Radiopharmaceutical therapy is appealing because it allows us to deliver radiation directly to cancer cells throughout the body. It acts as a systemic delivery system but remains targeted based on the presence of specific markers on tumor cells. That ability to treat disease throughout the body while maintaining precision is very exciting.
Another important question in sequencing is whether therapies must always be given sequentially or whether combination strategies may sometimes be beneficial. Of course, more treatment is not always better. For example, the [phase 3] PEACE-III trial [NCT02194842] evaluated the radiopharmaceutical radium-223 [Xofigo] in combination with enzalutamide [Xtandi] in patients with metastatic castration-resistant prostate cancer and bone-dominant disease.1
Encouragingly, the study [data] demonstrated an overall survival [OS] benefit that appeared to be maintained over time. Findings like these suggest that, for certain patient populations, combination strategies may provide meaningful benefit. At the same time, they also raise new questions about other populations that might benefit from similar approaches.
How has the concept of treatment deintensification evolved in recent years, and what does it mean for oncologists and patients?
As we continue to focus on personalization, we’re always trying to balance evidence from clinical trials with the needs and priorities of the individual patient in front of us. Some patients may prioritize treating the cancer as aggressively as possible, while others may want to ensure that certain aspects of their quality of life are preserved.
Those conversations can guide discussions about treatment deintensification. For example, radiotherapy, such as external beam radiation therapy or brachytherapy, is often used in combination with androgen deprivation therapy [ADT] for patients with higher-risk prostate cancer, both in the newly diagnosed setting and in the postoperative setting.
Although this combination has demonstrated benefit, an important question is whether ADT can safely be omitted in certain patients. Work presented at this year’s meeting, including the POSEIDON [meta-analysis], analyzed individual patient data from multiple randomized phase 3 trials to determine whether the addition of ADT consistently provides an OS benefit across all patient groups.2
One takeaway from the analysis was that certain patients, particularly those with lower prostate-specific antigen [PSA] levels of less than 0.5 ng/mL, may not experience a clear OS benefit from the addition of ADT to treatment regimens. However, there are several caveats, including the fact that the data span many years and therefore do not incorporate some of the newer tools we now have, such as biomarkers and prostate-specific maturation antigen [PSMA]-PET imaging.
Even so, the findings reinforce an approach that many of us already take in practice. Rather than focusing on a single factor, such as PSA level alone, we consider the broader clinical context, including PSA trends over time, features of the original pathology, and findings from imaging or restaging scans. Taking all these factors into account allows us to move toward a more personalized and selective treatment approach, where deintensification may be appropriate for certain patients without compromising cancer outcomes.
Looking ahead, continued progress in biomarker research and genomic testing will be critical, particularly as these tools become more widely available and begin to play a larger role in guiding prostate cancer treatment decisions.
How can oncologists practicing in the community help preserve patient QOL?
I often say that care is delivered in the community; that’s where most patients receive treatment. Although academic centers may be prominently represented at conferences and in research presentations, many patients enrolled in these studies are treated at community sites by community oncologists.
Preserving QOL begins with conversations. We need to help patients understand the trade-offs associated with different treatment options, including the likelihood of achieving certain outcomes and the potential costs of pursuing those outcomes. Those costs can include short-term and long-term adverse effects [AEs], but also financial burdens, time commitments, and time away from work or family.
These discussions are important across the entire spectrum of prostate cancer, from early-stage disease to advanced metastatic disease. A patient’s goals may change over time, depending on where they are in their cancer journey. Community oncologists, who often maintain long-term relationships with patients and their families, play a key role in recognizing those evolving priorities.
Another important area involves the use of patient-reported outcome tools. These tools can help clinicians identify periods when patients may be struggling with AEs or other challenges that might not otherwise be captured during routine clinical visits. Importantly, these assessments should extend beyond physical symptoms to include psychosocial and emotional well-being, such as energy levels, ability to engage in daily activities, and reintegration into normal life.
Community oncologists are uniquely positioned to help capture these data because they frequently continue caring for patients long after treatment ends. Combining patient-reported outcomes with objective measures such as imaging and laboratory data will be essential as we…move toward more personalized care.
Which ongoing studies or emerging therapies in prostate cancer are you most excited about, and how might they shape the treatment landscape?
There is so much happening in this space that it’s difficult to highlight just one study. In general, I’m most excited about ongoing research exploring both treatment intensification and deintensification, particularly studies evaluating new combination approaches.
One example is the [phase 3] ECOG-ACRIN EA8191 trial [NCT04423211], also known as the INDICATE trial, which incorporates PSMA-PET imaging as an integrated biomarker in patients who experience biochemical recurrence after prostatectomy. The trial includes different study arms depending on the PET findings—whether the scan is negative, shows disease confined to the pelvis, or identifies disease outside the pelvis.
The study is asking 2 key questions. First, can intensifying systemic therapy alongside standard pelvic radiation and 6 months of ADT improve outcomes? Specifically, investigators are evaluating whether adding 6 months of the androgen receptor pathway inhibitor apalutamide [Erleada] could enhance outcomes without requiring prolonged systemic therapy.
The second question involves patients whose PSMA-PET scans reveal disease outside the pelvis or in bone. For these individuals, the trial is examining whether [administering] metastasis-directed radiation therapy to those sites in combination with standard treatment and short-term systemic therapy can further improve outcomes.
These questions are particularly important because most of our historical evidence and staging systems were developed using conventional imaging such as CT scans, MRIs, and bone scans. As PSMA-PET imaging allows us to detect disease earlier and with greater precision, we need to determine how our treatment strategies should evolve accordingly.
Beyond this study, there are many important trials underway across cooperative groups such as ECOG-ACRIN, NRG Oncology, Alliance, and SWOG. These studies span the entire prostate cancer spectrum—from prevention and active surveillance to advanced metastatic disease that is resistant to ADT.
References
- Gallardo E, Tombal BF, Choudhury A, et al. Final overall survival results from the EORTC 1333/PEACE-3 trial: enzalutamide with or without radium-223 in metastatic castration-resistant prostate cancer. J Clin Oncol. 2026;44(suppl 7):15. doi:10.1200/JCO.2026.44.7_suppl.15
- 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