Prostate cancer is often aggressive and continues unnoticed expansion after the prostatectomy or complete prostate removal. When taking repeated PSA exams after the surgery, sometimes it is discovered that the cancer has managed to expand beyond the prostate in patient’s body into pelvic lymph nodes or metastases in pelvic bones. Physicians call it oligometastatic prostate cancer or prostate cancer with isolated proximal metastases (according to several sources, quantity measurements are <3 or <5) — most frequently they localize in pelvic lymph nodes or bone tissues.
A patient and a physician must decide together about the further treatment tactics. The available contemporary therapy methods vary — repeated surgery, conventional radiotherapy by radiating the entire pelvis, chemotherapy, including hormone therapy, which has many adverse side effects and to which a resistance develops with time, as well as the newest method which has proved itself in the world — radiosurgery with CyberKnife.
Before choosing the radiosurgery, one must take positron emission tomography exam that can precisely show very tiny nodi of cancer cells, besides they are often discovered in earlier stages when other diagnostic methods cannot spot them. PET/CT exam with preparation 68Ga-PSMA, which is specific to the prostate cancer, is recognized to be the most precise method for diagnosing the prostate cancer. PET/CT exam with 68Ga-PSMA is especially crucial for cancer patients having recurrence after previous conventional surgery or radiotherapy. PET/CT exam provides invaluable information both for a physician to elaborate a precise further treatment plan and the patient as it increases his chances to get well. PET/CT exam, which precisely spots the metastases, in combination with a precisely targeted radiosurgery by means of CyberKnife, is currently the most progressive method for treating isolated and proximal prostate cancer metastases.
Primary prostate cancer has been treated with CyberKnife in the Radiosurgery Centre of Sigulda Hospital since June 2016. Results are good. As of the beginning of this year we started applying radiosurgery for treating metastatic prostate cancers. Radiologist-therapist Dr Māris Mežeckis, who is the first to introduce the radiosurgery in Latvia as means of treatment of the prostate cancer, tells more about the procedure.
How can a radiosurgery help patients with metastases developed from the prostate cancer?
There are evidence available at the global level showing that radiosurgery is a safe, tolerable and efficient method in case of oligometastatic prostate cancer (prostate cancer with several isolated, proximal metastases) to treat metastases in lymph nodes and bones. Due to this method further spread of the cancer is slowed down both in terms of biochemistry and clinically, and it is proved that one can wait 2 more years before starting the hormone therapy.
What should a patient do if he had previously had surgical operations or conventional radiotherapy, yet his PSA has increased again and there is a suspicion of cancer metastases?
The new strategy for treatment of oligometastatic prostate cancer would be as follows: if there is biochemical recurrence after the radical prostatectomy and PSA starts increasing once again, it is important to detect the location of the recurrence. Therefore PET/CT is a must and preferably with Ga-PSMA isotope, which is specific to the prostate cancer, to determine the location of malignant cells. Afterwards, on the basis of the exam results, physicians decide on the method to apply in further treatment — be it radiosurgery, conventional surgery or combination of the two.
What is the operational principle of radiosurgery?
Radiosurgery is based on a precision beam therapy which aims at damaging DNA of a cancer cell that regulates all activities of the cell. When DNA is damaged, the cell lives for a while, but then it perishes and absorbs, sometimes remains as sclerotic tissue. It may happen not at once, the cells go on living some more time and they might even divide. In case of a metastatic prostate cancer it is worth doing the control 3 to 6 months after the radiosurgery sessions.
How is it possible that CyberKnife precisely radiates merely the cancer nodi without affecting the surrounding healthy tissues?
Special markers are used for this purpose and a robot uses them as clear reference points when directing the beams with utmost precision. A marker actually is a thin golden thread inserted in a lymph node, where a metastasis is present, through a needle during the ultrasound control. This procedure is carried out by an interventional radiologist. CT and MRI afterwards clearly show its location. By combining the images obtained from CT and MRI presenting marker’s location, we can obtain precise volume and contour of tumour’s metastases. The procedure is slightly uncomfortable for the patient. The needle delivering the golden thread is a little bit thicker than the regular injection needle. If we’d want to do anaesthesia, the needle delivering it is even thicker than the marker’s needle therefore we don’t really want that.
How many sessions are required when treating prostate cancer metastases?
If we are to speak about the number of sessions, potentially better effect is gained if higher doses are delivered in fewer sessions. But we have to take into account that the surrounding tissues sometimes restrict our tactics. If a nodus is located far from the crucial tissues, it is possible to deliver high-dose radiation in a single session; no therapy is needed afterwards and the patient is healed. If we speak of lymph nodes in the pelvis, intestines are located rather close and it is dangerous to deliver the entire dose in a single session, because it can cause burns, ulcers in the intestines. The therapy is usually divided into 3 fractions or sessions. Nevertheless, we consider each case individually.
What is current experience in treating prostate cancer metastases with radiosurgery in Latvia?
In the beginning of the year we had the first patient with recurring prostate cancer, but currently we have done the same procedure to one foreign patient and two other patients are in a preparatory phase.
- Please tell me more about the first patient.
The patient is 63 years old man, who was diagnosed with a prostate cancer in 2013 and he had surgical operation, prostatectomy, in the university hospital. Unfortunately, one year later PSA levels started increasing in the blood and the patient had to attend 30 sessions of conventional radiotherapy, during which so-called prostate lodge was radiated assuming that recurrence could be there, but I must say that it is a “blind luck”. Historically it was really an option, when there were no possibilities to take PET/CT exam and to locate cancer metastases precisely. I must admit that the routine still goes on. In case of our patient it was not the best solution, because he is very motivated person and was looking for alternatives. The patient was not initially informed about a possibility to have PET/CT, that is, he was not offered a chance to detect the location of the nodus. Therefore radiation of the lodge could have been in vain or perhaps it hit the cancer cells only partially.
