The Effectiveness of Therapeutic Radionuclides (Lutetium-177) for Prostate Cancer Treatment in Germany
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One of the reports from the final meeting of the reputable Society of Nuclear Medicine and Molecular Imaging (SNMMI) [1] in 2019, was completely devoted to the use of Lutetium-177 PSMA targeted therapy for prostate cancer.
For the last 10 years the number of clinical trials addressing the effectiveness and safety of this technique has increased 6-fold – from 17 trials in 2010 to more than 110 in 2019.
Nowadays, Peptide Receptor Radionuclide Therapy (PRRT) is a part of the protocol for the high-tech treatment of advanced prostate cancer and it is utilized at leading medical facilities all over the world.
According to statistics obtained during the international VISION and LuPSMA trials, the use of Lutetium-177 leads to a significant improvement in the results of laboratory tests and PET-CT (more than 57% of patients) and also improves quality (more than 70% of patients) and expectancy of life (more than 45% of patients).
At the moment, the only country where PSMA therapy with Lutetium-177 is certified and used with the highest efficiency, is Germany. Scientists from the German Cancer Research Center and the University Hospital Heidelberg, were the first to create a carrier molecule PSMA-617. This is based on the same properties of which radioisotope therapy with Lutetium-177 is. Thanks to this carrier molecule, Germany has accumulated a unique evidence base and also practical experience regarding the application of this technique.
More than 500 courses of radionuclide treatment for metastatic prostate cancer are carried out in the country annually. In Israel, Turkey and other countries, PSMA therapy with Lutetium-177 is a novel therapeutic option. No more than 100 patients receive such treatment annually. In addition, there is a lack of qualified doctors and the necessary technical bases in these countries. Due to this, the quality of the procedure and its effectiveness are limited.
Content
- Indications for Lutetium-177 PSMA Therapy
- Comparison of the Effectiveness of Lutetium-177 PSMA Therapy and Other Treatment Methods (VISION trial)
- The Use of Lutetium-177 in Resistance to Hormones and Chemotherapy (LuPSMA trial)
- Specificities of Lutetium-177 PSMA Therapy
- Follow-up Monitoring Upon Lutetium-177 PSMA Therapy Completion
- Planning of Lutetium-177 PSMA Therapy Abroad with the Booking Health Company
Indications for Lutetium-177 PSMA Therapy
According to the modern protocols for prostate cancer treatment, Lutetium-177 PSMA therapy is used as a second-line therapy, undergone when the surgical and medical options have already been exhausted. This is due to the unique application of this technique. Radioactive Lutetium is delivered to the tumour cells by a special PSMA-617 molecule carrier, developed by the specialists from the University Hospital Heidelberg and the German Cancer Research Center. Many oncologists prescribe Lutetium therapy in the following clinical cases:
- Metastatic prostate cancer, including bone and lymph node lesions
- Prostate cancer recurrence, after surgical treatment and/or chemotherapy
- Tumour resistance to chemotherapy drugs when applying several treatment regimens
- Tumour resistance to hormone therapy (castrate-resistant cancer)
- The presence of absolute contraindications for surgery or pharmacotherapy (the general health condition of a man does not allow him to undergo surgery or take aggressive pharmacological drugs)
One of the important conditions for achieving high treatment efficacy is a good expression of PSMA receptors by tumour cells. The high density of PSMA receptors on the surface of cells of the primary tumour and metastases is a guarantee that they will accumulate radioactive Lutetium during the procedure and subsequently receive a high dose of radiation. Unfortunately, in the case of the development of certain mutations, cancer cells lose their membrane receptor for PSMA. In such cases, peptide receptor radionuclide therapy cannot be carried out.
To assess the expression of the necessary receptors, the patient undergoes PSMA PET/CT with radioactive isotope prior to his treatment. The radionuclide firmly binds to atypical cells, thereby making them visible on the tomogram. PSMA PET/CT can be used for the clarifying and differential diagnostics of prostate cancer, the detection of distant metastases and the selection of treatment tactics. In addition, a radioactive isotope disintegrates very quickly, so the patient can leave the hospital shortly after the procedure is finished, without any mandatory isolation in a specialised department.
