'25 at 25': Transforming prostate cancer treatment through the STAMPEDE clinical trial

12 Sep 2024

Prostate cancer is the second most common cancer in the UK and the most common cancer in men. Every year in the UK, around 52,000 people are diagnosed with prostate cancer. Of those diagnosed between 2020-21, 19% had metastatic disease, meaning it had already spread elsewhere in the body. Around 10,000 had locally-advanced disease, meaning it was at high risk of spreading.

In the early 2000s, the main treatment available for these patients was hormone therapy. This deprives the body of the hormone testosterone, which prostate cancer needs to grow. But standard hormone therapy cannot stop the tumours from growing indefinitely, and patients soon ran out of options. There was an urgent need for better treatments to help people with advanced prostate cancer to live longer.

Over the last 18 years, almost 12,000 people volunteered to help researchers improve prostate cancer treatment by taking part in one of the largest ever prostate cancer clinical trials: STAMPEDE.

STAMPEDE aimed to find the best way to treat people with newly diagnosed, advanced prostate cancer by adding new treatments to standard-of-care hormone therapy.

The trial has been a huge collaborative effort. Since recruitment opened in 2005, STAMPEDE has involved 165 researchers and over 5,000 NHS staff working across 126 hospitals in the UK and Switzerland.

In STAMPEDE, the team at the MRC Clinical Trials Unit at UCL pioneered a new type of clinical trial using the multi-arm multi-stage (MAMS) design. The efficiency of the MAMS design means STAMPEDE has made progress that may have taken many decades in a traditional clinical trial. In less than 20 years, the trial has evaluated 10 different treatments and changed the standard-of-care for prostate cancer four times.

Docetaxel

In 2015, STAMPEDE showed that adding the chemotherapy drug docetaxel to standard hormone therapy helped people with metastatic prostate cancer to live longer. Doctors already prescribed docetaxel to treat prostate cancer after hormone therapy had stopped working. But in STAMPEDE, researchers looked at using it earlier, when people were first starting long-term hormone therapy.

On average, STAMPEDE found that upfront docetaxel added 22 months to people’s lives, compared with standard treatment alone. This led the NHS to approve the use of docetaxel in combination with hormone therapy for these men. Docetaxel is now widely offered as part of standard treatment.

Radiotherapy

Thanks to 2011 results from another trial called PR07, radiotherapy became part of the standard-of-care, alongside hormone therapy, for people whose cancer has not yet spread beyond the prostate. But researchers were still unsure about the benefits of radiotherapy when the cancer had already spread at the time of diagnosis.

In 2020, STAMPEDE found that radiotherapy did in fact improve survival in men whose cancer had spread – but only if the cancer had spread to just a few places around the body.

This ground-breaking finding challenged a commonly held belief among doctors at the time, that there was no point in targeting the prostate itself once the cancer had spread. The results also informed NHS England’s decision to recommend radiotherapy for this group of men in 2020.

Abiraterone

The trial has also helped make a newer kind of hormone therapy called abiraterone more widely available. When STAMPEDE’s abiraterone arm opened in 2012, doctors usually saved this drug for people whose prostate cancer had already spread, and when hormone therapy had stopped working. But, like docetaxel, STAMPEDE tested whether abiraterone should be used earlier, at the start of long-term hormone therapy.

2017 results showed giving abiraterone upfront helped people with advanced prostate cancer to live longer. Abiraterone also helped reduce the risk of the cancer spreading, returning or worsening.

In 2023, NHS Scotland approved the use of abiraterone in patients with prostate cancer which had not yet spread elsewhere, but was at high risk of spreading. This decision was based on data from STAMPEDE providing evidence that abiraterone reduced the risk of death or the cancer spreading. Although these changes haven’t yet been approved in the rest of the UK, the researchers and wider prostate cancer community continue to push for NHS England and Wales to follow in their footsteps.

In September 2024, the STAMPEDE team will release results from the final two comparisons, testing metformin (a drug used to treat type 2 diabetes) and transdermal oestradiol hormone patches (an alternative way to deliver hormone therapy).

Thanks to the advances driven by STAMPEDE and other research, people diagnosed with prostate cancer now live up to four years longer on average than when the trial began in 2005. And none of it would have been possible without the 12,000 people who volunteered to take part in STAMPEDE.

STAMPEDE’s legacy will continue with STAMPEDE2, a second clinical trial in patients whose cancer has spread beyond the prostate. STAMPEDE2 will continue delivering impactful research and improvements in care for the prostate cancer community.

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