Lutetium-177 PSMA therapy as the first-line treatment for metastatic prostate carcinoma.

Patient oncology history.

Clinical assessment before therapy.

The patient presented with significant symptoms consistent with extensive bony metastatic disease:

• Left leg weakness — suggesting either bone metastases or related neurological impingement
• Left hip pain — consistent with documented bone metastatic involvement
• Muscle wasting in the arms and legs — reflecting both age-related sarcopenia and disease burden
• PSA >2,000 ng/ml at presentation — an extremely elevated marker consistent with extensive PSMA-expressing disease

Pre-therapy Ga-68 PSMA PET-CT imaging was performed to confirm eligibility for radioligand therapy — demonstrating widespread PSMA-avid disease consistent with extensive bone involvement.

Patient counselling & consent.

Given the patient's extensive metastatic disease and the possibility of bone marrow involvement, a detailed counselling session was conducted before therapy initiation. The patient and family were informed about the disease extent, the rationale for upfront radioligand therapy as opposed to standard hormone therapy first, and the realistic expectations of treatment.

Informed written consent was obtained after the patient and family had time to consider the information and ask questions. The decision to proceed with upfront Lu-PSMA therapy — rather than starting with standard androgen deprivation therapy (ADT) — was made jointly with the patient, taking into account his preference for an approach that could provide pain relief alongside disease control.

Treatment protocol.

The patient received Lutetium PSMA therapy following our department's standard radioligand therapy protocol. The protocol specifies the radiopharmaceutical, the dose schedule, the administration route, and the supportive measures required to protect dose-limiting organs (particularly the kidneys, which are exposed during PSMA radioligand therapy).

Each infusion was preceded by intravenous saline hydration (renal protection protocol) to minimise nephrotoxicity risk from radioligand uptake in the kidneys. The patient remained in a shielded suite during and immediately after the infusion in line with AERB radiation safety standards. Dose-rate monitoring was performed before discharge.

PSA response timeline.

The primary biochemical marker for prostate cancer response — PSA (prostate-specific antigen) — demonstrated a near-complete decline over the course of the 2-cycle therapy programme:

This is a near-complete biochemical response — the order-of-magnitude reduction in PSA reflects substantial tumour cell destruction across the multiple PSMA-expressing metastatic sites. PSA response in prostate cancer correlates with both disease burden and treatment response, making this a clinically meaningful surrogate for the imaging changes observed.

Imaging before & after.

Treatment response was assessed with repeat Ga-68 PSMA PET-CT after the second cycle. The post-treatment scan demonstrated significant reduction in PSMA uptake across most of the previously identified lesions — consistent with a good partial response per standard criteria.

The imaging response correlates with the biochemical PSA response — both reflect substantial reduction in viable PSMA-expressing tumour cells. The pattern of response (widespread reduction across multiple sites rather than focal response at single sites) is consistent with the systemic delivery of the radioligand therapy.

Symptomatic response.

Beyond the biochemical and imaging response, the patient experienced meaningful improvement in his presenting symptoms and quality of life:

The absence of major side effects — particularly the absence of bone marrow suppression in a patient with possible marrow involvement, and the absence of xerostomia — reflects both the targeted nature of PSMA radioligand therapy and the careful patient selection and dose protocol used.

What this case illustrates.

This case demonstrates the clinical principle that radioligand therapy can be considered upfront in selected patients with extensive metastatic prostate cancer, particularly where the disease is PSMA-expressing on imaging and where the patient has symptoms that radioligand therapy can address (bone pain, in this case). The standard of care is to begin with androgen deprivation therapy (ADT); however, ADT has well-documented quality-of-life implications, and patients with extensive PSMA-positive disease may benefit from a different sequencing approach.

Two clinical observations stand out from this case:

• The near-complete biochemical response (PSA >2,000 to 10.2 ng/ml) after just 2 cycles suggests that high-burden PSMA-positive disease can be highly responsive to radioligand therapy when delivered as a frontline option, before the disease has been modified by prior treatment
• The absence of typical side effects — particularly the absence of xerostomia — suggests that careful patient selection and meticulous infusion technique can mitigate the most common adverse events

This case does not establish upfront Lu-PSMA as standard of care for all metastatic prostate cancer patients — that conclusion would require larger prospective studies. However, it does illustrate that the option exists for selected patients, and that the team has experience administering this approach with documented outcomes. The decision to use Lu-PSMA as first-line therapy versus the conventional ADT-first sequence is made on a case-by-case basis at our centre, after detailed discussion of the trade-offs.

Backed by peer-reviewed research.

This is not an isolated case. Dr. Dharmender Malik (our senior consultant and a co-investigator on this patient's care) published a peer-reviewed case report in Clinical Nuclear Medicine describing the same approach — upfront Lu-PSMA radioligand therapy in treatment-naive oligometastatic prostate cancer — demonstrating excellent response to a single dose:

The published paper and this case study together illustrate that upfront Lu-PSMA is an approach our team has formally documented in the medical literature — not just delivered clinically, but contributed back to the evidence base of nuclear medicine. For prospective patients considering this approach, the published case report on PubMed provides an additional layer of independent peer-reviewed validation.