Pittsburgh researchers have uncovered a striking mismatch between the patients receiving focal therapy for prostate cancer and the men for whom current clinical guidelines support the approach. In a national analysis published in JAMA, the investigators found that approximately half of the men treated with focal therapy had either low-risk disease, for which treatment may be unnecessary, or high- and very high-risk disease, for which the limited evidence supporting focal therapy may not be sufficient. The findings do not suggest that focal therapy should be abandoned. Instead, they raise a critical question about how rapidly emerging cancer technologies move from specialized centers into routine clinical practice—and whether treatment is reaching the patients most likely to benefit.
Focal therapy is designed to treat only the portion of the prostate containing clinically significant cancer rather than removing or irradiating the entire gland. Depending on the technology used, clinicians may destroy targeted tissue with heat, freezing, ultrasound energy or other forms of image-guided ablation. The concept is biologically and clinically attractive: by limiting treatment to the tumor-bearing region, physicians hope to preserve more of the surrounding prostate and reduce complications associated with whole-gland surgery or radiation. Those complications can include urinary incontinence, erectile dysfunction and other changes that may substantially affect quality of life. Yet the precision of the procedure depends on accurately identifying the important cancer within the prostate, determining whether disease is truly localized, and ensuring that untreated tissue does not contain clinically meaningful tumor.
The study was led by Quoc-Dien Trinh, M.D., M.B.A., professor and chair of the Department of Urology at the University of Pittsburgh School of Medicine. Researchers used information from the National Cancer Database to examine treatment patterns among 1,179,384 men aged 50 and older who were diagnosed with nonmetastatic prostate cancer between 2010 and 2023. Of those patients, 15,672 received focal therapy. The database provides a broad view of cancer care across the United States, allowing investigators to evaluate how treatment is being used beyond the highly selected populations typically enrolled in clinical trials. When the researchers compared the treated men with contemporary risk-based recommendations, they found that about half fell outside the groups for whom focal therapy is generally supported.
The central issue is the biological diversity of prostate cancer. Risk classification is based on factors such as prostate-specific antigen levels, tumor grade, the extent of cancer in biopsy samples and clinical imaging findings. Men with low-risk disease often have tumors that grow slowly and may never threaten their health. For many of these patients, active surveillance—regular monitoring with blood tests, imaging, repeat biopsies and clinical assessment—can avoid or delay treatment without compromising the opportunity for cure. Focal therapy in this setting may expose a patient to procedural risks and long-term side effects without providing a clear medical advantage over observation. Treating a tumor that is unlikely to progress can turn a condition suitable for monitoring into a source of avoidable harm.
The opposite concern applies to men with high- or very high-risk prostate cancer. These tumors are more likely to extend beyond the original focus, invade surrounding tissue or eventually spread to other parts of the body. Destroying a visible or biopsy-confirmed lesion may not eliminate microscopic cancer elsewhere in the prostate or beyond it. For such patients, surgery, radiation combined with hormone therapy, or other multimodal treatments may offer stronger evidence for durable cancer control. Focal therapy can be highly targeted, but that strength can become a limitation when the disease is biologically aggressive or more extensive than imaging reveals. A treatment that controls one tumor focus may not adequately address the full burden of a high-risk cancer.
For appropriately selected men with intermediate-risk disease, however, the balance can be different. These patients may have cancer significant enough to warrant intervention but localized enough that treatment confined to the dominant tumor could be reasonable. The strategy seeks to preserve healthy tissue while controlling the lesion most likely to determine the cancer’s behavior. Modern imaging, particularly multiparametric magnetic resonance imaging, can help identify suspicious areas and guide targeted biopsies, while advanced navigation systems can assist in planning ablation. Even so, imaging and sampling are imperfect. Prostate cancer may be multifocal, with clinically important disease distributed in separate regions that are difficult to detect or treat through a single targeted procedure.
The researchers stress that their analysis describes treatment patterns rather than proving that every individual procedure was inappropriate. The National Cancer Database does not contain all of the information needed to judge the clinical reasoning behind a treatment decision. It does not fully capture participation in clinical trials or prospective registries, and it lacks detailed long-term outcomes such as cancer recurrence, metastasis, retreatment, side effects, quality of life and treatment cost. A patient outside a guideline-supported category may have received focal therapy as part of carefully monitored research, or because other medical considerations made conventional treatment less desirable. Conversely, a patient who appears to fit an accepted category may still have disease features that make focal therapy unsuitable.
That limitation also highlights a broader challenge in modern medicine: the gap between technological promise and definitive evidence. New procedures can spread quickly when they offer an appealing combination of precision, reduced invasiveness and fewer visible side effects. But a lower short-term burden does not automatically mean equivalent long-term cancer control. Prostate cancer can take many years to recur or progress, making extended follow-up essential. A procedure that preserves sexual or urinary function in the first months after treatment must also be evaluated against the possibility of residual cancer, repeated treatment or delayed recognition of progression. The most meaningful comparisons will require prospective studies that track both oncologic outcomes and the patient’s lived experience over time.
The findings may therefore serve as a warning against treating focal therapy as a universal middle ground between active surveillance and whole-gland treatment. The appropriate choice depends on tumor biology, disease volume, anatomical location, imaging quality, biopsy findings, the expertise of the treatment team and the patient’s priorities. It also requires a clear discussion of uncertainty. Men considering focal therapy should understand that the approach may involve continued surveillance, additional biopsies or retreatment, and that evidence for long-term cancer outcomes remains less mature than it is for established treatments in many risk groups. Shared decision-making is particularly important when the potential benefit is preserving quality of life but the consequences of undertreating a dangerous cancer could be serious.
As focal therapy continues to expand, better patient selection could determine whether the technology fulfills its promise or becomes another example of innovation outpacing evidence. The Pittsburgh team says future research should identify the biological and imaging features that predict successful treatment, clarify which patients require additional therapy, and measure outcomes over long periods. The researchers also caution that procedures performed outside Commission on Cancer-accredited centers may not be represented in the database, meaning the national number of treated patients could be higher than reported. Their overarching message is not that focal therapy has no place in prostate cancer care, but that precision treatment must be matched with precision selection. For each patient, the goal is to choose an intervention that reflects the aggressiveness and distribution of the cancer while protecting quality of life wherever safely possible.
Subject of Research: Focal therapy use and guideline concordance in men with nonmetastatic prostate cancer.
Web References: https://www.urology.pitt.edu/people/quoc-dien-trinh-md-mba ; https://hillman.upmc.com/cancer-care/prostate ; https://www.cdc.gov/prostate-cancer/statistics/index.html
References: JAMA. DOI: 10.1001/jama.2026.12411
Image Credits: UPMC
Keywords: Prostate cancer, focal therapy, active surveillance, cancer treatment, urology, oncology, prostate cancer risk, precision medicine, JAMA, University of Pittsburgh
