Transforming the future of prostate cancer treatment

Manchester researchers are helping shape a future where men with prostate cancer receive more personalised treatments that improve survival while reducing unnecessary side effects, building on landmark clinical trials that have transformed care worldwide.

Prostate cancer is the most commonly diagnosed cancer in the UK, with one in eight men diagnosed during their lifetime. Although advances in diagnosis and treatment have transformed outcomes, a significant challenge remains: identifying which patients need intensive treatment, which therapies will benefit them most and how to minimise the long-term consequences of care.

Over the past two decades, the STAMPEDE clinical trials programme has helped change prostate cancer treatment internationally, bringing together researchers, clinicians and patients to generate evidence that has improved survival and reshaped standards of care. Dr Ashwin Sachdeva, Clinical Senior Lecturer in Urology at The University of Manchester and Consultant Urological Surgeon at The Christie NHS Foundation Trust, is now helping build on this legacy through research into treatment that is best matched to each patient.

Two decades of progress

The original STAMPEDE trial recruited nearly 12,000 men across 126 centres, including those with high-risk localised prostate cancer and those newly diagnosed with metastatic disease, where the cancer has spread to distant parts of the body. This trial was led by a multi-institutional team, including researchers at University College London, The Institute of Cancer Research, London, and Manchester.

By testing several treatments within one major programme, researchers were able to identify which approaches improved survival and which offered fewer benefits.

The findings have helped change international treatment guidelines on at least five occasions. They demonstrated that radiotherapy to the prostate can improve survival for some men whose cancer has spread. The trial also established the benefits of abiraterone, a medicine that reduces the hormones which help prostate cancer grow.

As part of the FASTMAN Prostate Cancer Centre of Excellence Programme, Manchester researchers analysed scans from thousands of patients recruited to STAMPEDE to assess how extensively their cancer had spread. Building on the trial's finding that radiotherapy to the prostate improved survival for men with limited spread, this analysis helped refine understanding of which patients were most likely to benefit.

The trial has also revealed important longer-term effects of treatment. By linking trial data with hospital records, researchers identified a high incidence of bone fractures among men receiving hormone therapy, and showed that zoledronic acid, a medicine that protects bones, reduced this risk in men whose cancer had spread. This work helped inform international recommendations for protecting bone health in prostate cancer, and shows how major clinical trials can continue improving care long after they have finished recruiting patients.

Towards more personalised treatment

While STAMPEDE established which treatments can improve survival, researchers now want to understand which patients will benefit most from each approach. 

STAMPEDE-2 is testing whether adding newer treatments to standard care improves outcomes for men whose prostate cancer has spread. These include radiotherapy directed at sites where the cancer has spread, and a treatment that delivers radiation directly to prostate cancer cells.

Building on these advances, Sachdeva is leading the development of STAMPEDE-3. The proposed trial will focus on men who have undergone surgery for high-risk prostate cancer, some of whom can remain at risk of the disease returning even after their prostate has been removed.

Although surgery is an established treatment, there is still limited evidence about which additional medicines are most effective afterwards. STAMPEDE-3 aims to test whether additional targeted treatments after surgery can improve outcomes. Within the trial, researchers will also evaluate biological markers - features of a cancer that may provide clues about how it behaves or responds to treatment - to investigate whether these can help identify which patients benefit most.

This could lead to a more personalised approach, helping some men avoid unnecessary side effects while ensuring those at greater risk receive additional treatment when they need it.

Patient and public involvement has also been central to the development of STAMPEDE-3, helping ensure the research reflects the priorities and experiences of those affected by prostate cancer.

Connecting discovery with patient care

Manchester's strength lies in bringing together surgeons, cancer specialists, laboratory scientists and data experts to translate research discoveries into better patient care. Working with samples donated by patients, Sachdeva and colleagues are developing new ways to understand why some prostate cancers are more aggressive or return after treatment, including forms linked to inherited genetic changes.

Across the UK, there are geographical and socioeconomic inequalities in prostate cancer diagnosis, including differences in how advanced the disease is when it is detected. Alongside this, researchers working with colleagues in Jamaica are investigating the biology of prostate cancer in African-Caribbean men, who are at increased risk of developing the disease. This includes studying genetic changes that may contribute to aggressive prostate cancer.

A new era of precision medicine

Looking ahead, researchers hope that advances in diagnosis, a better understanding of prostate cancer and more targeted treatments will help doctors identify the most effective care for each patient. This could reduce unnecessary side effects while improving the chances of preventing the disease from returning.

Building on the international impact of STAMPEDE, the next generation of research could transform care for men undergoing prostate cancer surgery, bringing the prospect of more effective treatment and longer, healthier lives closer to reality.