Advanced Metastatic Prostate Cancer Treatment: Comparing Lutetium-177 — Actinium-225 — Radium-223 Therapies
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Nuclear medicine involves the use of radioactive isotopes to target cancer and its distant metastases. In fact, this is an advanced type of radiation therapy that reliably detects all malignant lesions and destroys them using ionized radiation, whilst minimizing any damage to the surrounding healthy tissue. Isotopes such as Lutetium-177-PSMA, Actinium-225-PSMA, and Radium-223 have been successfully used in the treatment of advanced prostate cancer. Lutetium-177-DOTATATE is used in the treatment of complex neuroendocrine prostate cancer. In fact, as the last-line therapy, nuclear methods can suppress the development of metastases of prostate tumors, prolong the patient's life, and significantly improve his life quality by eliminating the pain syndrome.
Content
- The role of nuclear medicine in prostate cancer treatment
- When should we use a specific method of nuclear medicine?
- In what cases are specific drugs used?
- What reactions and side effects can occur?
- What is the effectiveness of the drugs?
- Below, you can see the hospitals where you can undergo Lutetium-177, Actinium-225, and Radium-223 treatment
- Radionuclide treatment in the world's leading hospitals with Booking Health
Lutetium-177 and Actinium-225 are PSMA-targeted therapies using different types of radiation (beta and alpha, respectively), while Radium-223 targets bone metastases. Lutetium-177 has a larger radiation range, Actinium-225 is more potent, and Radium-223 is specific for bone metastases.
These treatments are typically recommended for patients with metastatic castration-resistant prostate cancer (mCRPC) who have not responded well to other treatments like hormone therapy and chemotherapy. The specific choice depends on the quantity and location of metastases, previous treatments, and overall health condition.
Common side effects include fatigue, nausea, and a temporary decrease in blood cell counts. Dry mouth may occur with PSMA-targeted therapies. Radium-223 may cause diarrhea. These side effects are generally manageable and less severe than those of traditional chemotherapy.
Clinical trials have shown promising results. For example, Lutetium-177-PSMA therapy has demonstrated PSA response rates of 40-60% and objective response rates of 40-50% in some studies. Actinium-225-PSMA has shown even higher response rates in early trials. Radium-223 has been shown to improve overall survival in patients with bone metastases.
The number of sessions varies by treatment. Lutetium-177-PSMA is typically given in 4-6 sessions, 6-8 weeks apart. Actinium-225-PSMA is often given in 2-4 sessions. Radium-223 is usually administered in 6 injections, 4 weeks apart. Each session involves an intravenous injection of the radioactive drug, followed by a brief period of isolation to manage radiation exposure.
The role of nuclear medicine in prostate cancer treatment
In the field of oncology, the success rate of innovative therapies often correlates with a significant improvement in the life expectancy of patients. The destruction of cancer cells using ionizing radiation has long been a standard treatment protocol for many cancers. However, radiation therapy often affects not only the tumor, but also the surrounding healthy tissue. In prostate cancer, this leads to unwanted damage to the bladder, intestines, liver, and other important organs. The narrowing of the irradiation zone and targeted irradiation of malignant foci are the principles that formed the basis for the development of radionuclide therapy.
Nuclear medicine offers a safer and more effective treatment for prostate cancer, with radioactive nuclides – radioactive isotopes of stable elements that recognize tumor cells and metastases and irradiate them with high precision. Individual radioisotopes can be incorporated into bone tissue, mimicking its normal elements; this property is used in the treatment of bone cancer metastases.
Isotope therapy is used in the advanced, metastatic stages of cancer, when other treatments have not led to an improvement in the patient's condition and did not slow down the further progression of the oncological disease. In particular, in cases of prostate cancer, treatment with drugs such as Actinium-225 and Lutetium-177 is carried out on men who have already undergone the following treatment methods without gaining any results:
- Surgical treatment (prostate resection when the cancer is detected at an early stage)
- Hormone therapy (testicular resection or long-term use of antiandrogenic drugs)
- Intensive chemotherapy (in some cases, this stage of treatment may be excluded)
The lack of response to standard treatments is a direct indication for the prescription of therapeutic radionuclides – Actinium-225-PSMA and Lutetium-177-PSMA.
