PSMAfore: Lu-177 PSMA therapy before chemotherapy shows benefit.

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

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:

1. Hormone therapy
2. Second hormone therapy (ARPI)
3. Chemotherapy
4. Lu-177 PSMA therapy (if PSMA-positive)

After PSMAfore and FDA label expansion, many oncologists are now considering:

1. Hormone therapy
2. ARPI
3. Lu-177 PSMA therapy (before chemotherapy)
4. 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.

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.