Prostate
Five reads on the same decision: whether ablating oligometastatic deposits changes disease course, and what systemic therapy belongs alongside it.
ARTO NCT03449719
ForOligometastatic CRPC, โค3 nonvisceral lesions, starting first-line abiraterone
92% v 68.3%
OR 5.34 (95% CI, 2.05 to 13.88; P = .001)
TL;DRAdding SBRT to abiraterone in oligometastatic CRPC: biochemical response 92% vs 68.3%, OR 5.34; PFS HR 0.35.
Surfaced from a review's discussed trials
The systemic backbone is fixed (AAP both arms), so the entire effect is RT-attributable: PFS HR 0.35 for ablating โค3 nonvisceral lesions. That isolates the metastasis-directed question in castration-resistant disease, where prior randomized MDT data sit in the hormone-sensitive setting. Dose and fractionation are not in the source text, which limits direct transfer.
In castration-resistant pts with three or fewer nonvisceral metastases starting first-line abiraterone, this supports considering metastasis-directed SBRT concurrently; it does not extend to visceral, higher-volume, or hormone-sensitive metastatic disease.
The randomized contrast is SBRT alone, since AAP is fixed in both arms: PFS HR 0.35 (95% CI 0.21-0.57) for ablating โค3 nonvisceral lesions. This moves the offer-MDT-at-castration-resistance decision, though dose, fractionation and target volume are absent from the source text, so technique transfer cannot be judged.
Systemic management is unchanged: both arms received first-line abiraterone and prednisone, so nothing here alters drug choice or sequencing. The read is whether to involve radiation oncology at the start of AAP in low-volume CRPC, with progression deferred (HR 0.35) but no survival endpoint reported.
Also covered Jul 7
8 details 5 trials watching
Multicenter randomized phase 2, 1:1 allocation, N=157 enrolled January 2019 to September 2022. Median follow-up not reported in source.
Oligometastatic castrate-resistant prostate cancer, defined as three or fewer nonvisceral metastatic lesions. Visceral disease excluded by definition.
Both arms received abiraterone acetate and prednisone (AAP). The experimental arm added concomitant SBRT, so AAP is a fixed backbone and the randomized contrast is radiotherapy alone.
SBRT to all sites of disease, delivered concomitantly with AAP. Dose, fractionation and target-volume detail are not reported in the source text, which gates how directly the result transfers to a given SBRT practice.
Primary: biochemical response, PSA decrease โฅ50% from baseline at 6 months. Secondary: complete biochemical response (PSA <0.2 ng/mL at 6 months) and progression-free survival. No survival endpoint reported.
No toxicity reported in source, so the added burden of ablating up to three lesions is unquantified. PSA endpoints are mechanically sensitive to removing PSA-producing deposits, and the 6-month timepoint precedes any durability read.
STOMP and ORIOLE established the randomized signal for metastasis-directed therapy in hormone-sensitive oligometastatic disease. ARTO's addition is that the signal persists on an ARSI backbone in castration-resistant disease, a setting those trials did not test.
The PFS HR 0.35 is the more meaningful of the two results, since it is less mechanically coupled to ablating PSA-producing lesions than the primary endpoint. What remains unsettled is whether deferring progression on an ARSI translates into anything durable, which a phase 2 sized for a 6-month PSA readout cannot answer.
Randomized phase 2 with a 6-month PSA surrogate primary endpoint; no OS, no reported toxicity, and phase 3 confirmation in CRPC is absent.
