Pre-SBRT ctDNA May Signal Early Progression Risk in Prostate Cancer
In this article
Pre-SBRT ctDNA May Signal Early Progression Risk in Prostate Cancer
In a secondary analysis of the TRAP trial, published in JAMA Network Open on 11 November 2026, 77 patients with oligoprogressive prostate cancer were grouped by circulating tumor DNA (ctDNA) before stereotactic body radiotherapy (SBRT): median progression-free survival was 3.0 months in ctDNA-positive patients and 7.8 months in ctDNA-negative patients. This finding may be valuable for risk stratification. But the analysis is not randomized: it cannot be separated whether the marker shows general prognosis or, specifically, benefit from SBRT. Below we explain what the study did, what it showed and what it could not show.
- What was found? Among patients with ctDNA detected in plasma taken before SBRT, median progression-free survival was 3.0 months, versus 7.8 months in those without it (log-rank p=0.003). Six-month progression-free survival was 21.1% versus 58.3%.
- Strength: The difference persisted after adjustment for age, PSA, prior chemotherapy and irradiated site (adjusted HR 2.18; p=0.009). The analysis was prespecified and the laboratory team was blinded to clinical data.
- How to read it: A secondary analysis of a single-arm, nonrandomized phase II trial. This data cannot tell whether the marker shows a poor course regardless of SBRT, or less benefit from SBRT.
- What it is not: It is not a study showing that selecting patients by ctDNA improves SBRT outcomes. The test has not yet been validated as a tool for treatment decisions; the authors also note that this could be tested in future studies.
Why does this topic matter?
In a patient with prostate cancer taking an androgen receptor pathway inhibitor (ARPI; abiraterone or enzalutamide), the disease sometimes progresses at only one or two sites while other lesions stay stable. This is called oligoprogression. Giving SBRT to the progressing lesions and continuing the ARPI is an approach that aims to keep the disease under control for a time without changing treatment straight away.
However, SBRT does not give the same benefit to everyone. The key question is being able to tell in advance who will benefit more and who less. Circulating tumor DNA (ctDNA) is a blood test that measures DNA fragments the tumor sheds into the blood; it may give clues about tumor burden. The secondary analysis of TRAP addresses this question.
The first TRAP results were presented earlier (ESTRO 2024) and the primary endpoint analysis was published in 2025; the trial is a single-arm phase II study testing SBRT in this patient group. The new analysis examines the relationship between pre-SBRT ctDNA status and progression-free survival in the same patients; that is, it investigates a marker that separates patients' courses, not the effect of the treatment.
How was the study conducted?
Patients gave blood before SBRT, received SBRT and continued the ARPI. The ctDNA results were not known during treatment; that is, they were not used in the SBRT decision.
Figure 1 · Flow of the study
The path patients followed in the TRAP secondary analysis
Study design and patients
| Feature | Reported | Why it matters |
|---|---|---|
| Study type | TRAP (NCT03644303): prospective, single-arm, nonrandomized phase II; 8 NHS sites in the United Kingdom. This is a prespecified secondary analysis | No comparison arm; a ctDNA effect specific to SBRT cannot be tested |
| Patients | Between October 2018 and February 2023, 81 patients were treated; pre-SBRT plasma was evaluable in 77. Criteria: PSA rise after at least 6 months of abiraterone or enzalutamide, and at most 2 progressing metastases suitable for SBRT | The results belong to this selected, oligoprogressive group of patients |
| Treatment | 30 Gy SBRT in 5 fractions over 10 days; the ARPI was continued | Because treatment was the same for everyone, differences between groups may come from patient characteristics rather than treatment |
| ctDNA test | PCF_SELECT: a next-generation sequencing panel directed at prostate cancer; run in a central laboratory by a team blinded to clinical data. 1 or 2 plasma samples before SBRT (two samples in 66 patients, one in 11). Detection in at least one sample counted as "positive" | It is a research test; this does not mean a test validated for routine clinical use |
| Groups | 19 patients positive (24.7%), 58 negative (75.3%). In the positive group the median PSA was 41.5 ng/mL (27.9 in the negative group), median age 76 (73), bone-only disease 57.9% (70.7%), lymph node disease 36.8% (24.1%) | The groups were not entirely similar at baseline; this may explain part of the difference |
| Follow-up | Median 24.5 months | The number of events was limited for some endpoints |
The table is compiled from the JAMA Network Open article. Data cutoff was 26 November 2025; the ctDNA analyses were performed between February and July 2025.
