Why We Treat Some Prostate Cancer With Focal IRE – NanoKnife©
Whilst most prostate cancers occupy large areas of the prostate, there are some that occupy less than half and often less than a quarter of the prostate gland. These more focal prostate cancers probably constitute about 20% of all prostate cancers. With high quality3T multiparametric MRI combined with template 3D transperineal biopsies and sometimes combined with PSMA PET scanning, it is now much more possible to identify this select group of patients. The advantage of focal treatments of the prostate with energy sources such as the NanoKnife allow eradication of the cancer with minimal side effects.
Whole-gland therapies such as surgery, radiotherapy and brachytherapy have a long and established track record in the treatment of multifocal and high grade prostate cancer. However, their use in more focal cancers may be regarded as overtreatment based on recent data from a large randomised trial (PROTECT trial ). Furthermore, radical prostatectomy, radiotherapy and brachytherapy have a significant side effect profile including urinary incontinence, impotence and rectal damage which are largely avoided by focal NanoKnife therapy.
Why Focal Nanoknife (IRE)
Of the different energy sources used to treat focal prostate cancer, these can largely be separated into thermal energies using freezing and heating and non-thermal energies. Thermal energies such as cryotherapy, high intensity focused ultrasound and laser therapy destroy all tissue including cellular and non-cellular elements as well as nerves and blood vessels and major structures such as rectum, bladder and sphincter. Furthermore, it is difficult to reliably get heat and cold into some tissues with high blood flow and calcification. NanoKnife (IRE) is a non-thermal ablative energy which selectively destroys cells whilst preserving non-cellular tissue elements.. Needles are placed into the prostate via the skin behind the scrotum and a high power electrical current is passed between the electrodes to destroy the cancer and approximately 1 cm of surrounding tissue . IRE has low toxicity on critical anatomical structures such as vessels, nerves (neurovascular bundle) and organs such as the rectum, bladder and urinary sphincter. This makes this technology particularly attractive in the prostate wherestructures such as the neurovascular bundle which supplies erections, the rectum and the sphincter are very close by. Furthermore, this energy source isextremely reliable in destroying the tissue irrespective of the nature of the tissue. Finally, this is arepeatable treatment whereas other therapies such as brachytherapy andradiotherapyare not.
How Is Focal IRE Done?
After a full workup to ensure that our patients are suitable for the program they then undergo a day surgery procedure which takes between 40 and 60 minutes. Depending on the extent of the cancer this may simply ablate the lesion, a quarter of the prostate or a half of the prostate. No prostate cancer cells are resistant to this treatment. Large areas can be treated with minimal side effects.
After the treatment patients stay in the day surgery unit for two to four hours and they are discharged home with a Foley catheter in place. Postoperatively pain is minimal and patients are discharged with tablets for mild pain, moderate pain, bladder spasms and relaxation of the prostate and antibiotics as required.
On day 2 a limited multiparametric MRI is performed. The Foley catheter is left in for two to five days depending on the extent of the treatment.
- Focal gleason large-volume Gleason 6 prostate cancer, Gleason 3+4=7 focal prostate cancer and Gleason 4+3=7 focal prostate cancer and select low-volume Gleason 4+4 prostate cancer.
- PSA < 15
- MRI identifiable tumour which correlates perfectly with targeted biopsies.
- Template biopsies confirmed nosignificant prostate cancer outside of this region or outside of that side of the prostate.
- Patient refuses standard therapies such as surgery, radiotherapy and brachytherapy.
- Patientover 55 and preferablyover 60.
- Patient fit for general anaesthesia.
- Patient accepts the need for ongoing monitoring.
We believe that this treatment is ideal for patients with limited cancer of intermediate grade (Gleason 3+4 or 4+3 or small Gleason 4+4 tumours). We do not believe that multifocal cancer or very high grade cancer should be treated with this focal therapy as the results of surgery, radiotherapy and brachytherapy in these more extensive cancers is much more established.
We have now treated 200 patients since February 2013.
All patients have been meticulously followed up ( 100% followup )with validated quality of life questionnaires and high quality MRIs and biopsies
Our current outcomes for focal irreversible electroporation in the primary setting (not after radiotherapy) is:
- 97% clearance of the primary tumour.
