Radioligand Therapy for Prostate Cancer (PSMA with Lutetium-177)

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What is PSMA Therapy?

Probably one of the most common malignant tumors in men is prostate cancer. In 2012 alone, more than 63,000 new cases were diagnosed in Germany, for example. PSMA stands for prostate-specific membrane antigen. However, upon closer inspection, what sounds complicated at first glance is quite simple: it is a surface feature of the prostate's tumorigenic degenerated cells that can produce the PSMA.

With the help of this therapy, the surface feature of the cancer cells can be detected, and a specific radioactive molecule (for example, lutetium-177-PSMA-617) can be docked onto them (lock-and-key principle). Thus, the cells can be made visible, and they can be specifically irradiated and destroyed in this way. Studies have shown that the therapy is well tolerated and that the clear majority of all patients respond to this therapy.

PSMA therapy is not yet a routine therapy for prostate cancer patients. However, it has already been proven that even in patients who have had progressive disease after conventional therapies, this therapy effectively prolongs life and has been shown to improve quality of life significantly. PSMA therapy has been used individually in Germany and Austria for more than eight years and has shown excellent results in numerous studies.

Who Is Eligible for PSMA Therapy?

Patients with prostate cancer who have advanced stages of the tumor disease refractory to treatment are eligible. This is done either in the context of studies or in the context of so-called individual therapeutic trials, following the respective legislation of the country. However, general approval of the therapy is imminent. The effectiveness of the treatment in earlier stages is currently the subject of prospective studies.

The extent to which therapy is helpful for the patient will only become apparent after several tests. Above all, imaging the target structure (PSMA) in the body by PET/CT is essential. Other blood parameters must also be checked to ensure the adequate function of the hematopoietic bone marrow and the kidneys. Affected patients should seek an informative discussion with their urologist or nuclear medicine specialist.

What Exactly Is the Procedure for PSMA Therapy?

The therapy itself is carried out intravenously via a venous catheter. Therefore, on the day of the treatment and during the following days, it is essential to drink a sufficient amount of fluids (approx. 2-2.5 liters per day) to minimize the strain on the body, especially the salivary glands and kidneys.

Lutetium-177 is the radioactive nuclide, and the carrier protein is the PSMA ligand. Since the two are coupled, and the PSMA is expressed almost exclusively by tumor cells, very efficient and targeted therapy is possible in this way. Once at the tumor cells, the lutetium-177 radiates about 1-2 mm into the surrounding tissue, sparing healthy portions. Thus, it doesn't matter where or how large or small the tumor cells are; the PSMA acts as a navigation system, guiding the radioactive drug directly to its target.

Before the patient leaves the clinic, a standardized measurement of the radiation emitted by the patient is made to comply with the legal requirements of radiation protection.

Are Side Effects and Complications to Be Expected?

As with any radionuclide therapy, side effects and complications can occur with PSMA therapy. In general, however, the treatment is very well tolerated. Occasionally, nausea may occur, but this can be treated with conventional medications. Taste disturbances and dry mouth (xerostomia) may also occur. Since the radiopharmaceutical is excreted through the urine and intestines, the patient should drink plenty of fluids and normally eat to keep up the activity of these organs high at all times.

PSMA is also bound in the salivary glands. Dry mouth may occur depending on the frequency of use and the radionuclide used (177 Lutetium vs. 225 Actinium). However, severe courses were observed only in the case of previous damage or use of the alpha emitter Actinium. Adequate protection of the salivary glands using drugs is not currently available. Discrete blood count changes, usually transient, may also occur, so blood count checks accompany therapy.

What Follows After Radioligand Therapy?

Usually, the patient can be discharged after completion of therapy, provided he or she has met the radiation safety requirements of the respective therapy country at that time. Approximately one month after completion of the therapy cycle, imaging by PSMA-PET/CT should be performed to monitor the success of the therapy to decide on further therapy cycles, if necessary.

Because the patient will be radioactive to some degree after therapy, hygiene and radiation safety instructions should be followed. These include keeping contact with other persons or groups (especially pregnant women and small children) short at the beginning. For this purpose, the patient receives a corresponding instruction sheet on which all important behavioral recommendations are listed.