Electroporation of lymph nodes

Electroporation of lymph nodes in prostate cancer

Targeted and gentle removal of affected lymph nodes without irradiation or surgery

Illustration 1: The lymphatic system.1

Prostate cancer often spreads into the surrounding lymph nodes. This is called lymph node metastases. The standard treatment is the surgical removal of all pelvic lymph nodes, which is a substantial intervention. Targeted radiation therapies can be an alternative, but these therapies severely restrict the options of follow-up treatments, which are unfortunately often necessary in case of scattered cancer. With NanoKnife, there now is the possibility for high-precision and minimally invasive treatment of lymph node metastases without radiation or surgery.

What are lymph nodes and lymph node metastases?

Lymph nodes are up to one centimeter large, bean-shaped organs, which are interlinked and connected to the so-called lymphatic system. They are also part of the immune system. In the lymph system, instead of blood, lymph fluid (called lymph) is transported. In this system the lymph nodes are the stations, where the lymph is filtered.

Lymph node metastases are the scattered cancer cells in lymph nodes (metastasization). They usually cause no symptoms. Usually they are detected either by modern imaging techniques or by the histological analysis of the lymph nodes themselves, when removed prophylactically during a surgery.

Illustration 2: The remodulation of lymphatic vessels, which pre-drives the metastasis in cancer.2

Case 1: The prostate itself has not yet been treated. When and how should (possibly) affected lymph nodes be treated or removed?

The radical surgical removal of the lymph nodes, also called lymphadenectomy, is still a standard method in prostate cancer. Most of these are performed within the prostate surgery (prostatectomy). While you get a realistic diagnostic value by getting more precise information about the affected lymph nodes compared to non-invasive methods (like MRT and PET), there still is a discussion about the true survival benefit of lymph node removal. The additional information gained is offset by massive side effects. The idea behind the radical lymphadenectomy is this: if the primary tumor and the infected lymph nodes are removed from the body, the cancer is also completely removed and the disease is healed.

Unfortunately human biology is not that simple: with every cancerous disease, cancer cells and their secretions and their micro vesicles are spread all over the body. For example, in every prostate carcinoma, cancer cells are found outside the “prostate capsule” (which actually does not exist, but only represents the outer layers of the organ) and in the blood. They can be detected by special tests. Only with this explanation can the high rate of recurrence after radical prostatectomy of more than 50% in some cases (depending on state of the disease) be understood. Especially with the diagnosis of lymph node metastases, removal of the lymph nodes is pretty unlikely to heal the cancer.

Recent studies suggest, that the “seed and soil” model is closer to the process of metastasis. If this assumption is confirmed, the current guidelines based on the cascade model have to be renewed.3

The ectomy of lymph nodes, in particular the preventive removal of pelvic lymph nodes (enhanced lymph node dissection, eLND) still is controversial. Despite all side effects, is it still better to remove them, than to treat them targeted if necessary? Here are some facts:

  1. The presence of lymph node metastases in prostate cancer has an effect on life expectancy (in cancerous diseases typically calculated as percentage survival probability after 5, 10 and 15 years, for example: 15-year survival rate). The existence of infected lymph nodes is a so called predictive factor for the 15-year survival rate.
  2. The number and the volume of all infected lymph nodes are linked to the 15-year survival rate. The more infected, the worse the prognosis.
  3. Removal of lymph node metastases seem to have a positive effect on the 15-year survival rate. Only conclusive randomized trials can clearly prove this assumption. Unfortunately these do not exist.
  4. Prophylactic removal of lymph nodes (eLND) against targeted systematic removal of lymph nodes only at a time when they are conspicuous in images (MRI or PET) and exceed a certain size is not sufficiently evaluated to find a conclusion.
  5. Modern imaging techniques (PSMA/Cholin-PET mpMRT) are very good for finding metastatic lymph nodes of a certain size (typically over 1cm). Microscopic metastases cannot be found, or there is limited capacity for finding them. Whether it makes any difference for the 15 year survival rate, what size the lymph nodes that are removed or treated is not sufficiently investigated, as explained under Point 4.
  6. The prophylactic removal does not replace regular follow-up checks with images and PSA value. Firstly, not all pelvic lymph nodes can be removed because they are very difficult to find during an operation. Second, the possibility of a further incidence of metastases in the rest of the lymph system or body is absolutely not eliminated by the removal of some lymph nodes. 

Case 2: The prostate cancer has already been treated or operated on but the PSA value increases again. The MRI or PET shows affected lymph nodes.

Despite the discussion about whether prophylactic removal (eLND), despite all side effects, is better than targeted removal after imaging techniques, this question no longer arises in many cases. The prostate has been removed totally or has been treated without the removal of the lymph nodes.

