Exploring Optimal Radiotherapy Strategies in High-Risk Prostate Cancer

Bridget F. Koontz, MD, FASTRO, spoke about a discussant presentation she gave regarding the role of concurrent hormone therapy and brachytherapy for prostate cancer In a conversation with CancerNetwork® at the 2026 ASCO Genitourinary Cancers Symposium.¹ Specifically, she provided her insights following the presentation of 2 separate abstracts, the POSEIDON meta-analysis and the phase 3 ASCENDE-RT trial (NCT00175396), which evaluated hormone therapy with concurrent postoperative radiation therapy and brachytherapy as a means of dose-escalation among patients with high-risk disease, respectively.^2,3

She began by underlining the role of radiation within the prostate cancer treatment landscape; Koontz expressed that radiation is largely effective in even aggressive disease histologies. Furthermore, her focus was to assess the data presented in the aforementioned abstracts and ascertain their relative place within optimal treatment strategy.

Other topics discussed included emergent data of T-cell engager use and its impact on radiosensitivity, which was included in another abstract presented at the conference.⁴ Moreover, Koontz, a radiation oncologist from Advent Health, outlined her involvement as the primary investigator of the phase 2 NRG-GU011 trial (NCT05053152), which will evaluate the role of hormone therapy among patients with oligometastatic disease.⁵

CancerNetwork: What was the background behind your presentation on improving radiotherapy outcomes?

Koontz: I was asked to discuss 2 abstracts presented during the first session of this year’s ASCO GU [conference]. Those abstracts explored the role of hormone therapy concurrent with postoperative radiation and the use of brachytherapy as a method of dose-escalating radiation for high-risk disease.

Radiation for prostate cancer is part of a multidisciplinary strategy; we collaborate with medical oncology and urology to determine the best approach for each patient. Patients often arrive with a misunderstanding of what radiation offers. I wanted to "level set" the room by emphasizing that radiation works exceptionally well for prostate cancer, even in very aggressive cases.

The focus of my talk was how to apply these new data to the patients currently in front of us. How do we tweak our approach to ensure great cancer outcomes and long disease-free intervals while remaining thoughtful about quality of life? It is a "Goldilocks" approach: we want to avoid both under-treating and over-treating.

What were the key takeaways from those abstracts?

The first was the POSEIDON analysis by Amar U. Kishan, MD, et al, which pooled data from 4 respective trials evaluating hormone therapy with concurrent postoperative radiation. Individually, these trials were likely underpowered to show a survival benefit. Furthermore, looking at early markers like PSA progression can be misleading; hormone therapy can suppress PSA levels temporarily without necessarily changing the underlying cancer biology.

By pooling the studies, the researchers gained the power to look at overall survival [OS]. This was impactful because we constantly debate the necessity and duration of hormone therapy. The analysis suggests that patients with lower-aggression disease—lower PSAs and less aggressive Gleason scores—likely do not need hormone therapy, as radiation alone works well. For more aggressive biologies, hormone therapy provides a benefit, but the key takeaway was that these patients probably do not need more than 6 months of treatment. That is excellent news, as men generally recover their testosterone levels well after 6 months, whereas 12 to 18 months of therapy can lead to permanent suppression.

The second study was the ASCENDE-RT trial, which provided a 15-year follow-up on patients [randomly assigned] to either external beam radiation alone or radiation with a brachytherapy boost. The hypothesis was that the boost would better eradicate disease within the prostate and improve survival. However, brachytherapy’s higher dose carries increased risks of urinary toxicity and urethral damage.

The results were a bit of a "dampener" on the universal use of brachytherapy; while there was perhaps a slight benefit in preventing death specifically from prostate cancer, there was no difference in OS. [Based on data from other studies] there [may still be] a role for brachytherapy, but it must be focused on high-risk patients where local control of the prostate is the primary driver of the outcome. Patients at high risk for nodal or metastatic disease should focus on systemic control rather than a local brachytherapy boost.

What are the most promising systemic agents or radiosensitizers currently being tested to overcome radioresistance?

I was very excited [about] a later session here at ASCO GU. There were some nice talks about upcoming systemic therapeutic options. I'm really excited about T-cell engagers. [Regarding] the question about whether it will impact radiation sensitivity, we don't know yet how that works. There’s an interesting interplay for prostate cancer and our immune systems. Traditionally, we have felt that a prostate cancer is an immunodepleted cancer. We don't really get a lot of immune response when we treat it, and it seems to be masked from our immune system very well. It's probably why it's such a prevalent cancer.

Radiation works, in part, by stimulating the immune system to attack these cancer cells. As they start to die, [they] perhaps present antigens that the immune system can use to attack. Anything—whether it's CAR-T, T-cell engagers, and where we’re headed [with] the other agents—may have an exciting benefit on the radiosensitization. It is still [in the] early days because, right now, they're looking at advanced disease, and it’ll be a while, so we’re ready to look at combination drugs plus radiation. That’s what I’m most excited about, so take a look at that session. It was a great session on advanced disease at ASCO GU prostate day, and there was a lot of great information about what's coming up.

Is there anything else you would like to highlight?

We also discussed 2 other abstracts that underscored the importance of multidisciplinary care. There is still much we don’t know, such as the interplay of hormone therapy in metastatic or oligometastatic disease.

Research is currently looking at biomarkers to help us find that "just right" treatment approach. I am the national [principal investigator] for an NCI study, the phase 2 NRG-GU011 trial (NCT05053152), which is finishing enrollment. We are evaluating the use of radiation with or without hormone therapy specifically for oligometastatic disease.

As physicians, we must look at the studies and then look at the patient in front of us to determine how that data applies to their specific biology and quality-of-life needs. It is an exciting time to be a prostate cancer physician.

References

1. Koontz B. Improving Outcomes for Radiotherapy.Presented at the 2026 ASCO Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA.
2. Kishan AU, Sun Y, Parker C, et al. Hormone therapy use and duration with post-operative radiotherapy for recurrent prostate cancer: an individual patient data meta-analysis. J Clin Oncol. 2026;44(suppl 7):305. doi:10.1200/JCO.2026.44.7_suppl.305
3. Tyldesley S, Pai HH, McKenzie MR, et al. Fifteen-year survival analysis from the ASCENDE-RT randomized trial of external beam boost versus brachytherapy boost in localized prostate cancer. J Clin Oncol. 2026;44(suppl 7):306. doi:10.1200/JCO.2026.44.7_suppl.306
4. Rathkopf D. New treatment options for patients with castrate-resistant prostate cancer. Presented at the 2026 ASCO Genitourinary Cancers Symposium; February 26-28, 2026; San Francisco, CA.
5. Testing the addition of the drug relugolix to the usual radiation therapy for advanced-stage prostate cancer, the NRG Promethean study. ClinicalTrials.gov. Updated January 14, 2026. Accessed March 10, 2026. https://tinyurl.com/mr2bp5zk