The standard therapies are the surgical removal of the prostate, called radical prostatectomy (RPE) (ancient Greek -εκτομία [-ektomía], “a cutting out of”) and radiation therapy (RT). Both aim at the total destruction of the prostate. The rationale behind this approach is the outdated belief that with the removal of the prostate, the cancer is completely removed from the body and the patient cured. That this is a fallacy is well proven by the fact that “liquid biopsy” can detect circulating tumor cells in the blood of every cancer patient, proving that cancer cells are always distributed throughout the body. Thus, even after the removal or total destruction of the prostate, cancer cells remain in the patient’s body, accounting for the relatively high recurrence rates after surgery and/or radiation therapy (see: Han Tables, Johns Hopkins University, Department of Urology).
Because of this, focal destruction of the tumor with preservation of the healthy parts of the prostate and, consequently, genitourinary function, is gaining attention.
The principle behind focal therapy can be concisely summarized with a question: “Why remove the whole prostate when the cancer is just in one area?”. The same treatment development as that for breast cancer has lead to a new mindset in which only the cancerous area and a small area surrounding the tumor is removed as opposed to the removal of the whole breast.
Through this approach, the side effects and complications following a focal therapy to the prostate are greatly reduced, with the primary objective of preventing the onset of incontinence and impotence. Focal therapies are less invasive than prostatectomy and therefore carry fewer risks, and side effects are greatly reduced. There are fewer complications such as bleeding, infection, injury to other organs and risk of death, along with reduced pain, shorter recovery and reduced aftercare and rehabilitation.
Focal therapies are new methods of treatment which have recently been made possible through more precise diagnostics and improved MRI technologies. The idea behind this technique is that only the cancerous tissue is treated so that as much healthy prostate tissue as possible is retained.
Accurate diagnostics and precise treatment execution are essential to a successful outcome. The healing time is massively shorter compared to that required following prostatectomy (see Point 2. IRE) and treatment also has a positive effect on maintaining functions such as continence and potency.
The classical therapies include the surgical removal of the prostate, with the objective that the prostate, including all cancerous tissues, is removed. Radiotherapy treatments also adhere to this same philosophy by treating the whole prostate. Hormone and chemotherapy treatments on the other hand exhibit their effects on the whole body and are mostly used in cases of metastatic prostate cancer.
The idea behind radical prostatectomy is the following: when the prostate is removed, then so is all the tumor tissue and the cancer is then “cured”. Unfortunately, human biology is not so simple: with every cancer, malignant cells are distributed throughout the body, leading to dissemination of the disease outside the “prostate capsule” (prostate capsule is a term used to describe the outside layer of prostate cells, not a capsule as such), and in the blood. It is through this process that, even after a prostatectomy, up to 30% of patients experience a recurrence, caused by cancer cells disseminated prior to prostate removal.
Active surveillance is offered to patients in an older age group diagnosed with a low grade carcinoma. The slow growth of these tumors means that it can often take decades before the cancer breaks through the prostate capsule or begins to metastasize. Therefore a simple planned observation is often the most prudent method of treatment.
Whether the patient is suitable to be treated with active surveillance depends upon personal and medical factors. Factors such as the patient’s age, general health, PSA value at the time of diagnosis, the PSA doubling time, Gleason score and tumor stage, along with the personal wishes of the patient. These factors will all need to be taken into consideration and should be thoroughly discussed with an expert following diagnostic examination and biopsy.
IRE is a new technique for tissue ablation, unlike other tissue ablation techniques such as HIFU (High Intensity Focused Ultrasound), RFA (Radiofrequency Ablation), laser treatment and cryoablation, which all use extremes of heat or cold to “melt down” and destroy tissues and structures within the treatment area through a process of coagulation necrosis.
IRE selectively destroys only cells. Other tissue constituents—such as collagen and elastin fibers, basal membranes and the interstitial matrix which are used to make up important structures such as nerves close to the prostate including the neurovascular bundle—remain intact and unaffected by the IRE process. The bladder, bladder neck, pelvic floor and rectum are also spared, meaning that side effects such as incontinence and impotence can in most cases be avoided.
The IRE treatment we use at Vitus is the NanoKnife IRE Soft Tissue Ablation System.
A further advantage of IRE is that no wound pain occurs following treatment as, unlike other treatment methods, IRE causes no inflammation and therefore no scarring. The tissue necrosis caused during the alternative methods of tissue ablation listed above, on the other hand, leads to scarring which increases with each follow up treatment. This means IRE can be carried out on numerous occasions. In addition, IRE treatment does not cause any complications which inhibit further surgical or radiotherapy treatments.
