kolkata, West Bengal, India.