Comparison of the Effectiveness of Lutetium-177 PSMA Therapy and Other Treatment Methods (VISION trial)
Lutetium-177 is selected as the main radionuclide for targeted therapy of prostate cancer because of its properties, such as its high affinity and firm binding to PSMA, prolonged accumulation in the tumour and metastases and high rate of excretion through the kidneys (high renal clearance). In the near future, the 3rd phase of the extensive, international clinical trial VISION [2], will be completed. This is a prospective, multicentre, randomised trial of the use of Lutetium-177 PSMA in the treatment of patients with metastatic castration-resistant prostate cancer. The researchers set themselves the goal of comparing the duration and life quality of men with prostate cancer during the treatment of Lutetium-177 PSMA, with men receiving standard treatment (including surgery, radiation therapy, chemotherapy and the use of hormonal drugs).
To participate in the VISION trial, the patients must meet the following requirements:
- Aged over 18 years
- Histological or cytological verification of diagnosis
- Laboratory (high PSA level) or image (ultrasound, tomography, skeletal scintigraphy) confirmation of cancer progression, the presence of at least 1 metastatic focus
- High density of PSMA receptors, according to the results of PSMA PET/CT
- Assessment according to ECOG scale from 0 to 2 (the scale comprehensively assesses the general condition of the cancer patient)
- Life expectancy of more than 6 months
Each patient underwent from 1 to 6 treatment procedures using Lutetium-177 PSMA, with a 6-week interval between treatment courses. The average total dose of Lutetium-177 was 7.4 GBq (200 mCi). Upon completion of the treatment cours, the researchers compared patients from the group which received Lutetium-177 therapy, with patients from the standard treatment group. The comparison was carried out according to the following criteria:
- Biochemical response to treatment (PSA, alkaline phosphatase, lactate dehydrogenase levels)
- Radiological response to treatment (scintigraphy, radiography, CT scan)
- Life quality
- Life expectancy without the disease progression
- Safety and tolerability of treatment
- Cost-effective treatment
The trial involves more than 750 patients from 9 countries (USA, Canada, Sweden, Germany, Israel, Belgium and others). According to the design of the trial [3], its final results will be published in May 2021. Nevertheless, the immediate results demonstrate that Lutetium-177 PSMA therapy leads to a significant improvement in biochemical and radiological parameters and improves the quality and general life expectancy of patients with metastatic prostate cancer. Radionuclide therapy is also more cost-effective as it reduces the total cost of treatment and the duration of hospital stays.
According to the results of modern clinical trials, new therapeutic radionuclides are being used to treat advanced prostate cancer. This separate article is devoted to the comparison of the effectiveness of various radionuclides for the treatment of advanced prostate cancer.
Case report
Patient Igor Buravkin, 51 years old, Russia. A prostate tumor was diagnosed during an examination for pain in the pelvic bones and spine. At the time of diagnosis, the man had more than 10 bone metastases and they had caused a pathological spinal compression fracture in the lumbar spine. The patient was recommended the targeted radionuclide therapy with Lutetium-177. As the technical base of the hospitals in his country was poor, the patient turned to foreign hospitals. He considered Charite University Hospital Berlin and University Hospital Carl Gustav Carus Dresden. Booking Health specialists carefully reviewed the clinical case and recommended the better option – Helios Hospital Berlin-Buch. The man underwent the full course of Lutetium-177 PSMA therapy. According to the results of follow-up PSMA PET/CT, the growth of metastatic lesions stopped. Igor is currently being prepared for a minimally invasive intervention on the spine for the restoration of vertebral bodies.
