Updated AUA Prostate Cancer Guidelines Favor Early Salvage Over Adjuvant Radiation
Sophia Kamran, MD, discussed the updated AUA guidelines on salvage therapy for patients with prostate cancer and their implications.
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Updated American Urologic Association (AUA) guidelines presented at the 2025 annual meeting mark a major shift in the management of prostate cancer recurrence, moving away from routine adjuvant radiation therapy and toward early salvage radiation.
The changes are supported by new data, according to Sophia Kamran, MD, who explained in an interview with Targeted OncologyTM, “there has been a transition away from adjuvant radiation therapy postoperatively, moving more toward salvage or early salvage radiation therapy. That shift comes from 3 large trials analyzed in a meta-analysis.”
In the interview, Kamran, associate professor of radiation oncology at Harvard Medical School, and Massachusetts General Cancer Center, shared insights into the updated AUA guidelines on salvage therapy for patients with prostate cancer and their implications.
Targeted OncologyTM: Can you provide an overview of the guidelines for salvage therapy?
Kamran: I was part of a large team, [and] I had the opportunity to help put together the salvage therapy guideline that was published last year. We [presented] an instructional course at the 2025 AUA Annual Conference, [and we talked] about what the guidelines say, updates since the previous version from 2013, and [reviewed] cases and common clinical scenarios. We discussed how to incorporate the guidelines into treatment options for patients.
What are some of the significant updates discussed?
There has been a transition away from adjuvant radiation therapy postoperatively, moving more toward salvage or early salvage radiation therapy. That shift comes from 3 large trials analyzed in a meta-analysis known as the ARTISTIC meta-analysis, which showed no difference in oncologic outcomes. Early salvage therapy allows patients time to regain continence and sexual function, improving quality of life.
That said, adjuvant therapy is not obsolete. There’s ongoing research for high-risk patients, including very young individuals or those with node-positive disease. These patients may still benefit from upfront adjuvant radiation therapy. It's an active area of investigation.
What role does risk stratification play in guiding the selection of salvage therapy according to the guidelines?
Certain risk factors guide our postoperative management. The guidelines include a helpful table outlining these, but key factors include disease grade, [prostate-specific antigen (PSA)] doubling time, PSA level at recurrence, and pathological features like node positivity, positive margins, extracapsular extension, and seminal vesicle invasion. We also consider patient age, comorbidities, and engage in shared decision-making when offering salvage therapies.
How do the guidelines advise on the timing and sequencing of salvage therapies?
There's no level 1 evidence on exact timing, but existing data show better long-term outcomes when salvage therapy is initiated early. As soon as patients meet criteria for biochemical recurrence, they should be referred to radiation oncology.
Even if PSA is undetectable postoperatively, patients with high-risk features should be counseled about the possibility of future therapy. In terms of sequencing, if salvage radiation and hormone therapy are both planned, hormone therapy can be started first, especially if the patient is still recovering from surgery. Hormone therapy can act as a bridge, but as long as it overlaps with radiation, that’s sufficient.
Is there anything in the guideline that discusses tools like prostate-specific membrane antigen (PSMA)?
Yes, this is an area of ongoing investigation. Novel molecular imaging, such as PSMA PET, is being increasingly incorporated. Current level 1 evidence has not included PSMA PET yet, but ongoing phase 3 trials are evaluating its impact on management and outcomes. We recommend using these imaging techniques if available, but they are not required. It is important to remember that they can yield false negatives. So, even if imaging is negative but the PSA is detectable and risk factors are present, salvage radiation therapy should still be offered.
Are there any ongoing research efforts or controversies that might be addressed in future guideline updates?
One major area is how molecular imaging will influence when and how to initiate salvage therapy. It may help define radiation fields, boost targets, and guide systemic therapy. Other areas include systemic therapy escalation, optimal duration, and whether to use androgen deprivation therapy alone or combine it with other agents like androgen receptor pathway inhibitors. There’s also excitement around incorporating biomarkers like Artera AI to guide treatment decisions. We are exploring how to integrate these into clinical practice.