These are modern drugs, in the development of which, scientists have corrected the shortcomings of earlier used isotopes: Lutetium-177 and Actinium-225 have low myelotoxicity, that is, they do not affect the spinal cord when treating metastases in the spine and other bones (the most typical localization of metastases in prostate cancer).
We will consider the features of the actions of various therapeutic radionuclides below.
When should we use a specific method of nuclear medicine?
What are the differences between methods of cancer treatment with nuclear medicine? Differences in the action of radionuclides are caused by two main parameters:
- The physical characteristics of the radionuclide in its composition are the type of radiation, the radiation radius of the surrounding tissues, and the half-life
- The characteristics of the radionuclide carrier molecule are the reliability and accuracy of its binding to tumor receptors
Radionuclide therapy entered the clinical practices of developed countries of the world more than 40 years ago. During this time, scientists have accumulated practical experience in the use of various radioactive isotopes in prostate cancer treatment and have identified the most effective and safe of them. As of today, the updated protocols for the treatment of cancer of various localizations include the use of 4 main medicines. These are as follows:
| Radionuclide | Indications for use | The principle of therapeutic action |
|---|---|---|
Lutetium-177-PSMA Beta radiation (high-energy electrons), half-life – 6.5 days | Metastatic castration-resistant prostate cancer, in particular with bone metastases | Lutetium-177 was the first radionuclide to receive FDA approval for use in prostate cancer treatment. The carrier molecule in this drug is PSMA, a prostate-specific membrane antigen. PSMA receptors on the surface of cancer cells serve as a unique target, to which a therapeutic radionuclide binds after intravenous administration. The radiation of Lutetium-177-PSMA extends to no more than 100-200 surrounding cells. |
Actinium-225-PSMA Alpha radiation (helium nuclei), half-life – 10 days | Metastatic castration-resistant prostate cancer, in particular with bone metastases | For the treatment of metastatic prostate cancer, Actinium-225 binds to the same molecular carrier as Lutetium-177-PSMA. The mechanism of action of the drug differs due to the replacement of the isotope: the action of Actinium-225 lasts 4 days longer, and the radius of action is limited to 1-2 surrounding cells. Due to this, Actinium-225 therapy is effective even in the absence of a satisfactory response to Lutetium-177. |
Lutetium-177-DOTATATE Beta radiation (high-energy electrons), half-life – 6.5 days | Neuroendocrine prostate cancer (NEPC) | In this case, the radioisotope Lutetium-177 binds to another carrier substance, namely the DOTATATE molecule. DOTATATE has a structural affinity for somatostatin receptors, which are abundant on the surface of neuroendocrine tumors. After intravenous administration, Lutetium-177-DOTATATE accumulates in neuroendocrine tumors of the prostate and destroys them, preserving the normal function of the bladder and intestines. |
Radium-223 Natural alpha radiation (helium nuclei), half-life – 11.5 days | Metastatic castration-resistant prostate cancer, in particular with bone metastases | In structure, radium is similar to calcium, which is the main structural element of bone tissue. Thanks to this, it integrates into the natural bone metabolism and specifically irradiates actively multiplying cells of bone metastases of prostate cancer. The alpha radiation of Radium-223 acts within 2-10 surrounding cells, and the drug, which is not absorbed by the bones, is quickly excreted through the intestines. According to data from clinical studies, when using the drug, malignant cells receive 8-9 times more radiation compared to healthy tissues. |
In what cases are specific drugs used?