The Use of Lutetium-177 in Resistance to Hormones and Chemotherapy (LuPSMA trial)
Another clinical trial called LuPSMA [4] studied the effectiveness of Lutetium-177 PSMA therapy. It was carried out in patients who did not have positive results after the use of anti-hormonal agents and chemotherapy. The LuPSMA intervention trial lasted 3 years and was carried out in accordance with the requirements of ANZCTR (Australian New Zealand Clinical Trials Registry). It was carried out in patients who met the following requirements:
- Aged over 18 years
- Life expectancy of more than 12 weeks
- Histologically confirmed prostate adenocarcinoma by biopsy or examination of material which was removed during surgical intervention
- Ineffectiveness of treatment by means of chemotherapy drugs from the taxane group and hormonal anticancer drugs
- Significant progression of the disease over the past 12 months according to the results of the PET-CT (occurrence of 2 or more new metastatic foci in the bones) or the progression of pain syndrome
- ECOG (Eastern Cooperative Oncology Group) scale score of less than 2 points
During the LuPSMA trial, all of the men underwent 4 Lutetium-177 therapy procedures. To better assess the response to treatment, the procedures were carried out within a 6-week period. The total radiation dose was determined depending on the weight of the patient, the activity of the tumour process and renal function; on average, it was 4-8 GBq. After each administration of the drug, the patients underwent quantitative SPECT / CT, according to the results, the specialists determined the degree of irradiation of the tumour and healthy tissues. Laboratory tests were also carried out – the PSA levels were assessed in dynamics and kidney and liver functions were monitored. In order to monitor changes in the condition of each patient carefully, the researchers carried out about 14 follow-up visits over 18 months of monitoring.
After a comprehensive analysis of the information obtained, the Australian Nuclear Science and Technology Organisation (ANSTO) provided the results of the trial at the meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI). Within the first 12 weeks of monitoring, the PSA levels decreased by more than 50% in half of the patients, while in 27% of men, the PSA levels decreased to 80% or more. According to the results of PET-CT and scintigraphy, the radiological improvement of more than 50% occurred in 57% of patients, and in 43% of them, this indicator reached 80% or more. The size of metastases in the bones and soft tissues decreased, the pain syndrome became less severe.
Currently, at least 8 clinical trials of Lutetium-177 PSMA therapy are being carried out at major clinics in Italy, Germany, Australia, the Netherlands and the USA. They are in the first (testing of methodology on healthy volunteers) and second phases (testing of methodology on patients with prostate cancer), therefore they are open to the inclusion of new patients. Thanks to this, men with prostate cancer can be treated in specialized centres in world-leading countries, without extra fees and at the expense of the trial organizers. To be a part of these trials, you need to contact a clinic which carries out the trial and undergo an examination there to check for compliance with the criteria. It is also important to prepare a package of documents and translate them into the official language of the country. The patients can do this on their own or with the help of a specialist in medical tourism.
Case report
Patient Oliver Davis, 47 years old, USA. Prostate cancer was diagnosed when the primary tumor had already metastasized at the spine, regional and distant lymph nodes. The patient was regularly treated according to the recommended scheme, however, follow-up scintigraphy and CT showed the growth of metastatic lesions and an increase in their number. Despite the young age of the man, life expectancy decreased to 6-8 months. This served as an indication for high-tech treatment – Lutetium-177 PSMA therapy. Unfortunately, the number of patients on the "waiting list" allowed him to undergo the first procedure no earlier than in 1.5 months. To speed up this process, the patient signed up for treatment at a foreign medical facility – University Hospital Frankfurt-am-Main, in Germany. The treatment began 12 days later. According to the results of the follow-up PSMA PET/CT, small metastases in the bones disappeared after the first procedure, while large ones significantly decreased in size. Currently, the life expectancy of the man is more than 18 months.
Specificities of Lutetium-177 PSMA Therapy
In the case of prostate cancer, advances in treatment options have led to improved survival rates and, consequently, increased life expectancy for many cancer patients. Lutetium-177 PSMA therapy is not complex – the standard intravenous infusion of the drug, as a rule, is not accompanied by any serious undesirable symptoms. The infusion takes no more than 30-60 seconds, after which the drug is actively distributed throughout the circulatory system and accumulates precisely in the tumour cells.
The technical complexity of peptide receptor radionuclide therapy requires the individual manufacturing of the drug for each patient and the compliance with radiation protection protocols. Prior to the treatment, imaging dosimetry (quantitative SPECT/CT) is carried out for the assessment of the accumulation of the radiopharmaceutical drugs in the tumour, metastases, kidneys, salivary and lacrimal glands. According to the SPECT/CT results, the doctor determines the necessary therapeutic dose of Lutetium-177.
According to the radiation protection protocol, the patient stays in a special room for up to 48 hours from the moment of the intravenous drug injection. Considering the rapid excretion of the drug by the kidneys during the first 2-4 hours, medical staff regularly assess the level of radiation in the room and note the dynamics of its decline. The patient can take personal items with him, including clothes, a mobile phone or tablet, books and a notebook. After discharge from the hospital, the patient takes his belongings with him, since they do not require special cleaning and are not a source of radiation.
