Prostate cancer is particularly suited to precision radiation because the prostate is a relatively small organ that can be targeted from multiple directions while attempting to limit exposure to surrounding tissues. SBRT delivers a high biological dose in a small number of treatment sessions, using advanced image guidance and treatment planning to account for organ motion and anatomy. In NRG-GU005, patients assigned to the SBRT group received 36.25 Gy in five fractions. Patients in the comparison group received MH-IMRT, delivered either as 70 Gy in 28 fractions or 60 Gy in 20 fractions. While conventional radiation may require several weeks of daily visits, SBRT can be completed in approximately one week, a difference that could reduce travel, treatment costs, time away from work, and the logistical burden on patients and families.

The trial enrolled 698 evaluable participants with intermediate-risk disease and was designed around two co-primary endpoints: disease-free survival and patient-reported health-related quality of life. Researchers assessed quality of life with the 26-item Expanded Prostate Cancer Index Composite, commonly known as EPIC-26. The instrument measures treatment effects in several domains, including bowel function, urinary irritative and obstructive symptoms, urinary incontinence, sexual function, and hormonal symptoms. For the primary quality-of-life analysis, investigators focused on whether patients experienced a minimally clinically important difference, or MCID, in bowel health or urinary irritative and obstructive symptoms. An MCID is intended to represent a change noticeable and meaningful to patients rather than merely a statistically measurable difference in a score.

At two years, 34.9 percent of men treated with SBRT experienced an MCID in the bowel domain, compared with 43.8 percent of those treated with MH-IMRT. The difference was statistically significant, with a p value of 0.034, indicating that the probability of observing such a result by chance alone was relatively low under the study’s statistical assumptions. Longitudinal analyses, which examine changes over time rather than relying on a single follow-up point, also associated SBRT with improved bowel-domain scores. The use of rectal spacers was linked to better bowel outcomes as well. These devices are placed between the prostate and rectum to increase physical separation, potentially reducing the amount of radiation delivered to the rectal wall during treatment.

The bowel result did not extend to the trial’s urinary co-primary endpoint. An MCID in urinary irritative or obstructive symptoms occurred in 33.7 percent of patients in the SBRT arm and 34.7 percent in the MH-IMRT arm. The difference was not statistically significant, with a p value of 0.68. Urinary irritation and obstruction can result from radiation-related inflammation or changes in the prostate and urethra, and the similar rates in both groups suggest that delivering radiation in five fractions did not substantially alter this aspect of recovery compared with moderately shortened IMRT. Because both quality-of-life domains had to meet the prespecified criteria for the co-primary endpoint to be considered positive, the urinary result meant that the trial did not fulfill its overall health-related quality-of-life objective.

The study also did not establish a disease-control advantage for SBRT. An interim analysis crossed the trial’s futility boundary for superiority, meaning that the accumulating data made it unlikely that SBRT would ultimately prove superior to MH-IMRT for disease-free survival. According to the investigators, this conclusion was driven solely by a higher number of biochemical failures in the SBRT group. Biochemical failure is generally identified through rising prostate-specific antigen, or PSA, after treatment. PSA is a sensitive marker of prostate activity, but a biochemical recurrence does not always immediately correspond to visible metastatic disease or a decline in overall survival. Longer follow-up remains important because prostate cancer can recur many years after initial treatment, and early PSA patterns may not fully predict long-term clinical outcomes.

The investigators reported additional differences in patient-reported genitourinary outcomes. SBRT was associated with lower incontinence-related quality of life, indicating a less favorable experience in that specific domain, while it was also associated with improved maintenance of erectile dysfunction compared with MH-IMRT. These findings illustrate why radiation comparisons cannot be reduced to a single measure of toxicity. A treatment may perform better for bowel symptoms while producing different trade-offs in urinary continence or sexual function. The prostate, rectum, bladder, urethra, and neurovascular structures occupy a tightly packed region of the pelvis, and radiation dose, fraction size, baseline function, anatomy, technical planning, and the use of protective devices can all influence late effects.

The NRG-GU005 results add to evidence from other randomized studies examining shorter prostate radiation schedules. The PACE-B trial previously showed that SBRT was non-inferior to conventionally fractionated or moderately hypofractionated radiation for disease control in an appropriate patient population. NRG-GU005 was designed to ask a more demanding question: whether SBRT could deliver superior disease-free survival while also producing a clinically meaningful improvement in selected quality-of-life outcomes. The answer was no under the trial’s predefined criteria. Nevertheless, the bowel findings may be relevant to shared decision-making, particularly for patients who value fewer treatment visits and are concerned about gastrointestinal effects. Physicians will still need to weigh these potential advantages against urinary and sexual side effects, baseline symptoms, prostate anatomy, rectal spacer availability, and the uncertainty surrounding long-term biochemical control.