What do the results say?
| Measure | ctDNA-positive (n=19) | ctDNA-negative (n=58) | Note |
|---|---|---|---|
| Median progression-free survival | 3.0 months (95% CI 2.7-5.9) | 7.8 months (95% CI 5.9-11.4) | Log-rank p=0.003. Median 6.0 months in all 81 patients |
| 6-month progression-free survival | 21.1% (6.6-41.0) | 58.3% (44.5-69.8) | Estimated rates; the intervals are wide |
| Hazard ratio (HR) | Unadjusted 2.30 (1.31-4.02); adjusted 2.18 (1.21-3.94), p=0.009 | Adjusted for age, PSA, prior chemotherapy and irradiated site; only ctDNA was associated with progression-free survival | |
| Time to new treatment or loss of life | Median 15.3 months | Median 29.6 months | Adjusted HR 1.57 (0.78-3.14), p=0.20; not significant |
| Overall survival | Median 27.2 months; 63.6% at month 24 | Median 33.6 months; 82.6% at month 24 | Adjusted HR 2.24 (0.93-5.42), p=0.07; not significant. Of 77 patients, 30 (39.0%) lost their lives |
In additional sensitivity analyses, such as Gleason score and number of samples, the hazard ratio stayed between 1.87 and 2.17. Serial ctDNA measurements and PSA response after SBRT were not addressed in this article.
Figure 2 · Progression-free survival by ctDNA status
Median (months) and 6-month rate (%); 19 ctDNA-positive and 58 ctDNA-negative patients. The bars compare only these two measures.
What does the marker show: prognosis or benefit?
This is the most important limit of this analysis. A marker can be saying two different things, and a nonrandomized study cannot tell them apart.
| Interpretation | What does it mean? | Seen in this study? |
|---|---|---|
| Prognostic | The disease of ctDNA-positive patients progresses faster whichever treatment they receive; the marker shows the general course | Consistent with this, but not proven |
| Predictive | ctDNA-positive patients benefit less specifically from SBRT; the effect of SBRT is clearer in negative patients | Also consistent with this, but it cannot be tested because there is no comparison group without SBRT |
| Both | The marker reflects both the general course and the response to treatment | Possible; cannot be distinguished |
What does it mean, and what does it not mean?
- Not randomized: Patients who did and did not receive SBRT were not compared. So it cannot be separated whether the marker is prognostic or predictive.
- Small positive group: Only 19 patients were ctDNA-positive. Confidence intervals are wide; the sample size was not predefined for the ctDNA analysis.
- Limited adjustment: Because events were few, only four clinical features could enter the multivariable model. The groups differed at baseline (for example, PSA was higher in the positive group).
- Single-arm study, one country: The results may apply to similar centers; access to validated ctDNA tests and laboratory infrastructure is needed.
- Nonsignificant secondary endpoints: For time to new treatment and overall survival the direction was the same, but the differences were not statistically significant.
- Protocol deviation: Because of COVID-19 disruption, 4 patients had no pre-SBRT sample and were left out of the analysis.
- This result does not change treatment for now: The ctDNA test is not a validated clinical tool for this purpose; the decision whether or not to give SBRT should not be made on a ctDNA result.
- Test access: PCF_SELECT, used in the study, is a research test. Its availability in Türkiye has not been verified in this article.
- Decisions are made together: In oligoprogression, SBRT, continuing the ARPI or changing treatment are decided by evaluating the oncologist, radiation oncologist and imaging findings together.
- Molecular tests: Tests looking at the genetic features of the tumor influence some treatment decisions in prostate cancer (next-generation sequencing, in Turkish).
- Clinical trials: Studies testing patient selection by ctDNA may open in future; you can discuss taking part with your doctor (what is a clinical trial?, in Turkish).
Questions you can ask your doctor
- Would my situation count as oligoprogression, and is SBRT an option?
- Should the ARPI be changed instead of SBRT or together with it?
- Would blood tests such as ctDNA guide me, or are they still at the research stage?
- Is there a clinical trial I could join?
Common misconceptions
- "If ctDNA is positive, SBRT does not work." No. This study made no comparison with a group without SBRT; SBRT was not shown to be useless in positive patients (how to read research results correctly, in Turkish).
- "Everyone who is ctDNA-negative benefits from SBRT." No. In negative patients too, median progression-free survival is 7.8 months, and this is information about the course, not proof of benefit.
- "A blood test now determines the treatment decision." No. The test has not yet been validated for this purpose (common misconceptions about cancer, in Turkish).