- Does the PFS benefit translate to overall survival n=102 ยท primary completion 2027-04 ยท randomised SBRT in oligomet CRPC on ARSi backbonerecruiting Metastasis-directed Therapy in Oligoprogressive Castration-refractory Prostate Cancer Phase 3n=246 ยท primary completion 2029-01 ยท phase 3 MDT in castration-refractory, up to 5 lesions
- SBRT-attributable toxicity when ablating up to three sites recruiting SBRT Versus Hypofractionated Radiotherapy for Biochemically Recurrent or Oligometastatic Prostate Adenocarcinoma Phase 3n=118 ยท primary completion 2030-01 ยท phase 3 powered on SBRT toxicity vs hypofx RTrecruiting Fractionated Stereotactic Radiotherapy Plus Second-generation Antiandrogen for Oligometastatic Castration-resistant Prostate Cancer Patients. Phase 2n=51 ยท primary completion 2030-05 ยท SBRT + abiraterone/enza in mCRPC, safety endpoint
- Whether benefit holds beyond three lesions recruiting HIghly MetAstatic Life Prolonging Therapy-Resistant Prostate Cancer: Role of Stereotactic Radiotherapy for Bone and Lymph Node Metastases (HIMARS) Phase NAn=18 ยท primary completion 2028-05 ยท volume-escalated SRT in high-volume mets, MTV endpoint
๐ Sources ยท ๐ 1 paper
Abstract
WOLVERINE
ForOligometastatic prostate cancer, up to 5 mets, mostly castration-sensitive
TL;DRIPD meta-analysis of 6 randomised phase 2 trials, 472 pts: MDT improved PFS (HR 0.44, 0.35-0.56), OS non-significant (HR 0.63, 0.39-1.00, p=0.051).
Surfaced from a review's discussed trials
The endpoint that survives every sensitivity cut is PFS (HR 0.44, and 0.46 excluding the observation-SOC trials), while OS stops at HR 0.63 (0.39-1.00, p=0.051). CRFS 0.58 in CSPC is the more decision-relevant signal, since delaying castration resistance is what MDT is being asked to buy. Nothing here resolves dose, target, or which oligo burden benefits.
In castration-sensitive oligometastatic prostate cancer with up to five lesions and a treated primary, this supports adding MDT for progression-free and castration resistance-free benefit; it does not establish an OS benefit, and the CRPC-only and untreated-primary populations are thinly represented.
The endpoint that survives every sensitivity cut is PFS (HR 0.44, and 0.46 excluding the observation-SOC trials), and CRFS 0.58 in CSPC is what MDT is being asked to buy. None of the constituent trials' dose, fractionation or target-selection choices are resolved by pooling, and rPFS carried Iยฒ=50% heterogeneity, so how to deliver MDT stays a local decision.
MDT deferred castration resistance (CRFS HR 0.58) in the castration-sensitive subset (n=257), which is the sequencing-relevant read: the question is whether local therapy buys time before ARPI escalation. Note the SOC arm actually got MORE second-generation ARPI (59.8% vs 50.4%), so the systemic backbone was not favouring MDT.
10 details 5 trials watching
Systematic review and individual patient data meta-analysis (X-MET collaboration), PROSPERO CRD42023479078. Searched Embase, PubMed, CENTRAL, MEDLINE and ClinicalTrials.gov to Nov 3 2023, updated May 4 2025; dual independent screening in Covidence, Cochrane RoB 2.0. Of 2975 studies screened, 7 phase 2 trials randomising 574 men were included.
Published randomised prospective trials in oligometastatic (up to five metastases) prostate cancer with data sufficient for PFS and OS. Most patients were castration-sensitive (n=375, 65%); ARTO enrolled entirely CRPC and the two EXTEND baskets a CRPC subset. The primary tumour had received prior definitive local therapy in 491 patients (85.5%), required in every trial except the EXTEND baskets and ARTO.
Co-primary: progression-free survival and overall survival. Secondary: radiographic PFS and castration resistance-free survival. Primary analysis restricted to the six trials randomising MDT plus SOC versus SOC, with both a random-effects trial-level analysis and a patient-level analysis stratified by trial.
Effect sizes are in the endpoint table. Trial- and patient-level estimates agreed closely on all four endpoints, and OS showed HR<1 in every individual trial without reaching significance in aggregate.
The constituent trials are the ones that currently drive MDT practice: STOMP and ORIOLE (small randomised phase 2, ADT-free intervals and progression), ARTO (MDT added to abiraterone in CRPC), the two EXTEND hormone baskets, and the prostate subgroup of SABR-COMET (16 men). Pooling them raises precision on PFS but cannot add the phase 3 evidence none of them supply, and the ongoing randomised phase 3 programmes remain the gate.