- 0% ongoing incontinence.
- Less than5% erectile dysfunction.
- No major (Clavien 3 or 4) complications.
- Less than10% recurrence in other parts of the prostate ( up to 5 year Follow up ), one third of which had successful redo treatments.
- Thirty patients had focal IRE after radiation with no major complications, < 5% mild incontinence and < 20% erectile dysfunction with 90% clearance of the primary tumour.
Currently we are conducting an international multicentre trial to evaluate the role of focal NanoKnife therapy in patients who failed radiotherapy (FIRE trial).
Quality of life questionnaires from our research team.
Multiparametric MRI at six months.
Transperineal biopsy at 12 months.
Possible PSMA PET scanning if these studies are indeterminate.
Ongoing Active Surveillence
- Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer
Prostate Cancer and Prostatic Diseases 2014, 1-5
Valerio M, Stricker P, Ahmed HU, Dickinson L, Ponsky L, Shnier R, Allen C, Emberton M
- Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control
Prostate Cancer and Prostatic Disease (2016) 19, 46–52
Ting F, Tran M, Bohm M, Siriwardana A, Van Leeuwen P, Haynes A, Delprado W, Shnier R, and Stricker P
- Step-by-Step Technique for Irreversible Electroporation of Focal Prostate Cancer: An Instructional Video Guide
J Vasc Interv Radiol. 2016 Apr;27(4):568
Ting F, Van Leeuwen PJ, Stricker P
- Feasibility and safety of focal irreversible electroporation as salvage treatment for localized radio-recurrent prostate cancer
BJU Int. 2017 Nov;120 Suppl 3:51-58. doi: 10.1111/bju.13991. Epub 2017 Sep 19
Scheltema MJ, van den Bos W, Siriwardana AR, Kalsbeek AMF, Thompson JE, Ting F, Böhm M, Haynes AM, Shnier R, Delprado W, Stricker PD
- Focal irreversible electroporation as primary treatment for localized prostate cancer
van den Bos W, Scheltema MJ, Siriwardana AR, Kalsbeek AMF, Thompson JE, Ting F, Böhm M, Haynes AM, Shnier R, Delprado W, Stricker PD
BJU Int. 2017 Aug 10. doi: 10.1111/bju.13983.
- Preliminary Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Detect Residual Prostate Cancer Following Focal Therapy with Irreversible Electroporation
Eur Urol Focus. 2017 Nov 1. pii: S2405-4569(17)30244-4. doi: 10.1016/j.euf.2017.10.007. [Epub ahead of print]
Scheltema MJ, Chang JI, van den Bos W, Böhm M, Delprado W, Gielchinsky I, de Reijke TM, de la Rosette JJ, Siriwardana AR, Shnier R, Stricker PD
- Pair Matched Patient Reported QOL following Focal IRE versus Robot Assisted RP : An alternative approach to study outcomes of a new PC Treatment. 2018
Submitted with minor revision World Journal of Urology
Scheltema M …. Stricker PD
- Genito-Urinary Function & QOL after Focal IRE of different Prostate Segments
Submitted to Diagnostic & Interventional Radiology 2018
Scheltema M …. Stricker PD
- Stricker PD. Nanoknife focal therapy. Invited speaker. 3rd Friends of Israel Urological Symposium 5-7th July 2016. Tel-Aviv, Israel.
- Tran M, Jackson B, Boehm M, Haynes A-M, Stricker P, Irreversible Electroporation for Focal Prostate Cancer: Safety, Short-term Functional and Oncological Outcomes. Poster Presentation. 68th Urological Society of Australia and New Zealand Annual Scientific Meeting 11th – 19th April 2015, Adelaide, South Australia
- Van den Bos W, Stricker PD et al. Focal Therapy Using IRE in prostate cancer. Synergy Miami, November 2016. Miami Beach, Florida USA.
