What Is Metastatic Castrate Resistant Prostate Cancer (mCRPC)?

Castrate Resistant Prostate Cancer is a type of advanced prostate cancer. In cases of Castrate Resistant Prostate Cancer, the cancer is no longer responding to treatment that lower testosterone levels. Additionally, there are signs of growth, including a rising prostate-specific antigen, even with the lowered levels of testosterone.

Lutetium-177 Prostate-Specific Membrane Antigen (PSMA) Therapy

Lutetium-177 Prostate-Specific Membrane Antigen Therapy (“Lu177 PSMA Therapy”) is a Nuclear Medicine radionuclide treatment that allows for highly specific and targeted radiation therapy used in the treatment of prostate cancer.

Lu177 PSMA Therapy is often used for metastatic Castrate Resistant Prostate Cancer (mCRPC).

How Does Lutetium-177 PSMA Therapy Work?

Prostate-Specific Membrane Antigen (PSMA) is a type II transmembrane glycoprotein that is found in concentrations 100-1000 times higher in prostate cancers as compared with normal tissue.

PSMA is an excellent target for radionuclide imaging and therapy as it is highly expressed in prostate cancers. Small molecule PSMA ligands allow for rapid targeting of the prostate cancer cells.

When these PSMA ligands are bound with Lu177 radionuclides, they act as a “magic bullet” delivery system allowing for targeted radiotherapy of prostate cancer cells.

What Are the Expected Outcomes of Lu177 PSMA Therapy?

Lu177 PSMA Therapy aims to reduce tumour volume and stop the growth of cancer.

Lu177 PSMA therapy has proven anti-tumour activity and safety in treating patients with metastatic Castrate Resistant Prostate Cancer (mCRPC) and is an ideal therapeutic option for patients who do not tolerate chemotherapy well or have extensive bone marrow involvement.

Lu177 PSMA therapies have shown trends towards Prostate-Specific Antigen (PSA) reductions, lengthening overall survival and progression-free survival, with generally mild and transient toxicities.

What Are the Potential Side Effects of Lu177 PSMA Therapy?

Aside from Prostate cancers, there are other organs and normal tissue that express PSMA antigens.

These include the salivary glands, bone marrow, kidneys, and small intestines. As such, these organs will be exposed to a small amount of radiation during therapy.

Approximately 10-20% of patients will experience a drop in blood cells (e.g. red blood cells, white blood cells, platelets), which is typically transient in nature (approximately 6 weeks), with the recovery of blood levels expected.

Approximately 10-20% of patients will experience a decrease in salivary production (Xerostomia). Additionally, some patients may experience side effects of nausea and fatigue, which is usually transient.

Who Will Benefit From Lu177 PSMA Therapy?

Patients with metastatic Castrate Resistant Prostate Cancer (mCRPC) are the ideal candidates for Lu177 PSMA Therapy.

Most patients who undergo Lu177 PSMA therapy are heavily pre-treated, typically with multiple chemotherapy and androgen deprivation therapy courses.

However, increasing data shows that patients who undergo Lu177 PSMA treatments earlier have better outcomes than heavily pre-treated populations.

What Are the Contraindications to Lutetium-177 PSMA Therapy?

Relative contraindications

• Impaired renal function (GFR < 40 mL/min)
• Impaired marrow function (platelet < 75 x 109/L, Hb < 90 g/L)
• Recent radiotherapy (6 weeks)
• Concomitant nephrotoxic drugs
• Uncontrolled intercurrent illness or poor ECOG status
• PSMA PET imaging showing poor tracer avidity
• FDG PET imaging showing high FDG avidity without correlative PSMA expression

Discussion with your physician regarding the potential risks and benefits of therapy will be needed before commencing treatment.

What Are the Initial Investigations Needed for Lutetium-177 PSMA Therapy?

Imaging Studies

• PSMA Positron Emission Tomography / Computed Tomography (PET/CT) scan within six months
• Fluorodeoxyglucose (FDG) PET/CT scan is optional

Blood Investigations

• Full Blood Count (FBC)
• Renal Function Test
• Prostate-Specific Antigen (PSA)
• Alkaline Phosphatase (ALP)
• Lactate Dehydrogenase (LDH)

Functional Status

• ECOG Status Score

What to Expect During Treatment With Lutetium-177 PSMA Therapy?

Lu177 PSMA therapy can be done on an outpatient basis. It is expected to take approximately 4-6 hours in total, and you will be in the Nuclear Medicine department for the duration of the therapy.

Intravenous lines will be required for the therapy, and you will be asked to consume fluids to maintain good hydration (approximate 1.0 – 1.5L fluid throughout the day).

The Lu177 PSMA therapy will be given as a slow infusion over 10 minutes and will be followed by a standard saline infusion. You will be given anti-vomiting medications (e.g. Ondansetron) prior to the Lu177 PSMA infusion.

After the infusion is complete, you are free to walk around the Nuclear Medicine department, but you will be advised to avoid prolonged close contact with other patients. Additionally, small meals can be provided after the procedure.

Once radiation levels are within acceptable limits, you will be free to leave the Nuclear Medicine department. If you require admission for observation, we will make the necessary arrangements.

An appointment for the follow-up will be confirmed or arranged for you before discharge.

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