PSMA PET-Directed Therapy (Lu-177 PSMA / Pluvicto®) for Prostate Cancer
How PSMA PET Imaging Helps Guide Targeted Radioligand Therapy
PSMA PET scans do more than detect prostate cancer. In selected patients with advanced disease, they also help determine whether PSMA-targeted radioligand therapy (RLT), including Lutetium-177 (Lu-177) PSMA therapy, may be appropriate.
What Is PSMA PET-Directed Therapy?
PSMA PET-directed therapy refers to treatment that uses findings from a PSMA PET scan to determine whether prostate cancer is likely to respond to PSMA-targeted radioligand therapy (RLT).
Unlike surgery or external beam radiotherapy, radioligand therapy circulates throughout the body and delivers radiation directly to prostate cancer cells that express prostate-specific membrane antigen (PSMA).
Because this treatment relies on cancer cells expressing sufficient amounts of PSMA, a PSMA PET scan is usually performed before treatment is considered.
Why Is a PSMA PET Scan Needed Before Treatment?
Not every prostate cancer behaves the same way.
Some cancers show high levels of PSMA, while others have little or no PSMA expression. Since radioligand therapy specifically targets PSMA, the scan helps determine whether the treatment is likely to reach the cancer effectively.
A PSMA PET scan helps specialists assess:
- Whether the cancer shows sufficient PSMA uptake
- Whether most or all metastatic deposits are PSMA-positive
- Whether there are areas of disease that may not respond well to PSMA-targeted therapy
- Whether another treatment strategy may be more appropriate
In many centres, PSMA PET imaging is an essential step in determining eligibility for treatment.
How Does PSMA-Targeted Radioligand Therapy Work?
Radioligand therapy combines two components:
- A molecule that specifically binds to PSMA on prostate cancer cells.
- A radioactive isotope that delivers radiation once it reaches the cancer.
After the treatment is administered through an intravenous infusion, the PSMA-targeting molecule circulates throughout the body, attaches to PSMA-positive prostate cancer cells, and delivers radiation directly to those cells.
This allows treatment to target cancer deposits in multiple parts of the body while reducing radiation exposure to much of the surrounding healthy tissue.
Although PSMA is highly expressed by prostate cancer cells, small amounts are also normally found in tissues such as the salivary glands and kidneys. This explains why some patients experience dry mouth or require monitoring of kidney function during treatment.
What Is Lutetium-177 (Lu-177) PSMA Therapy?
Large international clinical trials have shown that PSMA-targeted radioligand therapy can improve outcomes in appropriately selected patients with advanced prostate cancer, leading to its adoption into international treatment guidelines.
The most widely used form of PSMA-targeted radioligand therapy uses Lutetium-177 (Lu-177), a radioactive isotope that emits beta radiation over a short distance.
One commercially available form of this treatment is Pluvicto® (lutetium Lu 177 vipivotide tetraxetan). It combines a PSMA-targeting molecule with Lutetium-177, allowing radiation to be delivered directly to prostate cancer cells identified through PSMA PET imaging.
Treatment is usually provided at specialised nuclear medicine centres and is commonly given over several treatment cycles, with each cycle separated by several weeks.
During treatment, patients are usually monitored with:
- PSA blood tests
- Blood counts
- Kidney function tests
- Assessment of symptoms
- Repeat imaging when appropriate
Who May Be Suitable for PSMA PET-Directed Therapy?
PSMA-targeted radioligand therapy is not suitable for every patient with prostate cancer.
It is generally considered for selected patients with advanced or metastatic prostate cancer, particularly when the disease has progressed despite standard treatments.
Suitability depends on multiple factors, including:
- PSMA PET findings
- Extent and distribution of cancer
- Previous treatments received
- Overall health and performance status
- Kidney function
- Bone marrow reserve
- Assessment by a multidisciplinary team
Because treatment decisions are complex, patients are usually assessed by specialists in urology, medical oncology, radiation oncology and nuclear medicine.
When Is PSMA PET-Directed Therapy Considered?
Although treatment recommendations vary between individuals and continue to evolve, PSMA-targeted radioligand therapy is generally considered in selected patients with advanced prostate cancer after assessment by a multidisciplinary team.
It may be considered in patients who:
- Have metastatic prostate cancer demonstrated on imaging.
- Show sufficient PSMA uptake on PSMA PET.
- Have previously received standard systemic treatments, depending on current clinical guidelines.
- Are considered suitable after assessment of their overall health and blood test results.
