Standard treatments for prostate cancer include surgical removal of the prostate gland, technically known as radical prostatectomy (RP) (from the ancient Greek -ectomy for cutting out), and radiation therapy. Both forms of therapy aim to destroy prostate tissue. This approach is based on the outdated assumption that when the prostate is removed, the cancer is also completely removed from the body and the patient is thus cured. That this assumption is not correct is shown by the so-called “liquid biopsy”. This procedure can be used to detect cancer cells in the blood of any cancer patient. So they are always distributed throughout the body. Consequently, cancer cells remain in the patient’s body even after the prostate has been removed or the prostate tissue destroyed. This also explains the relatively high recurrence rates (the cancer coming back) after surgery and/or radiation therapy (see Han Tables, Johns Hopkins University, Department of Urology: More .)
For this reason, focal therapy is increasingly coming into focus. Here, only the tumor itself is destroyed. The healthy areas of the prostate, and thus the functions of the urogenital tract (which are essential for erectile function and potency), are preserved.
The principle of focal therapy can be summed up in one question, “Why remove the entire prostate if the cancer is only in one part?” In the treatment of breast cancer, this development has already led to a treatment approach in which only the cancerous tissue and a small area around the cancerous tissue are removed, instead of removing the entire breast.
In this way, side effects and complications can also be significantly reduced in the treatment of prostate cancer. The primary goal here is to prevent incontinence and impotence from occurring. Focal treatments are less invasive than prostate removal and are therefore associated with fewer risks and side effects. Complications such as bleeding, infection, and injury to other organs, as well as death, occur less frequently. At the same time, the treatment is less painful, patients recover faster, require less follow-up care and rehabilitation time.
More precise diagnostics and improved MRI technology have made the new treatment methods of focal therapy possible. The idea behind this is to remove only the cancerous tissue if possible and to preserve as much healthy prostate tissue as possible. The success of the treatment depends on accurate diagnostics and precise implementation of the treatment. The healing time is much shorter than for prostatectomy (see 2. IRE). In addition, important functions such as continence and potency can be better preserved with focal therapy.1
The classic methods of treatment include surgical removal of the prostate. In this procedure, the prostate gland, including all the tissue affected by the cancer, is removed. Radiation therapy also follows this philosophy and treats the entire prostate. Hormone therapy and chemotherapy, on the other hand, affect the entire body and are most often used for metastatic prostate cancer.
The rationale behind radical prostatectomy is as follows: If the prostate is removed, all tumor tissue disappears and the cancer is “cured”. Unfortunately, human biology doesn’t work that simply. In any cancer, malignant cells are distributed throughout the body via the blood. Thus, the disease also spreads outside the so-called “prostate capsule”.
Active Surveillance: Wait and Watch
Active Surveillance is offered to patients who are elderly and have been diagnosed with low-grade carcinoma. Because tumors in the prostate grow very slowly, it often takes decades before the cancer breaks through the prostate capsule or begins to metastasize. It is therefore often the most sensible treatment to simply continue to monitor the tumor.
Whether patients are eligible for Active Surveillance depends on personal and medical factors. These include a patient’s age, general health, PSA levels at the time of diagnosis, PSA doubling time, Gleason Score, and tumor stage – and, of course, the patient’s own wishes. All these points must be considered and discussed with the attending physician.
1. Guillaumier, Stephanie, et al. “A multicentre study of 5-year outcomes following focal therapy in treating clinically significant nonmetastatic prostate cancer.“European Urology74.4 (2018): 422-429.
IRE (Irreversible Electroporation) is a new technique for tissue ablation. It differs from other procedures such as HIFU (high-intensity focused ultrasound), RFA (radiofrequency ablation), laser treatments and cryoablation. This is because these methods use extreme heat or cold to “melt down” the treated tissue and cause the cells in question to die.
IRE spares the surrounding tissue
IRE selectively destroys cells; other tissue components such as collagen and elastin fibers, basement membranes and the interstitial matrix, remain intact and are not affected by the IRE procedure. Nerves close to the prostate and the vascular nerve bundle are thus spared. The bladder, bladder neck, pelvic floor and rectum are also not affected. Thus, side effects such as incontinence and impotence can be avoided in most cases.