In the summer of 2021, the FDA (Food and Drug Administration) approved Lutetium-177-PSMA-617 for the treatment of castration-resistant metastatic prostate cancer. Clinical trials are also being conducted on the use of this drug in the earlier stages of prostate cancer. To date, indications for the use of Lutetium-177-PSMA-617 are as follows:
- Confirmation of metastatic stage of prostate cancer with metastases in bones, lymph nodes, and lungs
- Failure to respond to hormone therapy and chemotherapy
- Contraindications to hormone therapy and chemotherapy
- Sufficient number of PSMA receptors based on preliminary PSMA-PET/CT with Gallium-68
What are the pros and cons of treatment with Lutetium-177-PSMA? Lutetium-177-PSMA therapy is the treatment of choice for men with metastatic prostate cancer who have not been successfully treated with hormone therapy and chemotherapy. Your doctor may recommend this treatment after prostate resection, antiandrogen drugs, and chemotherapy. When replacing these types of treatment with Lutetium-177-PSMA therapy, you will no longer need to constantly take pills.
The alternative treatment with Actinium-225-PSMA is carried out under similar conditions and after the ineffectiveness of 1-2 courses of treatment with Lutetium-177-PSMA. Actinium-225-PSMA binds more strongly to tumor receptors, its half-life is 60% longer than the half-life of Lutetium-177, and the radius of action is only 1-2 cells (as opposed to 100-200 cells for Lutetium-177).
Actinium-225 has emerged as a promising radiopharmaceutical in the management of metastatic prostate cancer, demonstrating potential superiority over the current standard, Lutetium-177. The versatility of Actinium-225 PSMA-targeted therapy is clinically significant, offering multiple integration points in the personalized treatment. Oncologists may administer Actinium-225 pre- or post-Lutetium-177 therapy, as a direct alternative, or in select cases, before chemotherapy initiation. This flexibility in treatment sequencing, combined with its high linear energy transfer and short tissue penetration range, positions Actinium-225 as a valuable innovative cancer treatment in the evolving paradigm of advanced prostate cancer targeted therapy.
What are the pros and cons of treatment with Actinium-225-PSMA? Actinium-225-PSMA therapy is the second stage of radionuclide treatment. It follows Lutetium-177-PSMA therapy if clinicians believe a more effective outcome can be achieved. When performing Actinium-225-PSMA therapy, you similarly do not need to constantly take pills. 82% of men respond to this type of treatment.
Radium-223 was developed by Bayer, primarily for the treatment of bone metastases in advanced prostate cancer. Bone metastases of prostate tumors activate osteoblasts, which are cells with intensive metabolisms that are responsible for building bones. Osteoblasts actively accumulate calcium ions, due to the structural similarity with which radioactive Radium-223 penetrates into metastases. Thus, Radium-223 is the drug of choice for
- Confirmed metastatic prostate cancer with osteoblastic bone metastases
- Absence (or a small number) of metastases in internal organs (lymph nodes, liver, lungs)
What are the pros and cons of treatment with Radium-223? Radium-223 therapy allows a patient to be rid of prostate cancer metastases in the spine and other bones. Your doctor will recommend Radium-223 if your bone pain worsens with hormone therapy and chemotherapy. Radium-223 does not accumulate in the prostate and can even be prescribed to men who have not had a prostatectomy.
Another modification of the isotope Lutetium-177, namely Lutetium-177-DOTATATE, is intended for patients with rare neuroendocrine prostate cancer (NEPC). Four cycles of treatment with Lutetium-177-DOTATATE, with an interval of 8 weeks between procedures, are prescribed in cases with:
- Contraindications to surgery or chemotherapy
- Ineffectiveness of previous surgery or chemotherapy
- Failure to accurately determine the characteristics of the primary tumor, the presence and number of metastases
In addition to treatment, radionuclides are also actively used in the diagnosis of prostate cancer. Due to the high accuracy and specificity of nuclear methods, such examinations are called "theranostics". Theranostics are personalized examinations that allow doctors to accurately visualize the tumor and metastases in a particular patient. Theranostics methods include imaging with Gallium-68-DOTATATE (neuroendocrine prostate cancer) and PSMA-PET/CT with Gallium-68 (prostate cancer).
What reactions and side effects can occur?
Today, in the clinical practice of specialized centers and departments of nuclear medicine, only radioactive isotopes with an optimal safety profile and, accordingly, minimal side effects are used. Radionuclide treatment is indicated for debilitated patients with advanced stages of cancer, and therefore, scientists and practitioners pay special attention not only to the effectiveness of the therapy but also to patients’ tolerability to it.
