Focal Therapy for Radiorecurrent Prostate Cancer

Recurrent prostate cancer after radiotherapy presents a significant clinical challenge due to its biological complexity and the variability in how it responds to treatment. Management requires a tailored approach that accounts for the extent and aggressiveness of the disease, patient health, and previous therapies. Androgen deprivation therapy (ADT) remains a foundational treatment for regional or distant recurrence, suppressing cancer growth by targeting androgen pathways. When combined with second-generation agents like abiraterone or enzalutamide, ADT can significantly delay progression and relieve symptoms.

For cases without metastatic spread, local recurrence may be better addressed through salvage therapies. Salvage radical prostatectomy (SRP) can offer a potentially curative option for selected patients, while salvage radiation techniques such as stereotactic body radiotherapy (SBRT), and low- or high-dose-rate (LDR/HDR) brachytherapy are viable alternatives. Minimally invasive approaches—including cryotherapy, high-intensity focused ultrasound (HIFU), and irreversible electroporation (IRE)—have shown promising outcomes when used as focal salvage therapies.

Exploring innovative treatments and participating in clinical trials remains crucial to improving outcomes and personalizing care for patients with radio-recurrent disease.

Targeted Treatments for Localized Recurrence After Radiotherapy

Approximately one in five men who receive radiotherapy for prostate cancer experience a local recurrence, where the cancer returns within the prostate itself. Historically, many such cases were managed with palliative approaches like watchful waiting or hormonal therapy. While hormone therapy can control cancer for 2–3 years, its long-term use may lead to side effects such as metabolic issues (diabetes, cardiovascular disease), bone loss, weight gain, gynecomastia, and fatigue.

Surgical removal of the prostate (prostatectomy) in these cases carries significant risks. Radiation-damaged tissue becomes fibrotic and difficult to operate on, increasing the likelihood of complications such as urinary incontinence (in nearly all patients), bowel damage requiring a stoma (about 1 in 20), and complete loss of erectile function. Additional radiation carries similar toxicity concerns and may be less effective if the cancer has already demonstrated resistance.

As alternatives, salvage HIFU, IRE, and cryotherapy have emerged as less invasive options. These focal therapies use imaging (MRI) and targeted biopsies to precisely identify and treat the cancerous area within the prostate, minimizing damage to surrounding healthy tissue and thereby reducing side effects.

A recent study from the UK involving 356 men who underwent focal therapy for post-radiotherapy recurrence reported that approximately 75% of patients remained progression-free after six years, avoiding the need for further surgery or hormonal therapy. Considering that recurrent prostate cancer tends to be more aggressive than the original tumor, these outcomes are encouraging. Moreover, severe complications were rare, with serious rectal injury occurring in only 0.3% of cases.

Although only a limited number of centers worldwide currently offer HIFU, IRE, and cryotherapy, their availability is expected to grow as more patients and physicians seek effective treatments with fewer side effects.

Mechanism and Rationale for Focal Therapy

Two-thirds of men with localized recurrence after radiotherapy have unifocal or unilateral disease, typically arising from the site of the original (index) lesion. Prostate cancer is usually multifocal, but the index lesion is the primary driver of progression and metastasis. Secondary lesions tend to be less aggressive and often remain dormant or are effectively eliminated by radiotherapy.

Research shows that in 89–100% of recurrences, the cancer re-emerges from remnants of the original index lesion. This supports the rationale for using focal therapies—such as HIFU, IRE, or cryotherapy—to specifically target the index lesion while sparing the rest of the prostate.

Prior to focal therapy, comprehensive imaging (e.g., whole-body MRI or PSMA PET/MRI) is essential to confirm that the disease is confined to the prostate. High-quality multiparametric MRI (mpMRI), PSMA PET/MRI, and mpMRI-guided biopsy are critical for accurate treatment planning.

Our preferred strategy involves ablation of the index lesion with a safety margin. Depending on disease extent, we may also perform quadrant, hemi-gland, or whole-gland ablation—though broader treatment areas are associated with a higher risk of side effects.