Treatment recommendations continue to evolve as new clinical trials become available.
What Are the Potential Benefits?
For appropriately selected patients, PSMA-targeted radioligand therapy may:
- Deliver treatment to cancer throughout the body
- Target PSMA-expressing prostate cancer cells
- Reduce PSA levels in some patients
- Improve cancer-related symptoms
- Slow disease progression
- Help maintain quality of life
The degree of benefit varies between individuals and depends on factors such as the extent of disease and response to treatment.
What Are the Possible Side Effects?
Most patients tolerate treatment reasonably well, although side effects can occur.
Common side effects include:
- Fatigue
- Dry mouth
- Dry eyes
- Nausea
- Temporary reduction in blood cell counts
- Mild changes in kidney function
Because the treatment contains radioactive material, regular blood tests are performed before each treatment cycle to ensure it remains safe to continue.
Can PSMA PET-Directed Therapy Cure Prostate Cancer?
For most patients receiving PSMA-targeted radioligand therapy, the aim is to control advanced prostate cancer rather than cure it.
Treatment may help:
- Slow disease progression
- Reduce tumour burden
- Improve symptoms
- Delay further progression
- Extend survival in appropriately selected patients
Research is ongoing to determine whether PSMA-targeted therapy may have a role earlier in the course of prostate cancer or in combination with other treatments.
The Importance of Multidisciplinary Care
PSMA PET-directed therapy is only one component of advanced prostate cancer management.
Treatment decisions often involve collaboration between:
- Urologists
- Medical oncologists
- Radiation oncologists
- Nuclear medicine physicians
- Radiologists
- Specialist nurses
Working together allows the multidisciplinary team to recommend the most appropriate treatment sequence based on the patient’s disease, previous therapies and overall health.
Frequently Asked Questions
Is PSMA PET the same as PSMA-targeted therapy?
No. A PSMA PET scan is an imaging test used to detect and stage prostate cancer. PSMA-targeted therapy uses the information from that scan to determine whether targeted radioligand treatment is likely to be effective.
Is Pluvicto® the same as Lu-177 PSMA therapy?
Pluvicto® is the brand name of one form of Lutetium-177 (Lu-177) PSMA radioligand therapy. It combines a PSMA-targeting molecule with the radioactive isotope Lutetium-177 to deliver targeted radiation to prostate cancer cells that express PSMA.
Does every patient with metastatic prostate cancer qualify for PSMA-targeted therapy?
No. Eligibility depends on several factors, including PSMA PET findings, previous treatments, the extent of disease, overall health and assessment by a multidisciplinary team.
How many treatment cycles are usually required?
Treatment is commonly given over multiple cycles, often around every six weeks. The exact number depends on the individual’s response, blood test results and the treating centre’s protocol.
Is hospital admission required?
Many patients receive treatment as a day procedure, although this varies depending on the treatment centre and individual circumstances.
Can PSMA-targeted therapy be combined with other prostate cancer treatments?
Yes. Depending on the clinical situation, it may be used before, after or alongside other treatments such as androgen deprivation therapy, androgen receptor pathway inhibitors or chemotherapy. The treatment sequence is determined by the multidisciplinary team.
PSMA-targeted radioligand therapy available in Malaysia?
Availability may vary between healthcare centres and over time. Patients who may be suitable for treatment should discuss the available options with their treating specialist or nuclear medicine team.
Can PSMA-targeted therapy be repeated?
Many patients receive multiple treatment cycles. Whether additional treatment is appropriate depends on how well the cancer responds, side effects, blood test results and overall health.
What happens if my PSMA PET scan does not show enough PSMA uptake?
If the cancer does not express sufficient PSMA, PSMA-targeted radioligand therapy may not be effective. Other treatment options may be recommended depending on the stage of disease and previous treatments.
Current Research
Research into PSMA-targeted radioligand therapy continues to evolve rapidly.
Researchers are studying whether PSMA-targeted radioligand therapy may benefit patients:
- Earlier in the course of prostate cancer
- Before chemotherapy in selected patients
- In combination with hormonal therapy
- Together with immunotherapy
- Together with other targeted treatments
As clinical evidence grows, the role of PSMA-targeted therapy is likely to continue expanding for appropriately selected patients.
Understanding Advances in Prostate Cancer Treatment
PSMA PET imaging and targeted radioligand therapy have expanded the treatment options available for selected patients with advanced prostate cancer. Understanding how these treatments work and when they may be considered can help patients and their families discuss the most appropriate management options with their healthcare team.