ctDNA could eventually give you and your doctors a clearer picture of what is happening after prostate cancer treatment. By looking for genetic material released by cancer cells, it may help you understand whether there are early molecular signs of residual disease, even when PSA results still appear reassuring.
For now, PSA remains the main test used to monitor you after treatment, while ctDNA is still being studied. If future research shows that it can reliably detect recurrence earlier, ctDNA could help your doctors make more personalised decisions about your follow-up care and treatment.
What Is Circulating Tumour DNA?
Circulating tumour DNA (ctDNA) consists of tiny pieces of DNA released by cancer cells into your bloodstream. Your body naturally releases DNA fragments as cells die and are replaced, creating what is known as cell-free DNA (cfDNA), but only a small portion comes directly from cancer cells.
Scientists can analyse ctDNA for genetic and molecular changes linked to prostate cancer, which is why you may hear it described as a “liquid biopsy”. Unlike a conventional biopsy, you do not need a visible tumour to be physically sampled, although the test depends on having enough tumour-derived DNA in your blood for laboratory techniques to detect it.
Is ctDNA the Same as PSA?
No. PSA and ctDNA measure different signals: PSA measures a protein linked to prostate cells, while ctDNA looks for genetic material released by cancer cells into your blood. After treatment, PSA remains the main test your doctors use to monitor you for possible recurrence.
ctDNA may give you extra information about the cancer’s molecular features, including changes linked to treatment resistance. However, it may not detect very early recurrence as reliably as PSA because small amounts of prostate cancer can release too little ctDNA into your blood.
PSA and ctDNA: What Is the Difference?
| Feature | PSA | ctDNA |
| What is measured? | A prostate-associated protein | Tumour-derived DNA fragments |
| Routine after prostatectomy? | Yes | No |
| Routine after radiotherapy? | Yes | No |
| Sensitivity in very low-volume prostate cancer | High and well established for routine follow-up, particularly after prostatectomy | Currently limited by low tumour DNA shedding |
| Can provide genomic information? | No | Potentially yes |
| Can currently guide standard salvage treatment? | PSA contributes to established decisions | Not routinely |
| Main current role | Standard follow-up and biochemical recurrence monitoring | Research, prognostic assessment and molecular profiling in selected settings |
Why Is PSA So Useful After Prostatectomy?
After a radical prostatectomy, most PSA-producing prostate tissue is removed, so your PSA should fall to a very low or undetectable level. This makes PSA a highly useful way for your doctors to monitor you for possible recurrence.
PSA can be measured at very low concentrations after prostatectomy, setting a high sensitivity benchmark for any new blood-based marker. ctDNA remains challenging in this setting because microscopic disease may release very little tumour DNA into your bloodstream.
How Is PSA Used After Radiotherapy?
After radiotherapy, your prostate remains in place, so PSA does not usually become undetectable straight away. Instead, your PSA can fall gradually, and doctors use changes from your lowest PSA level to monitor you for possible recurrence.
ctDNA could theoretically help your doctors distinguish between normal PSA changes and signs of recurrent cancer. However, you should know that there is not enough evidence yet to use ctDNA routinely, so PSA remains the standard follow-up test.
What Does Minimal Residual Disease Mean?
Minimal residual disease means a very small amount of cancer remains after treatment, but it may be too small for standard scans to detect. You may have no visible signs of cancer, yet a few remaining cells could eventually grow and cause recurrence.
Researchers hope ctDNA could help your doctors detect these tiny amounts of cancer through a blood test. However, you should know that ctDNA does not detect every case, and its reliability in early prostate cancer is still being studied.
Could ctDNA Detect Recurrence Before PSA?
Researchers are investigating whether ctDNA could identify molecular residual or recurrent disease before a clinically meaningful PSA rise, but it has not been shown to outperform PSA for routine post-treatment surveillance. Low-volume prostate cancer often releases very little ctDNA, which currently limits sensitivity.
Newer ctDNA tests are showing promising results, but more research is needed. For now, you should continue regular PSA monitoring while researchers assess whether ctDNA can provide you with earlier information about recurrence.
Why Is Prostate Cancer ctDNA So Difficult to Detect?
Small prostate cancers may release very little DNA into your bloodstream. When only a few cancer cells remain, ctDNA may fall below current detection limits.
This makes microscopic residual disease difficult to detect reliably. Researchers are developing more sensitive assays, but early-recurrence detection remains investigational.