Frequently Asked Questions
- What was found in the TRAP secondary analysis?
- Median progression-free survival was 3.0 months in 19 patients who were ctDNA-positive before SBRT and 7.8 months in 58 negative patients (p=0.003). The adjusted hazard ratio was 2.18.
- Does this result show that ctDNA predicts benefit from SBRT?
- No. Because the study is single-arm and not randomized, it cannot be separated whether the marker shows general prognosis or benefit specific to SBRT.
- What is ctDNA?
- Circulating tumor DNA (ctDNA) is DNA fragments that pass from tumor cells into the blood. It is measured from a blood sample and may give clues about tumor burden.
- What can patients expect from this result?
- No change in treatment should be expected in the short term. Whether ctDNA is useful for selecting patients will become clear through future studies designed for that purpose.
Glossary
- Oligoprogression
- A situation in which, during treatment, the disease progresses at only a few sites while other lesions stay stable.
- SBRT (stereotactic body radiotherapy)
- A radiotherapy method that delivers a high dose to a small area precisely, in a small number of sessions.
- ctDNA (circulating tumor DNA)
- DNA fragments that pass from tumor cells into the blood; measured from a blood sample.
- ARPI
- Androgen receptor pathway inhibitor; drugs such as abiraterone and enzalutamide that target the androgen (male hormone) pathway.
- Progression-free survival
- The time or proportion of patients in which the disease has not progressed or the patient has not lost their life after treatment.
- Hazard ratio (HR)
- A measure comparing the rate of an event between two groups. A value above 1 means the event is more frequent in the first group.
- Prognostic marker
- A measure that gives information about the course of the disease whichever treatment is given.
- Predictive marker
- A measure that shows in advance how much benefit will be gained from a specific treatment. Proving this generally requires a randomized comparison.
- Single-arm study
- A study in which all patients receive the same treatment and there is no comparison group.
- Phase II study
- A relatively small research stage in which first signs of a treatment's effect are sought.
DROZDOGAN Academy Commentary
A secondary analysis showing that a blood test before SBRT in oligoprogressive prostate cancer can distinguish early progression risk, but that cannot answer what the marker means.
⚡ Why it matters
Knowing in advance who will benefit more from SBRT could help treatment planning in future. A blood test holds the possibility of offering this in a noninvasive way.
✅ Strengths
A prespecified analysis from a prospective trial; central ctDNA measurement by a team blinded to clinical data; one or two samples; an association that persisted after adjustment; similar hazard ratios across different sensitivity analyses.
⚠️ Limits
Not randomized and no control arm; the positive group is only 19 patients; group imbalances; no significance for overall survival and time to new treatment; the test is for research purposes.
🩺 In practice
We do not decide whether or not to give SBRT on the basis of ctDNA. We treat this finding as context for discussing with the patient the possibility of rapid progression, not as a criterion for treatment decisions.
❓ Open questions
Does SBRT add benefit in ctDNA-negative patients? Which alternative is better in positive patients? What does serial ctDNA measurement add? How will the test be validated for routine use?
Conclusion: Pre-SBRT ctDNA is a strong candidate for risk stratification in oligoprogressive prostate cancer. To be usable for patient selection, it needs to show benefit in randomized trials.
- This article was prepared in November 2026.
- The figures are taken from the full text of the JAMA Network Open article. The primary endpoint analysis of TRAP (IJROBP) was not examined directly in this article; information on the trial's first results is summarized from a news source and was not used as numerical data.
- Because the study is not randomized, the results should not be interpreted as a benefit of SBRT. The diagrams are simplified. The Academy commentary is ours.
- This article is not medical advice; make decisions about your health together with your doctor.
Sources
- Reid A, Tran A, Thakali S, et al. Circulating Tumor DNA in Oligoprogressive Prostate Cancer Treated With Stereotactic Radiotherapy: A Prespecified Secondary Analysis of a Nonrandomized Clinical Trial. JAMA Netw Open. 2026;9(11):e2643400. jamanetwork.com
- Stereotactic Body Radiation Therapy for Oligoprogressive Disease in Androgen-Suppressed Prostate Cancer: Primary Endpoint Analysis of the TRAP Trial. Int J Radiat Oncol Biol Phys. 2025. redjournal.org
- CURE. SBRT and Hormone Therapy May Delay Advanced Prostate Cancer Progression. 20 May 2024. curetoday.com
Was this article helpful?
Your feedback helps us improve our content.
