Focal Therapy Shows Similar Survival to Surgery for Radiorecurrent Prostate Cancer

An international multicenter study compared salvage focal therapy with radical prostatectomy for men with prostate cancer that returned after radiotherapy, finding statistically inconclusive differences in long-term cancer outcomes but markedly different complication profiles. The matched analysis estimated 10-year cancer-specific survival at 92% after focal therapy and 99% after prostate removal surgery, though given sparse cancer-specific deaths and a small 10-year follow-up tail, the comparison was statistically inconclusive rather than confirming similar survival.

The study, published in JAMA Oncology, included 923 men eligible for matching, with 419 treated with focal therapy and 504 treated with prostate removal surgery. Researchers applied statistical matching to construct balanced treatment groups, pairing patients 1 to 1 based on radiotherapy type, time between treatments, recurrence risk group, age, prostate-specific antigen level, prostate volume, grade group, T stage, and androgen-deprivation therapy use.

Cancer-specific survival at 5 years was 99% for both treatments in the matched cohort. Regression modeling produced a subdistribution hazard ratio of 0.45, with a 95% CI ranging from 0.05 to 4.00, indicating substantial uncertainty regarding the magnitude and direction of any survival difference.

Overall survival at 5 years was 90% following focal therapy and 83% following prostate removal surgery. Ten-year overall survival estimates were 57% following focal therapy and 72% following prostate removal surgery.

Perioperative complications were reported more frequently following prostate removal surgery. Any complication occurred in 5.7% of focal therapy patients and 59.9% of surgery patients. Major complications occurred in 1.4% and 12.5% of patients, respectively. Undergoing salvage radical prostatectomy was associated with significantly increased odds of any complication (adjusted odds ratio, 24.20; 95%CI, 12.94-45.27; P < .001) and major Clavien-Dindo grade 3-5 complications (adjusted odds ratio, 9.31; 95% CI, 3.42-25.36; P < .001).

Focal therapy offers a different strategy from surgery. Energy-based treatments such as high-intensity focused ultrasound or cryotherapy destroy only the region containing recurrent tumor, leaving the remaining prostate tissue untreated with the goal of reducing complications. For focal therapy in the study, 77.6% received high-intensity focused ultrasound and 22.4% cryotherapy, with 57.5% overall receiving quadrant ablation.

Prostate removal surgery after radiotherapy is technically challenging because radiation alters tissue structure and healing capabilities. Severe toxic effects are common, including high rates of erectile dysfunction and urinary incontinence. Surgery procedures included 74.6% open radical prostatectomy and 25.4% robot-assisted radical prostatectomy with or without nerve-sparing and lymph-node dissection.

Radiotherapy can deliver excellent long-term cancer-specific survival for prostate cancer, while disease recurrence still occurs in a quarter of patients within 10 to 15 years. Cancer-specific mortality following recurrence is 20% to 35% within 5 to 10 years. Most men with prostate cancer recurrence after radiotherapy get androgen-deprivation therapy, a noncurative treatment with adverse effects. Hormone-resistant disease typically develops within 3 years. A substantial share of recurrences remain confined to the prostate, creating an opportunity for another localized treatment aimed at the tumor itself.

The focal therapy group was culled from the prospective 2006-2024 UK HIFU Evaluation and Treatment and International Cryotherapy Evaluation registries (9 centers) and the prospective 2014-2018 UK Focal Recurrent Assessment and Salvage Treatment cohort study (phase 2b FORECAST trial; 6 centers). The salvage radical prostatectomy group was pulled from a 2000-2021 international retrospective registry (12 centers in 8 countries). Median patient age at salvage focal therapy and radical prostatectomy were 71 and 66 years, respectively.

Separately, a phase 2 trial of a novel cooled laser focal therapy device (ProFocal; Medlogical Innovations) demonstrated promising short-term results. The ProFocal Laser Therapy for Prostate Tissue Ablation study enrolled 100 men with localized prostate cancer at a tertiary center in Australia. The ProFocal system comprises a surgical diode laser, a fiberoptic laser applicator with diffusing tip and, uniquely, temperature feedback monitoring to prevent overheating and tissue charring.

At 3 months, 84% of treated patients had no ISUP Grade Group 2 or higher prostate cancer detected within the treatment zone on biopsy, meeting the study's primary endpoint for treatment success. Overall, 77% of patients had no ISUP 2 or higher prostate cancer on any of their 3-month post-treatment biopsies. The median treatment time was 60 minutes (IQR, 47-70 minutes).

At 3 months, 28% reported adverse events, such as hematuria and erectile dysfunction; only 1 event was Clavien-Dindo grade 3. Functional outcomes were generally preserved. Erectile dysfunction occurred in 12% of patients, with a 15% mean decline in Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite sexual domain scores. Urinary function showed a modest decline, with a 4.5% decrease in EPIC urinary domain scores, while other patient-reported functional measures remained stable.

The Italian Society of Urology released a position statement on focal therapy for localized prostate cancer. The panel identified the ideal candidate for focal therapy as a patient with a unilateral, localized, multiparametric MRI-visible lesion, harboring intermediate-risk prostate cancer (ISUP Grade Group 2) and a life expectancy greater than 10 years. The different energy sources used in focal therapy (cryotherapy, high-intensity focused ultrasound, irreversible electroporation, and transperineal laser ablation) offer comparable oncological and functional outcomes. The choice of energy modality primarily depends on tumor location, physician expertise, and local availability of the technology.

The findings position focal therapy and prostate removal surgery as competing treatment options with statistically inconclusive differences in long-term cancer outcomes and markedly different risk profiles. Treatment decisions require balancing uncertain survival differences against the known potential for treatment-related morbidity.