Research Insight
Earlier sequencing approaches struggled to detect ctDNA in localised prostate cancer. In a study of 112 patients, ctDNA was not detectable using the tested methods before prostatectomy, including in patients who later experienced recurrence.
More recent ultrasensitive tumour-informed methods have improved detection. A 2024 European Urology study using the INVAR approach detected preoperative ctDNA in approximately 16% of patients with localised prostate cancer, and detectable ctDNA was associated with a greater risk of biochemical recurrence and metastasis. These findings support ctDNA as a promising risk-stratification biomarker, but they do not prove that it detects recurrence earlier than PSA.
What Is a Tumour-Informed ctDNA Test?
A tumour-informed ctDNA test analyses your original cancer tissue to identify genetic changes specific to your tumour. It then uses these markers to create a personalised blood test that can look more closely for cancer DNA in your bloodstream.
This approach may improve sensitivity, but it also requires your tumour tissue to be available and analysed first. Even if you receive a negative result, you should know that it does not always mean no cancer remains, as there may simply be too little ctDNA in your blood to detect.
Does a Positive ctDNA Result Predict Recurrence?
The meaning of a positive ctDNA result depends on when the blood sample is taken and which assay is used. In localised prostate cancer, pre-operative ctDNA detection has been associated with more aggressive disease and a higher risk of recurrence, so it can act as a prognostic marker rather than proof of residual disease after treatment.
For post-treatment ctDNA to be used reliably as a marker of residual disease, researchers need to show that the assays are sufficiently accurate and that acting on the result improves patient outcomes. For now, you should view a positive result as a potential risk signal rather than definite proof of recurrence.
What Is a Tumour-Agnostic ctDNA Test?
A tumour-agnostic ctDNA test does not need a personalised map of your original cancer. Instead, it looks for common genetic or molecular changes in your blood, which may make testing easier for you and your doctors.
This approach is promising, particularly for detecting signs linked to more advanced disease. However, you should know that background DNA changes can affect your results, so these tests are not yet established for routine recurrence monitoring.
Can Normal Blood Cells Create False ctDNA Signals?
Yes. As you get older, normal blood cells can develop mutations that release DNA into your bloodstream, potentially causing a ctDNA test to mistake these changes for cancer-related signals.
Modern tests can reduce this risk by checking your blood cells alongside the tumour DNA. However, you should know that false-positive and false-negative results can still occur, so your doctors need to interpret the results carefully before using ctDNA for routine recurrence monitoring.
Can a Negative ctDNA Test Rule Out Recurrence?
No. A negative ctDNA result cannot reliably rule out microscopic prostate cancer. Small amounts of disease may release too little tumour DNA to detect. You should therefore continue your recommended PSA follow-up even if ctDNA is negative. PSA remains the established routine marker after treatment.
Clinical Tip
If you are offered a ctDNA test, ask which assay is being used and whether it is tumour-informed. Also ask what a negative result can realistically exclude. Do not reduce or stop PSA follow-up because ctDNA is negative. Small amounts of localised disease may remain below the test’s detection limit.
Could ctDNA Tell Doctors More Than Whether Cancer Is Present?
PSA can show your doctors that prostate cancer activity may be present, but ctDNA could provide more information about the cancer’s genetic features. This may help your doctors understand changes linked to tumour behaviour, treatment response, or resistance.
In the future, regular ctDNA testing could potentially show how your cancer changes over time. For you, its most useful role may be helping doctors assess the biological risk of recurrence rather than simply confirming whether cancer is present.
Could ctDNA Help Decide Who Needs Treatment After Surgery?
ctDNA could eventually help identify people at higher risk of recurrence after surgery. Future trials may show whether it can guide closer monitoring or studies of additional treatment.
A reliable negative result might also help avoid unnecessary treatment. However, ctDNA is not yet established for routine post-prostatectomy treatment decisions.
Could ctDNA Change the Timing of Salvage Radiotherapy?
ctDNA could give you and your doctors extra information when deciding when to consider salvage radiotherapy after surgery. If tumour-specific DNA is detected alongside a rising PSA, it may help you understand whether you have a higher risk of progression.
However, these uses are still being studied and are not established treatment pathways. You should not delay your treatment decisions while waiting for a ctDNA result outside a properly designed clinical study.
How Is Prostate Cancer Followed After Curative Treatment Today?
PSA remains the main test used for your routine follow-up after surgery or radiotherapy. Your doctors usually monitor PSA regularly and look at changes over time, including how quickly it may be rising, rather than relying on a single result.
