“Introducing the ultimate technology in Precision Medicine for Prostate Focal Therapy.”

“TSPA is the only technology designed for Prostate Focal Therapy”

These bold claims announce the availability of Tissue Sparing Prostate Ablation (TSPA), known by its brand name as Encage. Encage uses a specific type of radiofrequency ablation (RFA), which basically cooks a tumor by running an electrical current produced by a radio wave through tissue. This generates heat that destroys the target tissue yet spares untreated tissue outside the area.

Radiofrequency ablation

RFA is not new. It has been in clinical use for three decades. It is viewed as an effective, versatile and relatively inexpensive safe treatment of isolated cancer tumors in the liver, kidney, adrenal gland, bone, lung and breast.^[i] Since it involved image-guided insertion of a slender electrode probe or coil, it is performed as a minimally invasive procedure under general or local anesthesia, and for some applications conscious sedation. Depending on the tumor and its location, post-treatment pain control may be necessary, including overnight hospital stay. However, with increasing technological improvement, pain may be minimal and able to be managed well.

Focal prostate cancer treatment

Traditionally, prostate cancer (PCa) patients had two fundamental treatment choices: either radical (whole gland) treatment by surgery or radiation, or deferring treatment in favor of monitoring PCa through Watchful Waiting (WW) or Active Surveillance (AS). The past two decades have seen increasing application of focal treatment aimed at destroying a focus of significant PCa while preserving quality of life (urinary, sexual and bowel function). Focal therapy thus became a middle ground between whole-gland treatment and deferred treatment.

Methods of applying focal treatment have included cryotherapy, HIFU, laser interstitial therapy (Focal Laser Ablation), irreversible electroporation, and vascular-targeted photodynamic therapy. Now, in addition to our own Focal Laser Ablation, we have added the latest focal therapy advances: Exablate (MRI-Guided Focused Ultrasound) and TULSA-PRO.

In 1998, a research team tested the feasibility of using RFA to treat prostate cancer.^[ii] In their study of 15 patients, 14 had prostatectomy following RFA, while one patient had a total gland ablation and was followed by PSA monitoring. The authors noted that in one of the prostatectomy specimens subject to ablation in both prostate lobes, tumor cells were still observed in one lobe upon post-surgery pathology exam.

More recently, RFA using the Encage device was clinically tested for focal therapy of PCa. As described in a 2018 paper by Lepor, et al.,

Radiofrequency ablation (RFA) allows for precise delivery of ablative energy to the prostate. Using the Encage™ device (Trod Medical, St Petersburg, FL), a corkscrew cage is manipulated into the prostate under TRUS guidance. Operating on the Faraday principle, thermal ablation is achieved through RFA induced hyperthermia within the boundaries of the treatment device. The challenge is optimal placement of the radiofrequency cage and contouring cage placement to the configuration of an intended ablation template.^[iii]

From 2014-2018, the H. Lee Moffitt Cancer Center and Research Institute conducted a clinical study designed to evaluate “the safety and efficacy of focal (targeted) Radio-Frequency Ablation (RFA) in men with low or intermediate-risk, clinically localized prostate cancer.” The study team reported their findings in a 2020 journal article:

• The study objective was to assess negative biopsy rate at 6 months post-RFA, track adverse events, and evaluate quality of life (urinary and sexual function).
• RFA was done under general anesthesia; bipolar probes with coil design were inserted transperineally under transrectal ultrasound guidance.
• 10 patients were treated, all of whom had stage T1c, Gleason score < 8, and PSA < 10. All patients had multiparametric MRI and transperineal mapping biopsy before treatment.
• RFA successfully ablated all PCa sites in 7 out of 10 patients.
• All patients were catheter-free and able to urinate the day of surgery.
• Adverse effects were low grade with the exception of one that required minor intervention.
• At 6 months, 2 out of 4 men who had normal baseline sexual function experienced ED.
• There were no instances of urinary incontinence or infection.^[iv]
• At 6 months, the negative biopsy rate was “comparable to previously reported studies

In August, 2020 CancerNetwork® spoke with the study’s first author, Ahmet Murat Aydin, MD about the study. He mentioned that all tumor ablations included 3-mm surrounding margins of normal tissue. With regard to cancer control, he noted, “The negative biopsy rate was comparable to previously reported studies using the similar ablative approach as ours,” though he did not specify exact data.^[v]

Questions remain

In a sense, the collective research and development for an ideal focal PCa treatment technology is a little like seeking the Grail. As I read the published study abstract, I was left with questions. If 7 out of 10 patients had successful ablations, what happened to the other 3? What was the 6-month biopsy rate?

