PRESERVE Two-Year Results: Is Oncological Control Durable With Focal Irreversible Electroporation in Intermediate-Risk Prostate Cancer?

KEY FINDINGS

• No new failures: No new treatment failure was detected at 24 months of follow-up. Of the 72 patients eligible for analysis, 68 (94.4%) completed the month 24 assessment; no new treatment failure was reported between 12 and 24 months.
• PSA: PSA continued to run below baseline in 97% of patients (66/68). No cancer was found in the single patient (1.5%) biopsied on clinical indication.
• Safety: No new device- or procedure-related adverse event was reported between 12 and 24 months.
• Month 12 primary outcome: In-field negative biopsy rate 71% (95% CI: 62-79); 84% when defined by the Delphi consensus criterion (95% CI: 76-90). Freedom from treatment failure was 80% in patients undergoing protocol biopsy.
• New AUA 2026 subanalysis: Mean IPSS fell from 8.1 to 6.1; however, significant improvement was observed mainly in men with a prostate volume below 80 cm³.
• Functional preservation: 84% of patients with good sexual function at baseline maintained erections sufficient for penetration at month 12.

Background: Why Is Focal Therapy on the Agenda?

In localized prostate cancer, radical prostatectomy and radiotherapy are standard treatments of proven oncological efficacy. However, because both approaches target the whole gland, they carry a certain cost in terms of urinary continence and erectile function. Particularly in intermediate-risk disease that is unifocal or of limited volume and visible on MRI, focal therapies targeting the "index lesion" are attracting increasing interest with the claim of striking a balance between oncological control and quality of life.

Irreversible electroporation (IRE) is a method that differs in this field in terms of its mechanism. Unlike thermal ablation techniques such as HIFU and cryotherapy, IRE neither heats nor freezes tissue. High-voltage, very short electrical pulses create permanent nanopores in the cell membrane and trigger a cell death resembling apoptosis. Because the collagen scaffold, vessel walls and nerve structures are relatively preserved, it offers a theoretical advantage in lesions adjacent to the neurovascular bundle. In addition, the "heat-sink" effect seen with thermal techniques does not apply to IRE.

Study Design

PRESERVE (NCT04972097) is a prospective, non-randomized, single-arm, pivotal IDE trial evaluating the safety and efficacy of focal IRE delivered with the NanoKnife System. It was conducted at 17 centres in the United States in collaboration with the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC).

Key Results

The 12-month primary analysis (European Urology, 2026)

In terms of functional outcomes, a mean change of +3 points was recorded in the UCLA EPIC urinary domain total score from baseline to month 12, and a mean change of -2 points in the IPSS total symptom score. 84% of patients with good sexual function at baseline maintained erections sufficient for penetration at month 12. On the safety side, CTCAE grade ≥3 adverse events were observed in 14 patients (12%); three of these were procedure-related grade 3 events.

The 24-month update (AUA 2026)

New subanalysis: prostate volume and lower urinary tract symptoms

A subanalysis presented at AUA 2026 and derived from the same cohort (Lokeshwar et al.) examined the course of lower urinary tract symptoms after focal IRE. Mean IPSS fell from a baseline value of 8.1 to 6.1 at month 12. However, this improvement was not homogeneous: significant symptom improvement was observed predominantly in men with a prostate volume below 80 cm³. Timothy D. McClure (Weill Cornell Medicine) emphasises that in prostates of 80 g and above, despite performing a volume-reducing procedure such as IRE, the volume could not be reduced to a level that would produce a noteworthy improvement in IPSS scores.

Implications for Clinical Practice

1. The second year is confirmatory for durability of oncological control, but not definitive

The absence of new treatment failure between 12 and 24 months and PSA curves remaining below baseline are a meaningful signal supporting the durability of the ablation effect. However, a careful reading is required here: protocol biopsy was not mandatory at month 24; only one patient was biopsied on clinical indication. These data therefore represent the absence of clinically detected new failure, not a pathological response rate confirmed by protocol biopsy. Given the natural history of prostate cancer, 5- and 10-year oncological outcomes will still be decisive.

2. Focal therapy is not a replacement for radical treatment but an alternative in the selected patient

PRESERVE is a single-arm trial; it contains no direct comparison with radical prostatectomy or radiotherapy. The 71% in-field negative biopsy rate is below the pathological control expected after surgery. Focal IRE should therefore not be presented as a substitute for a patient who is suitable for and prefers radical treatment. The appropriate candidate profile is a patient with a single index lesion clearly visible on MRI, a disease map established by systematic and targeted biopsy, Grade Group 2-3 intermediate risk, and the ability to adhere to a rigorous follow-up protocol.

