What randomized trials are underway testing PSMA PET–guided salvage radiotherapy and when will results be reported?
Executive summary
Three categories of randomized trials are actively testing whether PSMA PET–guided changes to salvage radiotherapy improve outcomes: a completed/phase‑II randomized study reported in meetings with a full report published in JAMA Oncology, multiple ongoing phase‑III trials including the international PSMA‑SRT study that follow patients for five years, and several protocolized phase‑III or randomized trials such as PERYTON and INDICATE whose results remain pending; retrospective series continue to show promising signals but cannot replace prospective randomized evidence [1] [2] [3] [4] [5] [6].
1. Phase II randomized evidence: an early positive signal now in press
A multicenter phase II randomized controlled trial (clinical trial NCT03525288) tested 18F‑DCFPyL PSMA‑PET/CT–guided intensification of salvage radiotherapy after radical prostatectomy and reported improved failure‑free survival at an interim analysis presented at EAU 2024, with the investigators concluding improved prostate‑cancer control for PSMA‑guided intensification [1]. That same randomized clinical trial was subsequently prepared for full publication in JAMA Oncology as a Radiology article, signaling a completed randomized phase II dataset now available in the peer‑reviewed literature [2].
2. The pivotal phase III “PSMA‑SRT” trial: designed for long follow‑up, results not yet mature
The randomized prospective phase III PSMA‑SRT trial (led by Calais and colleagues) was designed specifically to test whether 68Ga‑PSMA‑11 PET/CT planning improves outcomes of salvage radiotherapy and represents the first phase‑III prospective effort of its kind; its protocol requires follow‑up until one of several endpoints or five years after randomization, meaning primary outcome results are tied to that multi‑year follow‑up window [3] [7]. Because the trial’s predefined follow‑up extends to five years, publicly reportable primary endpoint results will only be available after sufficient events and post‑randomization time accumulate; the sources do not give a fixed calendar date for final reporting [3] [7].
3. Other randomized phase‑III protocols: PERYTON and INDICATE among those recruiting or planned
The PERYTON trial is a published phase‑III protocol testing PSMA PET/CT–guided hypofractionated salvage prostate‑bed radiotherapy after prostatectomy, representing another large randomized effort to define whether PET guidance can safely alter fractionation and target volumes; the protocol publication confirms the trial’s existence but does not include final outcomes [4]. The INDICATE concept was described at ASCO‑GU 2024 as a trial that incorporates PSMA PET/CT into intensification strategies (systemic therapy or metastasis‑directed therapy), with metastasis‑free survival as a primary endpoint for at least one arm, but the presentation did not provide mature results or a public completion date [5].
4. Smaller trials and de‑escalation studies: registered but sparse on timelines
At least one registered study (NCT07234981) focuses on PSMA‑PET guided de‑escalation of salvage radiation, indicating randomized questions in both directions—intensify where PET shows disease and de‑escalate when PET is negative—but the ClinicalTrials.gov record referenced provides limited public detail on enrollment timing or expected primary‑endpoint reporting [8]. Several centers have also embedded PSMA guidance into randomized comparisons of systemic therapy added to salvage RT (mentioned at ASCO‑GU), further broadening the randomized landscape though without firm result dates in the public abstracts [5].
5. Why randomized data matter and where the evidence stands now
Multiple retrospective and single‑institution analyses report high response rates and safe toxicity profiles when PSMA PET guides salvage radiotherapy, but these series cannot eliminate selection bias or definitively show outcome gains versus standard planning [6] [9] [10] [11]. That gap is why the phase II randomized trial and the ongoing phase III programs are crucial; the phase II trial provides encouraging randomized signal now published, while the phase‑III trials (PSMA‑SRT, PERYTON and others) will provide the definitive evidence once their pre‑specified follow‑up windows—commonly five years—are complete [1] [2] [3] [4].
6. Practical expectation for when results will appear
One randomized phase II trial already reported interim results and now has a JAMA Oncology full report (EAU 2024 presentation and JAMA Oncology publication) marking the first randomized positive evidence in this space [1] [2]. Phase‑III trials such as PSMA‑SRT explicitly plan five‑year follow‑up, so primary outcome reporting will depend on when accrual completed and the five‑year clock elapsed—sources confirm the design but do not provide a single calendar date for results release [3] [7]. PERYTON and INDICATE remain active protocolized phase‑III efforts with outcomes pending in their own timelines [4] [5].