Extended Focal Ablation of Localized Prostate Cancer With High-Frequency Irreversible Electroporation

Abstract

IMPORTANCEFocal therapy of prostate cancer must balance the oncologic outcome and functional outcome. High-frequency irreversible electroporation (H-FIRE) can destroy cancer cells while selectively preserving surrounding nerves and blood vessels, but no clinical trials have been conducted, to our knowledge. OBJECTIVE To evaluate the efficacy and safety of H-FIRE in the treatment of localized prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS This was a single-group, objective performance criteria, nonrandomized controlled trial. Recruitment began on May 2, 2018, and ended March 27, 2019. The follow-up duration was 6 months. This was a multicenter trial conducted at 4 tertiary teaching hospitals in China. Patients with low or intermediate risk of biochemical recurrence of localized and locally advanced PCa were eligible. Key inclusion criteria were serum prostate-specific antigen (PSA) level less than 20 ng/mL, clinical stage of T2c or less, and Gleason score of 7 or less. Data were analyzed from January 20 to February 20, 2021. INTERVENTION H-FIRE ablation of all lesions identified with biopsy. MAIN OUTCOMES AND MEASURESThe primary end point was 6-month clinically significant PCa (csPCa), which was defined as any biopsy core with Gleason score of greater than or equal to 7, or Gleason score of 6 plus maximum cancer core length of greater than 3 mm or an increase from the original cancer burden. Secondary outcomes were calculated in patients who actually received H-FIRE treatment.RESULTS A total of 117 patients (median [IQR] age, 67 [62-73] years) were recruited from 4 centers, and 109 patients (27 [24.8%] low risk and 82 [75.2%] intermediate risk) actually received H-FIRE. Median (IQR) PSA level was 9.0 (6.0-12.7) ng/mL. Among the 100 patients who underwent biopsy at 6 months, the 6-month csPCa rate was 6.0% (95% CI, 2.2%-12.6%; P < .001; 1 in the treatment zone and 5 outside the treatment zone). Superiority criteria vs the historical control of 20% was achieved. PCa was detected in 14 patients, with a Gleason score of 7 in 2 patients and 6 in the remaining 12 patients. At 6 months, median (IQR) PSA level was 1.08 (0.4-3.2) ng/mL, median (IQR) International Prostate Symptom Score was 4.5 (2.0-9.5), and median (IQR) International Index of Erectile Function 5 score was 2.0 (0.5-12.5). Superiority vs the 20% historical control was also met in the subgroup analysis that only included the 57 patients with Gleason score of 7 at baseline (3.5% 6-month csPCa; 95% CI, 0.4%-12.1%). CONCLUSIONS AND RELEVANCEThe rate of 6-month csPCa with H-FIRE ablation was lower than the historical control using other energy platforms.

Focal Therapy for Prostate Cancer—Moving Beyond Technology Assessment

“…We believe the data presented by Wang et al are reasonable in demonstrating histologic efficacy of the ablation technique they studied. Nonetheless, the broader clinical questions essential to establish focal therapy for prostate cancer remain unanswered—namely in whom is this therapy oncologically effective and how should we define oncologic efficacy?…”

“…Wang et al provide histologic efficacy data for an energy modality for the focal treatment for localized prostate cancer . The study offers a promising proof of concept in the continuing development and refinement of techniques for focal treatment in prostate cancer.…”

Irreversible electroporation and electrochemotherapy in oncology: State of the art

“…Pathological analysis showed that there was no viable prostate cancer within the ablation zone, which had been replaced by tissue necrosis and inflammatory response [48] Clavien-Dindo Grade III-IV adverse event observed. A risk of recurrence or residual tumor of 3% at 6 months and 2.7% at 12-months was demonstrated [49,50]. Disease-free survival, defined as avoidance of whole gland therapy or metastasis/death related to prostate cancer was 96.75% at 3 years [49].…”

Boosting the Immune Response—Combining Local and Immune Therapy for Prostate Cancer Treatment

“…IRE is the permeabilization of cell membranes with electrical pulses, which affect membranous electrochemical potentials, creating pores in a lipid bilayer [ 238 ]. IRE has been already used in PC management, both as a focal therapy, and as the whole gland ablation [ 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 ]. The procedure is based on needle electrodes, which are placed inside or nearby the targeted tissue.…”