Electroporation for Prostate Cancer – Early Clinical Trials

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Dr Lyn Oliver AM PhD
Retired Medical Physicist

New Technique


Information for Patients and Profession

Ablation of the prostate by an electroporation technique is on a ‘better healthcare technology’ clinical trial. The technique offers high cure rate with minimal side effects.

Background

Prostate cancer is the number one cancer incidence for men. And, as this series has explained, it’s not simple for men to decide what might be the best mode of treatment for their prostate cancer. For instance, the pathology, extent of the cancer and the patient’s general physical fitness need to be considered before choosing the optimum treatment.

And, if the medical specialist advises treatment, the patient must also consider the potential after-affects of erectile dysfunction, urinary incontinence and bowel toxicity that surgery and (to a much lesser extent) modern radiation therapy techniques may cause.

The Current Options

Surgery, external IMRT beam radiation therapy and brachytherapy are the mainstays for prostate cancer treatment. Some patients may opt for a less common prostate ablation technique by ultrasound.

Clinical results indicate a cure rate of about 95% for surgery or radiation therapy if it is early-stage prostate cancer. But there’s still a need to develop a more suitable high cure rate technique that avoids the complications of erectile dysfunction, urinary incontinence and bowel toxicity.

IRE – A New Ablation Technique

Ablation of the prostate by an electroporation technique has now been developed sufficiently for clinical trials to begin. IRE has been undergoing a world first clinical trial at approved expert prostate cancer centres. The irreversible electroporation (IRE) technique potentially offers the same high cure rate but with none of the current unwanted complications.

St Vincent’s Hospital, Sydney  is one of 50 centres approved for this IRE clinical trial. Professor Phillip Stricker is a leading international urological specialist in prostate cancer care. Each IRE centre is using the same protocol approved by the US Food and Drug Administration.

Subjecting cells to irreversible electroporation (IRE) by an electric current causes extensive or permanent permeabilisation of the cell membrane. This eventually leads to cell death. The nucleus of the cell becomes unstable due to the leakage of potassium and sodium ions across pores produced in the cell’s membrane. The resultant osmotic imbalance disrupts cellular homoeostasis and causes cell apoptosis.

The technique causes minimal thermal damage in the tissues and the original researchers named this process – non-thermal irreversible electroporation (NTIRE). By positioning the electrodes in the tumour site, NTIRE can selectively ablate the prostate cancer tissues with minimal damage to blood vessels and nerve system in and around the treated volume.

Saviour of the nerves and blood system is important because it avoids causing post-surgery complications such as erectile dysfunction, urinary incontinence and bowel toxicity.

The Ablation Method

Dr Stricker had previously pioneered the development of surgery techniques for prostate brachytherapy and robotic surgery in Australia. He was able to easily adapt the methods he used for the two high-technology techniques for the new IRE procedure.

The NanoKnife unit is specially designed and built for electroporation treatment. It enables the surgeon to insert a calculated number of electrode needles of fixed spacing to repeatedly apply short, 80μs high voltage pulses to the prostate cancer tissue.

The equipment needs to be electrically safe to use during the patient’s surgery under sterile theatre conditions. While deliberately applying the very high current/voltage pulses to the patient’s prostate, the surgical staff must also be protected from receiving an accidental electric shock.

The technique used to insert the electrodes into the image targeted prostate cancerous tissue is similar to that described for the brachytherapy technique. The electrode/needles are inserted into the prostate via a selected number of holes in the grid template spaced 5mm apart. Using an ultrasound probe inserted in the rectum, the surgeon can view a 3 – D image of the needles as they are inserted into the prostate.

Developing the Technique

The IRE method to treat patients was not developed overnight. It involved years of extensive research and development on animal subjects to fully understand the cellular mechanisms that lead to irreversible damage of normal and cancerous cells. The design and engineering safety features of the Nanoknife apparatus had to be perfected and made electrically-safe for patients treated surgically.

The method for calculating the distribution of the electric field around each of the electrode needles inserted into the prostate tissue is also entirely different to the method used to calculate the distribution of radiation dose received from brachytherapy radioactive sources.

Brachytherapy and IRE techniques are both critically reliant on the accurate insertion of the needles in the patient’s prostate cancer tissues.

Successful electroporation treatment depends on the:

• precise distance between the needles;
  
• length of the needles;
  
• size of the voltage pulse;
  
• pulse length of the pulse; and
  
• number of pulses applied.
  

The optimum electrical parameters were initially established from treating dogs that had prostate cancer.