Imaging may be used when it could guide treatment decisions. For routine follow-up, ctDNA remains investigational and should not replace established PSA monitoring.
UK Guidance Note
Current NICE guidance bases follow-up after radical prostate cancer treatment on PSA rather than ctDNA. PSA should be checked no earlier than six weeks after treatment, at least every six months for the first two years and then at least annually. The exact follow-up plan should be discussed with your urology team and can vary according to your treatment, PSA trend and clinical risk.
ctDNA is not currently part of routine NICE follow-up for non-metastatic prostate cancer. It should therefore be regarded as an investigational biomarker that may complement established assessment in the future rather than replace current PSA-based surveillance.
Are Clinical Trials Testing ctDNA After Prostatectomy?
Yes. Researchers are testing whether ctDNA can help your doctors detect minimal residual disease after prostatectomy and identify patients who may have a higher risk of recurrence.
These approaches remain investigational in non-metastatic prostate cancer, so you should not expect ctDNA to guide your treatment routinely yet. Future research needs to show that using ctDNA results to change your care actually improves outcomes compared with PSA, pathology and imaging alone.
Why Is Earlier Detection Not Always Better?
Finding recurrence earlier does not automatically mean earlier treatment improves outcomes. The result must also lead to a useful treatment decision.
- Unclear treatment benefit: An early ctDNA signal may appear before doctors know whether treatment should change.
- Normal PSA or scans: ctDNA could be positive while established tests still appear reassuring.
- Possible anxiety: An uncertain result may cause worry without providing a clear next step.
- Evidence is needed: Researchers must show that acting on ctDNA results actually improves outcomes.
For ctDNA to become useful in routine follow-up, earlier detection must improve treatment decisions. Earlier information alone is not enough.
Will ctDNA Eventually Replace PSA?
Current evidence suggests that ctDNA is more likely to complement PSA than replace it, particularly because PSA remains well established and highly sensitive after prostatectomy. Instead, it may give you and your doctors extra information about residual disease and tumour behaviour.
In the future, your doctors may use both tests together for monitoring. However, more research is needed to prove that ctDNA improves your treatment decisions and outcomes.
Myth vs Fact
| Myth | Fact |
| ctDNA has already been proven to detect prostate cancer recurrence earlier than PSA. | No. This remains an important research question. |
| A negative ctDNA result proves there is no residual cancer. | No. Microscopic prostate cancer may release too little ctDNA to detect. |
| ctDNA and PSA measure the same thing. | No. PSA is a protein marker, while ctDNA measures tumour-derived genetic material. |
| A positive preoperative ctDNA result proves cancer remains after surgery. | No. Preoperative detection is primarily a prognostic marker of more aggressive disease. |
| Any DNA mutation found in plasma must come from prostate cancer. | No. Clonal haematopoiesis in blood cells can create misleading variants in some assays. |
| ctDNA can currently determine when salvage radiotherapy should start. | No. It remains investigational for this purpose. |
| ctDNA will probably make PSA unnecessary. | Current evidence suggests it is more likely to complement PSA than replace it. |
Key Takeaways
- ctDNA is tumour-derived DNA that can be measured in blood, but localised prostate cancer often releases very little of it.
- PSA remains the established routine follow-up test after prostatectomy and radiotherapy.
- Ultrasensitive tumour-informed ctDNA tests can identify a subgroup with higher recurrence risk, but they have not been shown to outperform PSA for routine surveillance.
- A negative ctDNA result cannot rule out residual or recurrent prostate cancer.
- ctDNA should not delay established PSA-based investigation or treatment decisions until prospective studies show that ctDNA-guided care improves outcomes.
Frequently Asked Questions
1. Could ctDNA detect prostate cancer recurrence earlier than PSA?
Researchers are investigating whether ctDNA can identify molecular residual or recurrent disease before a clinically meaningful PSA rise, but it has not been shown to outperform PSA for routine post-treatment surveillance. PSA remains the main test used to monitor you after treatment.
2. What is ctDNA and how can it be used for prostate cancer?
Circulating tumour DNA (ctDNA) consists of small fragments of DNA released by cancer cells into your bloodstream. A blood test can analyse these fragments for genetic or molecular changes linked to prostate cancer. This approach is often described as a liquid biopsy.
3. Is ctDNA the same as a PSA test?
No. PSA measures a protein associated with prostate cells, while ctDNA looks for genetic material released by cancer cells. ctDNA may provide additional information about tumour biology, but PSA remains the established method for monitoring recurrence after treatment.
