Prostate cancer is one of the most common cancers in men. In addition to traditional therapies, such as radical removal of the prostate and radiation, a new treatment strategy is establishing itself with focal therapy. As has long been the case with other cancers, focal therapy does not involve removal of the entire organ or radiation. Instead, only the tumor is treated in a minimally invasive and gentle manner. Focal therapy for prostate cancer is not suitable for every patient and requires precise diagnosis. If certain criteria are met, irreversible electroporation (IRE), can be performed as a gentle method with few side effects in patients with localized prostate cancer.
IRE - What is it?
Irreversible electroporation (IRE) of the prostate is a technique for the focal treatment of prostate cancer. IRE is performed with the NanoKnife®. Voltage pulses of different strengths and only a few microseconds in length are used to destroy the cell wall of the tumor cells. This is where the term "NanoKnife" comes from - virtually an electronic scalpel that opens the cell wall.
For which patients is this method suitable?
IRE is suitable for patients who qualify for focal therapy for prostate cancer. It is also a potential alternative for patients who do not want surgery or radiation or are unsuitable for them for health reasons.
How does IRE work?
In the treatment of prostate cancer using IRE, thin electrodes are placed in the tumor areas via the perineum. Voltages of several thousand volts are then applied between every two electrodes. Strong electric fields create pores in the cell walls of the cancer cells located within the treatment field. These pores no longer close, hence the term "irreversible electroporation." The cancer cells are destroyed by this pore formation.
The prostate carcinoma
In industrialized countries, prostate carcinoma is the most common cancer in men and the second leading cause of cancer death. In particular, the introduction of the tumor marker PSA led to an increased diagnosis of prostate carcinomas in early stages (keyword overdiagnosis). When prostate cancer is diagnosed, both the patient and his treating physician are often faced with a difficult decision. The therapy recommendation for prostate carcinoma is based on specific criteria. For early stage tumors confined to the prostate , several standard treatment options (active surveillance, surgery, radiation) are available. However, the optimal treatment strategy is unclear.
Relevance of the general condition
Before a decision for or against a form of therapy is made, the general condition, life expectancy and tumor characteristics of each patient should be assessed. Life expectancy plays a more important role than biological age.
In the case of advanced patient age or reduced life expectancy, the patient's concomitant diseases reduce the risk of dying from prostate cancer. That is, patients die with the prostate cancer, but not from the tumor. Of course, the treatment wishes of the affected men must also be taken into account.
Side effects
The well-established therapeutic procedures, radiation and surgical removal of the prostate offer excellent local tumor control, but can be associated with sometimes significant side effects.
The consistent further development of surgical techniques using laparoscopy and robot-assisted surgery (Da Vinci) has led to an improvement in terms of blood loss, wound pain and length of hospital stay. However, there are conflicting data regarding a significant reduction in side effects as well as improved tumor control.
Active surveillance is now an established approach for less aggressive tumors. Active surveillance requires the patient to undergo follow-up examinations (PSA, palpation of the prostate and rebiopsies) at regular intervals. If the disease process progresses, the patient is advised to switch to definitive therapy.
For patients, active surveillance can be a psychological burden. They therefore opt for a radical therapy with all its consequences and side effects (keyword overtherapy). Furthermore, men who in the course of active surveillance no longer formally fulfill the criteria for continuing surveillance receive definitive radical therapy.
The aim of focal therapy is to open up a possible middle way for these patients between radical therapy on the one hand and active surveillance on the other.
Treatment options for localized prostate carcinoma
"The diagnosis of prostate cancer is tough - for men, it often means the end of the world. That's why it's particularly important to my colleagues and me to work on new methods for the benefit of our patients. Precise diagnostics are a prerequisite for selecting the best method."
Active monitoring
Radical prostatectomy
External beam radiotherapy (EBRT)
Focal therapy
Diagnostics
Up to now, diagnosis of suspected prostate cancer has consisted of palpation of the prostate (so-called digital rectal examination, DRU) and determination of a blood value, the so-called prostate-specific antigen (PSA).
In the case of abnormal findings, an ultrasound-guided biopsy of the prostate was performed via the rectum. Today, this procedure is increasingly viewed critically. Today, the primary goal is to avoid biopsies. However, if biopsy is necessary, the biopsy should precisely and safely target the tumor. Furthermore, the biopsy must ensure that no other tumors are present in the rest of the prostate . This is of utmost importance for planning a focal therapy. The solution is robot-assisted mpMRI/TRUS fusion and mapping biopsy of the prostate.
No focal therapy without robot-assisted mpMRI/TRUS fusion and mapping biopsy.