“This major clinical trial teaches us not only about state-of-the-art radiation technology, but also about the biology of radiation effects on prostate cancer and normal organs responsible for basic human functions,” Mitchell Machtay of Penn State, NRG Oncology’s group deputy chair and chief scientific officer, said in a statement. Rodney J. Ellis of the University of South Florida, the study’s lead author, said the trial was not positive overall but noted that SBRT produced a favorable outcome in the EPIC-26 bowel domain and not in the urinary irritative or obstructive domain. He emphasized that additional follow-up is needed to clarify longer-term outcomes. The trial was supported by the National Cancer Institute through the National Clinical Trials Network and conducted by NRG Oncology, a research group formed from the legacy Radiation Therapy Oncology Group, National Surgical Adjuvant Breast and Bowel Project, and Gynecologic Oncology Group programs. For now, the findings suggest that SBRT is a time-saving alternative with a distinct quality-of-life profile, not a universally superior replacement for MH-IMRT.

Subject of Research: SBRT versus moderately hypofractionated IMRT for localized intermediate-risk prostate cancer

Article Title: Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial

News Publication Date: August 13, 2026

Web References: https://pubmed.ncbi.nlm.nih.gov/42593775/

References: Ellis RJ, Pugh SL, Yu JB, et al. “Stereotactic Body Radiotherapy vs Moderately Hypofractionated IMRT for Localized Intermediate-Risk Prostate Cancer: A Randomized Clinical Trial.” Journal of the American Medical Association. 2026. doi:10.1001/jama.2026.12627.

Keywords: prostate cancer, SBRT, stereotactic body radiation therapy, IMRT, hypofractionated radiotherapy, NRG-GU005, radiation oncology, quality of life, EPIC-26, disease-free survival, PSA, rectal spacers

Hormone patches are as good at controlling locally advanced prostate cancer as the injections typically used to deliver hormone therapy, according to the results of a large clinical trial led by UCL (University College London) researchers.

Men with cancer that has spread just outside the prostate are given hormone therapy to suppress levels of testosterone which the cancer needs to grow. Most commonly this is done by injections of drugs that block testosterone production.

The new study, published in The New England Journal of Medicine, found that patches that lower testosterone by delivering oestradiol (a form of oestrogen) through the skin were as effective as injections at preventing the cancer from spreading, and caused fewer side effects.

The current standard of care, injections of LHRH agonists (luteinizing hormone-releasing hormone agonists), requires multiple hospital or GP visits, whereas oestradiol patches can be put on by patients at home.

In addition, side effects including hot flushes, bone density problems and risk factors for heart disease (such as higher cholesterol, blood glucose and blood pressure) were less common among men using patches compared to LHRH agonists, although breast tissue swelling was more common in the patches group.

Oestradiol patches are currently not licensed in the UK to treat prostate cancer, but the researchers hope that they will be made more easily available so men with prostate cancer have more choice of treatment.

Lead author Professor Ruth Langley (MRC Clinical Trials Unit at UCL) said: “We believe our findings should lead to men with locally advanced prostate cancer being able to choose which hormone therapy suits them best. For some men, for instance, hot flushes can be very debilitating, and so the patches could greatly increase their quality of life.”

For the study, 1,360 men with locally advanced, non-metastatic prostate cancer (i.e. that had not spread to other parts of the body) were randomly assigned to receive either oestradiol patches or the current standard of care injections.

After three years or more, the research team found both treatments had similar effects in controlling prostate cancer – 87% of people in the oestradiol group were alive without their cancer spreading, compared to 86% in the standard-of-care group.

The team also compared the side effects of the two approaches. Side effects from LHRH agonists come not only from lower levels of testosterone but also from lower oestrogen levels. That is because most oestrogen in men is converted from testosterone.

Oestradiol patches add oestrogen to the body (which causes less testosterone production) so side effects related to low oestrogen levels, such as hot flushes, are much reduced.

Among those using patches, only 44% reported any hot flushes compared to 89% in the injection group. However, breast tissue swelling (gynaecomastia) was more frequent with patches, affecting 85% of participants compared to 42% of those on injections.