The SOC arm was not one thing: observation in all or part of STOMP, ORIOLE and COMET-SABR, and second-generation ARPI use differed between arms (59.8%, n=134 in SOC vs 50.4%, n=125 in MDT), which cuts against MDT rather than for it. Four abstract-only randomised primary analyses could not supply IPD and were excluded, and the prostate contribution from SABR-COMET is 16 men.
PFS is where the estimate is tight and consistent; OS is where the question stays open, and at p=0.051 the honest read is an underpowered signal, not a negative result. The endpoint most likely to matter to practice is CRFS (HR 0.58) in castration-sensitive disease, because deferring castration resistance is the outcome MDT is being asked to deliver.
Pools only phase 2 trials with non-blinded randomisation and mixed SOC; co-primary OS missed (p=0.051). Supports existing MDT practice rather than establishing level 1 evidence.
- Does MDT extend overall survival in a phase 3 population active Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients Phase 3n=550 ยท primary completion 2026-06 ยท phase 3 SBRT to all oligomets, 550 pts, mHSPCrecruiting Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for Oligometastatic pRosTate Cancer Phase 2/3n=464 ยท primary completion 2026-09 ยท seamless ph2/3, CRPC-free survival, PET-directedrecruiting Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer Phase NAn=118 ยท primary completion 2031-12 ยท randomised ph3 MD-SBRT vs standard tx, 1-3 mets
- Optimal dose, fractionation and target selection for prostate MDT recruiting OligoCare TwiCs (Trials Within Cohorts) Trial Comparing Acute Toxicity in Single-fraction vs Multiple-fraction SBRT for Metastasis-directed Treatment (SPRINT) Phase NAn=302 ยท primary completion 2029-02 ยท single- vs multi-fraction SBRT, acute toxicity 1ยฐ EPrecruiting SBRT Versus Hypofractionated Radiotherapy for Biochemically Recurrent or Oligometastatic Prostate Adenocarcinoma Phase 3n=118 ยท primary completion 2030-01 ยท ph3 SBRT vs hypofx RT in oligomet/BCR prostate
- Upper bound on metastasis number that still benefits
๐ Sources ยท ๐ 1 paper
Abstract
ORIOLE NCT02680587
ForHormone-sensitive oligorecurrent prostate ca, 1-3 mets on conventional imaging, ADT-free
19% vs 61%
7/36 vs 11/18, P=.005
TL;DR6-mo composite progression 19% vs 61% with SABR (P=.005); mPFS not reached vs 5.8 mo, HR 0.30.
Surfaced from a review's discussed trials
The actionable RT parameter is target selection, not dose: 16 of 36 SABR pts had PSMA-avid lesions left untreated because planning was blinded to PET, and those men progressed at 38% vs 5% by 6mo (distant MFS 6.0 vs 29.0mo, HR 0.19). That argues total consolidation of PET-avid disease, so PSMA-PET-based planning is the decision this moves.
In hormone-sensitive oligorecurrent prostate cancer with 1-3 conventionally imaged mets and no recent ADT, this supports deferring ADT with SABR to all PET-avid sites; it does not speak to de novo synchronous oligometastatic or castration-resistant disease.
Target selection, not dose, is the transferable parameter: planning was blinded to PSMA-PET, so 16/36 SABR pts had avid lesions untreated, and they progressed 38% vs 5% at 6mo with distant MFS 6.0 vs 29.0mo (HR 0.19). That argues for PET-based planning and total consolidation of avid disease. Dose and fractionation are not reported in source text.
The comparator here is observation with ADT deferral, not a systemic regimen, so the read is about sequencing: SABR pushed median PFS from 5.8 months to not reached in men deliberately kept off ADT. Whether that delay costs anything downstream is untested at 18.8 months median follow-up.
11 details 5 trials watching
Phase 2, 2-arm randomized trial across 3 US radiation facilities affiliated with one university hospital. 80 men screened, 54 randomized 2:1 to SABR or observation, accrual May 2016 to March 2018, data cutoff May 20 2019. Median follow-up 18.8 months (range 5.8-35.0).
Recurrent hormone-sensitive prostate cancer with 1 to 3 metastases detected on conventional imaging (CT, MRI, or bone scan), asymptomatic, arisen within the prior 6 months, no larger than 5.0 cm. Prior definitive treatment of the primary required; salvage prostate-bed or pelvic RT allowed. No ADT within 6 months of enrollment or 3 or more years total. Median age 68 in both arms; Gleason grade ran higher in the observation arm (mean 8 vs 7).