Treatment with NanoKnife is usually completed within 24 hours and rehabilitation and aftercare are not required.
2.1. Irreversible Electroporation for tissue ablation purposes has only recently been developed and acquired approval for use in human subjects: approved by the FDA (Food and Drug Administration) in the USA, with CE certification for use in Europe. This method is based upon strong short-pulsed, electrical field-based tissue ablation therapy. RE (Reversible Electroporation) has already been used for decades in cell research to temporarily create pores in cell membranes in order to allow larger molecules to pass through. During IRE the pores created are much larger, so that they are then unable to close up again. This process allows water to flood into the cells until the greater inner pressure causes the cell to burst. The debris left over after treatment has not been thermally altered, and therefore the molecules can be reused.
2.2. Three characteristic properties differentiate IRE from other minimally invasive techniques and require consideration.
Tissues are not "cooked" as with HIFU and RFA. In these through processes, burnt tissue reactions such as pain inflammation and scarring typically occur. Sensitive organs within the immediate vicinity of the prostate such as the bladder, rectum, bladder neck, urethra and the neurovascular bundle can be damaged with other focal therapy treatment methods, but are spared during IRE and remain unaffected by treatment.
IRE does not destroy all tissue within the treatment area with a melting coagulative process but rather facilitates selective cell destruction. The IRE process can be thought of as the demolition of a concrete and steel building. Whilst previous methods would mean the detonation of the whole structure, IRE would result in the removal of the concrete walls leaving an intact steel skeleton requiring only the installation of replacement walls. All other structures remain intact, e.g. collagen and elastin fibers, basal membranes and interstitial matrix, vessels, nerves, muscles, tendons and fascias are either preserved or are able to regenerate following treatment.
The treatment area in IRE is sharply defined, allowing the treatment to be precisely confined from the beginning, with no tissue damage occurring outside the treatment area. The junction between the treatment area, where 100% of the cells will be destroyed, and the surrounding tissue in which no tissue damage will occur consists of only a 2-3 cell layer. With all other ablation methods, whether thermal ablation (HIFU, RFA, laser treatment, etc.), radiotherapy, or high precision proton therapy, this border area of partial tissue damage and uncertain cancer cell destruction can be as much as centimeters wide.
The favorable treatment characteristics demonstrated by IRE could mark the beginning of a new era in cancer treatment. The main advantages of this treatment within the prostate are that the prostate is a small organ surrounded by many sensitive neighboring structures. IRE is unique in that it makes a highly precise treatment possible whilst sparing surrounding sensitive structures with only minimal side effects.
3.1. The most important reason for this discrepancy lies in the rapid progress being made in medical science compared with the out of date teaching methods used to train doctors. Medical knowledge has a half life of approximately 3 years, whereas the training undertaken to become a doctor takes at least 6 years for a basic medical degree, followed by 4-6 years’ consultant training and possible 3-5 years of specialist training. Over this 10-year-plus period, only approximately 12.5% of the medical knowledge developed within this time frame will still be valid. In addition, most new doctors can be skeptical about new techniques and improvements.
3.2 The evaluation of new techniques is also antiquated. Clinical studies for new treatments with control groups can take between 5 and 10 years, a process which can take even longer in slower pathological processes such as prostate cancer. Often, by the time study results are available, the method which was examined is already obsolete, or mistakes in the study design are discovered (i.e. new evidence has come to light since the start of the study, etc.) These discrepancies can often mean that the results of these clinical studies are partially or even fully invalid.
3.3. Despite these facts the current S3 Guidelines for prostate cancer are based upon classical treatment evaluation in the form of "evidence-based medicine".
There are many factors which also play a part. Take radiotherapy for example. Radiotherapy is financially very well supported and, over the past few years, many hospitals have expanded their radiotherapy departments and installed new very expensive radiotherapy machines (linear accelerators) at an investment cost of many millions of euro. However, new developments in the more precise photon therapy have lead to conventional radiotherapy becoming rapidly outdated and now almost obsolete.
It is, however, not only the hospitals who are standing in the way of development in radiotherapy but also governments who ignore or obstruct the development of photon therapy treatment with the argument that this treatment method has not yet been thoroughly evaluated. New photon therapy equipment is expensive and when this treatment method is recommended in the S3 Guidelines then enough equipment must be available to treat all patients. Should the hospitals be unable to achieve this level of new equipment then the additional funding to replace conventional radiotherapy equipment with proton therapy machines must be subsidized by the state.
