ASCO Genitourinary Cancer Symposium 2026: Prostate Cancer Recap
Expert Perspectives · Keira Smith · 2026-04-29
At the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancer Symposium in San Francisco, emerging data offered fresh perspectives on combination therapies and novel treatment strategies in prostate cancer. After returning from the meeting, OncData Editorial Board member Dr. Stephen Freedland sat down with Dr. Alicia Morgans, Genitourinary Medical Oncologist at Dana-Farber Cancer Institute, to discuss several key trials highlighting progress and ongoing challenges in optimizing care.
Combination Therapy in mCRPC
One of the focal points was the updated overall survival data from the PEACE-3 trial, which evaluated enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer (mCRPC). Dr. Morgans emphasized the importance of context, noting that “enzalutamide was a very powerful control,” particularly in an androgen receptor pathway inhibitor (ARPI)–naive population.
With mature data now available, the combination demonstrated sustained benefit. “This is the final data set, this is mature data,” Dr. Morgans confirmed, “the overall survival (OS) really holds up at this follow-up time point.” While identifying eligible patients remains challenging, she concluded that for patients for whom enzalutamide is a good fit, it is ready for primetime.
A clinical anecdote reinforced this point. Dr. Morgans described a patient who initially declined intensified therapy but rapidly progressed to mCRPC within six months. Enzalutamide presented a promising option, and the patient ultimately embraced the combination approach, particularly given his bone-predominant disease.
PARP Inhibitor Combinations
Another major highlight was updated survival data from trials combining ARPIs with poly-ADP ribose polymerase (PARP) inhibitors in patients with homologous recombination repair (HRR) mutations. These studies continue to explore whether upfront combination therapy outperforms sequential treatment.
Dr. Morgans noted that earlier findings showed strong radiographic progression-free survival benefits, and now overall survival data reinforce the approach: “the median OS for the combination was around 68 months, certainly longer with the combination than with the other two in sequence—demonstrating that it wasn't just radiographic progression-free survival (rPFS), it was OS as well.”
However, questions remain regarding real-world applicability, particularly as fewer patients present without prior ARPI exposure. As Dr. Morgans explained, “understanding whether they work after prior exposure is the thing that's still on the table.”
When Intensification Falls Short
Not all combination strategies proved beneficial. A phase 3 trial evaluating cabazitaxel added to radiation and androgen deprivation therapy (ADT) in high-risk localized prostate cancer failed to improve outcomes.
Despite optimism for intensification, Dr. Morgans noted, “we did not see a clear benefit to the addition of cabazitaxel to standard of care.” These findings align with other studies, such as ENZARAD, suggesting that more treatment is not always better in this setting.
Still, the discussion highlighted an important nuance. As Dr. Freedland pointed out, there may be subsets of patients, particularly those with very high-risk disease, who could benefit from escalation. Identifying these patients remains a key research priority.
T-Cell Engagers
Among the most exciting developments were early-phase results for prostate-specific membrane antigen (PSMA)–targeted T-cell engagers. These novel immunotherapies aim to activate the immune system against prostate cancer cells.
Dr. Morgans described the phase 1 findings as exciting, particularly given the favorable safety profile: “there were no dose-limiting toxicities, and the overall incidence of grade ≥3 adverse events was low.” Notably, cytokine release syndrome (CRS) was manageable, mostly limited to grade 1 or 2.
Efficacy signals were also striking, with 91% of patients having a PSA50—an unusually strong result for a phase 1 trial. These therapies may eventually expand treatment into outpatient settings and potentially earlier disease states.
PSMA Targeting
With existing PSMA-targeted therapies like lutetium-177, the emergence of T-cell engagers raises important sequencing questions. Dr. Morgans suggested that different mechanisms may suit different patients: “we'll have the opportunity, hopefully, to use multiple PSMA-targeted agents over time.”
She added that treatment decisions will hinge on factors such as disease burden and tolerability, emphasizing that “we'll have to be very thoughtful about when the best time for any patient may be.”
Dr. Freedland expressed optimism for this approach as well, concluding, “In prostate cancer, we’ve been jealous of other tumors because of the PD-L1 activity that we don’t really see in prostate cancer. To no longer have prostate cancer be a cold tumor, and to have the T-cell engager look like it’s working, is pretty exciting. So, stay tuned.”
Key Takeaways
Combination therapy with enzalutamide and radium-223 shows durable survival benefit in select ARPI-naive mCRPC patients and is “ready for primetime” in the right context.
PARP inhibitor and ARPI combinations demonstrate significant overall survival advantages over sequencing in HRR-mutated populations.
Treatment intensification in high-risk localized disease does not universally improve outcomes, highlighting the need for better patient selection.
PSMA-targeted T-cell engagers show early promise with strong PSA responses and manageable toxicity.
The future of prostate cancer care will rely heavily on precise sequencing and personalization across an expanding array of therapies.
About the Speakers
Stephen Freedland, MD, is a Professor of Urology and the Warschaw Robertson Law Families Chair in Prostate Cancer at Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center. He is also the Director of the Center for Integrated Research in Cancer and Lifestyle and the Associate Director for Education and Training at Samuel Oschin, and he holds a Staff Physician appointment at the Durham VA Medical Center in Durham, North Carolina. Dr. Freedland has published over 700 articles and served on numerous AUA and ASCO guideline panels for prostate cancer. His research interests include cancer health disparities, risk stratification, and the role of diet, lifestyle, and obesity in cancer.
Alicia Morgans, MD, MPH, is a Genitourinary Medical Oncologist and the Director of the Survivorship Program at Dana-Farber Cancer Institute. She specializes in the treatment of prostate cancer and other genitourinary malignancies, with interests in survivorship, quality of life, shared decision making, and patient-reported outcomes. Dr. Morgans also serves as President of the Medical Advisory Board for ZERO, a nonprofit organization dedicated to supporting prostate cancer education and research funding.