SABR to metastatic sites, with treatment planning blinded to PSMA-PET, so PET-avid lesions outside the conventional-imaging map were left untreated in 16 of 36 SABR pts. Dose and fractionation are not reported in the source text. Local control 98.9% at 6 months.
Primary: progression at 6 months, a composite of PSA rise, radiographic progression on conventional imaging, symptomatic progression, ADT initiation for any reason, or death. Secondary: SABR toxicity, 6-month local control, PFS, Brief Pain Inventory QoL, and concordance between conventional imaging and PSMA-PET.
No grade 3 or higher adverse events in either arm. No differences in Brief Pain Inventory scores between arms or within either arm over time.
Sits alongside STOMP, the other randomized trial of metastasis-directed therapy versus surveillance in oligorecurrent hormone-sensitive disease, and reaches the same directional conclusion from an independent population. What ORIOLE adds is the PSMA-PET consolidation question, which STOMP's choline-PET-selected design could not isolate.
The composite primary is driven partly by ADT initiation for any reason, a clinician decision made without blinding in an open trial, so the treating team's knowledge of arm allocation can move the endpoint directly. The PET-untreated-lesion comparison is a within-arm post-randomization subgroup (19 vs 16 men), not a randomized contrast, and the men whose conventional imaging missed more disease plausibly had more disease to begin with.
The trial makes two distinct claims and they carry different weight. That SABR beats observation on a 6-month composite in a 54-man phase 2 is a signal, not a standard; that leaving PSMA-avid disease untreated tracks with earlier and more distant failure is the finding that changed how the field plans these treatments, even though it rests on an observational contrast inside one arm.
CONSORT flow
Phase 2, N=54, 6-month composite primary including ADT initiation, median f/u 18.8mo. Hypothesis-generating for MDT; no OS or definitive endpoint.
- Does deferring ADT via SABR change overall survival n=162 ยท primary completion 2031-04 ยท randomises RDT alone vs RDT + ADT, PFS primary
- Optimal SABR dose and fractionation for prostate oligometastases recruiting OligoCare TwiCs (Trials Within Cohorts) Trial Comparing Acute Toxicity in Single-fraction vs Multiple-fraction SBRT for Metastasis-directed Treatment (SPRINT) Phase NAn=302 ยท primary completion 2029-02 ยท single- vs multi-fraction SBRT, acute toxicity primary
- Does PSMA-PET-guided total consolidation improve outcomes prospectively recruiting Treatment With Darolutamide +/- Radiation Therapy for Patients With a Castration Resistant Cancer and Metastases Detected by Functional Imaging Phase 3n=336 ยท primary completion 2029-10 ยท phase 3 darolutamide +/- SBRT to functional-imaging metsn=1000 ยท primary completion 2030-12 ยท prospective registry, PSMA PET-guided directed RTrecruiting Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer Phase NAn=118 ยท primary completion 2031-12 ยท randomised MD-SBRT vs SOC, PSMA-PET-defined 1-3 mets
๐ Sources ยท ๐ 1 paper
Abstract
EAU 2026: What Evidence Do We Have from Intensification with SBRT?
TL;DRSession review of MDT in oligometastatic prostate: ARTO the only randomised OS signal; no effect sizes reported in source.
Reported via UroToday โ
Selection is the weak point, not delivery: eligibility still rests on a lesion count of up to five, while the PSMA PET burden analysis cited suggests imaging-derived burden stratifies more finely. Adding Ra-223 to MDT (RAVENS) gained neither PFS nor MFS, so intensifying the radiation side has no support yet; the live decision is whether to ablate at all outside metachronous oligorecurrence.
In metachronous oligorecurrent hormone-sensitive disease with a low lesion burden, this supports MDT to delay progression and defer systemic therapy; it does not extend to de novo synchronous presentation, where STAMPEDE2, PLATON, TERPS and OLIGOPRESTO are still accruing.