3.4. A further reason is that the cost carriers (e.g. the public health fund or health insurance company) prefer to pay for treatments for which the follow-up costs can be calculated, even when these treatments are more expensive compared to cheaper treatments where the number of treatments required and the follow-up costs are unknown. In this industrial sector, it is simpler to follow the status quo than to manage change.
3.5. Unfortunately, the question as to whether focal therapies will be included in the S3 Guidelines remains open. There has already been enough scientific knowledge about the success of focal therapies available for a number of years. However long term clinical studies demonstrating statistical analysis over a 10-15 year time frame are not yet available.
3.6. One number that should be considered before undergoing a prostatectomy procedure is that the survival rate following prostatectomy is only 1% higher than that seen with patients undergoing active surveillance (Urologic Oncology 2012, Focal therapy of prostate cancer: energies and procedures). In our opinion such an aggressive treatment should only be considered in cases where a radical therapy is vital in order to stay alive and not as a routine treatment choice.
4.1. A prerequisite to undergoing NanoKnife treatment is a high resolution, multi-parameter MRI examination of the prostate. If you have not already had such an examination, please arrange an appointment here with us at your earliest convenience. Additionally, we recommend that a 3D biopsy is carried out prior to focal NanoKnife treatment. Precise treatment requires 3D biopsy results data combined with detailed MRI images to exactly determine tumor distribution within the prostate and to guide thorough treatment. Contact us.
4.2. Many lesions are microscopic and cannot be demonstrated on imaging, not even with high resolution MRI, but may be detected in a biopsy sample.
4.3. In cases of a large carcinoma for which the whole prostate must be ablated it may be possible to forego the 3D biopsy.
4.4. In cases where a small focal lesion is seen on MRI for which a low Gleason score (<7—demonstrating that probes from other areas were negative), then a 3D biopsy is not necessary. In these cases it can not be ruled out that next to the main lesion, the so called index lesion, other satellite lesions are not present. There is evidence to suggest that it is justifiable to treat the index lesion leaving the satellite lesions without reducing the survival rate of the patient. This approach must undergo further testing in specific individual cases.
Using the available MRI imaging alongside the transrectal biopsy results, it can be considered whether a transperineal 3D biopsy is required or whether you can be treated without this additional information. Treatment carried out without the 3D data will however result in a reduction in treatment accuracy.
Here in our institution, we have carried out more prostate cancer treatments with NanoKnife than anyone in the world. The total number has been around 600 treatments as of June 2017. Summaries of the data regarding side effects (incontinence and impotence) as well as oncological data have been published on several conferences. A commented presentation from 2015 can be found here.
Both in terms of side effects and oncological outcome, our data shows significant advancements compared to previous treatment modalities. The data however is not gathered by a prospective clinical trial, therefore has limited scientific meaning. However, contrary to radiation or prostatectomy, IRE is a gentle procedure operating on a cellular level which can be repeated indefinitely, even in case of a recurrence.
No medical procedure can guarantee 100% success. Human biology is too complex for that sort of success, and the individuality of each human is too great.
Current prostate cancer treatments offer no guaranteed cure and also bring considerable side effects (approximately 70% impotence and 10-50% incontinence), demonstrating a focal therapy with IRE to be a very interesting alternative.
In many cases, IRE treatment may be the best approach to treatment of prostate cancer purely due to the fact that the tumor ablation is carried out within confines of the treatment field and that side effects are very low. Every case is closely monitored in connection with suspected primary side effects such as impotence and incontinence.
It must also be taken into consideration that IRE is not a magic cure for tumors in all stages. We take care to advise you of all of the relevant treatment methods available in connection with your particular case and stage of disease and discuss them in relation to your own specific personal priorities and preferences before we carry out any treatment.
The treatment with NanoKnife takes approximately 2 hours to complete and is carried out under general anesthetic. A urinary catheter will be inserted and will stay in place for approximately 12-48 hours. Following treatment you will require just a one night in-patient stay under the care of a doctor in a private clinic or a hotel. After a total of 24 hours you will normally be able to return home. Most patients do not have any pain caused by the NanoKnife treatment, but do however find the urinary catheter to be rather annoying.
We have already successfully treated many patients. NanoKnife is produced by a company called AngioDynamics and is approved not only in the USA by the FDA (Food and Drug Administration) but also in Europe (CE certification), and in Germany (medical product laws for medical treatments in humans). This approval refers to tissue ablation in the whole of the human body including the prostate. So you can see that you will be in no way a guinea pig.
IRE is still seen as an experimental method of focal prostate cancer treatment, as to date there are no long term study results available, neither for focal therapy in general nor for prostate cancer treatment using NanoKnife (see Point 2).