Tissue necrosis, as induced by the other methods mentioned above, leads to scarring. This intensifies with each subsequent treatment. Unlike other procedures, IRE treatment does not cause scars. Therefore, the IRE can be repeated many times. Another advantage of IRE is that there is no soreness after treatment. IRE therapy also does not lead to any complications that would stand in the way of subsequent surgery or radiation therapy.
At Vitus, we use the NanoKnife IRE ablation procedure for IRE treatment. Treatment with NanoKnife is usually completed within 24 hours and requires no further follow-up treatment.
2.1 Irreversible electroporation for tissue ablation – a new development
IRE is approved for use in humans in both the U.S. and Europe: In the U.S., the FDA (Food and Drug Administration) has approved the procedure for general tissue ablation. In Europe, it is approved for use by the CE marking. The method is based on the ablation of tissue by strong, short pulsed electric fields.
Reversible electroporation (RE) has been used for decades in cell research to temporarily create pores in cell membranes through which larger molecules can enter the interior of the cell. The pores created by IRE are still considerably larger, so they cannot close again. Water can penetrate the cell in this way until the pressure inside causes it to burst. The molecules that remain after treatment have not been thermally altered, so the body can reuse them.
2.2 Differences to other minimally invasive procedures
IRE therapy does not “cook” the treated tissue as HIFU and RFA do. In the other procedures, the burned tissue triggers typical reactions, such as pain, inflammation and scarring. Sensitive organs in close proximity to the prostate, such as the bladder, rectum, bladder neck, urethra, and vascular nerve bundle, may be affected by other focal therapy procedures. IRE, on the other hand, spares these organs so they are not affected by treatment.
IRE does not destroy all tissue in the treatment area, but allows selective destruction of cells. The IRE process can be thought of as the demolition of a building that is made of concrete and steel. While previous methods would have collapsed the entire building, IRE removes only the concrete, leaving the steel skeleton intact. Thus, only the walls need to be replaced again. In IRE, all other structures, such as collagen and elastin fibers, basement membranes and interstitial matrix, vessels, nerves, muscles, tendons and connective tissues either remain intact or can regenerate after treatment.
Precise delimitation of the treatment area
The treatment area is precisely defined in IRE. In this way, the treatment can be precisely narrowed down right from the start. No tissue outside the treatment area is damaged. The transition between the area where cells are destroyed one hundred percent and the surrounding tissue, where no cell damage occurs, consists of only two to three cell layers. For all other ablation methods, whether thermal ablation (HIFU, RFA, laser, etc.), radiation therapy, or proton therapy, this borderline area can be several centimeters in size. There, tissue is partially destroyed and it is unclear whether all cancer cells have been killed.
The advantages of the IRE procedure may lead to the beginning of a new era in cancer treatment. IRE is particularly suitable for prostate treatment because the prostate is a small organ, immediately surrounded by many sensitive structures. IRE is unique because it allows extremely precise treatment and spares surrounding structures. That is why there are minimal side effects.
3.1 Medical progress
The main reason for this discrepancy is the speed of medical progress – especially when compared to the outdated teaching methods used in physician training. Medical knowledge has a half-life of about three years. Physician training, on the other hand, takes at least six years for the first medical degree. Add to that another four to six years of residency training and possibly another three to five years if specializing. In this period of ten or more years, only about 12.5 percent of medical knowledge retains its validity. In addition, at the beginning of their careers, most physicians initially approach innovations and technical progress with skepticism.
3.2 Clinical trials are lengthy
Clinical trials with control groups can take five to ten years for new treatments. For slowly progressing pathological processes, as is the case with prostate cancer, these procedures may take even longer. Often, when the study results are finally available, the method under investigation is already out of date, or errors in the study design are discovered (e.g., because there have been new findings since the study began). Such inconsistencies can then lead to the study results being partially or even completely invalid.