MDT is being asked to earn its place on selection, not technique: the up-to-five lesion cutoff is the enrolment gate across these trials, and RAVENS found no PFS or MFS gain from adding Ra-223 to ablation. Outside metachronous oligorecurrence the RT case is unproven, with STAMPEDE2, PLATON, TERPS and OLIGOPRESTO still accruing.
The systemic read is de-escalation, not addition: SOLAR (21 pts) asked whether testosterone can recover with PSA suppressed after MDT, and WOLVERINE delayed castration resistance without a significant OS gain. ARTO's OS and PCSS signal sits in castration-resistant disease, so it does not license dropping systemic therapy in hormone-sensitive pts.
9 details 3 trials watching
- ๐ EAU 2026 thematic session talk (Fonteyne, Ghent), a round-up of prior trials, not a new dataset
- ๐ De novo synchronous evidence is thin; STAMPEDE2, PLATON, TERPS and OLIGOPRESTO still accruing
- ๐ SOLAR (21 pts) asked whether testosterone can recover with PSA suppressed after MDT
- ๐ Eligibility still keys on a lesion count of up to five; PSMA PET burden proposed as a finer stratifier
- ๐ MDT evidence by setting, as characterised in the session (no effect sizes reported in source)
Trial Setting Reported signal STOMP / ORIOLE Metachronous oligorecurrent HSPC Local control, delayed progression, minimal toxicity RADIOSA Oligorecurrent HSPC ADT + MDT improved PFS vs MDT alone WOLVERINE Oligometastatic PCa PFS and rPFS improved, CRPC delayed, OS not significant ARTO Castration-resistant oligometastatic PFS plus OS and PCSS improved vs SOC alone RAVENS Oligometastatic PCa Ra-223 added to MDT: no PFS or MFS gain - ๐ ARTO framed as the first randomised trial suggesting an OS and PCSS benefit from adding MDT
- โ ๏ธ That OS signal is one trial, in castration-resistant disease, and unreplicated in this evidence base
- โ ๏ธ WOLVERINE gained PFS, rPFS and delayed CRPC, but no significant OS difference
- โ ๏ธ SOLAR vs SATURN (synchronous vs metachronous) is a cross-trial comparison, hypothesis-generating only
- Does MDT benefit de novo synchronous oligometastatic HSPC? not yet Radiotherapy for Prostate and Oligo-metastatic Lesions in Patients With Low-burden Oligo-metastatic Prostate Cancer Phase NAn=30 ยท primary completion 2025-09 ยท prospective prostate + oligomet RT in low-burden OMPCrecruiting Prostate Radiotherapy and Metastasis-Directed Therapy in Synchronous Oligometastatic Prostate Cancern=700 ยท primary completion 2028-12 ยท 700-pt registry, MDT SBRT in de novo synchronous
- Can systemic therapy be safely de-escalated after MDT?
- Which imaging or biomarker metric selects MDT candidates? not yet Maximal Cytoreductive Therapies on Post-treatment Metastases in Pts With mHSPC During Apalutamide Plus ADT Treatment Phase 2n=47 ยท primary completion 2025-12 ยท post-ADT PSMA PET oligopersistence gates MDT
๐ Sources ยท ๐ 1 paper
Abstract
RADIOSA NCT03940235
ForMetachronous oligorecurrent hormone-sensitive prostate cancer, โค3 lesions
TL;DRcPFS 32.2 vs 15.1 mo, HR 0.43, adding 6 months of ADT to ablative SBRT in metachronous oligorecurrence.
Surfaced from a review's discussed trials
The RT is nearly free here: one G3 event (left ureter stenosis) and no late toxicity across 105 pts treated to a stated BED >100 Gy, so the entire cost of this decision is 6 months of castration. SBRT alone still gave 15.1-mo cPFS, the benchmark for deferring systemic therapy in a selected pt.
In a man with metachronous oligorecurrence, three or fewer nodal or bone lesions after radical local treatment, this supports adding a short ADT course to ablative SBRT over SBRT alone; it does not extend to synchronous, higher-volume, or castration-resistant disease.
The RT side of the decision is nearly free: one G3 event (left ureter stenosis) and no late toxicity at a stated BED >100 Gy. The 15.1-mo SBRT-alone cPFS is the benchmark that ablative prescription buys, so a softer nodal dose is not this control arm.
