The scientists of the German Cancer Research Center have developed a biologically active substance PSMA-617, targeted to bind to prostate cancer cells. The biologically active substance is labeled by various radioactive substances. Binding to a weakly emitting diagnostic radionuclide, it will expose prostate tumors and their metastases in PET. Being labeled by a strongly emitting therapeutic radionuclide, PSMA-617 can destroy the cancer cells in a targeted manner. The first clinical use of the radiopharmaceutical was promising.
Prostate carcinoma is the most common cancer among men. After local therapy (surgery and/or radiation) for advanced prostate cancer, an additional anti-hormonal treatment is often prescribed. After a prolonged anti-hormonal therapy, the cancer cells frequently become resistant to these medicines, so later, upon tumor progression, chemotherapy often remains the only option. A further treatment options for patients with prostate cancer can be a PSMA-therapy. PSMA (prostate-specific membrane antigen) is a protein propagating on the surface of the prostate cancer cells. This allows using the same in radiation diagnostics and therapy of these tumors by combining the substance associated with PSMA with a radioactive nuclide (177 Lu, ß-emitter). For PSMA therapy, the radioactive emission (beta radiation) may exercise a direct therapeutic effect on tumor cells. Being associated with a weakly emitted specific diagnostic radionuclide, PSMA-617 can detect very small aggregates of prostate cancer cells in PET (positron emission tomography) studies.
Upon PSMA radionuclide therapy, the radioactive emission (ß-radiation) may exercise a therapeutic effect directly on the tumor cells while sparing the healthy surrounding tissues.
The treatment goal is inhibition / delay of the tumor cell growth, while covering the metastases (in bones, soft tissues, and the like).
Metastatic prostatic carcinoma cells bear on their surface a so-called high-density prostate-specific membrane antigen (PSMA). The ligands binding to PSMA can be radioactively labeled, and including by radionuclides used for therapeutic purposes, such as 177-lutetium. This type of therapy is feasible for patients with metastatic prostate cancer, which are no longer affected by the prior conventional systemic therapy, i.e. chemotherapy. In agreement with the attending urologists/oncologists, especially considering the exclusion of subsequent treatments, such as the second and third cycle of chemotherapy due to the possible low effectiveness, side effects and comorbidities, as well as at the patient's request, the chemotherapy with a high degree of side effects should be avoided.
Treatment methods and procedure:
Preparation for treatment:
in the course of preparation and planning of this treatment, various studies are carried out: blood tests, including a differential blood count, liver and kidney function tests, as well as PSA.
This allows assessing the risks and side effects to the other organs (e.g., hematopoietic spinal cord) and monitoring the same since an early treatment stage.
During the preparation for treatment, it is required to conduct a PSMA scintigraphy or PSMA-PET-CT to assess whether the PSMA-therapy is feasible and promising. Besides, it is required to conduct a preliminary bone and salivary gland scintigraphy. In order to determine the indications for PSMA, the findings of the other studies, as well as pictures of the previous surveys, e.g., diagnostic computed tomography (CT) or Choline-PET-CT, are useful.
Lutetium-177-PSMA ligands bind PSMA to cells carrying the prostate cancer on their cell membranes. Due to radioactive rays with a short exposure, the cell growth is prevented at a depth of a few millimeters only; they are damaged or destroyed.
PSMA treatment is carried out after conversation with a clinic department physician on the day for which the treatment is scheduled. The salivary gland scintigraphy is performed, unless it was conducted on the day before. It is also required to conduct a preliminary renal scintigraphy to determine their functions and the kidney outflow ratio.
On the treatment day, you must be sober. The department physician will introduce venous catheters into both of your hands. About 2 hours before the treatment start, we will apply an ice pack to your lower jaw to protect your salivary glands so that they were cooled and thus bled to a lesser extent. This implies a lesser accumulation of radioactive substances in the salivary glands. Before treatment, an injection of saline solution will be administered to protect your kidneys. Following this, a healing radioactive substance is injected. It is introduced with a syringe for about 10-15 seconds. If you have any side effect during or after treatment (e.g., nausea), please, inform the department staff to receive the appropriate drugs suppressing the side effects.
About 15-30 minutes and 2-4 hours after the healing injection, we conduct a general scintigraphy to monitor the activity distribution and measure the radiation load on the kidneys, respectively; simultaneously, a tube of blood is taken to evaluate the radioactive dose in the blood and bone marrow at each sampling. During the hospital stay, the radiation dose rate is determined, and the necessary blood sample is taken.
On the day of discharge, a repeated general scintigraphy of the whole body is carried out to visualize the PSMA distribution (the scintigraphy is performed 24 and 48 hours later, when required, depending on the used nuclide). Once the radioactive radiation emitted by the patient's body is below the regulatory threshold, the patient can be discharged.
In accordance with the Regulations on Radiation Protection, the treatment can be carried out in a hospital setting only, and the patient must stay in the radiotherapy department for four days.
Typically, the hospital stay takes 3 to 4 days.
To estimate the radiation dose received, we appoint your next visit to us for scintigraphy of the whole body, and for blood sampling 6 to 9 days after treatment. The final scintigraphy is performed about 7 to 10 days after treatment.
The total permitted amount of therapeutic radioactivity is not introduced within a single session. In most cases, the treatment is carried out in several separate cycles, during which you will stay in our department for eight weeks with intervals.
In most cases, a laboratory monitoring for about 10 weeks, every two weeks, is required. PSA checks must be carried out 4 and 8 weeks after therapy. Depending on the survey findings and the patient’s overall condition, the PSMA therapy is normally conducted in three cycles.
To evaluate the effectiveness of the preceding treatment cycle, a repeated PET/CT is performed about a week before the second treatment cycle. Besides, before each new cycle of therapy, you shall pass the blood count, as well as liver and kidney function tests in order to detect the eventual deterioration of their condition and the bone marrow status on a timely basis. Please, include the relevant examinations in your schedule.
Eventual risks and complications
In general, the treatment is well-tolerated. Sometimes, there are side effects, such as nausea and vomiting (medically treatable), taste sensation disorders and xerostomia (partially, temporarily), as well as fatigue. PSMA is excreted by kidneys, liver and bladder. Therefore, we must pay attention to an adequate intestinal activity and stimulate the same, when required. Along with this, a sufficient amount of liquid should be consumed. The liver and kidney functions shall be checked after treatment, too. The following organs at risk are the salivary and lacrimal glands, to which PSMA is bound. In order to minimize the damage to the salivary glands, they are cooled for a long period of time, thereby minimizing the risk of a long-term damage and loss of the gland functions (xerostomia). Besides, it can lead to a temporary change in the blood pattern.
The Regulations on Radiological Protection require that the patient stayed in radiation medicine ward with a protective screen.
The visitors are not allowed in a shielded area. However, you will be able to receive the essentials from your family through the attendants. For your stay in the hospital, please, take comfortable casual clothes, nightwear and ordinary personal hygiene products. You should also take the items required for your pastime (e.g., magazines, books, laptop, handicraft items, etc.). They are not "irradiated" during treatment, and can subsequently be used in everyday life.
The radio, TV and telephone are at your disposal in the wards.