3.3 Multiple influencing factors play a role
Despite these facts, the S3 guidelines for prostate cancer are based on the classical methods of evaluating treatment procedures according to the principles of evidence-based medicine. In addition, many other factors play a role. Take radiation therapy, for example. This method of treatment is well supported financially. In recent years, many hospitals have expanded their corresponding departments and invested several million euros in new, very expensive radiotherapy equipment (linear accelerators). However, new developments in more precise photon therapy have meant that conventional radiotherapy has quickly become obsolete and is now virtually obsolete.
But it’s not just hospitals that are standing in the way of new developments in radiation therapy. Governments also ignore or impede the dissemination of treatment procedures using photon therapy on the grounds that these procedures have not yet been evaluated carefully enough. If a treatment method is recommended in the S3 guidelines, the appropriate equipment must also be available to treat all patients – but new photon therapy equipment is expensive. If hospitals fail to provide sufficient new equipment, the government will have to subsidize the purchase of photon therapy equipment to replace conventional radiation therapy.
3.4 Plannability of treatment costs
Another reason is that payers (e.g., public health insurers or private health insurers) prefer to pay for treatments where subsequent costs can be planned – even if these therapies cost more than less expensive procedures where the number of treatments and subsequent costs are unknown. In this industry, it is easier to maintain the status quo than to implement change.
3.5 Long-term studies are missing so far
Unfortunately, the question remains open so far whether focal therapies will be included in the S3 guidelines. For several years now, we believe there has been sufficient scientific evidence on the success of treating prostate cancer with IRE. However, there are no long-term studies to date that can show clinical results over a period of 10 to 15 years.
This point has been taken up several times by the German Society of Urology. Furthermore, there is a 2017 scientific publication that, while noting the tremendous potential of IRE as a treatment for prostate cancer, advises against its routine nor clinical use.1
Nevertheless, publications on focal therapy in general2 and on IRE specifically 3,4,5,6,7,8 are published at regular intervals. These scientific publications provide new data on IRE in prostate cancer, and take a more sophisticated look at the statistical requirements of clinical evaluation in focal therapies using IRE/NanoKnife.
3.6 Think well about prostate removal
One number is important to keep in mind if you are considering undergoing a prostatectomy: Survival after prostatectomy is only one percent higher than in patients who chose Active Surveillance, or observation and monitoring of prostate cancer (Urologic Oncology 2012, Focal therapy of prostate cancer: energies and procedures). In our opinion, such an aggressive treatment method should only be considered if radical therapy is essential to stay alive – and not as a routine treatment of choice.
1 Wendler, J. J., et al. “Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.” World journal of urology35.1 (2017): 11-20.
2. Guillaumier, Stephanie, et al. “A multicentre study of 5-year outcomes following focal therapy in treating clinically significant nonmetastatic prostate cancer.” European urology74.4 (2018): 422-429.
3. Scheltema, Matthijs J., et al. (2018). Pair-matched patient-reported quality of life and early oncological control following focal irreversible electroporation versus robot-assisted radical prostatectomy. World Journal of Urology (2018): 1-7.
4. Van den Bos, Willemien; Scheltema, Matthijs J.; Siriwardana, Amila R.; Kalsbeek, Anton M. F.; Thompson, James E.; Ting, Francis et al. (2017): Focal irreversible electroporation as primary treatment for localized prostate cancer. In: BJU international. DOI: 10.1111/bju.13983.
5. Van den Bos, Willemien, et al. “Focal irreversible electroporation as primary treatment for localized prostate cancer.” BJU international 121.5 (2018): 716-724.
6. Scheltema, Matthijs J., et al. “Feasibility and safety of focal irreversible electroporation as salvage treatment for localized radio-recurrent prostate cancer.” BJU international 120 (2017): 51-58.
7 Scheltema, Matthijs, and Jean de la Rosette. “Irreversible Electroporation of Prostate Tumors.” Irreversible Electroporation in Clinical Practice. Springer, Cham, 2018. 215-222.
