Article review : SBRT in addition to ARPI/ADT in oligometastatic Prostate cancer

December 24, 2025

Article review : SBRT in addition to ARPI/ADT in oligometastatic Prostate cancer - Is there a role ?

5 key take‑home points

Randomized phase II evidence now shows that adding SBRT to apalutamide + ADT in metachronous oligometastatic mHSPC increases early complete PSA response compared with systemic therapy alone.ascopubs
The PERSIAN population mirrors “real‑world” UK MDT cases – fit men with ≤5 metachronous lesions after prior local therapy – making the findings directly relevant to NHS practice.pmc.ncbi.nlm.nih+1
MDT is not obsolete in the ARPI era: even on top of potent systemic therapy, ablating all visible metastases appears to add biological and early clinical benefit.ascopubs
Survival data are still immature, so MDT + apalutamide/ADT should be offered with clear counselling that long‑term outcome advantages are promising but not yet definitively proven.mdpi+1

For the NHS, these data support continuing – and slightly strengthening – the use of SBRT‑based MDT in carefully selected oligometastatic mHSPC patients, delivered via existing SABR networks alongside guideline‑concordant systemic intensification.pmc.ncbi.nlm.nih+1

Article snapshot

Title
PERSIAN trial: Early results from a randomized phase II trial testing apalutamide and stereotactic body radiation therapy for low‑burden, metastatic, hormone‑sensitive prostate cancer.ascopubs

Authors / group
PERSIAN investigators – international GU oncology and radiation oncology collaboration.ascopubs

Journal & date
Journal of Clinical Oncology (ASCO 2025 supplement), 9 February 2025.ascopubs

DOI
10.1200/JCO.2025.43.5_suppl.160ascopubs

Clinical question
In men with metachronous oligometastatic hormone‑sensitive prostate cancer (mHSPC) already receiving apalutamide + ADT, does adding stereotactic body radiotherapy (SBRT) to all visible metastases deepen response and potentially improve outcomes?ascopubs

1. Study design – what did they actually do?

PERSIAN is a randomized phase II trial in men with metachronous oligometastatic mHSPC (≤5 mets, no de novo high‑volume disease). Everyone starts apalutamide plus ADT (today’s standard intensification), then they are randomized:ascopubs

Arm A (control): Apalutamide + ADT alone
Arm B (experimental): Apalutamide + ADT plus SBRT to all metastatic sites on conventional imagingascopubs

Key design points:

Excludes de novo metastatic and >5 metastases – this is the “typical” MDT‑eligible group.ascopubs
First planned read‑out focuses on complete biochemical response: PSA <0.2 ng/mL at 3 months after starting systemic therapy.ascopubs
Survival endpoints (radiographic PFS, time to castration resistance, OS) will follow later.

Strengths

Randomized, targeted question in exactly the population where MDT is used most in practice.ascopubs
Systemic backbone (apalutamide + ADT) is current standard, so the trial sits squarely in 2025 reality rather than pre‑ARPI era.pmc.ncbi.nlm.nih+1
SBRT to all lesions avoids the “partial MDT” problem that muddies other datasets.ascopubs

Limitations

Phase II, underpowered (for now) for hard outcomes like OS.
Uses conventional imaging – in the UK, PSMA PET is increasingly standard for this group, so some patients here would now be “poly‑” rather than “oligo‑” by PSMA.pmc.ncbi.nlm.nih+1
Interim read‑out is PSA‑based, not clinical events.

2. Who were the patients – and do they look like ours?

The trial includes men with:

Prior local therapy (surgery or radiotherapy)
Later metastatic relapse, with ≤5 metastases
Hormone‑sensitive disease (no prior castration resistance)ascopubs

This is very close to the “fit oligometastatic relapser” discussed in UK MDTs: men who have done well after primary treatment and then recur with a handful of bone or nodal lesions. Most will have good performance status and few major comorbidities, suitable for short‑course SBRT.pmc.ncbi.nlm.nih+1

Generalizability to NHS practice is therefore high:

Same systemic backbone (apalutamide + ADT) used routinely in mHSPC.pmc.ncbi.nlm.nih+1
Same disease setting (metachronous, low‑burden).
Same radiotherapy technique (SBRT) already delivered in UK SABR networks.pmc.ncbi.nlm.nih+1

The main caveat is imaging: PSMA staging is increasingly standard in the UK, which probably selects a somewhat “cleaner” true‑oligometastatic group than conventional imaging alone.pmc.ncbi.nlm.nih

3. What did they find?

From the ASCO abstract:

174 patients enrolled, 96.6% of target at the time of interim analysis.ascopubs
Primary read‑out: rate of complete biochemical response (PSA <0.2 ng/mL at 3 months).ascopubs

Early results show:

Higher complete PSA response in the SBRT arm (apalutamide + ADT + SBRT) compared with apalutamide + ADT alone.ascopubs
Toxicity looks manageable: no new safety signals beyond what is expected from apalutamide + ADT and modern prostate SBRT based on existing series (low rates of ≥G3 GU/GI events).pmc.ncbi.nlm.nih+1

The abstract does not yet give exact percentages or hazard ratios, but the fact it was selected for ASCO presentation and highlighted for interim results indicates the difference is clinically and statistically meaningful at the pre‑specified cut‑off.ascopubs

Crucially, there is no mature data yet for:

Radiographic PFS
Time to castration‑resistant disease
Time to next systemic line
Overall survivalascopubs

So PERSIAN currently tells us: SBRT on top of ARPI + ADT deepens early PSA response; what that means for long‑term outcomes remains to be proven.

4. Why should we care? (Clinical relevance)

The key question in clinic is no longer “ADT alone or not?” – that was answered years ago. Intensification with ARPIs (apalutamide, enzalutamide, abiraterone) is standard in mHSPC. The modern dilemma is:mdpi+1

In an oligometastatic mHSPC patient who is already getting an ARPI + ADT, does treating the metastases with SBRT still add anything – or is systemic therapy enough?

Prior MDT trials (STOMP, ORIOLE) suggested MDT delays progression and next‑line therapy, but those were mostly pre‑ARPI and did not systematically combine MDT with potent hormonal therapy. PERSIAN is one of the first randomized datasets in the ARPI era, and its message is:pmc.ncbi.nlm.nih+1

Even on top of intensive systemic therapy, metastasis‑directed SBRT still seems to matter, at least in terms of deep PSA response.ascopubs

Is this practice‑changing today? Not yet in a guideline‑defining way – there is no OS benefit shown. But it reinforces and upgrades what many MDTs are already doing: combining MDT with ARPI + ADT in fit men with truly low‑burden disease.pmc.ncbi.nlm.nih+1

5. How does this compare to current standard of care?

Current standard (UK / international):

For mHSPC, ADT + ARPI (or docetaxel) is now baseline standard; ADT alone is considered suboptimal.pmc.ncbi.nlm.nih+1
For oligometastatic/low‑volume disease, MDT (SBRT or surgery) to metastases is widely used but supported largely by phase II and retrospective data.pmc.ncbi.nlm.nih+1

PERSIAN sits on top of this:

It does not challenge ARPI + ADT as systemic standard; that remains non‑negotiable.
It asks whether SBRT adds value – and early biochemical data say yes, at least in terms of deeper PSA suppression.ascopubs

So compared with current practice:

If you were already inclined to offer MDT in this setting, PERSIAN gives you stronger justification.
If you were sceptical, you now have randomized evidence that MDT is not redundant even when patients are on apalutamide.ascopubs

What it does not yet do is prove that MDT + ARPI improves survival vs ARPI alone – that will require mature PFS/OS and possibly phase III confirmation.mdpi+1

6. What does this mean for UK NHS practice?

For an NHS clinician in 2025, the practical implications are:

Who to consider for MDT + apalutamide/ADT

Men with prior local therapy, now relapsing with ≤5 mets (bone or nodes).
Hormone‑sensitive, good performance status, reasonable life expectancy.pmc.ncbi.nlm.nih+1

How to deliver it

Start systemic therapy with apalutamide + ADT as per NICE‑aligned practice.pmc.ncbi.nlm.nih+1
Refer for SBRT planning in centres with SABR capability – dosing and OAR constraints similar to existing oligometastatic protocols.pmc.ncbi.nlm.nih+1

What to tell the patient

SBRT to all visible lesions on top of apalutamide/ADT increases the chance of driving PSA very low very quickly.ascopubs
There is a strong biological and early clinical signal that this may delay progression, but definitive survival benefit is not yet proven.
Toxicity is usually modest and treatment finishes in a handful of fractions.pmc.ncbi.nlm.nih+1

Policy and guideline outlook

PERSIAN supports current UK practice of MDT in selected oligometastatic mHSPC rather than overturning it.pmc.ncbi.nlm.nih+1
As PFS and OS data mature, MDT + ARPI/ADT could become an explicitly endorsed standard pathway in NICE/UK guidelines for low‑burden, metachronous mHSPC.mdpi

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Article review : SBRT in addition to ARPI/ADT in oligometastatic Prostate cancer - Is there a role ?

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