Follow-up Monitoring Upon Lutetium-177 PSMA Therapy Completion
The first follow-up examination is carried out before the patient is discharged from the hospital. This includes a general examination, assessment of kidney and liver function according to the biochemical blood test, as well as a diagnostic CT scan. Tomography allows the doctor to assess the distribution of the radionuclide in the body and the activity of its accumulation in the target areas – bone metastases, metastases in soft tissues and lymph nodes and the primary tumour. Additionally, radiologists determine the absorbed dose of radiation. This helps to assess the response to treatment and to plan further therapy. In a case with good overall health and satisfactory examination results, the patient is discharged from the hospital for further outpatient monitoring.
Upon discharge, men are monitored by an oncologist and/or urologist:
- PSA blood test. Normally, the PSA levels decrease by more than 90% from the initial levels and remain stable and low. A PSA blood test is an easy-to-use and informative test, which confirms persistent remission of the disease.
- PSMA PET/CT is performed for initial assessment of the treatment effectiveness and subsequently, in suspicion of recurrence. Images, which were obtained using PSMA PET/CT, show the size of the foci in the prostate, bones and lymph nodes. With their help, the doctor can assess the dynamics of regression or tumour growth, as well as its activity.
The results of long-term monitoring show a decrease in PSA levels in more than 50% of men. Moreover, the average duration of the remission after Lutetium-177 PSMA therapy is more than 13 months and more than 78% of patients overcame the 2-year survival threshold. The achievement of such Lutetium-177 success rate in men with metastatic cancer is significant progress in the treatment of the advanced stages of this pathology.
Case report
Patient Martin Ulsson, 52 years old, Sweden. A prostate tumor with a size of 1.5 cm was detected during a preventive examination. At the time of diagnosis, the patient had no severe complaints about well-being, but the doctors detected a metastatic lesion of the sentinel lymph nodes. Taking into account the small size of the primary tumor, a da Vinci radical prostatectomy was performed. Despite the active postoperative treatment, the disease continued to progress – the foci of bone lesions were detected and a severe pain syndrome occurred. The necessity of Lutetium-177 PSMA therapy was accepted by the tumor board, with the participation of a clinical oncologist, radiologist, urologist and general practitioner. After the first procedure, the PSA levels decreased by 60%. After a repeated procedure, the patient used painkillers up to 3 times a week, instead of their intake 2-3 times a day prior to the course of radionuclide therapy.
Planning of Lutetium-177 PSMA Therapy Abroad with the Booking Health Company
Peptide receptor radionuclide therapy is carried out at specialized medical facilities which comply with strict radiation protection protocols and have access to the production of drugs for treatment using Lutetium-177 PSMA. In addition to the selection of a clinic, it is important for the patients to find a competent doctor who will select the necessary dosage of the drug and the duration of the therapy course and will also carry out regular follow-up examinations.
In the absence of experience in treatment abroad, it is more convenient for the patients and their families to utilize the help of the Booking Health company. Booking Health is a medical tourism operator which has been organizing the treatment of men with prostate cancer abroad for more than 10 years. The specialists at Booking Health will provide the following benefits for the patient and his family:
- Selection of the right clinic based on the annual qualification grading
- Establishment of communication directly with your doctor or team of specialists (oncologist, radiologist, urologist)
- Preliminary treatment or diagnostic program, which will not repeat previous examinations
- Сlinic services at a favourable price, without overpricing and additional coefficients for foreign patients (saving up to 50%)
- Booking the appointment or procedure on a desired date
- Monitoring of the medical program at all its stages
- Insurance against an increase in the cost of treatment in the case of any potential complications (coverage of 200,000 euro, the insurance will be valid for 4 years)
- Buying and, if necessary, forwarding medicines to the home country
- Сommunication with the clinic upon treatment completion
- Control of invoices from the clinic
- Organization of additional examinations or remote consultations with the doctor, following results of the follow-up examination in the home country
- Booking a hotel, airline tickets and transfer organization
Choose treatment abroad and you will be sure to 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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