8. Scheltema, Matthijs J., et al. “Impact on genitourinary function and quality of life following focal irreversible electroporation of different prostate segments.” Diagnostic and Interventional Radiology 24.5 (2018): 268.
4.1 The first steps
NanoKnife treatment must be preceded by an examination of the prostate with a high-resolution multiparameter MRI. If you have not had such an examination, please make an appointment for it as soon as possible. Depending on your medical condition, we additionally recommend a 3D biopsy prior to NanoKnife treatment. Accurate treatment requires detailed MRI scans as well as data obtained by 3D biopsy, if necessary, to accurately determine the location and distribution of the tumor in the prostate in order to perform treatment.
4.2 Biopsy for very small tumors
Many cancer sites are microscopic and cannot be visualized by imaging techniques, not even by high-resolution MRI. However, they can potentially be detected in a sample taken in biopsy.
4.3 Biopsy not absolutely necessary in some cases
For a large carcinoma requiring ablation of the entire prostate, 3D biopsy may not be necessary.
If MRI shows a small cancer site with a low Gleason score (<7 and samples from other areas negative), a 3D biopsy may also not be necessary. In these cases, although it cannot be excluded that other lesions exist in addition to the main tumor, the so-called index lesion. However, there is evidence to suggest that treating only the index lesion but not the satellite lesions does not decrease patient survival. However, this approach needs to be further examined in individual cases.
If MRI is performed in addition to a transrectal biopsy, consideration should be given to whether a transperineal 3D biopsy is necessary or whether treatment is possible without the additional information obtained. However, without the 3D data, treatment accuracy is reduced.
Here at our facility, we have performed the most prostate cancer treatments with NanoKnife in the world. In total, we have treated about 1400 patients in this way. Summaries of our data regarding side effects (incontinence and impotence) as well as oncological data have already been presented at several congresses. Here you can find a commented presentation from 2015.
In terms of both side effects and oncologic outcomes, our data show significant progress compared with firmly established treatments. However, the data were not collected as part of a clinical trial. Their scientific validity is limited for this reason. Nevertheless, unlike radiation therapy or prostatectomy, IRE is a gentle procedure that works at the cellular level and can be repeated as many times as needed, including recurrences.
No medical procedure can offer a one hundred percent guarantee of success. Human biology is too complex for that and the differences between individuals are too great.
The current, common treatment methods for prostate cancer do not guarantee a cure and entail considerable side effects (impotence in about 70 percent of cases, incontinence in 10 to 50 percent of patients).A focal therapy with IRE is therefore a very interesting alternative.
In many cases, IRE treatment may be the best treatment approach because the tumor tissue is treated only within the treatment area and side effects are therefore very low. Each case is closely monitored for possible associated symptoms such as impotence and incontinence.
However, IRE is not a miracle treatment against all tumors at all stages. We will advise you on all available treatment options for your particular case and stage of disease. Before we begin any treatment, we will discuss with you the various options, your priorities and preferences.
NanoKnife treatment lasts about two hours and is performed under general anesthesia. A bladder catheter will be placed, which will be pulled out by your urologist or by us after about 10 to 14 days. After the treatment you will spend one night under medical supervision in our private clinic. After a total of 24 hours after treatment, you can usually go home. For most patients, NanoKnife treatment does not cause pain, but they find the bladder catheter slightly annoying.
We have already successfully treated many patients. NanoKnife is manufactured by a company called AngioDynamics and is approved by the FDA (Food and Drug Administration) in the USA as well as in Europe (CE marking) and in Germany (according to the Medical Devices Act). These approvals cover tissue ablation throughout the body, including the prostate. So you would not be a guinea pig at all.
IRE is still considered an experimental method of focal therapy for prostate cancer because to date no results of long-term studies are available, neither for focal therapy in general nor for the treatment of prostate cancer using NanoKnife (see point 2).
Given the poor outcomes achieved by conventional prostate therapies (impotence in 70 percent of patients, incontinence in 10 to 50 percent, a 30 percent recurrence rate, and a 5-year survival improvement of only one percent with prostate removal), we must assume that a new procedure with fewer side effects will be better – even if long-term results are still pending.
