Oncology Decoded

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, wound the clock back to 2025 to discuss the key findings and clinical developments that may propel the genitourinary oncology field forward. Following a breakdown of last year’s breakthroughs in kidney cancer and bladder cancer care, the hosts reviewed the biggest headlines and milestones of 2025 related to prostate cancer management and research. 
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. Together, they spoke about several major prostate cancer happenings throughout 2025, including but not limited to:
·      The FDA Approval of the Phase 3 ARANOTE Trial (NCT04736199) Regimen

o   In June 2025, the FDA approved darolutamide (Nubeqa) for patients with metastatic castration-sensitive prostate cancer (CSPC) based on findings from the phase 3 ARANOTE trial.
o   Topline data showed a median radiographic progression-free survival (rPFS) that was not reached (NR) with darolutamide vs 25 months (95% CI, 19-NR) with placebo (HR, 0.54; 95% CI, 0.41-0.71; P <.0001).
o   This approval may grant easier access to darolutamide, especially for the treatment of patients who are older or who present with certain neurocognitive disorders.
·      The FDA Approval of the Phase 3 AMPLITUDE Trial (NCT04497844) Regimen

o   December 2025 saw the FDA approval of niraparib and abiraterone acetate (Akeega) plus prednisone for adults with suspected or deleterious BRCA2-mutated CSPC.
o   Supporting data from the phase 3 AMPLITUDE trial showed a median rPFS that was not estimable (NE; 95% CI, 41 months-NE) in the niraparib arm vs 26 months (95% CI, 18-28) in the placebo arm among 323 patients with BRCA2-mutated disease.
o   This approval for patients with BRCA2-mutations reinforces the importance of conducting upfront genetic testing.
·      Phase 3 PSMAddition Trial (NCT04720157)

o   Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT) significantly prolonged rPFS vs ARPI/ADT treatment alone among patients with prostate specific-membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer (HR, 0.72; 95% CI, 0.58-0.90; P = .002).
o   Other data from ESMO Congress 2025 showed that the lutetium Lu 177 combination numerically improved the overall response rate at 85.3% (95% CI, 79.9%-89.6%) vs 80.8% (95% CI, 74.8%-85.8%) in the control arm.
o   The safety profile observed in the trial may raise questions over whether it is worthwhile to administer all 6 cycles of lutetium Lu 177 to patients.

References

FDA approves darolutamide for metastatic castration-sensitive prostate cancer. News release. FDA. June 3, 2025. Accessed January 20, 2026. https://tinyurl.com/yhde24zj

FDA approves niraparib and abiraterone acetate plus prednisone for BRCA2-mutated metastatic castration-sensitive prostate cancer. News release. FDA. December 12, 2025. Accessed January 20, 2026. https://tinyurl.com/rcxaj98

Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Ann Oncol. 2025;36(suppl 2):S1627-S1628. doi:10.1016/j.annonc.2025.09.101

As part of ushering in the new year, Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, looked back on the most exciting advancements that shook up the genitourinary oncology landscape throughout 2025. Specifically, they highlighted the clinical trial readouts, regulatory milestones, and other breakthroughs that made 2025 a “remarkable year” in kidney cancer and bladder cancer care.

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. Together, they reviewed several key moments in kidney and bladder cancer research, including but not limited to:

·      The FDA Approval of The EV-303 Trial (NCT03924895) Regimen

o   In November 2025, the FDA approved a neoadjuvant/adjuvant regimen consisting of pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) plus enfortumab vedotin-ejfv (Padcev) for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin.

o   “Incredible” data from the phase 3 KEYNOTE-905/EV-303 trial supported the approval, which showed an improvement in event-free survival with the enfortumab vedotin combination vs surgery alone (HR, 0.40; 95% CI, 0.28-0.57; P <.0001).

o   The approval may lead to a “paradigm shift” in the treatment of this MIBC population. 

·      The Phase 3 POTOMAC Trial (NCT03528694)

o   Data showed a meaningful disease-free survival (DFS) improvement when adding durvalumab (Imfinzi) to Bacillus Calmette-Guérin (BCG) among patients with BCG-naïve, high-risk NMIBC (HR, 0.68; 95% CI, 0.50-0.93; P = .0154).

o   Frontline immunotherapy-based regimens may “complicate” how to think about treating patients with NMIBC later down the line.

·      The Phase 3 RAMPART Trial (NCT03288532)

o   Adjuvant treatment with durvalumab (Imfinzi) plus tremelimumab-actl (Imjudo) improved DFS compared with active monitoring among patients who underwent resection of primary renal cell carcinoma (RCC; HR, 0.65; 95% CI, 0.45-0.93; P = .0094).

o   Following previous unsuccessful trials assessing immunotherapy in adjuvant RCC, the results of RAMPART demonstrate how immunotherapy can work in this space.

