Prostate cancer affects over 299,000 men in the United States annually, yet the five-year cancer-specific survival rate stands at 97%. The challenge is not just treating cancer but doing so without devastating side effects that significantly impair quality of life.
Traditional treatments, radical prostatectomy (removal of the entire prostate) and whole-gland radiation, remove or destroy the entire gland even when cancer is confined to a small area. Radical prostatectomy leads to erectile dysfunction in up to 30% of men and urinary incontinence in 70-80%. Radiation causes similar rates of dysfunction in 30-50% of patients.
Given these side effects, 10-30% of men report regret about how they managed their prostate cancer. Many want active treatment rather than surveillance but are unaware that less invasive options exist. Advances in multiparametric MRI now allow clinicians to precisely locate and characterize tumors before treatment, making targeted approaches more feasible.
Focal therapy treats only the cancerous area within the prostate rather than the entire gland, aiming to eliminate the disease while preserving surrounding healthy tissue and its functions. This approach has attracted growing interest as a middle ground between active surveillance and whole-gland treatment.
High-intensity focused ultrasound (HIFU) uses precisely aimed sound waves to heat and destroy targeted prostate tissue. The Sonablate device was used in this series. HIFU was introduced at this institution in 2024, explaining its small representation in the study cohort.
Cryoablation destroys tissue by rapid freezing using ultrathin probes inserted through the skin. The Endocare and Galil probe systems were used. Cryotherapy has been used for whole-gland and focal prostate treatment for decades and has an established safety record.
Irreversible electroporation (IRE), marketed as NanoKnife, applies electrical pulses that permanently damage cell membranes, killing tumor cells. Unlike heat or cold-based methods, IRE can be applied near sensitive structures like nerves and blood vessels with less collateral damage, making it attractive for lesions close to the neurovascular bundle responsible for erections.
All 45 patients in the study underwent pre-treatment multiparametric MRI within three months of therapy. Patient selection was based on Grade Group 1-2 disease and favorable-to-intermediate risk classification. PSA was measured at 4-6 weeks, then at 3, 6, and 12 months post-procedure, with an MRI at one year.
The study included 45 patients: 4 treated with HIFU, 20 with cryoablation, and 21 with IRE. Mean patient age was 70.1 years. Two-thirds (67%) received focal treatment of a specific lesion, and 33% received hemi-gland treatment of half the prostate. Nearly 29% had received prior treatment for prostate cancer, reflecting focal therapy's use in the salvage setting after radiation or prior ablation.
The majority of patients (78%) had favorable intermediate-risk prostate cancer, with 67% having Grade Group 2 disease. Mean preoperative PSA was 7.7 ng/mL. IRE had the fastest operative time at 43 minutes, versus 65 minutes for cryoablation and 114 minutes for HIFU, a statistically significant difference.
Only 3 patients (all cryoablation) underwent post-treatment biopsy during the study window, all showing biochemical recurrence with Grade Group 2 cancer. No patients developed metastasis or died during the median 6-month follow-up. Mean post-treatment PSA dropped to 3.1 ng/mL overall, with statistically significant reductions for IRE and cryoablation individually.
The overall complication rate was 36%, but only 4% of all cases had complications graded Clavien-Dindo IIIa or above, meaning major complications were rare. This compares favorably with radical prostatectomy, which carries approximately 9% serious complication rates.
Before treatment, 60% of patients already had erectile dysfunction (ED) and 51% had lower urinary tract symptoms (LUTS), reflecting the older patient population. Post-treatment, only 2 new cases of ED developed (one IRE, one cryoablation), and 5 new cases of LUTS appeared (two IRE, three cryoablation). This represents a meaningful preservation of baseline function.
The literature confirms these results. A review of 49 focal therapy studies found that the vast majority reported low to moderate impact on sexual function, with only two studies reporting severe sexual side effects. Focal cryoablation studies show 74-98% of men who were potent before treatment maintained erections sufficient for sexual intercourse.
Urinary continence outcomes were particularly strong. Multiple large series reported 95-100% pad-free rates after HIFU or cryoablation. IRE showed especially strong continence rates, with several series reporting essentially 100% pad-free outcomes, compared to approximately 70-80% rates following radical prostatectomy.
One important nuance is that focal therapy specifically targets only the tumor-bearing area, directly preserving neurovascular bundles and the sphincter mechanism responsible for continence and erections. Whole-gland treatments, by definition, affect all these structures regardless of where the cancer sits.
One of the unique contributions of this study is its inclusion of cost data, a factor largely absent from the focal therapy literature. Mean cost of IRE was USD 3,762 and mean cost of cryoablation was USD 4,648, with no statistically significant difference between them. The overall mean cost across both modalities was USD 3,805.
These costs represent operating room disposable supplies and machinery rental only. Anesthesia costs and operating room block time were excluded, meaning the true total costs to the healthcare system are likely higher. No cost data were available for HIFU patients in this series.
Published economic modeling using Markov models found that focal therapy had lower overall costs and higher quality-adjusted life year gains compared to radical prostatectomy or radiation therapy. One Brazilian study estimated the cost of HIFU treatment at approximately USD 1,100 per patient, though cost structures differ substantially between countries.
Given that no focal therapy modality appears to be significantly superior to another in functional or oncologic outcomes, cost should become a more prominent factor in treatment selection decisions. IRE's combination of lower operative time and comparable cost makes it potentially attractive from a resource-efficiency standpoint.
Despite growing clinical use, focal therapy is not currently endorsed by the American Urologic Association or the NCCN guidelines for primary treatment at any prostate cancer risk level. The exception is salvage HIFU and cryoablation for patients who relapse after radiation therapy, where guidelines do support focal approaches.
The European Association of Urology is somewhat more permissive, stating that HIFU and cryoablation may be considered for select patients in clinical trials or prospective cohort studies. The FALCON consensus project has published recommendations for refining partial gland ablation, representing the most recent attempt to build expert consensus around best practices.
The absence of randomized clinical trials comparing focal therapy to radical prostatectomy or radiation is the key evidence gap. The only randomized trial in the field compared vascular-targeted photodynamic therapy to active surveillance, showing lower disease progression in the focal therapy group, but this does not directly answer the comparison against curative whole-gland treatment.
Designing such a trial is challenging because the ideal patient population is difficult to define, cancer localization must be confirmed pre-treatment, and meaningful survival outcomes may require decades of follow-up. Many urologists are already using these therapies in clinical practice outside trials, driven by patient preference and the improving precision of MRI-guided biopsy.