Written by Dr. Roupen Odabashian MD, FRCPC
Oncologist | Founder, MeDucation AI | Updated October 2026
Conflict of interest, up front: I'm a practicing hematologist-oncologist and I founded MeDucation AI, which sells a physician-written heme/onc question bank and other board-prep tools. Nothing below changes based on that. VISION is a trial you need to know cold regardless of what product you study with, and I'll tell you where our tools fit and where they don't.
VISION at a glance
Element | What VISION showed |
|---|---|
Design | Open-label, 2:1 randomized, Lu-177-PSMA-617 plus standard care vs. standard care alone[1] |
Population | PSMA-positive mCRPC after at least one ARPI and one or two taxane regimens[1] |
Imaging-based PFS | 8.7 vs. 3.4 months, HR 0.40 (99.2% CI 0.29-0.57, p<.001)[1] |
Overall survival | 15.3 vs. 11.3 months, HR 0.62 (95% CI 0.52-0.74, p<.001)[1] |
Grade 3+ adverse events | 52.7% vs. 38.0%[1] |
FDA approval | First targeted radioligand therapy approved in this setting, based on VISION[2] |
What did the VISION trial actually test?
VISION randomized 831 patients 2:1 to Lu-177-PSMA-617 at 7.4 GBq every six weeks for four to six cycles plus protocol-permitted standard care, versus standard care alone[1]. Protocol-permitted standard care specifically excluded chemotherapy, immunotherapy, radium-223, and investigational drugs[1], which matters because it means the comparator arm was a true "best supportive/standard care" arm rather than an active chemotherapy comparator. The trial had two primary endpoints, imaging-based progression-free survival and overall survival, powered for hazard ratios of 0.67 and 0.73 respectively[1]. Enrollment ran from June 2018 to October 2019 across sites in North America and Europe[1], and results were published by Sartor and colleagues in the New England Journal of Medicine[1].
Who was eligible for VISION?
VISION enrolled men with progressive, PSMA-positive mCRPC who had already received at least one androgen receptor pathway inhibitor and one or two taxane-based chemotherapy regimens, and who were on a GnRH analog or had undergone bilateral orchiectomy[5]. PSMA positivity was defined on Ga-68 gozetotide PET as at least one tumor lesion with uptake greater than normal liver[5]. Patients were excluded if they had PSMA-negative lesions above size thresholds: organ lesions of 1 cm or more, lymph nodes of 2.5 cm or more in short axis, or bone lesions with a soft tissue component of 1 cm or more[5]. In the trial population, 92% had ECOG performance status 0 or 1 and 8% had ECOG 2, and ECOG status was a randomization stratification factor[5].
This matters because VISION answers the question for PSMA-selected patients. It does not tell you what Lu-177-PSMA-617 does in patients who were not screened with PSMA PET.
What were the VISION trial results, with hazard ratios?
Both primary endpoints were positive, and the magnitude of benefit is why this became a boards-worthy trial rather than a footnote.
Endpoint | Lu-177-PSMA-617 + SOC | Standard care alone | Hazard ratio |
|---|---|---|---|
Imaging-based PFS (median) | 8.7 months | 3.4 months | 0.40 (99.2% CI 0.29-0.57)[1] |
Overall survival, all randomized patients (median) | 15.3 months | 11.3 months | 0.62 (95% CI 0.52-0.74)[1] |
Overall survival, rPFS analysis subset | not separately reported as median | not separately reported as median | 0.63 (95% CI 0.51-0.79)[1] |
Time to first symptomatic skeletal event (median) | 11.5 months | 6.8 months | 0.50 (95% CI 0.40-0.62)[1] |
Objective response (complete + partial) among patients with measurable disease | 9.2% complete, 41.8% partial (n=184) | 0% complete, 3% partial (n=64) | not applicable[1] |
Grade ≥3 adverse events | 52.7% | 38.0% | not applicable[1] |
Median follow-up was 20.9 months[1]. The overall survival benefit held up even after adjusting for patients in the control arm who crossed over to post-protocol chemotherapy (adjusted HR 0.64, 95% CI 0.51-0.80)[1]. Time to deterioration on both the FACT-P quality of life score and the Brief Pain Inventory pain intensity score also favored the Lu-177-PSMA-617 arm[1]. A separate summary of the trial describes the overall survival benefit as approximately four months and a 60% reduction in the risk of progression or death[2], consistent with the hazard ratios above.