At the Prostate Center, now Vitus Privatklinik, in Offenbach, we have treated more than 1400 patients with prostate cancer and published the results at all major radiology congresses.
Contact us if you would like us to send you scientific publications.
Please refer to item 2 “What is IRE?”
We regularly treat patients whose tumor has spread to the neighboring structures of the prostate, such as seminal vesicle, pelvic floor, etc.. In most cases, at this tumor stage, it is necessary to perform other treatments, such as anti-hormone therapy, in addition to focal therapy. However, there is evidence that even in the advanced stage of the disease, a reduction in tumor size has a positive effect on the success of treatment.
Because IRE does not damage structures such as large blood vessels, even lymph nodes affected by metastases that are in close proximity to them can be treated with the NanoKnife procedure.
IRE can also be synergistically combined with immunotherapy, for example monoclonal antibodies. For more information contact us.
Whether these measures are curative or merely palliative, i.e., whether they contribute to healing or merely alleviate discomfort, depends on the circumstances. Often, combination therapy is the most appropriate approach for advanced stage tumors.
After previous treatment, whether surgical or, for example, using HIFU (high-intensity focused ultrasound), scars often appear, making further surgery difficult. In addition, further surgery or HIFU treatments are often associated with an increased risk of impotence or incontinence. Radiation therapy makes the treated tissue so fragile that surgery is virtually impossible. In addition, it is not possible to repeat conventional radiotherapy immediately after radiation treatment has already been performed. Too much damage would be done to surrounding structures, such as the bowel and bladder.
In these cases, IRE (Irreversible Electroporation) can be used to treat recurrences in a minimally invasive manner, with minimal risks and no additional burden to the patient. IRE thus represents a unique method for the treatment of tumor tissue at otherwise inoperable sites. IRE treatment can be repeated as many times as needed. The only prerequisite for such treatment is precise diagnosis by MRI. We have successfully treated several complicated cases with residual tumor tissue. However, long-term experience and statistics are not yet available for this.
Yes, we have already had great success with the use of NanoKnife in BPH. The advantage of NanoKnife is the selective ablation of cells responsible for hyperplasia. A typical advantage of NanoKnife treatment is that there is hardly any pain involved. This is because only cells are destroyed, but no tissue necrosis is caused in the process. BPH can also be treated at the same time as a tumor. In fact, when tumor and BPH occur at the same time, it often happens automatically.
During surgery or laser treatment, the prostate is accessed from the outside through the urethra (intraprostatic urethral portion). This causes injuries to these organs. In IRE, however, access is through the perineum directly into the BPH in the transition zone. The intraprostatic urethral portion and the seminal mound (colliculus seminalis), which play an important role in ejaculation, remain uninjured.
In Germany, statutory health insurers generally only cover the costs of treatment procedures recommended in the S3 guidelines for prostate cancer. These are prostatectomy, radiotherapy, chemotherapy and hormone therapy. In some cases, the local statutory health insurances cover the costs abroad.
We recommend that you discuss your individual case with your health insurance company and negotiate coverage. Treatment costs for prostatectomy may be much more expensive than successful focal therapy, both in the short term (hospitalization costs) and in the longer term (treatment complications, permanent damage).
The cost of multiparameter MRI, 3D biopsy, and NanoKnife treatment depends heavily on the individual case. For an assessment in your case and an accurate estimate please contact Contact us contact us.
General anesthesia is required for the muscles to relax and for the IRE procedure to be performed safely. Therefore, the health limiting factors for IRE treatment are the normal risks associated with general anesthesia. Therefore, the question of whether general anesthesia is possible must be clarified by the responsible anesthesiologist. It is therefore necessary that a health assessment be performed prior to treatment, including diagnostic tests such as a stress ECG, blood tests, X-ray, ultrasound, etc. A full cardiac evaluation may also be required to clarify a complete assessment of your general health and anesthetic capability.
If you are interested in IRE treatment and/or a personal consultation, contact us please.