Focal therapy for prostate cancer: rationale and treatment opportunities

Abstract

Focal therapy is an emerging treatment modality for localised prostate cancer that aims to reduce the morbidity seen with radical therapy, while maintaining cancer control. Focal therapy treatment strategies minimise damage to non-cancerous tissue, with priority given to the sparing of key structures such as the neurovascular bundles, external sphincter, bladder neck and rectum. There are a number of ablative technologies that can deliver energy to destroy cancer cells as part of a focal therapy strategy. The most widely investigated are cryotherapy and high-intensity focussed ultrasound. Existing radical therapies, such as brachytherapy and external beam radiotherapy, also have the potential to be applied in a focal manner. The functional outcomes of focal therapy from several phase I and II trials have been encouraging, with low rates of urinary incontinence and erectile dysfunction. Robust medium- and long-term cancer control outcomes are currently lacking. Controversies in focal therapy remain, notably treatment paradigms based on the index lesion hypothesis, appropriate patient selection for focal therapy and how the efficacy of focal therapy should be assessed. This review articles discusses the current status of focal therapy, highlighting controversies and emerging strategies that can influence treatment outcomes for the future.

Keywords: Focal ablation; focal therapy; future perspective; outcomes; prostate cancer; rationale.

Fig 1

Diagrammatic representation of focal therapy strategies. The red lesion represents clinically significant prostate cancer and the green lesion represents clinically insignificant prostate cancer. The yellow circles represent the neurovascular bundles and the blue rectangle represents the ablation zone. Lesion-targeted therapy is represented by (a)–(c). In (a), unifocal ablation preserves the contralateral neurovascular bundle. In (b), although clinically significant cancer is present bilaterally, one neurovascular bundle is still spared. In (c), clinically insignificant cancer near the second neurovascular bundle is not treated. Only the index lesion is treated, allowing preservation of one neurovascular bundle. In (d), an example of region-targeted therapy, hemi-ablation, is presented.

Fig 2

Magnetic resonance imaging (MRI) appearances before and after focal high-intensity focussed ultrasound treatment to the prostate. A T2-weighted prostate MRI image of a man with presenting prostate-specific antigen of 7.7 ng/ml is given in (a). A scanner with a 1.5 Tesla magnet and a pelvic phased array coil was used to capture images. An anterior prostate tumour is indicated by the red circle. Transperineal template prostate biopsies confirmed high volume Gleason 3 + 3 disease. The patient underwent focal high-intensity focussed ultrasound treatment of the tumour. Six months after treatment, the patient underwent repeat MRI and the T2-weighted MRI image obtained is given in (b). The ablation cavity can be seen with no evidence of residual cancer. Prostate-specific antigen at this time was 1.1 ng/ml.