2025 year in review: Breakthroughs in urologic oncology during a year of unprecedented awareness

2025 will likely be remembered as a pivotal chapter in urologic oncology. Scientific progress was unmistakable—radioligand therapy moved earlier in the treatment sequence, bladder-sparing technologies advanced, and circulating tumor DNA (ctDNA) evolved into a clinically actionable tool. Yet the momentum of the field was amplified by something far less predictable: a sudden surge in public attention. Earlier in the year, former President Joseph R. Biden disclosed that he had been diagnosed with and undergone treatment for prostate cancer. The response across the nation was immediate and resounding. Men began asking about prostate-specific antigen (PSA) testing; families sought guidance on imaging, risk stratification, and survivorship; and conversations that often remained private became openly discussed. It was a reminder that awareness is not always driven by guidelines or conferences—sometimes, it comes from a human moment on a national stage.

Against this backdrop, the field advanced in meaningful and lasting ways. In the area of advanced prostate cancer, radioligand therapy moved upstream. A major shift occurred with the FDA’s expanded indication for 177Lu-PSMA-617 (Pluvicto), now available before taxane chemotherapy for metastatic castration-resistant prostate cancer.¹ Supported by the phase 3 PSMAfore trial (NCT04689828),² this update demonstrated significant improvements in progression-free survival in men previously treated with androgen receptor pathway inhibitors. Beyond regulatory impact, this change prompted clinicians to reevaluate sequencing strategies, marrow preservation, and optimal timing—reshaping treatment patterns that had only recently felt settled.

There was also good news for men with biochemical recurrence (BCR) after surgery and radiation therapy. Management of BCR gained important clarity. Data from EMBARK (NCT02319837)³ and PRESTO (NCT03009981)⁴ helped address questions that clinicians face daily: Who benefits from treatment intensification? How long is treatment necessary? Do all patients require prolonged systemic therapy? These trials reinforced a more tailored approach—highlighting that finite androgen receptor signaling inhibitor (ARSI) plus androgen deprivation therapy (ADT) benefits selected patients with high-risk BCR, and that PSA doubling time, prior local therapy, and individual risk factors should guide decisions. In addition to metastasis-free survival, we now have overall survival data for men treated with combination therapy on the EMBARK regimen.

For men with metastatic hormone-sensitive prostate cancer, we have additional information on treatment intensification. Real-world experience with triplet therapy continued to grow. Although enthusiasm remained strong, it became increasingly clear that fit patients with high-volume disease derived the greatest benefit, whereas many others were well served by ADT plus an ARSI alone. Treatment escalation became more deliberate rather than automatic. In the metastatic castrate-resistant space, PARP combination therapy demonstrated benefit in select patients. PARP-ARSI combinations saw more measured adoption than anticipated, with approvals focused on patients with pathogenic HRR mutations. The emphasis on molecular selection echoed the field’s continuing move toward personalized, biologically informed therapy. Together, these developments made prostate cancer care in 2025 more precise, intentional, and aligned with patient-specific risk.

Although prostate cancer dominated the public conversation, bladder cancer saw some of its most consequential advances in years. Gains in bladder cancer included new intravesical therapies with new technologies, and a new minimal residual disease milestone in advanced disease. There were 2 new intravesical therapy approvals in 2025. Mitomycin for intravesical solution (Zusduri; formerly UGN-102) received FDA approval for recurrent low-grade, intermediate-risk non–muscle-invasive bladder cancer (NMIBC),^5,6 offering an office-based, nonsurgical alternative for patients who previously cycled through repeated procedures. The agency also approved the gemcitabine intravesical system, Inlexzo (formerly TAR-200).⁷ This system introduced sustained drug delivery over weeks—transforming management options for patients with BCG-unresponsive high-risk NMIBC who are unwilling or unable to undergo cystectomy. These innovations also brought changes to workflow, logistics, infection prevention, and follow-up, requiring teams to adapt their approach to intravesical care. It was also reported that oncolytic immunotherapy shows promise, with CG0070 continuing to demonstrate durable activity in BCG-unresponsive NMIBC,⁸ sustaining interest in novel immune-based intravesical platforms.

