©Art Inc / istock

The PSMA-guided methods are not only used as diagnostic tools but also serve as key components for highly precise and effective therapies for prostate cancer. We spoke with Dr. Brumberg, Senior Consultant in the Department of Nuclear Medicine at the Medical Center – University of Freiburg, about this innovative approach.

What is PSMA-targeted therapy for prostate cancer? 

PSMA stands for “prostate-specific membrane antigen”—a protein that is particularly common on the surface of prostate cancer cells. PSMA-guided diagnostics and therapy use radioactive substances that specifically bind to these PSMA structures. There are two main applications: (i) PSMA-PET imaging, a diagnostic procedure for detecting cancer cells in the body (ii) PSMA radioligand therapy for targeted irradiation of cancer cells from within the body

For which patients is PSMA targeted radioligand therapy particularly suitable? In which stages of prostate cancer is it most commonly applied? 

The therapy is mainly suitable for patients with advanced prostate cancer in whom the cancer has already metastasized, conventional hormone therapies are no longer effective, and chemotherapy has already been performed or is not possible. PSMA PET imaging is also used to check whether the cancer cells produce high levels of PSMA, as high PSMA expression is a prerequisite for successful therapy. PSMA radioligand therapy is most commonly used in the metastatic stage when other forms of treatment have already been exhausted.

What is the typical treatment process for a patient?

The treatment process is relatively straightforward:

1. Preliminary examination and treatment planning: outpatient appointments with PSMA-PET/CT to check whether the cancer cells express sufficient PSMA, renal scintigraphy, and blood tests to rule out any relevant contraindications

2. Treatment day: on the day of admission to the hospital, the radioactive drug is injected into a vein, followed by measurements for individual dosimetry

3. Inpatient stay for 3 days in the nuclear medicine therapy ward

4. Repeat: usually 4-6 treatments at intervals of 6-8 weeks

5. Follow-up care: regular check-ups with blood tests and imaging using PSMA-PET

Are the radiopharmaceuticals used in PSMA radioligand therapy safe? Are there any side effects or long-term risks? Are there contraindications?

Radiopharmaceuticals are considered relatively safe because they act in a targeted manner. Possible side effects often include fatigue and weakness, nausea (usually mild), dry mouth, or a temporary drop in blood counts. Rarely, kidney dysfunction or a severe drop in white and/or red blood cells may occur. PSMA radioligand therapy should not be performed in cases of severe kidney dysfunction or severely impaired bone marrow function (contraindications), among other factors.

Can this therapy replace chemotherapy?

PSMA radioligand therapy is not a substitute for chemotherapy, but it can be an alternative. PSMA radioligand therapy is often used when patients have already received chemotherapy or when patients cannot tolerate chemotherapy or are too weak for chemotherapy. In most patients, both therapies are applied one after the other.

Can this method completely cure prostate cancer?

A complete cure is rarely possible in advanced prostate cancer. However, PSMA radioligand therapy can significantly slow tumor growth, relieve pain and discomfort, improve quality of life, and prolong life compared to the best supportive care. In the VISION study, which was important for the approval of PSMA radioligand therapy, approximately 40-50% of patients responded well to treatment with a PSA decline of more than 50% and, in some cases, a significant reduction in metastases. The therapy is an important addition to the treatment of advanced prostate cancer and offers new hope to many patients, even if it does not usually lead to a complete cure.

What new developments or improvements do you expect in PSMA radioligand therapy?

Promising developments are already evident in current and planned studies on the earlier use of PSMA radioligand therapy in less advanced stages of prostate cancer and in combination with other treatments, such as immunotherapy. In addition, new radiopharmaceuticals with improved efficacy and fewer side effects are being researched.