By: Dan Sperling, MD

Prostate cancer therapies have evolved, and continue to evolve, in the direction of reducing side effects while controlling the cancer. The earliest effective treatments were directed at the entire gland, based on the assumption that prostate cancer is always a multifocal disease (scattered throughout the prostate gland). Whole-gland treatments (surgery, radiation and thermal ablation by means of extreme heat or cold) come with varying risks of urinary, sexual or bowel side effects that negatively impact normal function. Impairment may be short- or long-term, and in many cases permanent.

Since the introduction of screening for prostate cancer (PCa) by the PSA blood test, the stage at which PCa is diagnosed has migrated downward from later stage disease to early stage, low risk disease. The idea of focal or targeted treatment for clinically qualified patients—the prostate equivalent of a breast lumpectomy—has become increasingly acceptable. Published data is encouraging, as side effect rates are shown to drop significantly while biochemical disease free rates are comparable to whole gland treatments for early stage, low risk disease.

In the U.S., focal ablation by cryotherapy (freezing) and laser (heat) are FDA-cleared. Other ablation methods available outside the U.S. include HIFU (heat) and photodynamic therapy (cell destruction by chemical sensitivity to a light source). All of these approaches produce tissue death, called necrosis, within the ablation zone. In other words, the ablation source does not discriminate which structures will be destroyed, so the treatment is applied in a way that encompasses the tumor, plus a margin of safety, yet avoids or spares nearby healthy tissues.

There is another FDA-cleared cancer treatment called Irreversible Electroporation (IRE) that can be used against PCa and other organ cancers (liver, pancreas, kidney, lung). It also goes by the brand name NanoKnife®. It operates differently than thermal ablation. The purpose of this article is to explain IRE and how it selectively kills cancer cells.

Cell structure

All living organisms are composed of tiny structures called cells, which hold the key to life. There are different types of cells with different functions, but most cells hold several pieces, especially a key component called the nucleus. The nucleus contains the DNA that determines the cell’s function. In humans and animals, each cell is a compartment contained by a membrane, a very thin flexible sac composed of proteins and phospholipids. The membrane acts as a wall between the inner liquid that supports cell function, and the outer environment composed of different liquids. The membrane’s proteins surround extremely tiny pores (nanopores) that can move molecules, such as nutrients, in and out of cells. As long as the membrane is intact, the cell safely functions until it is programmed to die off. The process of cell death is called apoptosis, which comes from two ancient Greek words, “apo” (away from) and “ptosis” (falling). Every day, millions of cells go through apoptosis and are disposed of by special clean-up cells.

Cancer cells also have a nucleus and are contained within a membrane. However, their DNA or gene structure is abnormal. They proliferate and function erratically.

Irreversible electoporation (IRE) of the prostate

Irreversible electoporation forces cells to die off by directing electrical energy into them. A number of electrodes in the form of long needles are inserted into the prostate under image guidance. The tips are spaced around the cancerous tumor. The needles are then connected to a generator. Very strong electrical fields are created into the tumor in ultra short pulses. The result forces the membrane’s nanopores to open. There are two types of electroporation:

a)      Reversible electroporation (RE) – the cell can withstand a certain amount of damage, after which it will repair itself and the pores will close. During the period of time they remain open, a chemotherapeutic substance can be introduced into the tumor and will be taken up by the cells. When the pores close, the cell will die (apoptosis) from the toxicity of the therapy.

b)      Irreversible electroporation (IRE) – if the electrical field is strong enough, the nanopores will not be able to close up nor can the cell heal itself. It is commonly believed that apoptosis occurs through the intermingling of the inner and outer liquids. This creates a naturally hostile inner environment for the cell, and it simply dies off (apoptosis).

In either case, the surrounding tissue, veins, nerves and ducts are not affected by the electric field. Healthy cells and tissue can regenerate in the treatment area.

Pros and cons

IRE has several advantages:

1. The actual treatment occurs in a matter of minutes. It is done under sedation because placing the electrodes takes the most time, but the treatment itself involves minimal to no pain and recovery is quick.
2. IRE is selective. It generally does not damage nerves, which are insulated in a current-resistant sheath up to a certain frequency. It preserves structures that are high in protein and collagen. Because it does not generate heat, there is no risk of the uneven ablation that can occur with thermal ablations due to the “heat-sink” effect that compromises the zone of extreme heat or cold.
3. Since IRE causes apoptosis of individual cells, there are none of possible side effects that can occur with wide necrosis (dead tissues) that results from ablation.
4. Image monitoring of IRE treatment can occur in real time through ultrasound, and potentially MRI and CT scans. Success can be quickly evaluated.
5. Patients go home the same day.
6. Many insurance plans cover IRE.
7. IRE is repeatable.

On the other hand, because it generates an electrical field, IRE is not indicated for patients who have pacemakers or a recent history of cardiac problems. There is a limitation on the size of the tumor that can be treated. Muscle relaxants must be administered due to strong muscular contractions that can occur during treatment. Finally, there is no long term data on how effective the treatment is.

Future articles will discuss specific research that has been done on IRE, particularly its use in the prostate.