The FDA has approved Pluvicto® (¹⁷⁷Lu-PSMA-617) for PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC) – extending its use beyond the castration-resistant setting for the first time. This is the third expansion of Pluvicto's approved use in the US, and the first to move the therapy outside metastatic castration-resistant prostate cancer (mCRPC) entirely.

A brief regulatory history:

1. March 2022 – Initial FDA approval, based on the VISION trial, for PSMA-positive mCRPC in patients previously treated with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy.
2. March 2025 – Expanded approval, based on the PSMAfore trial, for PSMA-positive mCRPC patients who had progressed on an ARPI but had not yet received chemotherapy – roughly tripling the eligible patient population at the time.
3. July 2026 – This latest approval, based on the PSMAddition trial, extends use to androgen pathway modulation-naïve or -sensitive disease (mAPMN/S)^[1] – the first-line metastatic setting, before cancer becomes castration-resistant.

Taken together, these approvals mean ¹⁷⁷Lu-PSMA-617 is now authorized across the full spectrum of PSMA-positive metastatic prostate cancer, from first-line hormone-sensitive disease through later-line castration-resistant disease.

What the new approval is based on

The decision follows results from the Phase III PSMAddition trial, which enrolled 1,144 patients with untreated or minimally treated mHSPC and at least one PSMA-positive lesion on PET/CT imaging. Patients received either ¹⁷⁷Lu-PSMA-617 in combination with standard hormone therapy (ADT plus an ARPI), or standard hormone therapy alone.

An updated analysis showed that adding ¹⁷⁷Lu-PSMA-617 reduced the risk of radiographic progression by 33% compared to hormone therapy alone, improving on the 28% figure reported earlier in the trial's primary analysis. Overall survival data are still maturing but show an early trend favoring the radioligand combination.

Why this matters for patients

Until now, ¹⁷⁷Lu-PSMA-617 was only available to the patients in the US after prostate cancer became resistant to hormone therapy. This approval allows PSMA-positive patients to access radioligand therapy at first-line diagnosis of metastatic disease – potentially delaying progression earlier in the disease course, when patients tend to be in better overall health and better equipped to manage any potential treatment-related side effects.

Already available at our institution

While this marks a new FDA approval in the US, ¹⁷⁷Lu-PSMA in the hormone-sensitive setting is not new to us – we have been offering radioligand therapy at this stage for some time, welcoming patients from Austria and abroad.

For physicians and patients navigating a new mHSPC diagnosis, this broader regulatory recognition may prompt more questions about eligibility and access. We're glad to support that conversation, whether through PSMA PET/CT diagnostics, treatment planning, or simply providing information to referring physicians.

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^[1] Since July 2026, the FDA has used the new term "metastatic androgen pathway modulation-naïve or -sensitive" (mAPMN/S) instead of mHSPC in its approval language. This renaming follows updated recommendations from the Prostate Cancer Working Group 4 (PCWG4), aimed at establishing more precise, standardized terminology for clinical trials and regulatory approvals. The previous term "hormone-sensitive" (mHSPC) was considered too imprecise, as it implies the disease reliably "responds" to hormone therapy – which is not clinically true in every case. In clinical practice, the term mHSPC remains in common use; we continue to use it in this article as the familiar designation.