Considering the poor results achieved using previous conventional prostate cancer therapies (70% impotence, 10-50% incontinence, 30% rate of recurrence and a 5 year survival rate advantage following prostatectomy of just 1%), it can be assumed that a new technique with fewer side effects is in any case better even when the long term results are not yet available.
Over 600 cases have been treated in the Prostate Center, now the Vitus Prostate Center, in Offenbach and the superior results have been published on every major radiology conference. Contact us for access to scientific publications.
Please see Point 2 ‘What is IRE?’.
We regularly treat patients with extension into neighboring structures such as the seminal vesicles, pelvic floor, etc. In most cases with these tumor stages a complementary accompanying therapy such as an antihormonal therapy must also be carried out alongside focal therapy. There is, however, evidence to suggest that a reduction in the tumor size in advanced stage disease has a positive effect on the success of treatment.
As IRE does not damage structures such as large blood vessels, even metastatic lymph nodes in close proximity to these to these structures can theoretically be treated with NanoKnife. Although not yet carried out, this type of treatment could be considered under certain circumstances. Treatment of other tumors, such as ear, nose and throat tumors, has already been undertaken.
Also, IRE can be synergistically combined with immunotherapy, for example monoclonal antibodies. Contact us for more information.
Whether these measures are just palliative or curative depends upon the individual circumstances, often a combination therapy is the most sensible approach to tumors in an advanced stage.
The treatment of recurrence following prostatectomy is a primary use of IRE, in which IRE exhibits special advantages. In many cases considered to be “beyond treatment”, IRE is often the only treatment option left.
Further to a previous treatment, whether surgical or HIFU, scarring often occurs, making re-operation difficult, and follow up surgery or HIFU is often linked to an increased impotence or incontinence risk. Due to post-treatment radiation induced effects, radiotherapy damage results in brittle tissues making re-operation following radiotherapy treatment virtually impossible. In addition, repeat of conventional radiotherapy treatment directly after a full dose radiotherapy treatment is not possible due to the radiation damage to important neighboring structures, e.g. intestines and bladder.
In these instances, IRE can be used in the minimally invasive treatment of recurrence, with minimal risk and without strain on the patient, and provides a unique method to treat residual tumor tissue in otherwise inoperable places. IRE treatment can be carried out as often as required. The only prerequisite for such a treatment is a precise diagnostic imaging MRI examination. We have already successfully treated several complicated cases of residual tumor, although as yet long term experience and statistics are unavailable.
Yes, we have already had good success with treatment of BPH using NanoKnife. The advantage of NanoKnife is the selective ablation of cells that are responsible for the hyperplasia (BPH is a cellular hyperplasia as opposed to, for example, uterine myoma). A characteristic advantage of treatment with NanoKnife is that there is hardly any pain, as only cells are destroyed, causing no tissue necrosis. BPH can also be treated at the same time as a carcinoma, which often happens automatically when BPH and carcinoma are both present.
Whilst for surgical and laser treatment access to the prostate is achieved through the urethra and intra-prostatic urethra, causing damage to these organs, access for IRE is achieved via the perineum directly into the BPH within the transitional zone area. The intra prostatic urethra and the colliculus seminalis, which are very important organs for normal ejaculatory function, remain undamaged.
We recommend that you discuss your particular case with your health insurance company and try to negotiate your particular case. Treatment costs for a prostatectomy both short term (e.g. a hospital stay) and long term costs (treatment complications and long term damage) could be much more expensive than a successful focal therapy.
The cost of a multiparametric MRI, a 3D biopsy and a NanoKnife treatment are very much case-dependent. Please contact us so that we can evaluate your case and give you an accurate quotation.
The limiting factors associated with IRE treatments are the normal risks associated with a general anesthetic. Therefore the question of whether the anesthetic is possible must be addressed by the responsible anesthetist. An assessment of your health may need to be carried out prior to treatment including diagnostic tests such as a stress ECG, blood tests, x-ray, ultrasound, etc. A full cardiological examination may also be required in order to make a fully accurate assessment of your general health and anesthetic risk factors.
The general anesthetic is actually only necessary because it provides the required muscle relaxation that allows the IRE procedure to be carried out safely. The treatment itself is otherwise minimally invasive and almost pain free. It is therefore theoretically possible that the procedure could be undertaken under local anesthetic (local anesthetic does not provide the required muscle relaxation therefore an alternative method of muscle relaxation would be required).
If you are interested in IRE treatment and/or a personal consultation please contact us.