The most common side effects of radionuclide therapy include:
- dry mouth – 87% patients;
- nausea – 50% patients;
- fatigue – 50% patients;
- anemia – 13% patients;
- thrombocytopenia – 13% patients;
- lymphocytopenia – 37% patients.
Most side effects are temporary and go away on their own within a few days/weeks after the end of the course of treatment. Radionuclide treatments cause fewer short- and long-term side effects than other therapies. If necessary, doctors prescribe symptomatic treatment, such as drugs, to correct anemia or improve a patient’s general condition.
What is the effectiveness of the drugs?
The effectiveness of treatment with radiopharmaceuticals is most objectively reflected in the results of clinical trials. Unlike the practice of individual doctors, even in the largest medical centers with nuclear medicine, clinical trials include hundreds and thousands of patients with the same diagnoses. They help to collect large amounts of reliable information about the effectiveness of individual drugs, the incidence of side effects, and the possibility of combining different treatments:
- According to the results of the VISION clinical trial, Lutetium-177-PSMA received FDA approval and the status of "breakthrough therapy" for metastatic hormone-resistant prostate cancer in 2021. This means that even the early clinical data strongly indicates the possibility of significant improvement in patients' conditions compared to all other therapies. After 1 or several courses of treatment with Lutetium-177-PSMA, the 5-year survival rate of patients with metastatic prostate cancer increased to 30%. The risk of disease recurrence also decreased; in 30-40% of patients, remission persisted for 2 years.
- The trials on Actinium-225-PSMA, as a more innovative pharmaceutical, are ongoing, but the results obtained so far show a 50-80% decrease in the number of metastases and a 90% decrease in PSA levels in 82% of men. A recent large-scale study, known as the WARMTH Act (Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer, mCRPC), has shown encouraging results for men with advanced prostate cancer. This study, conducted from January 1, 2016, to May 31, 2023, focused on patients whose cancer had spread to other parts of the body and no longer responded to hormone therapy. In 2020, trials began on the combined use of Lutetium and Actinium-225-PSMA.
- Radium-223 was studied in the ALSYMPCA clinical trial in 921 men. According to the results of the trial, the drug increased the average overall survival by 3.6 months, reduced the risk of death by 30% and significantly reduced the risk of developing pathological spinal fractures. At the same time, it also reliably reduced pain syndrome developing against the background of bone metastases, which made it possible to classify it as an effective method of symptomatic therapy. The drug received FDA approval back in 2013.
Thus, therapy with Lutetium-177, Actinium-225, and Radium-223 significantly improves the condition of most patients with advanced stages of prostate cancer. This treatment is clearly indicated for men with hormone-resistant prostate cancer with metastases to the bones, lymph nodes, liver, and lungs.
The ability to choose between different isotopes allows doctors to personalize the treatment for each patient and achieve excellent therapeutic results.
Below, you can see the hospitals where you can undergo Lutetium-177, Actinium-225, and Radium-223 treatment
Treatment with radioactive isotopes is offered by the Nuclear Medicine Centers and specialized departments of large university hospitals. Some of the leading medical facilities that a patient from any country in the world can contact are listed below:
- University Hospital Rechts der Isar Munich, Department of Nuclear Medicine. The department is headed by Prof. Dr. med. Wolfgang Weber, whose specialization is radionuclide cancer therapy. The professor has prepared more than 250 articles for leading scientific journals, including the Journal of Clinical Oncology.
- University Hospital of Ludwig Maximilian University of Munich, Department of Nuclear Medicine. The department is headed by Prof. Dr. med. Peter Bartenstein. For more than 35 years, he has been actively engaged in the examination and treatment of patients using radionuclide methods, as well as research work. More than 460 scientific reports by professor Bartenstein have been published on Internet resources and in the scientific literature.
- University Hospital Frankfurt am Main, Department of Nuclear Medicine. The head of the department is Prof. Dr. med. Frank Grunwald. The professor has over 30 years of experience in the treatment of patients with radionuclide methods and is one of the best German specialists.