References

FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. FDA. November 21, 2025. Accessed January 5, 2026. https://tinyurl.com/bdfhmhnk

De Santis M, Palou Redorta J, Nishiyama H, et al. Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. Lancet. 2025;406(10516):2221-2234. doi:10.1016/S0140-6736(25)01897-5

Larkin J, Powles TB, Frangou E, et al. First results from RAMPART: An international phase III randomised-controlled trial of adjuvant durvalumab monotherapy or combined with tremelimumab for resected primary renal cell carcinoma (RCC) led by MRC CTU at UCL. Ann Oncol. 2025;36(suppl 2):S1750. doi:10.1016/j.annonc.2025.09.110

In the latest episode of Oncology Decoded, hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, broke down the treatment decision-making process for patients who present with oligometastatic kidney cancer. The experts zeroed in on this topic following their attendance at the 2025 International Kidney Cancer Symposium (IKCS), which featured a variety of sessions discussing the oligometastatic treatment setting.

The conversation opened with an aim to better define what oligometastatic disease constitutes for patients. Bupathi noted how patients can present with synchronous, metachronous, or oligoprogressive cancer based on when metastases appear around the time of diagnosis. Furthermore, the specific nature of a patient’s metastases may influence their treatment course. For example, in the case of a patient with de novo metastatic clear cell disease and lung metastases, Bupathi recommended the use of systemic therapy followed by cytoreduction, and the possibility of nephrectomy plus stereotactic body radiotherapy directed to the metastases.

Garmezy also emphasized distinguishing between de novo and recurrent disease, as both types necessitate the development of different treatment goals. For patients with recurrent oligometastatic disease, the primary goal of therapy may entail increasing the cure rate or extending treatment-free survival, depending on individual circumstances. Moreover, specific patient factors may influence the decision on whether to combine immunotherapy with radiotherapy.

In terms of standardizing a therapeutic approach for patients who present with oligometastatic disease, the hosts stressed the importance of strengthening efforts across multidisciplinary clinics and collaborating with radiology colleagues to better identify which sites of metastasis are progressing in patients. 

Bupathi is an 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, an executive cochair of the Genitourinary Cancer Research Executive Committee at SCRI, and a medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers.

Following the European Society for Medical Oncology (ESMO) Congress 2025, Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, met to discuss the presentations and data sets that may have the biggest impacts across genitourinary (GU) cancer care. 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.

Bupathi and Garmezy outlined the top 5 abstracts from the meeting that have the potential to change or inform clinical practice across different GU malignancies. Notable presentations in bladder cancer, prostate cancer, kidney cancer, and other patient populations included the following:

#5: Phase 3 CAPItello-281 Trial (NCT04493853)

In the CAPItello-281 trial, combining capivasertib (Truqap) with abiraterone acetate, prednisone, and androgen deprivation therapy (ADT) prolonged radiographic progression-free survival (rPFS) among patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (HSPC).1 Data revealed a median rPFS of 33.2 months (95% CI, 25.9-44.2) in the capivasertib arm vs 25.7 months (95% CI, 22.0-29.9) in the placebo arm (HR, 0.81; 95% CI, 0.66-0.98; P = .034).

#4: Phase 3 RC48-C016 Trial (NCT05302284)

Combining disitamab vedotin (PF-08046051) with toripalimab-tpzi (Loqtorzi) in the frontline setting significantly improved outcomes vs standard chemotherapy among patients with HER2-expressing locally advanced or metastatic urothelial carcinoma, according to data from the RC48-C016 trial.2 Per blinded independent review committee (BIRC) assessment, the median PFS was 13.1 months (95% CI, 11.1-16.7) in the disitamab vedotin arm and 6.5 months (95% CI, 5.7-7.4) in the chemotherapy arm (HR, 0.36; 95% CI, 0.28-0.46; P <.0001). Additionally, the median overall survival (OS) was 31.5 months (95% CI, 21.7-not evaluable [NE]) vs 16.9 months (95% CI, 14.6-21.7) in each respective arm (HR, 0.54; 95% CI, 0.41-0.73; P <.0001).

#3: Phase 3 RAMPART Trial (NCT03288532)

Findings from the RAMPART trial showed that adjuvant therapy with durvalumab (Imfinzi) plus tremelimumab-actl (Imjudo) following renal cell carcinoma (RCC) resection improved disease-free survival (DFS) compared with active monitoring.3 The 3-year DFS rates were 81% in the durvalumab/tremelimumab arm vs 73% in the active monitoring arm across the intent-to-treat (ITT) population (HR, 0.65; 95% CI, 0.45-0.93; P = .0094). Additional data revealed that the DFS benefit associated with the durvalumab combination may have been driven by outcomes observed in the higher-risk population (HR, 0.52; 95% CI, 0.34-0.80; P = .0016).

#2: Phase 3 PSMAddition Trial (NCT04720157)

Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus ADT and an androgen receptor pathway inhibitor (ARPI) demonstrated statistically significant improvements in rPFS among patients with prostate specific-membrane antigen (PSMA)–positive metastatic HSPC in the PSMAddition trial.4 Data showed improvements with the lutetium Lu 177 vipivotide tetraxetan regimen vs an ARPI plus ADT alone in terms of rPFS (HR, 0.72; 95% CI, 0.58-0.90; P = .002) and OS (HR, 0.84; 95% CI, 0.83-1.13; P = .125).