When the analyses again showed increased PSA levels, the patient approached us in the Radiosurgery Centre in Sigulda Hospital, as he was looking for alternative treatment methods. In cooperation with the Nuclear Medicine Centre we got the patient examined with positron emission tomography and CT scan. PET/CT revealed that the patient had three metastases in lymph nodes — one between aorta and the spinal cord, the second lied where aorta diverges into two pelvic arteries and the third one was located in front of the bladder. In case of this particular patient we planned that two pelvic metastases in lymph nodes would be removed in a surgical operation and we’d radiate only one metastasis near the spinal cord, because the tumor nodus stands together with a vertebra and it is anatomically easier for CyberKnife to track the metastasis, taking the vertebra as a reference point as it accurately targets the nodus. Such combination of methods would be cheaper for the patient but surgeons refused to operate, because they thought they would not be able to precisely find the metastases in the pelvic lymph nodes and the blood vessels could be dangerously damaged. We decided to place markers and to target all three metastases with CyberKnife.
In case of this particular patient there was another challenge — the patient has a hip prosthesis which made us adjust the technology. Beams by which we control the patient’s position go under 45 degree angle and the nodus turned out to be placed in a location where the hip prosthesis is a barrier to the beams if the patient lies on his back. Therefore the planning and entire therapy was tailored to this patient.
When and how you are going to evaluate whether the radiosurgery was successful?
Control examinations for patients who had recurrence or metastases are waiting ahead, and it is too early to judge the efficiency. In case of ogliometastases, basing on the clinical studies, our tactics is as follows: PSA analyses 3 months later, where we look for changes, another PET/CT 6 months later to make sure whether the radiated nodi are inactive and no new nodus has appeared.
We will evaluate the results of this particular patient after 3 months. The first and the simplest indicator is PSA level in a blood test. If it drops and reaches even 0, the therapy is efficient. If PSA remains even slightly increased, PET/CT exam can be repeated after 6 months to see whether the tumor is still active at the same location and that would mean that the cancer cells have not reacted completely, and to also see whether any new nodus has developed.
The very method of the therapy is actually local, because CyberKnife precisely radiates only those nodi which we see at that moment — both in the prostate and at locations where they’ve spread. It does not rule out a possibility that cancer cells circulate in blood and theoretically can fix in a new location. The advantage of this radiosurgery procedure is that it can be repeated. Of course, there is one shortcoming, namely, the high costs of the procedure.
In case of a repeated radiosurgery, it is more dangerous if a new nodus develops near previous ones, because it means we cannot deliver such a high dose of radiation. It is a nuance to be considered, but the therapy itself can be repeated, if necessary.
Could this particular patient have been treated with the radiosurgery in the very beginning when the cancer was located in the prostate and had no metastases?
Speaking of this particular patient, we cannot be sure that we would be able to spare recurrence if he had been treated with CyberKnife instead of the surgery. We immediately recommend PET/CT exam to those patients to whom we assign radiosurgery procedure for treatment of primarily found prostate cancer. Then we can tell that there are no cancer cells in the surrounding lymph nodes. But also in this situation PET/CT exam does not give 100% guarantee, nevertheless, it necessarily reduces the risk to very considerable degree. However, there can be a patient who has received the best therapy and still has 1-2% likelihood of development of metastases. It is a problem.
What other methods are used to treat the prostate cancer and what are the advantages of the radiosurgery in comparison to other methods?
The major problem is lack of many alternatives. All other methods that can be applied when metastases are found in a patient are systemic or locally affect much larger area inside the body, such as the entire pelvis in case of the conventional radiotherapy. Both the affected tissues and the surrounding tissues are radiated in the conventional radiotherapy. It is not possible to precisely target only the cancer tissues.
Speaking of hormone therapy, it is a golden standard, a standard therapy offered in medical consiliums in cases when the tumor has spread. As we know, hormone therapy is effective for 3-4 years, but then its efficiency reduces as hormone-refractory state develops and tumor cells become more insensitive to the hormones. Then the only option left is chemotherapy.
By including radiosurgery in tactics to treat metastases, we try to push the hormone therapy as far as possible. Due to the radiosurgery method the further expansion of the cancer is slowed down both in terms of biochemistry and clinically, and world experience shows that one can wait 2 more years before starting the hormone therapy.
Global evidence is collected in series of cases of patients treated in one clinic. For majority of patients it was efficient and makes it possible to stay away from chemotherapy or hormone therapy, which adversely affects the patient’s well-being, for a long time.
How would you describe the cooperation with urologists? Is radiosurgery with CyberKnife recommended as an alternative in case of the metastatic prostate cancer?
We usually treat patients who come to us because other methods did not heal them completely. That is the situation. Urologists are basically surgeons and they have surgical interest, therefore they also might be sceptical in recommending the new methods. It will take some more years before we have enough multicentre studies and radiosurgery is included in the guidelines for the local sceptics to listen. But so far the results are very good. For instance, radiosurgery as a method for treating primary tumours has a rather long history, approximately 10 years already, and there are multicentre studies available in this regard. Last year USA published a multicentre study proving 98% efficiency of CyberKnife depending on tumour malignancy. Also the recurrence therapy shows good results and studies continue.
Generally I can say that PET/CT exam, which precisely spots metastases, in combination with a precisely targeted radiosurgery by means of CyberKnife, currently offers the most progressive method for treating isolated and proximal prostate cancer metastases.
Early detection of ogliometastases and precise examinations makes it possible to start proactive therapy and stop local spread of disease, to postpone hormone therapy and, possibly, to fully recover from the cancer, if micrometastases have not managed to develop and CyberKnife has managed to destroy the isolated metastases.