The number of patients experiencing bone fractures five years after entering the trial was 2.8% in those who started on oestradiol patches versus 5.8% of those started on injections.  

Previous studies comparing oestradiol patches to LHRH agonists have shown that overall quality of life scores are better in men receiving the patches compared to the injections.

Simon Grieveson, Assistant Director of Research at Prostate Cancer UK, said: “Hormone therapy is an extremely common and effective treatment for prostate cancer, currently given through regular injections. But for many men it can cause quite significant side effects.

“Results from the PATCH/STAMPEDE trials have shown that hormone patches like these, delivered through the skin, are just as effective at delaying cancer progression. The skin patches also resulted in fewer men experiencing hot flushes, however breast tissue swelling was more common.

“These skin patches are more convenient and less invasive and could give men greater choice in their treatment based on what’s important to them and how they live their lives.”

Caroline Geraghty, senior specialist nurse manager at Cancer Research UK, said: “Prostate cancer remains the most common cancer in men in the UK – that’s why we must continue to find new breakthroughs in treating the disease. Thanks to research, over 8 in 10 men diagnosed with prostate cancer will now survive for 10 years or more. As well as finding more effective treatments, we need to find ways to make them kinder too.

“This trial has done exactly that – it shows that hormone patches are just as effective as traditional injections at controlling locally advanced prostate cancer, while being much easier and gentler to administer. This should give men greater choice over their treatment in the future, allowing them to live not just longer lives, but better lives.”

Dr Duncan Gilbert, a Consultant Clinical Oncologist from Sussex who recruited many patients to the trial, who is also based at the MRC Clinical Trials Unit at UCL, said: “Seeing these positive results published is a testament to all of the patients that took part in the trial and the hard work undertaken by research teams at UK hospitals over many years. The ease of administration and improved side-effect profile offers real choice for patients and I look forward to this option for testosterone suppression being available to the wider population of patients needing treatment for prostate cancer.”

The oestradiol patches used in the trial are the same as those used in hormone replacement therapy (HRT) to treat symptoms of the menopause in women. These patches are currently not licensed to treat prostate cancer, meaning they need to be prescribed “off-label” (i.e. outside approved use). Some healthcare providers may be reluctant to do this.

For these patches to be approved as a prostate‑cancer treatment, a manufacturer would need to apply for a licence covering this new use. In the UK this is handled by the Medicines and Healthcare products Regulatory Agency and in the US by the Food and Drug Administration. An easier and faster option is for a company that already sells oestradiol patches for another purpose to apply to extend its existing licence so that it also covers prostate cancer.

Professor Langley said: “We hope these patches can be made more easily available to treat prostate cancer so that men have the benefit of a choice of treatment.”

The participants in the study were recruited from the UCL-led PATCH and STAMPEDE trials between 2007 and 2022 from 75 centres in the UK. The study was sponsored initially by Imperial College London and then UCL and funded by Cancer Research UK and the UKRI Medical Research Council (MRC) Clinical Trials Unit.

UCL’s commercialisation company, UCL Business Ltd, is currently working with Professor Langley and her team to support potential licence applications for the patches, including engaging with potential manufacturers and licence holders with the aim of the treatment becoming widely available for patients.

UK prostate cancer figures

Prostate cancer is the most commonly diagnosed cancer in the UK, and one in eight men will be diagnosed in their lifetime. Each year, more than 64,000 men are diagnosed with the disease, with around 12,000 men dying annually. The stage at which prostate cancer is detected varies across the UK, with substantial regional differences, but a significant proportion of men (between 20% and 30%) are diagnosed with locally advanced or late‑stage disease. In the UK around 540,000 men are living with or after prostate cancer.

Journal

New England Journal of Medicine

Funder

Cancer Research UK,
UCL,
Medical Research Council,
MRC Clinical Trials Unit at UCL

The crux of the debate lies in differentiating aggressive prostate tumors that require prompt intervention from indolent tumors that may never impact a patient’s lifespan or quality of life. Historically, widespread prostate cancer screening using prostate-specific antigen (PSA) testing led to a substantial increase in the diagnosis of low-risk cancers. This, in turn, caused many men to undergo invasive treatments such as prostatectomy or radiation therapy, often exposing them to side effects like urinary incontinence and erectile dysfunction without clear survival benefits.

