Theranostics is an approach based on vectorized internal radiotherapy that consists of using a single pharmaceutical agent, possessing both diagnostic and therapeutic properties, by simply substituting the attached isotope. The diagnostic imaging thereby obtained makes it possible to check whether the therapeutic target is present before administering the treatment to the patient. This method is one of the targeted therapies in oncology and is in keeping with a personalised approach to medicine. In the case of prostate cancer the approved isotope treatments used include Radium-223 and Lutetium-177-PSMA. When injected intravenously these agents target the specific strictures of cancer cells to deliver local radiation while minimising the effects on healthy tissue.
Theranostics is intended principally for men with metastatic prostate cancer for whom initial hormone therapy has failed and who have received at least one line of chemotherapy, except in the case of ineligibility or refusal.
Theranostic treatment requires a precise organisation consisting of four principal stages :
Pre-evaluation
Before starting treatment a detailed assessment of the patient is needed to determine eligibility. This stage includes advanced imaging examinations , notably a PSMA PET scan, to confirm the expression of specific tumour targets. A blood test is also carried out to assess the condition of the bone marrow as well as the kidney and liver functions. These parameters serve to establish whether or not the patient is a good candidate, to anticipate possible side effects of the treatment and to optimise its effectiveness. A consultation with a nuclear doctor will then be scheduled to discuss the results, the treatment and the instructions to be respected.
>> To find out more about a PSMA PET scan
Procedure for administration
Radium-223 is administered in the form of an intravenous injection, generally in six cycles at four-week intervals.
Lutetium-177-PSMA is administered by intravenous perfusion in 4 to 6 cycles every 6 to 8 weeks.
Hospitalisation
This treatment usually requires a short period of hospitalisation. For Radium 223 the treatment is on an out-patient basis and the procedure lasts 1 to 2 hours. Lutetium-177-PSMA, which is eliminated by the urine during the first 12 hours, is administered in a metabolic chamber and an overnight hospitalisation is necessary.
Follow-up
Strict monitoring is essential after each cycle. This includes regular PSA tests to monitor the tumour response as well as imaging examinations to assess the development of metastases. Although side effects are less frequent than in the case of chemotherapy, they are closely monitored with possible adjustments for subsequent cycles if the patient’s condition requires it. This follow-up stage is essential to ensure maximum effectiveness of the treatment while minimising risks.
Theranostics presents a number of advantages :
- Targeted effectiveness : Irradiation of the tumour cells while preserving healthy tissue. Reduction in tumour marker levels and in the number and size of metastatic lesions.
- Improvement of symptoms: Reduction of cancer-related symptoms, especially bone pain.
- Quality of life: Fewer side effects than chemotherapy.
Theranostics is generally well tolerated but like any medical treatment it can have side effects.
For Radium-223, the most frequently reported complications are of a haematological nature (anaemia and thrombocytopenia.) These effects are linked to the impact of the radiotherapy on the bone marrow, although this toxicity is usually moderate.
As to Lutetium-177-PSMA, this can cause temporary tiredness and a dry mouth, the result of the salivary glands being exposed to the radiopharmaceutical. Although rare, cases of kidney toxicity have been observed, especially in patients with an impaired kidney function prior to treatment.
Other side effects include temporary pain at the site of bone metastases, often interpreted as a sign of responding to treatment. This pain, known as “bone flares”, can usually be relieved with standard analgesics.
In the long term, the risk of serious complications is low but attentive surveillance is essential for early detection of any side effect. Regular monitoring with PSA tests and imaging examinations serve both to assess treatment effectiveness and patient safety.
The radiopharmaceutical treatment revolution
Theranostics, especially with Lutetium-177-PSMA, has revolutionised the treatment of advanced prostate cancer. Recent clinical trials, notably the VISION and TheraP trials, have made it possible to validate its effectiveness in treating metastatic castration-resistant prostate cancer (mCRPC). Treating these patients is particularly complex due to the rapid progression of the disease despite hormone therapy and frequent resistance to standard therapies such as chemotherapy.
The Willy Grégoir Prostate Cancer Clinic and the Jules Bordet Institute Department of Nuclear Medicine are proud to have participated in the VISION trial as investigator, testimony to our commitment to these innovative treatment solutions.
VISION, a phase 3 clinical trial, showed a significant improvement in global survival (15.3 months compared to 11.3 months) and in radiographic progression- free survival (8.7 months compared to 3.4 months) among patients receiving Lutetium-177-PSMA combined with the best standard treatment compared to the standard treatment alone. These results highlight the capacity of the radioligand in offering an effective treatment option for patients who have exhausted other lines of treatment.
TheraP, a phase 3 trial, compared Lutetium-177-PSMA to cabazitaxel (chemotherapy) and showed a better reduction of PSA, of 50% or more, among 66% of patients in the Lutétium-177-PSMA group compared to 37% in the chemotherapy group. Although global survival has not shown any significant difference, Lutétium-177-PSMA has been favoured for its PSA response levels and less severe side effects than those associated with cabazitaxel.
Current research is looking at the possible use of this treatment at earlier stages of the disease. For example, the Splash trial is evaluating the effectiveness of Lutetium-177-PSMA before chemotherapy among patients with mCRPC, while the LuTectomy trial is looking at its use as a neoadjuvant before a radical prostatectomy. At the same time, new more powerful isotopes, such as Actinium-225-PSMA or Lead-212-PSMA, are being developed. The preliminary results of these trials show a promising potential for a wider and earlier application of this revolutionary technology.
The Jules Bordet Institute was the first centre in Belgium to use this type of targeted treatment and has become a centre of excellence of global renown. A number of research trials on new theranostic approaches are currently being conducted at the Department of Nuclear Medicine and you could be invited to participate as part of your treatment at the Willy Grégoir Prostate Cancer Centre.