The patients were not an easy crowd. All had presented with high-risk features at initial diagnosis: the median biopsy Gleason score clustered at 8, more than 42 percent had extraprostatic extension (pT3b), 20 percent already harbored positive lymph nodes at surgery, and over a third had incomplete resections. Yet when their prostate-specific antigen (PSA) began climbing after first-line therapy, modern gallium-68 or fluorine-18 PSMA-PET/CT scans pinpointed the culprits — 172 metastases in total, roughly 80 percent nodal and 20 percent bone — while disease burden remained low, with a median pre-SBRT PSA of just 1.66 ng/mL.

The treatment itself was strikingly uniform. Each PSMA-avid lesion defined the gross target volume, wrapped in a 1-to-5-millimeter planning margin depending on location, and received an ablative dose to the surrounding 70 percent isodose line of either a single 18-to-21-Gy fraction or three 8-Gy fractions. The CyberKnife robotic platform tracked lesions stereoscopically — bone tracking in 92.4 percent of cases, fiducial markers in the rest — allowing sub-millimeter accuracy that spared surrounding bowel, bladder, and spinal cord. Most series treated one or two metastases; the median planning target volume was a mere 3.31 cubic centimeters.

Toxicity data read like a wish list. Across 95 treatment series, 93.5 percent of patients experienced no acute or late adverse events at all. The six acute grade 1 events comprised temporary fatigue, diarrhea, nausea, and single cases of pain, proctitis, and polyuria; only one patient developed a late symptom, a persistently painful bone metastasis. No event exceeded grade 1. That stands in sharp contrast to trials combining SBRT with elective nodal radiation or hormone therapy, where grade 2 and 3 genitourinary and gastrointestinal toxicity rates have reached double digits, and to systemic therapy arms in the STAMPEDE and LATITUDE trials, where 47 to 63 percent of patients suffered grade 3 or worse adverse events.

Local control was equally impressive. Among 117 metastases re-assessed by repeat PET/CT, 89.7 percent remained locally controlled — 93.5 percent for lymph nodes but only 76 percent for bone lesions. The authors attribute the nodal-bone gap to the protective microenvironment of the bone marrow, which shelters cancer cells, and possibly to hypoxia within bone lesions, which blunts radiation efficacy. PSA response after SBRT was seen in 70.5 percent of series, with the median post-treatment nadir falling to 0.58 ng/mL roughly four months after treatment.

The headline endpoints tell the story of a bridge. Median biochemical progression-free survival was 6 months — short by conventional standards, but the strict definition used (a PSA rise of more than 0.2 ng/mL from nadir) and the aggressive histology of the cohort (63 percent with Gleason 8 or higher) make direct comparisons tricky. Median SBRT-free survival, meaning the time before a second course became necessary, was 23 months, and 43 of the 60 patients actually received repeat SBRT courses with no predefined upper limit. Median ADT-free survival reached 32 months, with 85.9 percent of patients still hormone-free at one year and 68.4 percent at two years. A third of the cohort finished follow-up without any treatment escalation whatsoever.

Prognostic modeling identified who fared worst. A high PSA nadir after SBRT, an initial pN1 nodal status at surgery, and a longer time to reach the PSA nadir all predicted shorter biochemical progression-free and SBRT-free survival on multivariable Cox regression. The authors suggest these patients could be steered earlier toward combination approaches — either standard ADT or androgen receptor pathway inhibitors such as abiraterone, enzalutamide, apalutamide, or darolutamide — rather than cycling through repeated focal treatments that may ultimately prove futile.

The rationale for attacking metastases this early rests on evolutionary biology. Genetic analyses of lethal metastatic prostate cancer have shown that the tumor clones responsible for fatal dissemination do not necessarily reside in the primary tumor but can emerge from any single metastasis. Meanwhile, early metastases detected by molecular imaging carry fewer high-risk DNA features and a better survival prognosis than those found later. The logic, then, is to intervene while the disease is still genetically tame — and to save the effective but toxic and finite systemic arsenal for when it is truly needed.

The Charité results compare favorably with prior prospective trials. The STOMP trial reported a median ADT-free survival of 21 months; Siva and colleagues described only a 48 percent two-year ADT-free rate; Mazzola’s bone-only cohort managed 13.5 months. The Berlin cohort’s 32-month median, achieved without ADT contamination and with a uniform ablative dose concept, is among the best reported. The second-largest number of metastases treated in any single analysis also strengthens the dataset, though the authors acknowledge the retrospective design, the absence of a control arm, and the lack of a predefined PSA cutoff triggering re-imaging or re-treatment as critical limitations.

Whether early oligo-recurrences inevitably progress into life-threatening disease remains an open question, and the authors concede that for some patients with gradual progression, observation might have sufficed. Still, they argue that establishing molecular imaging plus focal SBRT as a first go-to option in oligo-recurrent prostate cancer is worthwhile: the procedure is swift, outpatient-based, locally ablative, essentially toxicity-free, and repeatable on demand. For patients anxious about the quality-of-life toll of permanent hormone therapy, the approach offers something rare in oncology — a way to buy nearly three years of normal testosterone levels while the clock on systemic therapy is deliberately held back.

Subject of Research: Health

Article Title: Bridging to systemic therapy: PSMA-PET-based early and repetitive stereotactic body radiotherapy for nodal and bone oligo-recurrent prostate cancer

Article References: Grün, A., Partyka, A., Galler, M., Schlomm, T., Böhmer, D., Miller, K., Zips, D., & Kalinauskaite, G. (2026). Bridging to systemic therapy: PSMA-PET-based early and repetitive stereotactic body radiotherapy for nodal and bone oligo-recurrent prostate cancer. Frontiers in Urology, 6, Article 1738508. https://doi.org/10.3389/fruro.2026.1738508

Image Credits: AI Generated

DOI: 10.3389/fruro.2026.1738508

Keywords: prostate cancer, PSMA-PET, SBRT, oligometastatic, radiation oncology, androgen deprivation therapy, metastasis-directed therapy, Charité Berlin, Bridging, systemic, therapy, PSMA-PET-based