PSMA-PET/CT–guided salvage radiotherapy yields favorable outcomes after prostatectomy

Data published in the Journal of the National Comprehensive Cancer Network show favorable 5-year outcomes when using prostate-specific membrane antigen (PSMA)-PET/CT to guide salvage radiotherapy for patients who experienced biochemical recurrence (BCR) following radical prostatectomy.¹

The findings specifically offered insights into how PSMA-PET/CT, which is more sensitive at low prostate-specific antigen (PSA) levels, may be used to optimize treatment intensification with whole-pelvis radiotherapy (WPRT) or androgen deprivation therapy (ADT).

“PSMA-PET/CT scans allow us to see exactly where cancer is and tailor treatment accordingly,” explained senior author Jeremie Calais, MD, PhD, director of the clinical research program in the department of Nuclear Medicine and Theranostics and associate professor at the David Geffen School of Medicine at UCLA, in a news release on the findings.² “Patients can get the therapy they need while avoiding unnecessary [adverse] effects, and even those with no visible disease can do very well with standard radiation.”

In total, the retrospective study included 113 patients who experienced BCR following radical prostatectomy. At the time of PSMA-PET/CT, the median age of participants was 67 years, the median PSA level was 0.4 ng/mL, and the median time from radical prostatectomy was 19.9 months. Upon imaging, 40.7% of patients had no visible lesions, 38.9% had a single lesion, 16.8% had 2 to 3 lesions, 1.8% of patients had 4 to 5 lesions, and 1.8% of patients had 6 to 8 lesions.

At a median follow-up of 59.4 months, the median progression-free survival (PFS) was 49.2 months. At 2- and 5-years, the PFS rate was 72.6% (95% CI, 64.3 to 80.8) and 48.7% (95% CI, 38.9 to 58.6), respectively. The median freedom from distant metastasis was 76.4 months. At 2 and 5 years, 85.8% (95% CI, 79.4 to 92.3) and 72.4% (95% CI, 63.6 to 81.1) of patients were free of distant metastasis, respectively.The median overall survival (OS) was not reached. OS rates were 100% at 2 years and 97.1% (95% CI, 94.1 to 100) at 5 years.

Patients with a negative PSMA PET/CT scan demonstrated the most favorable outcomes. Among these patients, the PFS rate was 78.3% (95% CI, 66.3 to 90.2) at 2 years and 62.4% (95% CI, 48.2 to 76.6) at 5 years. M1b–M1c patients had the least favorable outcomes. PFS was notably similar between TrN0M0 and N1/M1a patients.

According to the authors, “This may reflect the ability of PSMA PET/CT–guided restaging and treatment to enable more comprehensive targeting of disease in patients, potentially leading to improved and potentially equivalent outcomes between locally recurrent and node-positive disease.”

The investigators also conducted prespecified secondary analyses on the impact of incorporating WPRT and ADT.In total, 55.8% of patients received WPRT and 67.3% of patients received ADT.

WPRT was not significantly associated with an improvement in PFS among those with T0N0M0 disease (n=46) compared with prostate bed radiotherapy alone (aHR, 0.87; 95% CI, 0.27 to 2.67; P = .80;). However, WPRT was linked with a significant improvement in PFS among those with TrN0M0 disease (n=19) (aHR, 0.12; 95% CI, 0.01 to 0.76; P = .035).

Further, ADT was not associated with an improvement in PFS among those with TrN0M0 disease (n=19) (aHR, 5.64; 95% CI, 1.12 to 41.3]; P = .051) nor T0N0M0 disease (n=46) (aHR, 0.67; 95% CI, 0.23 to 1.91), but was significantly associated with a PFS improvement among those with nodal or distant metastasis (n=48) (aHR, 0.37; 95% CI, 0.16 to 0.90; P = .024).

“This research underscores the value of incorporating PSMA-PET/CT findings into clinical guidelines when deciding whether to add whole-pelvis radiation or hormone therapy to salvage radiation after prostate surgery,” added lead author John Nikitas, MD, a resident in the department of radiation oncology at UCLA Health, in the news release.² “We also found that traditional measures such as PSA level were not strongly linked to long-term response, highlighting the importance of imaging-based, rather than PSA-based, decision-making.”

The authors did note several limitations of the current study, including its non-randomized, retrospective design and the lack of standardized treatment protocols. They note that further research is necessary to confirm their findings. They also referenced several ongoing studies to further clarify the role for PSMA-PET in patients with recurrent disease, including the phase 3 PSMA-SRT trial (NCT03582774), the phase 2 PEACE-V STORM trial (NCT03569241), the ADOPT trial (NCT04302454), and the observational PSICHE trial (NCT05022914).

"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," concluded E. Christopher Dee, MD, of Memorial Sloan Kettering Cancer Center, who was not involved in this research.³ "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. It's a step forward in making prostate cancer care more precise and effective and can inform future prospective research in the secondary/salvage radiation space."

REFERENCES

1. Nikitas J, Smith CP, Armstrong WR, et al. Five-year outcomes after prostate-specific membrane antigen PET/CT-guided salvage radiotherapy following radical prostatectomy. JNCCN. 2026;24(2). doi:10.6004/jnccn.2025.7102

2. Study shows advanced PET/CT imaging can help improve long-term outcomes for men with recurrent prostate cancer. News release. UCLA Health. February 9, 2026. Accessed February 10, 2026. https://www.uclahealth.org/news/release/study-shows-advanced-petct-imaging-can-help-improve-long

3. New study in JNCCN unlocks important information about how to treat recurring prostate cancer. News release. National Comprehensive Cancer Network. February 9, 2026. Accessed February 9, 2026. https://www.prnewswire.com/news-releases/new-study-in-jnccn-unlocks-important-information-about-how-to-treat-recurring-prostate-cancer-302682612.html