More concerning is a topic not addressed in the Aydin, et al. study: circulating tumor cells following RFA of cancerous tumors. I found two studies on this topic.

a) 2015 paper by Chudasama, et al. may be the first study on RFA of lung tumors and its effect on releasing circulating tumor cells (CTCs) into the bloodstream; by testing before-and-after blood samples of 9 RFA patients, the authors found elevated numbers of CTCs in 7 out of 9 patients, which they attributed to the manipulation and RFA of the lung tumors.^[vi]

b) Perhaps even more powerful, Zhu, et al. (2021) studied the release of CTCs during RFA of prostate cancer tumors implanted in lab animals. They write, “Clinical and experimental findings have disclosed a high recurrence rate after radiofrequency ablation (RFA), which might be due to the dissemination of malignant cells into the vasculature during ablation… Our study thus suggests that the ablative procedure of prostate tumors causes immediate tumor cell dissemination and increases distant metastasis.”^[vii]

Clearly, more focal RFA for PCA studies using larger numbers of patients and longer-term follow-up are needed. While the pilot study conducted at Moffitt is promising, with “comparable” results to other focal ablation modalities, I find the suggestion of released CTCs disturbing—more science is needed there, too.

Finally, I suggest that the designers of the TSPA patient website revise the wording of their claims. If, indeed, RFA of prostate tumors is shown to circulate tumor cells, raising the risk of metastatic PCa, it can hardly be the “ultimate technology” for focal PCa treatment. Likewise, the device manufacturers of systems that deliver focal cryo, focal HIFU, and Focal Laser Ablation can hardly be pleased to see TSPA labeled as “the only technology designed for Prostate Focal Therapy.” Not only is the claim inaccurate, but TSPA is simply a new kid on the block of proven, respected methods of delivering thermal energy for the focal destruction of PCa tumors.

To sum up, it is to the advantage of PCa patients to have an array of proven options. If TSPA fulfills its promise and joins the ranks of focal therapies, it may not be the Grail, but it provides one more way for doctors and patients to match a treatment to the disease. In today’s world, that IS each man’s best choice.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Friedman M, Mikityansky I, Kam A, Libutti SK et al. Radiofrequency Ablation of Cancer. Cardiovasc Intervent Radiol. 2004; 27(5): 427–434.
[ii] Zlotta AR, Djavan B, Matos C, Noel JC et al. Percutaneous transperineal radiofrequency ablation of prostate tumour: safety, feasibility and pathological effects on human prostate cancer. Br J Urol. 1998 Feb; 81(2):265-75.
[iii] Lepor H, Gold S, Wysock J. Focal Ablation of Prostate Cancer. Rev Urol. 2018; 20(4): 145–157.
[iv] Aydin AM, Gage K, Shillon J, Cheriyan SK et al. Focal bipolar radiofrequency ablation for localized prostate cancer: Safety and feasibility. Int J Urol. 2020 Oct;27(10):882-889.
[v] “Focal Bipolar Radiofrequency Ablation is a Potential Treatment Modality for Localized Prostate Cancer.” CancerNetwork interview. Aug. 23, 2020. https://www.cancernetwork.com/view/focal-bipolar-radiofrequency-ablation-is-a-potential-treatment-modality-for-localized-prostate
[vi] Chudasama D, Rice A, Anikin V, Soppa G, Dalal P. Circulating tumour cells in patients with malignant lung tumors undergoing radio-frequency ablation. Anticancer Research. 2015 May; 35(5):2823-2826.
[vii] Zhu X, Wei C, Zhang Y, Meng Z, et al. Monitoring radiofrequency therapy-induced tumor cell dissemination by in vivo flow cytometry. Cytometry A. 2021 Jun;99(6):593-600.