A recent study published in JAMA Oncology by researchers at the University of Michigan sheds new light on shifting trends in the surgical management of prostate cancer, particularly focusing on Grade Group 1 tumors—the lowest-risk category. By analyzing data from more than 180,000 men who underwent prostate cancer surgery between 2010 and 2024, the team identified a remarkable decline in the rate of radical prostatectomies performed for these low-risk lesions. Their findings suggest a growing recognition of the value of active surveillance protocols and more refined diagnostic techniques in mitigating unnecessary surgical interventions.

Active surveillance, an approach wherein physicians monitor patients closely through serial PSA measurements, magnetic resonance imaging (MRI), and targeted biopsies, allows for timely intervention only if the cancer demonstrates signs of progression. This strategy addresses the problematic overtreatment of indolent tumors while preserving the opportunity for curative therapy when truly needed. The Michigan study found that nationally, the proportion of men undergoing surgery for low-risk prostate cancer fell from approximately one-third in 2010 to less than 10% by 2020. Even more striking was the data from Michigan, where a coordinated statewide quality improvement initiative known as MUSIC (Michigan Urological Surgery Improvement Collaborative) helped reduce this figure from one in five in 2012 to fewer than one in 35 in 2024.

This trend towards selective management is not accidental; rather, it reflects concerted efforts driven by evolving clinical guidelines and enhanced diagnostic tools. Earlier in the decade, the U.S. Preventive Services Task Force (USPSTF) issued recommendations against routine PSA screening due to concerns over overtreatment and consequent harms. However, in response to accumulating evidence, the USPSTF revised its stance in 2018, advocating for shared decision-making between patients and clinicians about screening, emphasizing the necessity to balance risks and benefits on an individual basis.

Despite these updated guidelines, many primary care physicians have remained reticent to resume screening programs, especially among men at higher risk for aggressive disease, such as African American men and those with a family history of prostate cancer. This hesitation contributes to underdiagnosis in some populations, underscoring the need for continued education and system-wide improvements. Unlike earlier eras when PSA screening was often reflexively followed by invasive interventions, current practice increasingly incorporates risk stratification, MRI imaging, and genomic classifiers that provide a more nuanced assessment of tumor behavior.

The researchers highlight that the marked decrease in surgical overtreatment is a testament to the effectiveness of active surveillance protocols, which rely on routine monitoring using PSA tests, multi-parametric MRI scans, and carefully targeted prostate biopsies. These techniques help differentiate tumors that may remain stable from those that show signs of advancement, guiding timely therapeutic interventions when necessary. By sparing men from needless surgeries and their attendant complications, this paradigm shift improves quality of life without compromising clinical outcomes.

Moreover, the decline in unnecessary prostatectomies has been observed consistently across various surgical practices, both at the local and national levels, suggesting a broad systemic improvement rather than isolated success stories. This demonstrates the successful translation of research findings into clinical practice and highlights the important role of coordinated efforts such as MUSIC, which disseminate best practices, facilitate data sharing, and promote adherence to evidence-based guidelines.

The study’s findings have profound implications for public health, especially as prostate cancer remains a significant burden, with nearly 300,000 new cases expected in the U.S. in 2024 alone. By adopting active surveillance more widely and refining screening protocols, medical professionals can reduce the physical and psychological toll on patients caused by overtreatment, optimize resource allocation, and focus therapeutic interventions on those who stand to benefit most.

Steven Monda, M.D., the study’s first author and a urologic oncology researcher, summarizes the overarching message: prostate cancer is not a monolithic disease, and many men diagnosed with low-risk tumors do not require immediate treatment. The challenge lies in distinguishing these patients safely and effectively. The observed trends of reduced surgeries for low-grade cancers signify that the combination of improved diagnostics and patient-centered care is beginning to overcome historical patterns of overtreatment.

In conclusion, this comprehensive analysis signals an encouraging paradigm shift in prostate cancer management. It underscores the critical value of active surveillance combined with advanced diagnostic modalities in sparing men from unnecessary surgical procedures while preserving the option for definitive treatment in those with more aggressive malignancies. This evolving approach aligns clinical practice with the nuanced biology of prostate cancer, offering hope for improved outcomes and quality of life for patients nationwide.

Subject of Research: People

Article Title: Trends in Surgical Overtreatment of Prostate Cancer

News Publication Date: 28-Apr-2025

Web References:
https://jamanetwork.com/journals/jama/fullarticle/10.1001/jamaoncol.2025.0963

References:
Monda SM, Borza T, et al. Trends in Surgical Overtreatment of Prostate Cancer. JAMA Oncology. 2025; DOI: 10.1001/jamaoncol.2025.096

Keywords: Health and medicine