#1: Phase 3 KEYNOTE-905/EV-303 Trial (NCT03924895)

Findings from the KEYNOTE-905/EV-303 trial showed improvements in event-free survival (EFS) among patients with muscle-invasive bladder cancer (MIBC) who were not eligible for or refused cisplatin-based chemotherapy following treatment with perioperative enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) with radical cystectomy and standard pelvic lymph node dissection.5 The median EFS was not reached (NR; 95% CI, 37.3-NR) in the enfortumab vedotin arm vs 15.7 months (95% CI, 10.3-20.5) in the control arm, in which patients underwent radical cystectomy and standard pelvic lymph node dissection followed by observation (HR, 0.40; 95% CI, 0.28-0.57; P <.0001).

References

Fizazi K, Clarke NW, De Santis M, et al. A phase III study of capivasertib (capi) + abiraterone (abi) vs placebo (pbo) + abi in patients (pts) with PTEN deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC): CAPItello-281. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 2383O.

Sheng X, Zeng G, Zhang C, et al. Disitamab vedotin (DV) plus toripalimab (T) versus chemotherapy (C) in first-line (1L) locally advanced or metastatic urothelial carcinoma (la/mUC) with HER2-expression. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA7.

Larkin J, Powles TB, Frangou E, et al. First results from RAMPART: an international phase III randomised-controlled trial of adjuvant durvalumab monotherapy or combined with tremelimumab for resected primary renal cell carcinoma (RCC) led by MRC CTU at UCL. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA93.

Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA6.

Vulsteke C, Kaimakliotis HZ, Danchaivijitr P, et al. Perioperative enfortumab vedotin plus pembrolizumab in participants with muscle-invasive bladder cancer who are cisplatin-ineligible: phase 3 KEYNOTE-905 study. Presented at European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA2.

Ahead of the European Society for Medical Oncology Congress (ESMO) 2025, Oncology Decoded hosts Manojkumar Bupathi, MD, MS, and Benjamin Garmezy, MD, convened to discuss the late-breaking abstracts and presentations in genitourinary cancer management they anticipated the most. 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.

The hosts reviewed upcoming trial data that may shift therapeutic standards across bladder cancer, prostate cancer, kidney cancer, and other genitourinary malignancy populations. Presentations of interest included those on the following studies:

- Phase 3 PSMAddition trial (NCT04720157)

o Investigators assessed whether the addition of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to androgen deprivation (ADT) and androgen receptor pathway inhibitors (ARPIs) could improve radiographic progression-free survival (rPFS) vs standard of care alone in patients with metastatic hormone-sensitive prostate cancer.

o Prior topline data showed a significant rPFS improvement in the lutetium Lu 177 arm.

o Findings may support moving radioligand therapy to an earlier prostate cancer treatment setting.

- Phase 3 KEYNOTE-905/EV-303 trial (NCT03924895)

o Patients with muscle-invasive bladder cancer who were ineligible for cisplatin were assigned to receive surgery plus perioperative pembrolizumab (Keytruda) and enfortumab vedotin-ejfv (Padcev) or surgery alone.

o According to previous topline results, statistically significant and clinically meaningful rPFS and overall survival (OS) improvements occurred in the enfortumab vedotin plus pembrolizumab arm.

o Data may pose questions about the future role that chemotherapy may play in the perioperative space among patients with MIBC.

-  Phase 3 RAMPART trial (NCT03288532)

o  Investigators evaluated durvalumab (Imfinzi) with or without tremelimumab-actl (Imjudo) among patients with resected primary renal cell carcinoma.

o If the data are positive, trials like RAMPART may clarify the role that immunotherapy can play in the perioperative treatment setting.  

References

An international prospective open-label, randomized, phase III study comparing 177Lu-PSMA-617 in combination with SoC, versus SoC alone, in adult male patients with mHSPC (PSMAddition). ClinicalTrials.gov. Updated September 23, 2025. Accessed October 15, 2025. https://tinyurl.com/ycbktner

Novartis Pluvicto™ demonstrates statistically significant and clinically meaningful rPFS benefit in patients with PSMA-positive metastatic hormone-sensitive prostate cancer. News release. Novartis. June 2, 2025. Accessed October 14, 2025. https://tinyurl.com/fedzdhfx

Perioperative pembrolizumab (MK-3475) plus cystectomy or perioperative pembrolizumab plus enfortumab vedotin plus cystectomy versus cystectomy alone in participants who are cisplatin-ineligible or decline cisplatin with muscle-invasive bladder cancer (MK-3475-905/​KEYNOTE-905/​EV-303). ClinicalTrials.gov. Updated August 28, 2025. Accessed October 15, 2025. https://tinyurl.com/5ddk6hrw

PADCEV plus KEYTRUDA significantly improves survival for certain patients with bladder cancer when given before and after surgery. News release. Pfizer and Astellas Pharma. August 12, 2025. Accessed October 15, 2025. https://tinyurl.com/mtnvfvv2

Renal Adjuvant MultiPle Arm Randomised Trial (RAMPART). ClinicalTrials.gov. Updated September 7, 2020. Accessed October 15, 2025. https://tinyurl.com/26w8whuk