The systemic question is duration, not agent: 6 months of LHRH started within a week of SBRT, 22 G1 events, all resolved. cPFS 32.2 vs 15.1 mo (HR 0.43) with no OS or castration-resistance readout leaves open whether this modifies disease or defers detection.
8 details 5 trials watching
Single-centre randomised open-label phase 2 at the European Institute of Oncology, Milan. 105 pts assigned 1:1 between Aug 1, 2019 and April 30, 2023; median follow-up 31 months (IQR 16-36). Modified intention-to-treat analysis, 3 pts lost to follow-up.
Metachronous oligorecurrent hormone-sensitive disease: biochemical progression after radical local treatment with โค3 lesions (pelvic nodal, extra-regional nodal, or bone) on next-generation imaging, ECOG 0-1. Median age 70 (IQR 65-75). Stratified by doubling time (โค3 vs >3 mo), node vs bone, and PET vs MRI.
30 Gy in 3 fractions every other day to all oligometastatic sites, or equivalent regimens by site. Stated EQD2 98.6 Gy (ฮฑ/ฮฒ 1.5 Gy) and BED >100 Gy, an ablative prescription rather than a symptomatic one, which is the dose the control-arm result belongs to.
6 months of ADT with an LHRH analogue in the combination arm, begun within 1 week before SBRT; no ADT in the control arm. The RT backbone is fixed across arms, so the randomised variable is the short systemic course alone.
Primary: clinical progression-free survival, assessed in 51 pts per group. No overall survival, ADT-free survival, or castration-resistance readout is reported in source.
Radiation contributed one G1 GI event; the only G3 was a left ureter stenosis in the combination arm, with no late toxicity in either group. The 22 G1 events were ADT-attributed and had resolved by last follow-up, so the harm ledger sits with the systemic course, not the RT.
STOMP and ORIOLE established MDT against observation in metachronous oligorecurrence, partly on the strength of keeping men off systemic therapy. EXTEND tested the mirror-image addition, MDT layered onto hormone therapy. This is the first randomised trial in this setting to report improved cPFS for the combination.
Progression was assessed unmasked, and PSA suppression from the randomised ADT gates the restaging that defines the event. Median follow-up sits below the combination arm's median cPFS of 32.2 mo, so the tail after testosterone recovery is thin. No biomarker separates the pts who would do well on SBRT alone.
Local and systemic therapy read as additive here rather than redundant, but the trade is priced in cPFS only. Whether 6 months is the right duration, and for whom SBRT alone suffices, is exactly what the investigators leave to future biomarker work.
CONSORT flow
Randomised, prespecified primary cPFS hit (HR 0.43). Single-centre, N=105, surrogate composite endpoint, so it supports adding short ADT to MDT rather than establishing it.
- Optimal ADT duration alongside metastasis-directed SBRT active Testing the Addition of the Drug Relugolix to the Usual Radiation Therapy for Advanced-Stage Prostate Cancer, The NRG Promethean Study Phase 2n=194 ยท primary completion 2029-02 ยท SBRT +/- relugolix vs placebo in oligomet CSPCn=162 ยท primary completion 2031-04 ยท randomises RDT +/- ADT in radiorecurrent oligomet CSPC
- Biomarkers identifying pts who do well with SBRT alone active Immune Response Evaluation in Oligorecurrent and Oligoprogressive Prostate Cancer Patients Treated With SBRT Phase NAn=40 ยท primary completion 2026-07 ยท immune profiling of SBRT + ADT in oligorecurrence
- Whether cPFS benefit translates to OS or delayed castration resistance active Prostate-cancer Treatment Using Stereotactic Radiotherapy for Oligometastases Ablation in Hormone-sensitive Patients Phase 3n=550 ยท primary completion 2026-06 ยท phase 3, n=550, SBRT + SOC in oligomet HSPCrecruiting Metastasis Directed Stereotactic Body Radiotherapy for Oligo Metastatic Hormone Sensitive Prostate Cancer Phase NAn=118 ยท primary completion 2031-12 ยท phase 3 MD-SBRT vs standard tx, failure-free survival