Robotic-assisted, perineal mpMRI/TRUS fusion and mapping biopsy of the prostate is a prerequisite for planning focal therapy. Transrectal biopsy of the prostate is insufficient for this purpose (see Study 1 below).
In order to avoid unnecessary treatment, it is important to distinguish between significant (requiring treatment) and insignificant (not requiring treatment) prostate carcinomas. This subdivision is based, among other things, on the fine-tissue (histological) examination of tissue samples from the prostate, so-called biopsies
Standard procedure is the systematic transrectal ultrasound-guided biopsy (TRUS). In this procedure, 10-12 biopsy cylinders are taken from the prostate via the rectum. However, the sensitivity of this traditional method is limited. It is 53% in autopsy studies. This means that a prostate carcinoma is simply often missed during the biopsy (Fig. 1). If detection of prostate carcinoma is successful with TRUS biopsy, the question arises as to whether the biopsy result actually correctly identifies the fine-tissue tumor stage. This is of immense importance for therapy planning or prognosis assessment of the disease.
In fact, the risk of misclassification, i.e. aggressive tumors are overlooked or underestimated in their aggressiveness, by conventional prostate biopsy is between 21% and 54% (Figs. 2 and 3). Ideally, the aggressive tumor requiring treatment should be targeted biopsied and classified (Fig. 4). This is the only way to ensure optimal and fully comprehensive counseling of the patient.
Prostate Biopsy
In the prostate shown, 2 tumors are localized: In the top center of the image, with dark center, an aggressive prostate carcinoma requiring treatment. In the image on the left, light blue, a non-treatment-demanding prostate cancer is shown.
Step 1
Both tumors in the prostate are not hit.
Step 2
The low-risk tumor is diagnosed, and the aggressive and dangerous tumor is overlooked.
Step 3
The relevant prostate carcinoma is only hit in the periphery and thus underestimated in its aggressiveness.
Step 4
This is how it should be. The prostate carcinoma in need of treatment is targeted.
What is mpMRI of the prostate?
The mpMRI of the prostate (= multiparametric magnetic resonance imaging of the prostate) is a modern imaging technique in the diagnosis of prostate cancer.
In this special MRI examination, a standard examination is combined with a contrast medium examination and a density measurement of the tissue. This allows an experienced radiologist to find regions within the prostate that are suspicious for cancer with the greatest probability. Often these are tumors , which are not reached by conventional punch biopsy. The mpMRI can distinguish clinically irrelevant tumors from aggressive tumors and thus help to avoid unnecessary interventions.We cooperate closely with the radiology department https://radiologie.merianiselin.ch/ of our premium partner, the Merian Iselin Klinik in Basel. A core team of 3 specialists is responsible here for the examination and reporting of mpMRIs of the prostate . With more than 500 examinations per year, we as referring physicians, but also our patients, can rely on a great experience and a very high expertise in this field.
What is robotic-assisted mpMRI/TRUS fusion and mapping biopsy?
Robotic-assisted, perineal mpMRI/TRUS fusion and mapping biopsy of the prostate is a prerequisite for planning focal therapy. Transrectal biopsy of the prostate is inadequate for this purpose (see Study 1 below). At alta uro, mpMRI/TRUS fusion and mapping biopsy of the prostate is performed in a standardized robot-assisted manner using the Mona Lisa System (biobot).
The images of the mpMRI examination are reviewed together by the radiologist and the treating urologist. Areas suspicious for tumors are marked. On the day of the biopsy, these marked images are read into the biopsy device used to check the removal of tissue from the prostate (prostate biopsy).
The biopsies are taken via the perineum and not via the rectum. This can virtually eliminate the risk of bacterial infection. The procedure is performed as a short inpatient procedure under anesthesia.
Studies show clearly accurate prostate cancer diagnosis
In the PRECISION study published in the renowned New England Journal of Medicine (2), it was shown for the first time with the highest scientific quality that the combination of MRI of the prostate followed by targeted fusion biopsy provides more precise results than conventional ultrasound-guided biopsy. Nearly 30% of study participants who received MRI had unremarkable findings. Consequently, these patients were spared a prostate biopsy, which the other participants in the study (without MRI of the prostate) underwent. Based on the MRI data and the targeted biopsy in the areas previously identified as abnormal, 38% were diagnosed with relevant prostate cancer. With standard biopsy, relevant prostate cancer was found in only 26% of patients. These results show that risk assessment of suspected prostate cancer by MRI and fusion biopsy is significantly more accurate than the previously practiced ultrasound-guided biopsy.In addition, this procedure reduces the diagnosis of prostate cancer that does not require treatment in most cases by 50%. Although these forms of prostate cancer do not pose a danger to the men affected, the diagnosis of "prostate cancer" often causes great psychological stress.