There were also advances in systemic therapy with the FDA approval of enfortumab vedotin-ejfv (EV, Padcev) plus pembrolizumab (Keytruda) in muscle-invasive bladder cancer.⁹ Updated long-term data reinforced the durability of EV plus pembrolizumab, with overall survival now approaching the 3-year mark.¹⁰ Perioperative studies gained traction and may reshape options for cisplatin-ineligible surgical candidates. In addition, minimal residual disease (MRD)–guided therapy became a reality in the urologic oncology space. Perhaps the most forward-looking advance came from the phase 3 IMvigor011 trial (NCT04660344), which validated the first ctDNA-directed approach in bladder cancer. MRD-positive patients receiving adjuvant atezolizumab (Tecentriq) experienced a significant survival benefit, whereas MRD-negative patients safely avoided unnecessary therapy.¹¹ This marks the beginning of MRD-guided care in urothelial carcinoma and sets the stage for broader adoption across other disease states.

Finally, prostate cancer awareness got a booster shot with the announcement of Biden’s diagnosis. This prompted new discussions among many men, conversations that have been avoided for years, improving engagement with screening and early detection. Yet 2025 also highlighted the persistent challenges of access. Radioligand therapy, advanced imaging, and device-based intravesical systems remain more available at large tertiary referral centers than in community or rural settings. For progress to be meaningful, the field must continue working to reduce disparities and ensure that access to innovation and treatment reaches all patients—not just those with geographic proximity.

Momentum heading into 2026 remains strong. Radioligand therapies will likely move even earlier. Device-based intravesical technologies may expand to additional NMIBC populations. MRD-guided approaches are poised to influence multiple tumor types. Antibody-drug conjugates will continue reshaping both metastatic and perioperative care. If 2025 showed us anything, it is the power of combining scientific progress with public engagement. Advances in urologic oncology were meaningful—but so was the conversation around them. Awareness, education, and equitable access will continue to define how these developments translate into improved care for all patients.

REFERENCES

1. FDA approves Novartis radioligand therapy Pluvicto for earlier use before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer. News release. Novartis. March 28, 2025. Accessed November 21, 2025. https://www.novartis.com/news/media-releases/fda-approves-novartis-radioligand-therapy-pluvicto-earlier-use-chemotherapy-psma-positive-metastatic-castration-resistant-prostate-cancer

2. Morris MJ, Castellano D, Herrmann K, et al; PSMAfore Investigators. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024;404(10459):1227-1239. doi:10.1016/S0140-6736(24)01653-2

3. Shore ND, de Almeida Luz M, De Giorgi U, et al. Overall survival with enzalutamide in biochemically recurrent prostate cancer. Presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. LBA87.

4. Aggarwal R, Hillman D, Xiao H, et al. Final results from PRESTO: a phase III open-label study of combined androgen blockade in patients (pts) with high-risk biochemically relapsed prostate cancer (BRPC) (AFT-19). Presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025. Berlin, Germany. Abstract LBA88. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/LBA88.html.pdf

5. FDA approves mitomycin intravesical solution for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. FDA. June 12, 2025. Accessed November 21, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mitomycin-intravesical-solution-recurrent-low-grade-intermediate-risk-non-muscle

6. U.S. FDA approves UroGen’s ZUSDURI (mitomycin) for intravesical solution as the first and only medication for recurrent low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). News release. UroGen. June 12, 2025. Accessed November 21, 2025. https://investors.urogen.com/news-releases/news-release-details/us-fda-approves-urogens-zusduritm-mitomycin-intravesical

7. U.S. FDA approval of INLEXZO (gemcitabine intravesical system) set to transform how certain bladder cancers are treated. News release. Johnson & Johnson. September 9, 2025. Accessed November 21, 2025. https://www.jnj.com/media-center/press-releases/u-s-fda-approval-of-inlexzo-gemcitabine-intravesical-system-set-to-transform-how-certain-bladder-cancers-are-treated

8. Tyson MD, Uchio EM, Nam JK, et al. BOND-003 cohort C- a phase-3, single-arm study of intravesical cretostimogene grenadenorepvec for high-risk BCG-unresponsive NMIBC with CIS. J Urol. 2025;213(5S2):e1. doi:10.1097/01.JU.0001111604.90306.91.02

9. FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. FDA. November 21, 2025. Accessed November 21, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer?utm_medium=email&utm_source=govdelivery

10. Mar N, Petrylak DP, Hoimes CJ, et al. Study EV-103 cohort H: neoadjuvant treatment with enfortumab vedotin (EV) monotherapy in cisplatin (cis)-ineligible patients (pts) with muscle invasive bladder cancer (MIBC)—3-year efficacy results. J Clin Oncol. 2025;43:4583. doi:10.1200/JCO.2025.43.16_suppl.4583

11. Powles T, Kann AG, Castellano D, et al. IMvigor011: A phase III trial of circulating tumour (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer. Presented at: European Society for Medical Oncology Congress 2025; October 17-21, 2025; Berlin, Germany. LBA8.