How does VISION compare with PSMAfore and TheraP?
VISION is not the only PSMA-targeted radioligand trial that matters for boards, and the differences in trial design are exactly the kind of detail exam writers like to test.
Trial | Population | Comparator | Key reported result |
|---|---|---|---|
VISION[1] | PSMA-positive mCRPC after an ARPI and prior taxane therapy | Standard care alone (chemo/immunotherapy/radium-223 excluded) | rPFS HR 0.40; OS HR 0.62[1] |
PSMAfore[3] | PSMA-positive mCRPC after one ARPI, taxane delay appropriate per investigator | Change to a second ARPI | Safety data reported in the PLUVICTO label; median PLUVICTO exposure 8.4 months, median cumulative dose 42.4 GBq[3] |
PSMAddition[4] | PSMA-positive metastatic hormone-sensitive (androgen pathway modulation-naive/sensitive) prostate cancer | ARPI alone | rPFS not reached in either arm, HR 0.72 (95% CI 0.58-0.90, p=0.002); OS data immature[4] |
How do you select patients with PSMA PET imaging?
Selection is PET-based, not just PSA- or biopsy-based, and that is a frequently tested point. Patients are selected for PLUVICTO using an approved PSMA PET imaging agent such as LOCAMETZ (or another approved PSMA PET product) based on PSMA expression in tumors[3]. The approval of Illuccix specifically for choosing patients with mCRPC for radioligand therapy in the pre-taxane setting extended this selection pathway to an earlier treatment line[2]. In VISION, the threshold for a qualifying scan required at least one lesion with uptake greater than normal liver, and patients with any larger lesion exhibiting uptake at or below liver background were excluded from the trial[5]. This two-part rule, a minimum positive lesion plus no discordant large lesion with low uptake, is the kind of detail that shows up as a trick answer choice.
How is Lu-177-PSMA-617 dosed, and what are the radiation safety precautions?
The approved regimen is 7.4 GBq (200 mCi) administered every six weeks for up to six doses[3]. A dose reduction of 20% to 5.9 GBq (160 mCi) is permitted once, with no re-escalation after that[3]. If a treatment delay due to an adverse reaction persists beyond four weeks, permanent discontinuation should be considered[3]. In the actual VISION study population, the median duration of exposure was 7.8 months, the median number of doses received was 5, and the median cumulative dose was 37.5 GBq[5].
Frequently asked questions about the VISION trial
What is the VISION trial?
VISION is an open-label, 2:1 randomized phase 3 trial of Lu-177-PSMA-617 plus standard care versus standard care alone in PSMA-positive mCRPC after at least one ARPI and one or two taxane regimens. It randomized 831 patients[1].
Did Lu-177-PSMA-617 improve overall survival in VISION?
Yes. Median overall survival was 15.3 vs 11.3 months (HR 0.62, 95% CI 0.52 to 0.74), and median imaging-based progression-free survival was 8.7 vs 3.4 months (HR 0.40)[1].
What toxicity should you expect with Lu-177-PSMA-617?
Grade 3 or higher adverse events occurred in 52.7% of the treatment arm vs 38.0% of controls. Fatal adverse events occurred in 3.6% vs 2.9%, and 11.9% of the treatment group discontinued because of adverse events[1].
Who was eligible for VISION?
Men with progressive PSMA-positive mCRPC after at least one ARPI and one or two taxane regimens, with at least one PSMA-positive lesion on Ga-68 gozetotide PET and no PSMA-negative lesions above the size thresholds[5].
