Men with localised prostate cancer have long been offered a choice between treating the whole gland and treating nothing. The ProtecT trial showed that, at ten years, deaths from prostate cancer were few whether men were assigned to active monitoring, radical prostatectomy or radiotherapy, although progression and metastasis were more frequent with monitoring (Hamdy et al., 2016). The companion report on patient-reported outcomes documented the price of radical treatment: urinary leakage and loss of erectile function were worst after surgery, and bowel symptoms after radiotherapy (Donovan et al., 2016). Many men, particularly those with intermediate-risk disease, find neither option comfortable.

Focal therapy was proposed as a third course. Onik et al. (2002) described cryoablation confined to the side of the gland containing tumour, with the explicit aim of preserving potency, and likened the idea to lumpectomy for breast cancer. Since then high-intensity focused ultrasound, cryotherapy, irreversible electroporation, vascular-targeted photodynamic therapy, focal laser ablation and focal brachytherapy have all been used to ablate part of the prostate (Valerio et al., 2017). The technologies differ, but the clinical questions they raise are the same.

This review addresses two of those questions: how patients should be selected and how they should be followed. Both have been the subject of formal consensus exercises, and both remain less settled than the volume of publication might suggest.

The article is a narrative review of the published literature. It relies on the diagnostic trials that underpin modern lesion localisation, on prospective and registry series of focal therapy, on systematic reviews of those series, and on Delphi consensus statements and guidelines. No formal search strategy was applied, and the sources were chosen for their influence on current practice. Salvage focal therapy after radiotherapy is not covered.

Prostate cancer is usually multifocal. Whole-mount studies of prostatectomy specimens found several separate tumours in most glands, but the largest focus accounted for most of the tumour volume and the secondary foci were typically small and of low grade (Wise et al., 2002). Genomic analysis of men who died of metastatic disease indicated that their metastases shared a single clonal origin (Liu et al., 2009). From these observations came the index lesion hypothesis: that one dominant focus drives the natural history of the disease, and that destroying it may be sufficient while small low-grade foci elsewhere are observed (Ahmed, 2009).

The hypothesis is reasonable and not proven. The lethal clone is not always the largest lesion, and the behaviour of untreated tissue over decades is unknown. Focal therapy is therefore best understood as treatment combined with continued surveillance of the remaining gland, a point that shapes both selection and follow-up.

Selection has three components: the grade and extent of the cancer, the confidence with which it has been localised, and the characteristics of the man himself. Table 1 summarises the criteria on which consensus statements broadly agree and the points that remain open.

The prospective development study of focal high-intensity focused ultrasound by Ahmed et al. (2012) established that unifocal and multifocal lesions could be ablated with a low rate of genitourinary side effects. Focal cryotherapy has been reported from a large national registry (Ward and Jones, 2012). A multicentre series from the United Kingdom reported five-year outcomes in men of whom most had intermediate- or high-risk cancer (Guillaumier et al., 2018), later extended to a larger cohort with longer follow-up (Reddy et al., 2022). A phase 2b study of MRI-guided focused ultrasound enrolled men with intermediate-risk disease (Ehdaie et al., 2022). Across these reports continence was preserved in the great majority and erectile function in most, while a minority of men required retreatment or went on to radical therapy.

The limits of this evidence are plain. Almost all of it is single-arm. The one large randomised trial, of padeliporfin vascular-targeted photodynamic therapy, compared treatment with active surveillance in men with low-risk cancer, a group for whom intervention is now seldom recommended (Azzouzi et al., 2017). An updated systematic review found that the quality of the evidence had improved little over five years and that definitions of success still varied between studies (Hopstaken et al., 2022). European guidelines accordingly advise that focal therapy be offered within a clinical trial or a well-designed prospective registry (Mottet et al., 2021).

Follow-up after focal therapy has to answer two questions at once: whether the ablation destroyed the target, and whether significant cancer has appeared in the untreated gland. Figure 1 places follow-up in the pathway of care, with the main tool used at each stage.

The central gap is comparative evidence. Randomised trials against radical treatment have proved difficult to recruit, because men who seek focal therapy are often unwilling to be allocated to surgery. Prospective registries with agreed selection criteria, a fixed biopsy schedule and standard definitions are the practical alternative, and their value depends on completeness of follow-up. Long-term data are also needed: prostate cancer evolves over decades, and most series report medians of only a few years. Further questions concern the place of prostate-specific membrane antigen imaging in selection, the validation of post-ablation MRI scoring, and whether a safe schedule can be defined that spares men repeated biopsy when imaging and PSA are reassuring.

Focal therapy offers men with localised, well-characterised, intermediate-risk prostate cancer a means of treating the dominant lesion with a low risk of incontinence and a moderate risk to erectile function. Its results depend on accurate localisation with mpMRI and combined biopsy, on restricting treatment to men whose disease fits the index lesion model, and on disciplined surveillance in which a control biopsy, not PSA alone, determines success. The evidence is still largely uncontrolled. Until comparative and long-term data are available, treatment within prospective registries or trials, with candid counselling about retreatment, is the defensible standard.

To be declared by the author(s) before publication.

To be declared by the author(s) before publication.