Bipolar radiofrequency ablation, a novel method for focal therapy of prostate cancer, appears a safe and feasible treatment option, according to findings from a pilot study.
First author Ahmet Murat Aydin, MD, urologic oncology fellow at H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, discussed the study results and their implications in an interview with CancerNetwork®.
CancerNetwork®: First, can you talk about the focal therapy of localized prostate cancer, its rationale and other focal therapy options?
Aydin: Sure. Prostate cancer has a variety of presentations. Low-risk localized prostate cancer (PCa) is usually clinically insignificant and shows a very favorable prognosis. In fact, overtreatment of low-risk localized PCa is associated with quality of life issues without any survival benefit. In 2016, the Protect Trial from the UK demonstrated that active surveillance was comparable to surgery and radiotherapy in terms of cancer-specific survival for low-risk localized PCa. However, about 10% of men on active surveillance still undergo definitive radical treatment each year. Pathological disease progression, PSA increase and patient choice are major drivers of demand for radical treatment. In this regard, focal therapy can provide an optimal control and minimize adverse events associated with radical treatment at the same time. So far, six different focal therapy modality were used for PCa: cryotherapy, high-intensity focused ultrasound, photodynamic therapy, laser interstitial thermotherapy, brachytherapy, and irreversible electroporation.
Can you please provide a little background on the novel treatment modality you assessed in this pilot study?
Focal bipolar radiofrequency ablation (fRFA) is a novel treatment modality which was never tested in PCa before. In our pilot study, we treated the patients with ENCAGE™ fRFA system (Trod Medical® Bradenton, FL). It has a unique design with its radio frequency-based helical ablation probe confining the electrical field between the bipolar electrodes and limiting the spread of energy beyond the destruction zone. Prior to the fRFA, all patients were evaluated with multiparametric prostate MRI and they underwent transperineal mapping prostate biopsy to identify cancerous sites. The fRFA were carried out under general anesthesia and transrectal ultrasound guidance. We ablated both cancer lesions, the 3-mm surrounding margins of normal tissue as well as non-index cancerous lesions in multifocal tumors.
What was the design of this study?
At Moffitt Cancer Center we conducted two subsequent prospective pilot trials between 2011 and 2017. We treated 10 patients with fRFA. All patients had cT1c PCa. Gleason score was less than 8 and PSA level was less than 10 ng/mL in all treated patients. We excluded patients with a prostate volume larger than 60 cc. Our goal was to evaluate treatment-related adverse events, quality of life and negative biopsy rate at 6 months after fRFA procedure.
What were the main findings of this pilot study and their potential significance?
Overall, fRFA was very feasible and safe. All adverse events were low grade and transient, with the exception of one grade 3 hematuria that required cystoscopy without coagulation. fRFA could also successfully ablate all cancer sites in 7 out of 10 patients. The negative biopsy rate was comparable to previously reported studies using the similar ablative approach as ours. At six months after fRFA, bowel, urinary and hormonal functions, and overall satisfaction remained stable in the treated patients. None of the patients had urinary incontinence, urinary retention or urinary infection. These are very promising data since urinary tract infection and urinary retention were reported in patients treated with other focal treatment modalities. We noted erectile dysfunction in two out of four patients who had normal sexual function at baseline prior to fRFA. Although unexpected, this is consistent with the literature since erectile dysfunction was reported up to 50% in the other focal therapy studies. However, we ablated all cancer-positive sites detected in mapping biopsy. Ablation of dominant lesion only might provide better sexual outcomes in the future studies. Secondly, we evaluated short-term outcomes however there is a probability of recovery of erectile function beyond 6 months.
What future areas of research do you see being explored for focal bipolar radiofrequency ablation following the release of this pilot study?
First of all, although focal therapy options appear to be comparable in terms of efficacy, each focal therapy modality has its own pitfalls. In this regard, I am particularly excited about potential role of fRFA since the feasibility and toxicity data is very encouraging in this pilot study. With that said, we definitely need to do further research to evaluate oncological and sexual function outcomes of fRFA. Another area of potential future investigation may be to look at efficacy of retreatment of residual cancer disease using repeat fRFA.
Beyond that, regardless of the focal therapy device, there are many exciting opportunities to improve focal therapy of PCa. There has been a lack of high-quality evidence regarding efficacy and safety of focal therapy so far. Nonetheless, a phase III randomized trial of focal therapy (PCM301 trial) demonstrated that focal vascular-targeted photodynamic therapy reduced the subsequent higher-grade cancer and conversion to radical therapy in patients with low-risk localized prostate cancer. This high-level evidence underscores the great therapeutic potential of focal therapy. Another good example for the opportunities is the continued rapid progress in imaging technology. We used transperineal mapping biopsy to detect cancer sites per study protocol. But even at that time, MRI-ultrasound fusion biopsy emerged as a novel diagnostic tool for PCa and proven to be advantageous over standard practice. I hope that with the future advances in the imaging technology, further refinement of patient selection and better targeting of tumors will become possible in the field of focal therapy.
Aydin AM, Gage K, Dhillon J, et al. Focal bipolar radiofrequency ablation for localized prostate cancer: Safety and feasibility. Published online ahead of print, August 6, 2020. International Journal of Urology 2020. doi: 10.1111/iju.14321
Financial Disclosure: Dr. Aydin has no conflict of interest. Trod Medical US, LLC provided the equipment and funding for the aforementioned study.