Key points
- PSMAfore studied Lu-177 PSMA therapy vs switching to a second hormone therapy in chemo-naive patients.
- Lu-177 PSMA therapy more than doubled progression-free survival (12 vs 5.6 months).
- FDA expanded Lu-177 PSMA therapy's label in 2025 to include this earlier population.
- Implication: Lu-177 PSMA therapy can now be considered earlier — potentially avoiding chemotherapy entirely.
What the trial tested
PSMAfore was a phase 3 randomized trial of 468 men with metastatic castration-resistant prostate cancer (mCRPC). All had progressed on a first androgen-receptor pathway inhibitor (like enzalutamide or abiraterone). None had had chemotherapy yet.
They were randomly assigned to either:
- Lutetium Lu-177 PSMA therapy, or
- A switch to a second androgen-receptor pathway inhibitor
What they found
- 12 mo — Median rPFS on Lu-177 PSMA therapy (vs 5.6 mo on ARPI switch)
- 2.14x — Improvement in PFS
- PSA response — Higher with Lu-177 PSMA therapy
- Quality of life — Better vs ARPI switch
Patients on Lu-177 PSMA therapy had significantly longer progression-free survival than those who switched to a second hormone therapy. Quality of life was also better in the Lu-177 PSMA therapy arm.
What this means in practice
Before PSMAfore, the standard sequence was usually:
- Hormone therapy
- Second hormone therapy (ARPI)
- Chemotherapy
- Lu-177 PSMA therapy (if PSMA-positive)
After PSMAfore and FDA label expansion, many oncologists are now considering:
- Hormone therapy
- ARPI
- Lu-177 PSMA therapy (before chemotherapy)
- Chemotherapy or other options later
For many patients, this means potentially avoiding chemotherapy entirely — or at least delaying it. Given how much chemotherapy can affect quality of life, this is a major shift.
Important nuance
PSMAfore showed Lu-177 PSMA therapy's superiority over a switch to a second hormone therapy — not over chemotherapy. Both Lu-177 PSMA therapy and chemotherapy remain effective options. Which to choose depends on individual factors: scan results, health status, prior tolerance, patient preference, cost, and availability.
This isn't a verdict that everyone should get Lu-177 PSMA therapy before chemotherapy. It's evidence that earlier Lu-177 PSMA therapy is reasonable for many patients — a conversation to have with your oncologist.
What patients should ask their oncologist
- "Given my situation, should we consider Lu-177 PSMA therapy before chemotherapy?"
- "Has my cancer been PSMA-tested? If not, can we?"
- "What does the PSMAfore data suggest about my likely benefit?"
- "If we choose Lu-177 PSMA therapy now, what happens if it stops working?"
Limitations of the trial
- Comparison was to a second hormone therapy, not chemotherapy
- Follow-up duration was relatively short — longer-term outcomes still being collected
- Specific subgroups may benefit differently
- Real-world outcomes may differ from trial outcomes
Bottom line
PSMAfore is one of the most important new pieces of evidence in prostate cancer treatment. It widens the window for Lu-177 PSMA therapy and gives patients a meaningful new option earlier in their disease. If you're facing a decision between switching hormones and trying Lu-177 PSMA therapy, the data now supports the latter for many patients.
Citation: Morris MJ et al. Lancet 2024.