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Summary of IRE Paper

Prostate Cancer and Prostatic Diseases – Focal irreversible electroporation for prostate cancer:

Reference: Prostate Cancer and Prostatic Disease (2016) 19,46–52; doi:10.1038/pcan.2015.47; published online 13 October 2015

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The Goals of IRE

“If irreversible electroporation could achieve equal or even better cure rates than conventional methods, AND not having the complications of incontinence and impotency, IRE may well be the preferred future mode of treatment.

But, since there’s currently insufficient clinical evidence on the success of irreversible electroporation for the treatment of prostate cancer (PCa) this paper was designed to evaluate the safety, short-term functional and oncological outcomes of focal IRE. The clinical study chose low to intermediate risk PCa cases.”

Advantages of NTIRE are:

• it maintains the immune system to all parts of the ablated tissue via the blood vessels;
  
• it provides a simple treatment technique using the needle electrodes;
  
• the electric treatment is applied in a short time (less than one minute) requiring reduced time for anesthesia and any surgical complications; and
  
• it can be monitored during the operation by conventional imaging techniques.
  

The Treatment Protocol

The trial took place from February 2013 to May 2014 with 32 patients receiving IRE at St Vincents’ Hospital, Sydney. The patients were specially chosen having low-intermediate risk prostate cancer and no previous prostate treatment.

Method

Their prostate tumour was ablated using 3–6 electrodes, encompassing a minimum 5-mm safety margin around the visible magnetic resonance image (MRI) lesion diagnosed by the specialist team’s radiologist.

Muscle paralysis was first administered, then 10 test pulses were delivered to verify the actual electrical field generated in the treatment zone.

• The voltage is  variable up to 3 kV with the pulse passing between two electrodes for a few microseconds.
  
• the electrodes were inserted 10 mm to 20 mm apart (depending on the prostate target dimensions) and a maximum electrode exposure length per needle was 20 mm.
  
• the distances between all electrodes were measured in the axial plane using trans-rectal ultrasound.
  
• the Nanoknife system was then programmed to deliver 90 pulses with pulse length of 70 μs.
  
• patients were discharged home on the day of surgical procedure.
  

The trial required that each patient be subjected to a fixed protocol following IRE treatment of:

• specific tests to assess complications;
  
• questionnaires (at 1.5, 3, 6 months);
  
• 6-month MRI; and
  
• a biopsy at 7-month.
  

The MRI and biopsy results were recorded for the regions inside, adjacent and outside the prostate tumour volume. 

Results

There were twenty-five men remaining in the final analysis. One patient was found to have Grade 3 (pathology) complications and five other patients had Grade 1 complications. There were no significant complications in urinary, sexual or bowel functions.

There were no suspicious in-field findings on MRI or biopsy in all patients. Five patients (21%) had suspicious findings in the volumes adjacent to the treatment zone for MRI with four (19%) which proved significant by biopsy. There were also two (8%) outer region sites with suspicious MRI findings of which one (5%) was a significant finding on biopsy.

For the five patients with significant findings on follow-up biopsy, one is awaiting repeat IRE, one had radical prostatectomy and three remained on active surveillance.

Authors’ Conclusions:

The Sydney Hospital research team concluded from their trial so far were:

1. For selected patients with low-intermediate risk prostate cancer, focal IRE appears to be a safe technique with minimal morbidity.
   
2. There were no recurrences in the treatment zone and 76% of patients were histologically free of significant cancer at 8 months.
   
3. Almost all recurrences were found to be adjacent to the treatment zone. This will be addressed by widening the treatment margins.
   

The clinical trial in all centres are continuing with further data obtained over time.

Lyn Oliver, 17 August 2017

(Revised 10 August 2019)

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Editorial Note:

If and when NTIRE clinical trials demonstrate that the technique’s prostate cancer cure rate is equal or better than the conventional treatment methods and there are none of the unwanted complications caused by conventional techniques, then patients will be able to consider NIRE as another option.

But looking at the down-side, new high-technology methods in medicine are expensive. For instance, the fees charged by surgeons are high and the NTIRE electrode needles are very expensive to purchase. The needles can only be used for the one operation. Additionally, the number of prostate cancer cases diagnosed each year far exceeds the workload that surgery can support. Radiation therapy helps to stop treatment waiting times from becoming unacceptably long.

Just as in its early-stage robotic surgery went through a shortage period for those who could receive treatment, referrals to a skilled NTIRE surgeon will be difficult, will be excessively expensive (compared to the other treatment options) and will not receive Medicare support at a level commensurate to the costs charged.

Despite the high cost, it could be tomorrow’s preferred option when NTIRE becomes a proven method with widespread use for prostate cancer patients. Only time will tell if that’s the case.

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This is a scientific and technically based article. It is not intended to provide medical advice and is for information only.

If you have any health problems or questions related to your health, then please consult your doctor.

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