Half of Focal Therapies in Prostate Cancer Are Given to Patients Outside Guidelines: A JAMA Analysis of 1.18 Million Patients

KEY FINDINGS

• Focal therapy is still rare: Only 1.3% (15,672 patients) of 1,179,384 patients with non-metastatic prostate cancer received focal therapy.
• Patient selection is problematic: 51.0% (7,985 patients) of those receiving focal therapy were in the low, high or very high risk group; only 49.0% (7,687 patients) were in the intermediate-risk group that guidelines open to discussion.
• Temporal trends diverge: While use in favourable intermediate-risk disease rose from 2.1% to 2.9%, it fell from 2.1% to 0.9% in high risk and from 1.8% to 0.5% in very high risk (P<0.001).
• No decline in the low-risk group: In this group, where active surveillance is standard, the rate rose from 1.8% to 2.2% (P=0.46).
• The technology has changed completely: Cryotherapy fell from 79.8% to 19.1% while laser ablation rose from 14.6% to 45.8% and other ablative methods including HIFU rose from 5.6% to 35.1%.
• Determinants of off-guideline use: Older age, low-risk disease, high comorbidity burden, non-private insurance reimbursement, treatment at a community hospital or a high-volume centre.

Background: The Promise and the Limit of Focal Therapy

Prostate cancer is the most frequently diagnosed cancer in men, with a lifetime risk affecting approximately one man in eight. Radical prostatectomy and radiotherapy have the strongest evidence base for long-term oncological control; however, permanent side effects such as urinary incontinence and erectile dysfunction represent a real cost for patient and physician alike.

Focal therapy sits in the middle of this dilemma: by targeting only the tumour-bearing region rather than the whole prostate, it claims to achieve oncological control while preserving healthy tissue, the sphincter mechanism and the neurovascular bundles. HIFU, cryotherapy, laser ablation and, in recent years, vascular-targeted photodynamic therapy are considered under this heading.

The problem is the distance between the claim and the level of evidence. The current AUA/ASTRO Clinically Localized Prostate Cancer Guideline (2026 Amendment) recommends that patients be clearly told that whole-gland or focal ablation is investigational in low and intermediate risk disease, emphasising the absence of high-quality data comparing focal therapy with standard treatments. In high-risk disease, ablation is not recommended outside a clinical trial.

Study Design

The team, with Professor Quoc-Dien Trinh, Chair of Urology at the University of Pittsburgh, as senior author, conducted a retrospective cross-sectional analysis of the US National Cancer Database (NCDB) together with investigators from UPMC, the University of Toronto, Harvard Medical School, IRCCS San Raffaele and the Cleveland Clinic.

Key Results

Temporal trends by risk group (2010 → 2023)

Change in the ablative technology used

This table shows that the technological backbone of focal therapy has been completely renewed over thirteen years. The era in which cryotherapy dominated has passed, giving way to laser ablation and HIFU-based approaches that provide more precise targeting under imaging guidance. Technological maturation, however, does not on its own guarantee the accuracy of patient selection.

Implications for Clinical Practice

1. This is a two-way mismatch

The findings do not paint a one-directional picture of "overtreatment". In low-risk patients, focal therapy means unnecessary intervention in a group in which active surveillance can be applied safely; in high and very high risk patients, the same procedure carries the risk of undertreatment. This second group requires radical surgery and/or a multimodal approach for long-term oncological control.

2. The right place: carefully selected intermediate-risk disease

At the current level of evidence, the most defensible field of use for focal therapy is unifocal or index-lesion-dominant intermediate-risk disease, well characterised on MRI and confirmed by targeted biopsy. The upward trend observed in the favourable intermediate-risk group (2.1% → 2.9%) can be read as a shift in the right direction.

3. Imaging and biopsy quality are decisive

The success of focal therapy depends entirely on the accuracy of the tumour map. A focal ablation performed without multiparametric MRI, PSMA PET/CT and systematic plus targeted fusion biopsy raises the risk of missing the index lesion to an unacceptable level. Multifocal disease is a variable not captured in the NCDB analysis but critical in clinical practice.

4. Shared decision-making must include the word "investigational"

When focal therapy is offered to a patient, it must be clearly shared that this approach is still regarded as investigational in guidelines, that there are no randomized data directly comparing it with standard treatments, and that the possibility of retreatment is real. Transparent information is the foundation of patient trust and treatment satisfaction.

5. Structural factors must not be overlooked

The increased likelihood of focal therapy at community hospitals, in the non-private insurance reimbursement group and in patients with a high comorbidity burden suggests that decisions are shaped not only by tumour biology but also by access, reimbursement and centre characteristics. This is a concrete target area for quality improvement work.

Limitations of the Study

• The NCDB covers only Commission on Cancer-accredited centres; focal therapies performed at non-accredited centres may not have been recorded - the true rate of use may be higher than reported.
• Long-term oncological outcomes, toxicity, quality of life, retreatment rates and cost data are not available in the database.
• Information on tumour multifocality, patient preferences and participation in clinical trials or prospective registries is not available; some cases classified as "off-guideline" may have been conducted under protocol.
• The retrospective design does not permit causal inference.

Conclusion

This analysis is not an argument against focal therapy; it is a caution about patient selection. The gain of the past twenty years in prostate cancer surgery has been the move away from "the same treatment for every patient" towards a risk-based, individualised management model. Focal therapy is a natural part of that model - but only when it rests on the right patient, the right imaging and the right biopsy foundation.

Progressing without sacrificing oncological safety to concern for quality of life, and without sacrificing quality of life to unnecessary radicalism, is the fundamental balance of contemporary uro-oncology. This study shows that the balance has not yet been fully struck at the scale of the United States; but that the marked decline observed in high-risk disease is a correction in the right direction.

References

• Cosenza A, Nguyen DD, Qian Z, et al. Focal Therapy for Prostate Cancer. JAMA. 2026. doi:10.1001/jama.2026.12411
• Clarke H. Focal therapy for prostate cancer frequently used outside guideline-supported groups. Urology Times, 14 August 2026.
• University of Pittsburgh / EurekAlert! Half of prostate cancer focal therapy use falls outside current guideline-supported groups. 13 August 2026.
• Eastham JA, Barocas D, Chu C, et al. Clinically Localized Prostate Cancer: AUA/ASTRO Guideline Amendment (2026). J Urol. doi:10.1097/JU.0000000000005060
• Medical Xpress. Half of prostate cancer focal therapy use found to fall outside current guideline-supported groups. August 2026.