Lutetium-177 PSMA (LuPSMA) radionuclide therapy

Lutetium-177 PSMA radionuclide therapy is used for treating patients with advanced prostate cancer. Prostate cancers, in particular those that have spread to other sites of the body or become resistant to hormonal therapies, express a unique substance on their cell surface called prostate specific membrane antigen (PSMA). LuPSMA radionuclide therapy involves using a radioactive molecule (Lutetium-177) and PSMA substance that specifically attaches to cells with high PSMA expression. This radioactive molecule is taken up into prostate cancer cells, or wherever the disease has spread and enables delivery of high doses of targeted radiation to sites of prostate cancer whilst sparing most normal tissues. This is called radionuclide therapy as it uses radiation to kill prostate cancer cells.

The use of LuPSMA therapy is largely for patients who have progressive metastatic hormone-resistant prostate cancer. You may be referred for this treatment if there is progression of your condition despite having undergone conventional therapy (such as hormonal treatment and chemotherapy). Hormonal treatment and other systemic therapies may control the disease for some periods of time, however many patients eventually suffer a relapse of the disease.

The benefits of this targeted radionuclide therapy may include shrinkage of tumours, a reduction in blood Prostate Specific Antigen (PSA) level, improvement in symptoms such as pain and a general improvement in well-being.

LuPSMA treatment is an outpatient treatment. It will be administered via an intravenous line into the veins of your arms.  

You will receive up to 4 -6 cycles of LuPSMA treatment at 6-8 week intervals.

Standard supportive drugs, hormonal therapy, biosphosphonate therapy or palliative radiotherapy while on LuPSMA therapy is permissible as clinically indicated. Concurrent chemotherapy while receiving LuPSMA therapy is currently not permitted.

It is important to tell your doctor about any treatments or medications you may be taking, including over-the-counter medications, vitamins or herbal remedies, acupuncture or other alternative treatments, and any changes to these medications during your LuPSMA therapy. 

Possible short term side effects (within weeks to months of treatment):

This is usually mild and, if needed, can be treated with anti-nausea medication.

These gland cells have PSMA-receptors, which LuPSMA will attach to. Therefore, the glands will receive radiation. This may result in inflammation (swelling) of the glands which may lead to pain or decreased production of saliva and/or tears. This will most likely be temporary and resolve with time. Permanent injury (e.g. reduced production of saliva or tears) is possible but is usually mild and can be alleviated with artificial saliva and tear drops.

This is usually temporary but may require increase in painkiller requirements.

As tumours die, this can result in flu-like symptoms including low grade fevers and fatigue.

The extent of blood count reduction may be influenced by prior therapies (e.g. chemotherapy). If you have very extensive bone metastases, this may also increase the likelihood of reduced blood count. Mild reduction in blood count that can be measured through blood tests without any resulting symptoms may be more common (between 1 in 10 and 1 in 100).

Reduced glomerular filtration rate of the kidneys has been observed following LuPSMA therapy, however this usually does not result in kidney dysfunction clinically for most patients. 

Longer-term side effects may include risk of developing secondary malignancies. The precise increase in risk is not known but thought to be very small (less than 1 in 100) and will depend somewhat on the radiation doses absorbed during the treatment. However, the risk of serious sequelae is relatively rare and typically involves blood disorders that may develop several years after treatment.

After each treatment, a whole body 2-dimensional scan and a more detailed 3-dimensional scan will be performed to see where the radiation has gone to. This scan will take approximately 45-60 minutes to complete. Most patients will feel well and be allowed to go home on the day of treatment.

However, you will be mildly radioactive for a few days and there may be some restrictions on close personal contact including with pregnant women or children.

Your blood will be taken and tested (full blood count, urea and electrolytes, liver function tests, PSA) at 14 and 28 days after the treatment.

Further LuPSMA treatments can be considered for patients who responded to initial cycles of LuPSMA but subsequently progressed, provided they continued to meet the eligibility criteria for treatment.