Studies cited: 1. van der Poel HG, van den Bergh RCN, Briers E, et al. Focal Therapy in Primary Localised Prostate Cancer: The European Association of Urology Position in 2018. Eur Urol. 2018;74(1):84-91. 2. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. New England Journal of Medicine. 2018;378(19):1767-77.
Our experts on the subject of nanoknife
"In the treatment of prostate cancer, the quality of life of those affected is our top priority. Focal therapy ideally complements our available treatment surgeries and bridges the gap between active surveillance and surgery or radiation."
Focal therapy - The targeted treatment method for prostate cancer
The standard approach in the treatment of prostate cancer is to remove or irradiate the entire prostate . Medical progress in recent years has led to the development of so-called focal therapy. This is a possible alternative to surgery, radiation and active surveillance. Focal therapy for prostate cancer is limited only to the part of the prostate that is actually affected by a tumor requiring treatment. Healthy tissue is spared and side effects are reduced.
The prostate is the only solid organ that is not yet standardly treated with focal therapy.
The concept of organ preservation has been standard in cancer therapy of other organs (e.g. breast cancer, renal tumors, etc.) for many years. In fact, the prostate is the only solid organ where this therapeutic approach is not used as standard.
For whom is this therapy suitable?
It is primarily suitable for men with localized prostate cancer in which the tumor has not yet spread beyond the boundaries of the prostate and formed metasases. The decision to undergo radical prostatectomy is influenced by several factors, including the extent of the tumor, the PSA (prostate specific antigen) level in the blood, the Gleason score (degree of tumor aggressiveness), and the patient's age and health.
What technology is used?
Elimination of the tumor: Remov al of the prostate can completely remove the primary tumor and cancer-causing cells, resulting in cure or a significant reduction in tumor growth.
Local control of the cancer: Prostatectomy aims to prevent spread of the prostate cancer to surrounding tissues or other organs.
Long-term survival benefits : Radical prostatectomy may improve long-term survival, especially if the tumor is localized and prognostic factors are favorable.
PSA monitoring: After surgery, blood PSA levels can be monitored as an indicator of possible cancer recurrence.
Risks, side effects and tumor control?
Radical prostatectomy carries risks such as infection, bleeding, injury, and wound healing problems. Possible disadvantages include urinary incontinence, erectile dysfunction, impaired hormone production, and psychological effects. A thorough consultation with the physician* is important to understand individual risks and choose the best treatment option.
Studies cited: 1. D'Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280(11):969-74.
2. Donaldson IA, Alonzi R, Barratt D, et al. Focal therapy: patients, interventions, and outcomes-a report from a consensus meeting. Eur Urol. 2015;67(4):771-7.
3. Tay KJ, Scheltema MJ, Ahmed HU, et al. Patient selection for prostate focal therapy in the era of active surveillance: an International Delphi Consensus Project. Prostate Cancer Prostatic Dis. 2017;20(3):294-9.
4. van der Poel HG, van den Bergh RCN, Briers E, et al. Focal Therapy in Primary Localised Prostate Cancer: The European Association of Urology Position in 2018. Eur Urol. 2018;74(1):84-91.
5. Guillaumier S, Peters M, Arya M, et al. A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer. Eur Urol. 2018;74(4):422-9.
Course of treatment
IRE is performed as a short inpatient procedure. Discharge is on the first day after treatment. A urinary catheter is inserted under anesthesia before the start of treatment to protect the urethra and prevent urinary retention after surgery. The bladder catheter is usually removed only a few days after the procedure.
The treatment must be performed under general anesthesia. The strong electric shocks would otherwise cause massive muscle contractions. During the procedure, the electrodes are placed over the perineum. A template (template like for "sinking ships") is helpful here. The template contains a coordinate system and holes that enable the surgeon to place the electrodes precisely. The coordinate system of the template is compared with the coordinates of the mpMRI of the prostate and the ultrasound, so that the electrodes can be placed in the correct position. Depending on the size of the tumor, two to six electrodes are required for the treatment. The electrodes are placed at a distance of 1.5 to 2 centimeters and inserted evenly deep into the tissue.
Step 1
Based on the data from mpMRI and mpMRI/TRUS-navigated fusion and template biopsy of the prostate, the IRE ablation field is planned individually
Step 2
Needle-shaped electrodes are inserted via the perineum (transperineally) into the tumor areas under ultrasound control.