- Siriwardana A, van den Bos W, Kalsbeek A, Thompson J, Ting F, Boehm M, Haynes A, Shnier R, Delprado W and Stricker PD. Focal Irreversible Electroporation (IRE) as a primary and salvage treatment for localised prostate cancer. USANZ 2017 Annual Scientific Meeting 24-27th February 2017, Canberra, Australia
- Scheltema, MJ, van den Bos W, Siriwardana AR, Kalsbeek AMF. Thompson JE, Ting F, Bohm M, Haynes AM, Shnier R, Delprado W, Stricker PD. Focal Irreversible Electroporation as primary and salvage treatment for prostate cancer. 5th Global Congress on Prostate Cancer. 28 – 30 June 2017, Lisbon Portugal
- Scheltema MJ, Chang JI, van den Bos, Bohm M, Delprado W, Gielchinsky I, de Reijke TM, de la Rosette J, Sirawardana AR, Shnier R, Stricker PD. Diagnostic Accuracy of Mulitparametric Resonance Imaging Following Prostate Cancer Focal Therapy with Irreversible Electroporation. 93rd Annual Meeting Western Section of the American Urological Association, 6 -10 August 2017, Vancouver British Columbia Canada
- Scheltema MJ, Chang JI, van den Bos, Gielchinsky I, de Reijke TM, Sirawardana AR, Bohm M, de la Rosette J, Stricker PD. Genito-Urinary Function and Quality of Life after Focal Irreversible Electroporation of Different Prostate Segments. 93rd Annual Meeting Western Section of the American Urological Association, 6 -10 August 2017, Vancouver British Columbia Canada
- Scheltema MJ, Chang JI, Bohm B, van den Bos W, Gielchinsky I, Kalsbeek AF, van Leeuwen PJ, de Reijke TM, Siriwardana AR, de la Rosette JJ. Stricker PD. Pair-matched Patient-reported Quality of Life following Focal Irreversible Electroporation versus Robot-assisted Radical Prostatectomy. 37th Congress of the Societe Internationale d’Urologie. 19-22 October 2017, Lisbon Portugal.
- Stricker PD Focal Nanoknife Therapy Invited speaker Tolmar National Symposium
|FOCAL IRE||NERVE-SPARING ROBOT-ASSISTED SURGERY|
|Minimally invasive||Keyhole surgery|
|Day surgery procedure.||One to two days in hospital|
|Two to five day Foley catheter.||Six day Foley catheter|
|Minimal recovery||Three to six week recovery|
|Mild discomfort.||Mild to moderate pain.|
|<1% Major Complications||< 1% major complications.|
|0% incontinence||1-2% ongoing incontinence.|
|< 10% impotence rate||10-30% impotence (recovery period required).|
|Suitable for unifocal tumours||Suitable for multifocal tumours.|
|15% recurrence rate.||PSA recurrence between 10 and 30% depending on extent of tumour.|
|Can be repeated.||Cannot be repeated|
|Needs active ongoing surveillance|
- Focal IRE treatment for the treatment of localised prostate cancer is safe.
- IRE is 97% effective in the eradication of the index lesion of the prostate.
- There is a < 15% recurrence rate in the rest of the prostate at five years of followup.
- IRE has low toxicity and lower common side effects compared to established treatments.
- IRE is suitable for recurrences after radiation therapy.
- Major complications have not occurred in our series of 200 patients with up to five year followup.
- MRI is useful in the followup of patients however it misses between 10 and 20% of recurrences which can only be picked up by transperineal biopsy.
- IRE ideally is used selectively in focal intermediate grade prostate cancer to avoid over treatment by more conventional treatments
- Multifocal intermediate and high grade prostate cancer generally are much more serious conditions than focal intermediate grade prostate cancer and until IRE can be shown to have
Professor Phillip Stricker, St Vincent's Clinic, St Vincent's Prostate Cancer Centre, Garvan Institute, Kinghorn Cancer Centre.
Team: Alexander Blazevski MD, Brian Yuen MD, John Chang MD, Jayne Matthews, Angela Papazoglou, Quoc Nguyen, Anne-Marie Haynes, Maret Boehm, Matthijs Scheltema MD, Willemien Van Den Bos MD, Ilan Gelchinsky MD
The NanoKnife© System has received FDA clearance and TGA clearance for the surgical ablation of soft tissue.