Speakers at the 2024 ASTRO Annual Meeting focused on the options for prostate cancer salvage therapy in cases of localized recurrence after definitive treatment. Next-generation imaging and the move toward stereotactic body radiation therapy (SBRT) are contributing to the evolving trends.

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 topics are presented here.

During a Presidential Symposium at ASTRO 2024, Ronald Chen, MD, FASTRO, MPH, gave a presentation on salvage therapy options for local recurrence after definitive radiotherapy. At the beginning of his talk, he noted recently published guidelines and the importance of offering some type of salvage therapy (eg, radical prostatectomy, cryotherapy, high-intensity focused ultrasound, or SBRT) to all patients with biopsy-documented recurrence who are candidates for such treatment.

We have been offering salvage radiation therapy after initial surgery or initial radiation for many years, but I think that there are 2 major areas of change. First, we have been moving toward hypofractionation, including SBRT, which is less burdensome to patients. Second, we have learned that prostate-specific membrane antigen positron emission tomography (PSMA PET) imaging gives us greater confidence in our ability to detect recurrent disease and its extent. Do we have 100% confidence in this? Absolutely not. We still cannot see microscopic cancer cells, but we can see more than we could before.

During his talk, Dr Chen noted that his first step in evaluating the patient for salvage therapy options is to obtain a PSMA PET scan and multiparametric magnetic resonance imaging (MRI). The PSMA PET, multiparametric MRI, and biopsy all help to identify a recurrence that is localized within the prostate. Dr Chen also thought that success rates with salvage therapy would likely rise across the board (ie, regardless of the treatment modality) with PSMA PET guidance and with the ability to identify more cases that are truly localized recurrences. Yes, we are mindful of the Will Rogers phenomenon, and, yes, additional studies are needed to see the long-term outcomes. However, my own view on this is a pragmatic one, and I think that salvage therapy outcomes will improve with PSMA PET guidance because we can save people from the toxicities of local therapy when we establish that they do not truly have local-only recurrence.

For me, another important take-home message from Dr Chen’s presentation was that, in light of all the available data, “radiation after radiation” is becoming a clearer choice. Historically, salvage radiation therapy after initial definitive radiation therapy was viewed as being too toxic. However, approaches such as radical prostatectomy, cryotherapy, and high-intensity focused ultrasound have, in fact, been associated with substantial toxicity after radiation. SBRT and, potentially, brachytherapy appear to have lower rates of grade 3 genitourinary toxicities. Dr Chen nicely integrated evidence from a number of sources, noting that the success rates for all the modern options for salvage therapy after initial radiation treatment are roughly equivalent (ie, approximately 50%, based on his definition of biochemical recurrence-free survival) and that SBRT and brachytherapy are associated with much lower rates of severe genitourinary toxicity.

If we look at some of the other work that was reported at ASTRO 2024, I think that the abstract by Devaki Shilpa Surasi, MD, et al reiterates the point that the PSMA-based imaging can, more often than not, lead to changes in radiation therapy treatment plans (abstract 1005). This was a pilot study using ¹⁸F rhPSMA-7.3 PET/MRI in men with biochemical recurrence after radical prostatectomy, and changes in the treatment plan were documented in 22 of 28, or approximately 79%, of patients. Now, the radiation was cancelled in some of these cases, but, in many others, the radiation was actually expanded to cover more of the fields. Again, it remains to be seen whether this practice will lead to better outcomes, but I do not see how this would not be better for the patient, by allowing those in whom the disease is clearly widespread to avoid salvage radiation therapy.

Looking beyond the horizon, the following question arises: Might PSMA-targeted radioligand therapy be used as salvage therapy for local recurrence after surgery or radiation, essentially taking PSMA-based guidance to the next level? For now, the answer is “no, not yet,” but the idea of using PSMA-directed therapy in this setting is clearly of interest and will be studied further. Currently, ¹⁷⁷Lu-PSMA-617 is approved by the US Food and Drug Administration (FDA) for PSMA-avid metastatic castration-resistant prostate cancer and is being studied in a number of earlier disease settings, including in taxane-naive patients. This whole area of radiopharmaceuticals is of great interest in radiation oncology, as it is in several other fields, and I think that we can look forward to many developments in the future.