PSMA PET/CT-Guided Radiation Exhibits Favorable Prostate Cancer Outcomes

The inclusion of PSMA PET/CT-guided management following salvage radiotherapy (sRT) exhibited favorable 5-year oncologic outcomes among patients treated for the first biochemical recurrence following radical prostatectomy, according to findings from a retrospective cohort analysis published in the Journal of the National Comprehensive Cancer Network (JNCCN).¹

Specifically, after a median follow-up of 59.4 months (IQR, 47.4-69.5) among 113 patients included in the study, the median progression-free survival (PFS) was 49.2 months. The respective 2- and 5-year PFS rates were 72.6% (95% CI, 64.3%-80.8%) and 48.7% (95% CI, 38.9%-58.6%). A total of 49.6% and 42.5% experienced biochemical and radiographic progression, with a median of 4.7 months (IQR, 0.8-14.7) between biochemical and radiographic progression.

Among 48 patients who experienced radiographic progression, 42 were identified by PSMA PET/CT. Additionally, of these 48 patients, 2 experienced in-field progression, and 46 experienced the development of new metastatic sites.

The median freedom from distant metastases was 76.4 months, with respective 2- and 5-year rates of 85.8% (95% CI, 79.4%-92.3%) and 72.4% (95% CI, 63.6%-81.1%). Moreover, the median freedom from start of new line of systemic therapy was not reached, with respective 2- and 5-year rates of 92.9% (95% CI, 88.1%-97.6%) and 82.7% (95% CI, 75.4%-90.1%). Subsequent therapies received included androgen deprivation therapy (ADT) with an androgen receptor pathway inhibitor (ARPI; 12.4%), ADT with dual ARPIs (3.5%), and an ARPI alone (3.5%).

The median overall survival (OS) was not reached, with 2- and 5-year rates of 100% (95% CI, 100%-100%) and 97.1% (95% CI, 94.1%-100%), respectively.

“The study…provides valuable real-world evidence that PSMA PET/CT–guided sRT produces favorable long-term outcomes, with nearly three-quarters of patients remaining free from distant metastasis at 5 years. These results underscore a fundamental evolution in how we approach biochemically recurrent prostate cancer, from anatomically based consensus guidelines to biologically informed, personalized treatment strategies,” Edward Christopher Dee, MD, from the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, wrote with coauthors in a commentary published in the same issue as the study.² “PSMA PET/CT enables unprecedented risk stratification, informs decisions about treatment intensification with whole-pelvis radiotherapy [WPRT] or ADT, and identifies oligometastatic disease amenable to consolidative therapy. However, improved detection capabilities must ultimately translate into improved patient outcomes, not merely stage migration.”

The retrospective analysis of 5 institutional review board-approved studies included patients with prostate cancer who underwent PSMA PET/CT scans between January 2016 and May 2021. They also had proven prostate adenocarcinoma, received prostatectomy, experienced a first biochemical recurrence, and underwent sRT within 3 months of restaging with PSMA PET/CT.

Those in the trial had a median initial PSA level of 8.0 ng/mL (95% CI, 5.4-14.0). Additionally, most patients had pathologic ISUP grade 3 disease (35.4%), pathologic stage pT2N0/Nx disease (44.2%), negative surgical margins (54.9%), and PSMA PET/CT staging of miT0N0M0 (40.7%). A total of 54.9% of patients had negative surgical margins, 40.7% had 0 visible lesions, and 38.9% had 1 visible lesion (38.9%). The median age at PSMA PET/CT was 67 years (IQR, 62-72).

The study evaluated PFS, freedom from distant progression, freedom from new lines of therapy, and OS from the start of sRT. An additional exploratory analysis included PFS for specific patient and treatment characteristics.

Among patients with T0N0M0 disease, the adjusted HR compared to those in the M1b/M1c cohort was 0.25 (95% CI, 0.11-0.57; P < .001). Moreover, those with N1/M1a (adjusted HR, 0.39; 95% CI, 0.18-0.89; P = .020) and those with TrN0M0 disease (adjusted HR, 0.39; 95% CI, 0.16-0.96; P = .038) had significantly improved PFS outcomes compared with the M1b/M1c cohort, yet pre-RT PSA did not (adjusted HR, 1.00; 95% CI, 0.86-1.11; P = .98).

In the T0N0M0 cohort, WPRT did not exhibit a significant PFS improvement (adjusted HR, 0.87; 95% CI, 0.27-2.67; P = .80), but in the TrN0M0 cohort, it did exhibit a significant improvement (adjusted HR, 0.12; 95% CI, 0.01-0.76; P = .035). Moreover, interaction term testing between stage and treatment with WRPT did not achieve significance (P = .76).

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):11-18. doi:10.6004/jnccn.2025.7102
2. Patel MS, Nagar H, Dee EC. PSMA PET–guided secondary radiotherapy: leveraging molecular imaging for biologically informed treatment. JNCCN. 2026;24(2):61-63. doi:10.6004/jnccn.2026.7008