4. Can a negative ctDNA result rule out prostate cancer recurrence?
No. A negative ctDNA test cannot reliably prove that no microscopic cancer remains. Very small amounts of prostate cancer may release too little DNA into your bloodstream for current tests to detect, so you should continue your recommended PSA monitoring.
5. Why is ctDNA difficult to detect in early prostate cancer?
Small amounts of residual prostate cancer may release very little tumour DNA into your bloodstream. This means there may not be enough ctDNA in a blood sample for the test to detect reliably, particularly when the disease burden is microscopic.
6. Does a positive ctDNA result mean prostate cancer has returned?
Not necessarily. Interpretation depends on when the sample is taken. Pre-operative ctDNA positivity can indicate more aggressive tumour biology and a higher recurrence risk, while the role of post-treatment ctDNA for proving microscopic residual disease remains investigational. Further evidence is needed to establish how such results should guide care.
7. What is a tumour-informed ctDNA test?
A tumour-informed ctDNA test analyses your original prostate cancer tissue to identify genetic changes specific to your tumour. A personalised blood test can then look for those changes in your bloodstream. Although this approach may improve sensitivity, it is still being investigated for non-metastatic prostate cancer.
8. Can ctDNA help doctors decide whether you need further treatment after surgery?
Potentially, but ctDNA is not yet established for routinely making treatment decisions after prostatectomy. Researchers are studying whether detecting molecular residual disease could identify people who may benefit from additional treatment while helping others avoid unnecessary treatment.
9. Is ctDNA routinely used to monitor prostate cancer after treatment?
No. ctDNA is currently a research tool rather than a routine replacement for PSA monitoring in non-metastatic prostate cancer. Your doctors may also use other information, such as pathology results and imaging, when assessing your risk and follow-up.
10. Will ctDNA eventually replace PSA for prostate cancer monitoring?
It is more likely that ctDNA, if proven useful, will complement rather than completely replace PSA. PSA is already widely available and well established for routine follow-up. Future monitoring could potentially combine PSA with ctDNA to provide additional information about recurrence risk and tumour biology.
Final Thoughts: Could ctDNA Become a New Tool for Prostate Cancer Recurrence Monitoring?
ctDNA could become a useful addition to prostate cancer follow-up by helping your doctors identify molecular signs of residual disease and assess your risk of recurrence. However, it is still being researched and cannot currently replace PSA. For now, your PSA results, pathology, clinical assessment and imaging where appropriate remain important when monitoring you after treatment.
If you want expert assessment for PSA changes or treatment options, contact Prostate Clinic London. We can discuss your first appointment and next steps.
References:
- National Institute for Health and Care Excellence (2019, updated 2021) Prostate cancer: diagnosis and management. NICE guideline NG131. Available at: https://www.nice.org.uk/guidance/ng131
- Hennigan, S.T. et al. (2019) ‘Low abundance of circulating tumor DNA in localized prostate cancer’, JCO Precision Oncology, 3, pp. 1–13. Available at: https://pubmed.ncbi.nlm.nih.gov/31528835/
- Pope, B. et al. (2024) ‘Ultrasensitive detection of circulating tumour DNA enriches for patients with a greater risk of recurrence of clinically localised prostate cancer’, European Urology, 85(4), pp. 407–410. Available at: https://pubmed.ncbi.nlm.nih.gov/38378299/
- Kopytov, S.A. et al. (2025) ‘Circulating tumor DNA in prostate cancer: a dual perspective on early detection and advanced disease management’, Cancers, 17(15), 2589. Available at: https://pubmed.ncbi.nlm.nih.gov/40805284/
- Sighinolfi, M.C. et al. (2026) ‘Liquid biopsy in non-metastatic prostate cancer: clinical evidence and future directions’, Cancers, 18(5), 800. Available at: https://pubmed.ncbi.nlm.nih.gov/41827734/
- Jensen, K. et al. (2021) ‘Association of clonal hematopoiesis in DNA repair genes with prostate cancer plasma cell-free DNA testing interference’, JAMA Oncology, 7(1), pp. 107–110. Available at: https://pubmed.ncbi.nlm.nih.gov/33151258/
- McKendry, K., Maurice-Dror, C. and Chi, K.N. (2026) ‘Cell-free DNA in prostate cancer and treatment selection’, Expert Review of Anticancer Therapy. Advance online publication, pp. 1–18. Available at: https://pubmed.ncbi.nlm.nih.gov/42269177/