3. Prostate volume is now a patient selection parameter

This is the most practical implication of the subanalysis. A significant proportion of patients with whom we discuss focal therapy also complain of lower urinary tract symptoms because of accompanying BPH and naturally hope that the procedure will also help those symptoms. The data show that in prostates of 80 cm³ and above this expectation may not be met. In these patients, separating the goals clearly from the outset - addressing the oncological goal and the functional goal separately and, if necessary, discussing a separate treatment plan for BPH - both creates realistic expectations and prevents dissatisfaction after treatment.

4. The follow-up protocol is an inseparable part of the treatment

By the nature of focal therapy, the risk of cancer developing in areas outside the ablation zone persists. Serial PSA measurement, follow-up with multiparametric MRI and, where necessary, protocol biopsy are mandatory. The decision for focal therapy is at the same time a commitment to long-term follow-up; it is not an appropriate option for a patient who cannot meet that commitment.

5. The multidisciplinary board and informed consent

The patient needs to hear the options of active surveillance, radical prostatectomy (robot-assisted - multi-port or single-port), radiotherapy and focal therapy comparatively, together with their levels of evidence. Pivotal-level prospective evidence for focal IRE currently extends to 2 years, and this information should be a natural part of the consent process.

Limitations of the Study

• PRESERVE is a non-randomized, single-arm trial and contains no comparator arm.
• The number of patients eligible for the 24-month analysis is limited to 72; not all of the full 121-patient cohort has reached this time point.
• Because there was no mandatory protocol biopsy at month 24, the possibility of undetected residual disease cannot be excluded.
• The follow-up period is short in terms of the natural history of prostate cancer.
• The trial was supported by the device manufacturer.
• The IPSS subanalysis is post-hoc in nature and should be regarded as hypothesis-generating.
• The results were obtained at high-volume centres and in experienced hands, and their generalisability should be interpreted in that context.

Glossary

• Irreversible electroporation (IRE): A non-thermal ablation method that causes cell death by creating permanent pores in the cell membrane with short, high-voltage electrical pulses.
• Focal therapy: Targeting only the index lesion containing the cancer rather than the whole prostate.
• In-field negative biopsy: The absence of cancer in a biopsy taken from the ablated area.
• IPSS: International Prostate Symptom Score; a questionnaire measuring the severity of lower urinary tract complaints.
• IDE trial: The regulatory framework in the United States permitting the clinical evaluation of a medical device before approval.

Conclusion

The 24-month PRESERVE data show that oncological control with focal irreversible electroporation in intermediate-risk prostate cancer is maintained into the second year and that the safety profile remains stable. This is one of the largest prospective pivotal datasets conducted in the field of focal therapy in the United States and places the field on solid ground.

Nevertheless, these findings should be read not as a thesis setting focal therapy against radical treatment but as an extension of the principle of the right treatment for the right patient. The prostate volume analysis from the same cohort is instructive in showing how much fine-tuning that principle requires: oncological suitability alone is not enough; functional expectations must also be consistent with anatomical reality.

In prostate cancer there is no single answer called "the best treatment". The best treatment is the one that fits the biology of the disease, the anatomy of the prostate and the patient's life priorities all at once. This decision should be made together, without haste and with all options discussed openly.

References

• George AK, Miocinovic R, Patel AR, et al. Irreversible Electroporation for Prostate Tissue Ablation in Patients with Intermediate-risk Prostate Cancer: Results from the PRESERVE Trial. Eur Urol. 2026;89(1):57-68. doi:10.1016/j.eururo.2025.06.003 (PMID: 40685282)
• McClure TD. Timothy McClure, MD, on 2-year PRESERVE trial results for focal IRE. Urology Times. 31 August 2026.
• AngioDynamics. AngioDynamics Announces Two-Year PRESERVE Trial Data Demonstrating Durable NanoKnife IRE System Outcomes in Intermediate-Risk Prostate Cancer. Press release, 13 May 2026.
• Lokeshwar SD, Ramirez J, Aronowitz S, et al. Lower Urinary Tract Symptom Improvement After Focal Irreversible Electroporation for Localized Prostate Cancer: 12-Month PRESERVE Trial Results. J Urol. 2026;215 (AUA 2026, IP37-18).
• Scheltema MJ, Geboers B, Blazevski A, et al. Median 5-year outcomes of primary focal irreversible electroporation for localised prostate cancer. BJU Int. 2023;131(S4):6-13. doi:10.1111/bju.15946
• ClinicalTrials.gov. NCT04972097.