The first thing we need is a good imaging technique of the whole body. PSMA/choline PET-CT or the multiparametric MRI are the imaging methods of choice for this purpose. After the lymph nodes have been localized, they have to be treated. If and when an anti-hormonal therapy will be started, does not depend on this question: the (visible) tumor mass in the body should always be kept as close as possible to 0—as carefully as possible.

Targeted focal treatment of lymph node metastases in prostate cancer—the gentle alternative

The focal therapy of metastases of infected nodes by means of IRE (Irreversible Electroporation), ECT (Electrochemotherapy) and their combination called IRECTis an effective but still a gentle image-controlled alternative to radiation therapy and surgery.

Illustration 3: Short-term electroporation of the cells, allowing molecules such as Bleomycin to pass the cell membrane.4

The treatment has to be performed only once, completed within 24 hours and usually is completely free of pain. Furthermore, there are no scars or radiation damage which would eliminate subsequent treatments. For this reason we will explain the IRECT here. Anyone who wants to understand the techniques used in detail is most welcome to read the following summary of the biophysics of pulsed electric fields. In case of the lymph node treatment (unlike the therapy of the prostate) surgery is usually done by computer-assisted systems in a CT.

Illustration 4: Cascination CAS ONE Infratorot VR-Computer Guidance System. 


The first important step: the precise diagnosis

Illustration 5: Diagnosed lymph node metastases (green arrows), clearly visible in the MRI.

For planning a therapy a precise diagnostic is absolutely necessary. The often practiced surgical approach “just to open it and look what is in there” is just as unacceptable as the “large-area irradiation, in order to catch everything”.

MRI (Magnetic Resonance Imaging) is the most valuable tool in precise localization, as well as screening and the early detection of lymph node metastases. However, the MRI is by far the most complex machine in modern medicine, with the result that there are few experts who can achieve optimal MRI imaging.

We are leading experts in MRI imaging of prostate carcinomas. Professor Stehling, our Director, is one of the leading personalities in the history of the development of MRI technology. He has been active in research at Siemens and with Sir Peter Mansfield, who received the Nobel Prize for his work in MRI.

In some cases, PET (Positron Emission Tomography) provides further specific information about the spread of malignant tumors in the body; especially in prostate carcinomas when combined with the PET tracer choline or PSMA (Prostate-Specific Membrane Antigens). We advise you to consult only experts.

Talk to us to schedule an appointment.

Comprehensive advice, diagnostic and therapy for lymph node metastaseseverything is gathered in our Vitus Prostate Center in Offenbach

The development of a concept for the therapy of a metastatic prostate carcinoma should be plannedbut especially continuously and personally supervised by experts. Treatments of the lymph nodes, irradiation, hormone therapy, but also chemotherapy and new immune therapies are often not coordinated during the therapy, indeed are often not even explained or offered. In one hospital there will be a surgeon, in the next clinic irradiation and in the next, the hormonal therapy. It does not have to be like this. We take care instead of just treating.

We recommend you get a second opinion before you decide on any therapy.

Talk to us

Illustration 6: In the Vitus Prostate Center in Offenbach, you can find the latest imaging techniques and therapy technologies for treatment of prostate cancer and lymph node metastases in one house.

References:

1. Brown, P. (2005). Unlocking the drains. Nature, 436(July), 456–458.

2. Stacker, S. a, Williams, S. P., Karnezis, T., Shayan, R., Fox, S. B., & Achen, M. G. (2014). Lymphangiogenesis and lymphatic vessel remodeling in cancer. Nature Reviews. Cancer, 14(3), 159–72. https://doi.org/10.1038/nrc3677

3. Zylka-Menhorn, Vera: “Karzinomchirurgie: Ist die Lymphadenektomie nicht mehr zeitgemäß?“ Dtsch Arztebl 2009; 106(26): A-1353 / B-1151 / C-1123.

4. IGEA GmbH.

Datta, Kaustubh, et al. “Mechanism of lymph node metastasis in prostate cancer.” Future oncology 6.5 (2010): 823-836.

Abdollah, Firas, et al. “More extensive pelvic lymph node dissection improves survival in patients with node-positive prostate cancer.” European urology 67.2 (2015): 212-219.

https://www.europeanurology.com/article/S0302-2838(14)00779-9/abstract/reply-from-authors-re-christian-stief-mere-extension-of-the-field-of-resection-cannot-be-the-answer-to-surgery-for-metastatic-spread-we-need-individualized-approaches-based-on-modern-imaging-techniques-eur-urol-2015-67-220-1-does-extended-pelvic-lymph-node-dissection-really-improve-survival-in-prostate-cancer-patients-with-node-positive-disease-or-is-it-the-will-rogers-phenomenon-again