Can we make hormone therapy kinder and smarter for prostate cancer? (ENHANCE trial)

Grant information

Reference: PTG25-CRUK-001
Researchers and institutions:
Professor Ananya Choudhury, The University of Manchester
Professor Peter Hoskin, The University of Manchester
Professor Allan Hackshaw, University College London
Award: £3,239,617.35 (funded jointly with Cancer Research UK) 

What you need to know

• Advanced prostate cancer is often treated with hormone therapy, but the full doses can cause side effects like fatigue and high blood pressure, making life harder for many men.

• The ENHANCE trial will compare standard doses of these treatments with half doses to see if men live just as long but feel better.

• If the lower doses work, treatment for advanced prostate cancer could be kinder, cheaper, and easier for thousands of men worldwide.

Why are we funding this research?

Hormone therapy is a common treatment for advanced prostate cancer. It works by either stopping your body from making testosterone, or by stopping testosterone from reaching the cancer cells. This helps to keep the cancer under control. Patients usually have two kinds of hormone therapy: androgen receptor pathway inhibitor (ARPI) therapy and androgen deprivation therapy.  

But the standard doses often cause unpleasant side effects like fatigue, hot flushes and high blood pressure. These issues can make everyday life harder and, in some cases, lead men to stop treatment early – which could put their health at risk. 

The ENHANCE trial is asking a bold question: do men really need the full dose of one of the hormone therapies (ARPI) to get the benefits? Early evidence suggests that lower doses might work just as well, but with far fewer side effects. If that’s true, it could make hormone treatment kinder, easier to stick with, and less costly for the NHS.  

What makes this project different is its focus on improving quality of life without compromising survival. It’s the first large trial of its kind in prostate cancer, and its results could influence care worldwide.  

What will the researchers do?

The ENHANCE trial will involve men whose prostate cancer has spread and who are about to start ARPI hormone therapy with enzalutamide, abiraterone, darolutamide or apalutamide. 

Normally, these drugs are given at full strength every day, but the researchers want to find out if half the usual dose works just as well. To do this, they’ll run a large study involving around 1,500 men across hospitals in the UK. 

As part of this, the research team will work to ensure that at least 10 per cent of men recruited are Black. This is crucial because Black men are more likely to get prostate cancer, and to be diagnosed at a later stage, yet Black men are traditionally underrepresented in research trials – meaning that decisions about their treatments may not be based on data that is as relevant to them.   

Each man who joins will be randomly assigned to one of two groups: one will take the standard dose of ARPI, and the other will take half the dose. But all men in both groups will still take the usual dose of the other type of hormone therapy (ADT). Doctors will keep a close eye on both groups over several years, checking how long the men live, how well the cancer is controlled, and how they feel during treatment. Fatigue – one of the most common and frustrating side effects – will be measured carefully, along with other symptoms like high blood pressure and hot flushes. The team will also track whether men are able to stay on treatment without stopping early because of side effects. 

Alongside this, the researchers will collect blood and urine samples to look for clues about which men do best on lower doses. They’ll also study the costs to the NHS, because if half doses work, it could save millions while making treatment kinder and easier to manage.

How will this benefit men?

The ENHANCE trial aims to make prostate cancer treatment not only life-extending, but life-improving.  

If the team finds that lower doses of these hormone therapies work just as well as the full dose, but with fewer side effects, it could change the way we treat advanced prostate cancer. Men could feel better, stay on treatment longer and keep their cancer under control without the constant battle with fatigue and other symptoms.