In the era of prostate-specific membrane antigen positron emission tomography (PSMA PET) imaging, confidence in the ability to intervene has grown. At the 2024 ASTRO Annual Meeting, speakers reviewed the evidence supporting metastasis-directed therapy for oligometastatic castration-sensitive prostate cancer (omCSPC).

Following these proceedings, featured expert William K. Oh, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Dr Oh’s clinical perspectives on these findings are presented here.

The general belief has been that, once the cancer spreads outside of the prostate, it should be considered widely metastatic. However, I think that there is a greater appreciation now that, in some patients, the disease may spread to relatively few locations at first. This raises the possibility of treating those sites with radiation—with stereotactic body radiation therapy (SBRT), in particular. Such treatment is intended to delay progression, delay the need for hormonal therapy, and, potentially, keep these patients alive longer with a better quality of life. I do not know that anyone believes for certain that we can cure these patients, but there is more and more hope that we can delay progression enough so that they might be able to achieve a functional cure, allowing them to live out their natural life span without dying from progressive prostate cancer.

During a Presidential Symposium at ASTRO 2024, several speakers touched on the current definitions of and treatment options for omCSPC. Phuoc Tran, MD, PhD, explored the line between localized disease and widely metastatic disease in his presentation, “The Space-Time Continuum in Metastatic Castration-Sensitive Prostate Cancer: The Final Frontier?” During his talk, he explained that disease volume, or number of metastases, was represented by “space,” and the nature of the oligometastatic presentation (ie, metachronous vs synchronous) was represented by “time.” Both space and time were considered probable phenotypes of oligometastatic biology.

We know that “metastatic” does not capture the heterogeneity of the biology of metastatic disease. A patient with a single lymph node that lights up on PSMA PET in the retroperitoneum is not the same as someone with 30 bone metastases, even though both patients have a TNM stage of IV. As noted by Dr Tran, there may be range in the number of lesions, perhaps as high as 7 or 8 lesions, that may correspond to potential benefit from radiation therapy; others have used different cutoffs of fewer than 5 or 3 lesions.

Recall the 2 influential but small randomized phase 2 studies that were published several years ago (ie, the STOMP and the ORIOLE trials). In both studies, patients with omCSPC received metastasis-directed treatment. In ORIOLE and STOMP, oligometastatic was defined as 1 to 3 metastases detectable by conventional imaging and as less than 3 bone or lymph node metastases, respectively. A key point in both trials was that hormonal therapy was not given, such that a delay in the initiation of ADT, or ADT-free survival, became an outcome of interest.

Since the time of STOMP and ORIOLE, however, there have been several important developments. First, we have entered into the PSMA PET imaging era. PSMA PET is not a perfect tool, but we can now see these lesions with much greater sensitivity and specificity than we could in the past. As a result, there is now greater confidence in our ability to identify patients who have a truly limited number of metastases. Another development is the continued discussion of whether hormonal therapy should be added in this setting. Clinical trials are now being conducted to try to define whether hormonal therapy is needed at all, and, if so, the optimal agent and duration.

During his presentation, Dr Tran highlighted the “time” component of the analogy. Patients with metachronous oligometastases generally do better than patients with synchronous oligometastases, which may reflect the biology of more indolent disease that takes more time to declare itself. The evidence is fairly strong for irradiating metachronous oligometastases and is less well defined in de novo synchronous oligometastatic presentations. In my own practice, we do consider SBRT even for the latter group, in part because the therapeutic index of radiation therapy has improved over the years. Radiation has gotten safer, and SBRT is more convenient than conventional fractionation. So, despite the fact that there is not yet an overall survival benefit of SBRT, the trend is to offer it to these patients for all the aforementioned reasons. And I agree with Dr Tran that some of these secondary end points, such as time off from ADT, can be important to patients.

Other omCSPC-related takeaways from ASTRO 2024 include that patients who seem to benefit from metastasis-directed interventions in particular have tumoral molecular changes that are indicative of faster-growing disease (abstracts 333 and 1103). Cancers that grow more quickly are the ones that seem to benefit the most from this kind of more aggressive intervention, whether it be radiation alone or the combination of radiation with hormonal therapy.

An important negative study that was presented at this year’s ASTRO meeting during the special session on late-breaking abstracts was the RAVENS trial (abstract LBA10). This was a randomized phase 2 trial that explored whether adding radium-223 to SBRT would improve outcomes in patients with oligometastatic disease, and the answer was that it did not. We will have to see whether other radiopharmaceuticals such as ¹⁷⁷Lu-PSMA might have a better effect. But, as of now, the RAVENS study was interesting in that it suggested that SBRT was enough in oligometastatic disease to delay progression.

This is clearly a hot topic and a rapidly evolving area. The published data are still relatively limited, coming from smaller trials; small but larger phase 3 studies are ongoing. In my own practice, I often give my patients ADT because my goal with SBRT is to try to delay progression for as long as possible. I may not give long-term ADT, but I do think that high-risk patients should receive ADT with SBRT. That said, studies seem to suggest that the patients with higher-risk cancer benefit from SBRT with or without ADT.