For decades, clinicians managing biochemical recurrence after radical prostatectomy have faced a familiar dilemma: prostate-specific antigen (PSA) rises, conventional imaging remains negative, and salvage radiotherapy (sRT) proceeds largely empirically. That paradigm is now being challenged by prostate-specific membrane antigen (PSMA) PET/CT, which can reveal recurrent disease at PSA levels once considered “below the radar.”
A new study published in JNCCN—Journal of the National Comprehensive Cancer Network provides some of the most mature outcome data yet on what PSMA-guided decision-making actually delivers in practice. Using real-world data from UCLA, investigators report five-year outcomes in men who underwent PSMA PET/CT–guided sRT following prostatectomy—and show that what the scan reveals meaningfully shapes progression-free survival.
“This research highlights the importance of facilitating routine PSMA PET/CT scans in patients with a biochemical recurrence of prostate cancer after surgery to remove the prostate gland,” said lead investigator John Nikitas, MD, of the UCLA Jonsson Comprehensive Cancer Center. “The information from these scans is strongly associated with long-term outcomes and frequently changes treatment recommendations.”
Seeing recurrence when PSA alone falls short
In the study, 113 patients with rising PSA after prostatectomy underwent PSMA PET/CT at a median PSA of just 0.4 ng/mL. At these levels, conventional imaging is notoriously insensitive. PSMA PET/CT, however, identified visible disease in nearly 60% of patients, including nodal and distant metastases beyond the prostate bed.
Crucially, PSA itself was not strongly associated with long-term outcomes. Instead, PSMA PET/CT stage was prognostic, with patients showing no visible disease (T0N0M0) experiencing the most favorable progression-free survival (PFS).
“We found that other measures, like PSA levels, were not strongly associated with long-term response to secondary/salvage therapy,” Nikitas noted.
This finding reinforces a growing consensus: PSA kinetics alone are an incomplete proxy for disease biology, particularly in the era of molecular imaging.
Tailoring treatment intensity based on anatomy—and biology
One of the most clinically actionable insights from the study lies in how PSMA PET/CT findings informed treatment selection.
For patients with no visible disease, whole-pelvis radiotherapy (WPRT) offered no significant benefit over prostate-bed radiotherapy alone. In contrast, among patients with local recurrence visible on PSMA PET/CT, WPRT was associated with significantly improved PFS. Meanwhile, in patients with nodal or distant metastatic disease, the addition of androgen deprivation therapy (ADT) was independently associated with better outcomes.
Taken together, these data suggest that PSMA PET/CT enables clinicians to escalate—or de-escalate—therapy with greater confidence.
“PSMA PET imaging lets us move from one-size-fits-all radiation therapy in the secondary/salvage setting to treatment that’s guided by the anatomy, and perhaps by extension, the actual biology of a patient’s prostate cancer,” commented E. Christopher Dee, MD, of Memorial Sloan Kettering Cancer Center, in an accompanying JNCCN commentary.
“This study shows that seeing where the cancer is, even at low PSA levels, may meaningfully shape treatment decisions and could potentially influence long-term outcomes.”
Five-year outcomes support a precision approach
With a median follow-up of nearly five years, the UCLA cohort demonstrated a five-year progression-free survival of 48.7%, freedom from distant progression of 72.4%, and an overall survival rate of 97.1%. Importantly, more than 80% of patients remained free from the need for additional systemic therapy at five years.
These outcomes compare favorably with historical salvage radiotherapy series that lacked PSMA guidance—and they underscore how improved staging can translate into more durable disease control, not just earlier detection.
As the commentary notes, PSMA PET/CT appears to enable “more nuanced treatment decisions,” including when to expand radiation fields, when to add ADT, and when to avoid unnecessary intensification altogether.
Precision medicine beyond technology alone
The implications extend beyond imaging. By localizing recurrence earlier and more accurately, PSMA PET/CT creates a framework for biologically informed secondary therapy, aligning with broader trends in precision oncology.
At the same time, both the study authors and commentators caution that PSMA PET/CT is not a panacea. Questions remain around optimal management for PSMA-negative patients, integration with genomic risk stratification, and how best to sequence systemic therapies in low-volume metastatic recurrence. Prospective trials—including PSMA-SRT, PEACE-V STORM, and ADOPT—are now underway to address these gaps.
Equity is another unresolved issue. Access to PSMA PET/CT remains uneven globally and even within high-income countries. As precision imaging becomes embedded in guidelines, ensuring equitable availability will be essential to prevent widening outcome disparities.
Still, the direction of travel is clear. The JNCCN study adds weight to the argument that PSMA PET/CT should no longer be viewed as an optional adjunct in biochemical recurrence, but as a decision-defining tool.