- University Hospital Carl Gustav Carus Dresden, Department of Nuclear Medicine. The head of the department is Prof. Dr. med. Jörg Kotzerke. The professor has been working with methods of radioisotope diagnostics and treatment for more than 30 years and is a board member of the German Society for Nuclear Medicine (DGN).
- University Hospital Erlangen, Department of Nuclear Medicine. The head of the department is Prof. Dr. med. Torsten Kuwert. The professor has been working in nuclear medicine institutes and university clinics for about 30 years, now he specializes in the treatment of prostate cancer and its metastases.
The cost of therapy depends on the level of the medical facility, the number of procedures, the need for hospitalization, and other factors. Information about treatment with therapeutic radionuclides is presented in the table below:
| Treatment for prostate cancer | Average cost of treatment |
|---|---|
| Treatment of Prostate Cancer with Metastasis by Lutetium-177-PSMA (LU-177) | Price by request |
| Treatment of Prostate Cancer with Metastasis by Actinium-225-PSMA | Price by request |
| Treatment of Prostate Cancer with Bone Metastases by Radium-223 | Price by request |
| Lutetium-177-DOTATATE (Lu-177-DOTATATE) therapy for neuroendocrine prostate cancer (NEPC) | Price by request |
From Colorado to Berlin: American Patient's Success with Lutetium-177 Treatment
Radionuclide treatment in the world's leading hospitals with Booking Health
PSMA therapy represents a significant advancement in precision medicine within the field of nuclear medicine and oncology, offering targeted treatment options for patients with advanced prostate cancer. While Lutetium-177 and Radium-223 have shown promise, Actinium-225 stands out due to its higher potency and ability to deliver more localized radiation to cancer cells, potentially improving treatment efficacy. The increasing use of these radioligand therapies has sparked interest from major pharma companies, despite the complex chemical processes and specialized facilities required for their production. As the clinical benefits of Actinium-225 become more apparent, industry forecasts suggest a growing market for this treatment, though its widespread adoption may be influenced by factors such as production capacity and price considerations.
Nuclear treatment planning, making the radioactive material, and providing high radiation shielding is a technically challenging process. That is why patients often cannot undergo prostate cancer treatment with Lutetium-177, Actinium-225, or Radium-223 in their home country and why they look for appropriate opportunities in foreign hospitals.
Booking Health is a medical tourism agent that has been organizing radionuclide treatment in leading Nuclear Medical Centers for prostate cancer patients from 75 countries, for over 12 years.
The Booking Health specialists will help you with the following important factors:
- selection of the most suitable center or department of nuclear medicine and departments of radiology, based on the annual qualification report;
- preliminary preparation of your diagnostic program and treatment for prostate cancer, without unnecessary repetition of previous studies;
- direct communication with your attending physician;
- provision of medical services at their real cost, without overpayments and extra charges for foreign patients (saving up to 50%);
- making an appointment with the doctor for diagnostics and treatment on your required date, allowing you to start treatment without being on a long waiting list;
- independent control of diagnostics and treatment at all stages;
- communication with the hospital after the completion of treatment;
- translation of your receipt, medical records, and recommendations for further treatment;
- control of the cost of medical services, return of any unspent funds;
- organization of additional diagnostic procedures and courses of therapy, if required;
- top-class service: airline tickets and transfers, organization of accommodation for the patient and the accompanying person;
- interpreting services and support from a personal medical coordinator 24/7.
Leave your request on the Booking Health website and a medical advisor or a patient case manager will contact you shortly. The company's employees will plan your further actions and will accompany you at all stages of your treatment.
Choose treatment abroad and you will for sure get the best results!
See the interview for more information:
RADIONUCLIDE TREATMENT OF PROSTATE CANCER IN GERMANY – interview with Prof. Dr. med. Stefan Dresel
Authors:
The article was edited by medical experts, board certified doctors Dr. Nadezhda Ivanisova and Dr. Vadim Zhiliuk. For the treatment of the conditions referred to in the article, you must consult a doctor; the information in the article is not intended for self-medication!
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Sources:
Translational Andrology and Urology
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