Today, a large number of methods have been developed to diagnose and treat prostate cancer in its early stages, and the success rate of treatment is increasing every year. However, in case of metastatic cancer, when the formation has gone beyond the prostate gland and spread to other organs and tissues, effective treatment at the first stages of the pathological process, more often than not, becomes ineffective, and minimally invasive interventions is no longer possible. The treatment in such a case is radiation therapy, but it acts not only on cancer cells, but also on the cells of surrounding healthy organs, which is accompanied by a large number of side effects, and this further undermines the body. Then, a new experimental method of treatment of prostate cancer with metastases («neglected» cancer) — PSMA-radiotherapy — can be a lifesaver
Radioligand therapy (RLT) with PSMA labeled with Lutetium-177 (Lu-177) is being performed at the Nuclear Medicine Clinic of the Ludwig-Maximilians-Universität München. This experimental treatment is intended for patients with metastatic prostate cancer who have disease progression despite hormonal or chemotherapy. Unlike Xofigo (Ra-223), patients with metastases outside the skeletal system, such as metastases to soft tissue or lymph nodes, can also be treated.
How does the treatment process work?
Many people have heard of a protein found in prostate cells, prostate-specific membrane antigen or PSMA. This substance is released during the development of prostate cancer and is used in the diagnosis of cancer recurrence or growth. Scientists have developed a special drug that binds to PSMA and increases in gland cells and metastases. After administration of the drug, positron emission tomography is performed, which allows you to see the places where the drug accumulates. Such a drug is Lutetium-177. This is a radionucleide, which after irradiation, begins to destroy metastases, while healthy organs and tissues remain untouched. Most importantly, there were no serious side effects after the treatment and the quality of life was at a fairly high level. The treatment is effective in approximately 40-60 percent of patients with metastatic prostate cancer.
Nuances of treatment
Prostate cancer cells usually carry prostate-specific membrane antigen (PSMA) on the cell surface. This membrane protein acts as a magnet for certain peptides, so-called ligands ( hence the name radioligand therapy) of PSMA (PSMA-DKFZ-617), which are radioactively labeled with a therapeutically effective beta emitter (Lu-177) (Lu-177-PSMA-DKFZ-617). The fact that the beta emitter Lutetium177 has a maximum energy of 0.5 MeV and penetrates tissues to a depth of no more than 2 mm makes it an ideal candidate for this purpose. Thus, even small foci can be irradiated with high precision without too much impact on the surrounding tissue.
Since the protein molecule specifically binds to the PSMA of tumor cells, the therapeutic agent accumulates after injection into the tumor. It then migrates through the bloodstream directly into the tumor tissue and results in targeted irradiation of the malignant cells. The radioactive radiation in human tissue, meanwhile, has a radius of action of only a few millimeters. Thus, a higher and more effective radiation dose can be directed directly against the cancer cells compared to radiation therapy.
Various clinical studies have shown that tumors can be slowed or significantly reduced in their growth with RLH. The therapy can reduce pain, lower PSA levels and significantly improve quality of life.
Conducting the procedure
The therapy is applicable to patients with tumors with sufficient PSMA expression on the cell surface that no longer respond to other treatments (hormone therapy, external beam radiation therapy or chemotherapy). Prior to Lu-177-PSMA-DKFZ-617 therapy, PSMA levels and the indication for ligand-assisted therapy must first be verified. This is the standard at the University Hospital Munich. In addition, the patient must have normal renal and bone marrow function. Additional preliminary examinations (e.g. renal scintigraphy, laboratory tests, etc.) are usually necessary. All tests and procedures can be performed at the Nuclear Medicine Clinic at the University of Munich.
The therapy is performed in the ward and lasts about 15 minutes (radioactive drug infusion). To reduce kidney damage, fluid infusions are administered through a vein immediately before, during and on the days following therapy. In addition, it is recommended to ensure adequate fluid intake on the day of therapy and on the following days, as this can reduce exposure of the kidneys and the whole body.
In the days following therapy, whole body scintigraphy is performed and blood samples are taken to monitor the level of remaining drug and its excretion from the body. After treatment, the ward should not be left for 48 hours. The patient can leave the hospital after 3 days of observation. After discharge from the hospital, laboratory monitoring of blood, liver and kidney parameters is done after about 2 and 6 weeks. This can be done at other clinics close to home.
Typically, at least three courses of treatment are given at 8-week intervals. In addition, follow-up visits at intervals (e.g. PET/CT, renal scintigraphy) will be used to assess treatment response, side effects and complications. If the response is good or the disease is stabilized, additional cycles of therapy can often be given as far as the blood picture and renal function allow.
The results show that no serious complications should be feared. However, despite all efforts, the therapy may lead to side effects and complications. Since the treatment is experimental, previously unknown risks, side effects and complications cannot be ruled out.
The following side effects and complications are currently known to occur:
— Fever after therapy
— Theoretically, allergic reactions can occur when a substance is administered, including anaphylactic shock
(however, this has never been observed before)
— Nausea, vomiting and loss of appetite.
— Occasional minor hair loss in the weeks following therapy
— In rare cases, changes in flavor
— Fatigue and exhaustion (may last up to several weeks after therapy)
The number of red blood cells, platelets and white blood cells may decrease after therapy. Thus, blood counts should be monitored 2 and 6 weeks after therapy. In isolated cases after repeated therapy there may be prolonged, in rare cases life-threatening restriction of bone marrow function with the need for blood transfusion.
Repeated therapy may reduce renal function, so it is checked before each course. In some cases, repeated therapy may lead to permanent loss of renal function with the need for dialysis.
In addition, repeated therapy can reduce saliva production and dry mouth. This can lead to an increased incidence of tooth decay. Changes in taste may also occur as a result of treatment.
In principle, radiation is associated with a risk of secondary malignancies, but these, if they occur, are delayed by several years to decades.
Since there is no long-term experience, there may be side effects that are not yet known.
Several liters of fluid should be drunk on the day of therapy to minimize the burden on the kidneys and exposure of other parts of the body (accelerated excretion).
About thirty minutes before and 4 hours after therapy, the salivary glands should be cooled with special packs to reduce blood flow. This is thought to reduce the accumulation of radioactivity in the salivary glands.
Many studies show examples of tumors decreasing in size several times in patients after 4 cycles of therapy.
Radioligand therapy is given for about 3 years.
Radioligand therapy is a breakthrough in the treatment of metastatic prostate cancer. It offers a high chance of prolonging the life of a patient for whom other treatment methods have become ineffective.
For questions about advanced prostate cancer treatment with SPMA therapy from leading German radiologists in Munich, please contact the head of the center «Clinic’s in Germany»