Step 3
Voltages of several thousand volts are applied between two electrodes at a time in the form of ultra-short pulses (10-100 millionths of a second).
Step 4
Strong electric fields cause irreversible breakdown of the cell membranes in the target area. Nanopores are formed, which lead to the death of the tumor cells.
Step 5
The body's own immune cells eliminate the destroyed tumor cells.
Step 6
Tumor cells are destroyed and degraded in the treatment field, the extracellular matrix is preserved. Anatomical structures (vessels, nerves and hollow organs) are spared.
Our experts on the subject of nanoknife
"I define the chances of success with IRE or generally with focal therapy in prostate cancer as follows: In the best case, we achieve complete and permanent tumor freedom. In the second best case, we buy ourselves time. Time to be able to live a life as unrestricted as possible by side effects of a radical treatment concept."
As with all tumor treatments, the healing success after IRE must be carefully monitored. This allows early detection of any complications or recurrence of tumors. A first imaging control (mpMRI of the prostate) takes place after 6-12 months, depending on the tumor. In addition, regular PSA level checks and control biopsies of the prostate are performed as part of follow-up care.
Side effects
In the studies performed to date, no serious complication has been observed in any prostate cancer patient treated with IRE (1-7).
Most patients could be treated with continence-preserving therapy. Only in one study, two patients were mildly incontinent after 12 months (1).
Erectile function was 66-100% during the follow-up period of 6-12 months.
Method safety
IRE has been convincing as a safe therapeutic method in the studies performed to date (4, 6, 8). Due to its localized use, IRE is associated with less impairment of quality of life and shorter hospital stay. After IRE, a sharp dividing line is found between healthy and treated areas (9). This precision spares adjacent structures such as blood vessels, nerves or the urethra (2, 10). In contrast to surgical procedures, there are no cosmetically disturbing skin scars or adhesions in the abdominal cavity.After IRE, there is a sharp demarcation line between the healthy and treated areas (9). This allows neighboring structures such as blood vessels, nerves or the urethra to be spared (2, 10). In contrast to surgical procedures, there are no cosmetically disturbing skin scars or abdominal adhesions.
Tumor control
The results of initial studies are promising, but long-term data on tumor control are still lacking. In the study by van den Bos, the control biopsy 6-12 months after IRE in patients treated with a safety margin of 10 mm showed a tumor in the treated area in 8.6% and a tumor outside the treated area in 9.8%. This translates into biopsy-confirmed tumor freedom in 81.6% of all patients. In simpler terms, 4 out of 5 men are tumor-free 6-12 months after IRE.
Studies cited: 1. Murray KS, Ehdaie B, Musser J, et al. Pilot study to assess safety and clinical outcomes of irreversible electroporation for partial gland ablation in men with prostate cancer. The Journal of Urology. 2016;196(3):883-90.
2. Onik G, Rubinsky B. Irreversible electroporation: first patient experience focal therapy of prostate cancer. Irreversible electroporation: Springer; 2010. p. 235-47.
3. Scheltema MJ, Chang JI, Böhm M, et al. 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. Ting F, Tran M, Böhm M, et al. Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control. Prostate cancer and prostatic diseases. 2016;19(1):46.
5. Valerio M, Dickinson L, Ali A, et al. Nanoknife Electroporation Ablation Trial: a prospective development study investigating focal irreversible electroporation for localized prostate cancer. The Journal of Urology. 2017;197(3):647-54.
6. Valerio M, Stricker PD, Ahmed HU, et al. Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer. Prostate cancer and prostatic diseases. 2014;17(4):343.
7. van den Bos W, Scheltema MJ, Siriwardana AR, et al. Focal irreversible electroporation as primary treatment for localized prostate cancer. BJU International. 2018;121(5):716-24.
8. Wagstaff PG, Buijs M, van den Bos W, et al. Irreversible electroporation: state of the art. OncoTargets and therapy. 2016;9:2437.
9. Van den Bos W, De Bruin D, Jurhill R, et al. The correlation between the electrode configuration and histopathology of irreversible electroporation ablations in prostate cancer patients. World journal of urology. 2016;34(5):657-64.
10. Li W, Fan Q, Ji Z, Qiu X, Li Z. The effects of irreversible electroporation (IRE) on nerves. PloS one. 2011;6(4):e18831
Irreversible electroporation
IRE - who offers the IRE?
The IRE (NanoKnife®) for the treatment of prostate carcinoma is offered throughout Switzerland only by alta uro in Basel.
Member of the Swiss Society of Urology Member of the Quality Register of the Swiss Society of Urology Certified cooperation partner of the German Cancer Society Certified medical advice center of the German Continence Society
