Prostate cancer: The latest potentially ‘practice-changing’ research

Prostate cancer is one of the most common cancers globally and affects approximately 4,000 men in Ireland every year. One-in-seven men will be diagnosed with the disease during their lifespan.¹

Research is ongoing to support clinical excellence in the screening and management of the disease and some recent findings have the potential to influence current recommendations and practice. This article takes a look at some recent and ongoing research in Ireland and around the world.

Potential advantages of a low-insulinaemic diet

A research team at Trinity College Dublin has been awarded funding by the Prostate Cancer Foundation to investigate the potential advantages of adopting a low-insulinaemic diet and improved lifestyle as preventive measures for prostate cancer.

Diet and lifestyle-induced hyperinsulinaemia has been linked with an increased likelihood of prostate cancer, as well as the progression of existing disease. Dr Sinead Flanagan, Adjunct Assistant Professor, Trinity College Dublin, will lead the study, and the results are anticipated to influence future clinical trials.

Loss of the tumour suppressor phosphatase and tensin homolog (PTEN), which is commonly inactivated in prostate cancer, is a strong independent risk factor for metastases and mortality from the disease. The study will also investigate the efficacy of PTEN as a biomarker to identify patients who are more likely to benefit from an insulin-lowering diet, lifestyle modifications, and statin therapy.

Optimising screening in Ireland and the UK

The National Screening Service in Ireland has joined the project team of Irish and European partners working on the PRAISE-U (PRostate cancer Awareness and Initiative for Screening in the European Union) initiative, which aims to reduce morbidity and mortality in prostate cancer and improve early detection and diagnosis.

The three-year project is co-funded by the European Union and comes in response to the European Commission Council Recommendation on strengthening prevention through early detection in 2022, which advised countries to evaluate cost-effective and practical ways to implement prostate cancer screening programmes.

Irish researchers, led by Mr David Galvin, Consultant Urologist, Mater Misericordiae and St Vincent’s Hospitals, Dublin, will examine the feasibility of population-based screening across the country using a home-based finger prick blood test that can be analysed for prostate-specific antigen (PSA).

The planned study will involve approximately 8,000 men in both urban and rural settings across all socioeconomic and ethnic groups, and varied populations such as migrants, homeless, and marginalised men.

The TRANSFORM trial – a £42 million research programme to find the optimal method of screening men for prostate cancer – has been launched by Prostate Cancer UK. TRANSFORM will compare the most promising tests and provide definitive evidence about the best way to screen for prostate cancer.

A diverse range of men from various ethnic and socioeconomic groups aged between 50 and 75, or from the age of 45 for black men, will be invited to take part in the trial, which will begin recruiting early next year.

Stage 1 of the trial will analyse approximately 12,500 men over a three-year period to evaluate potential screening options including fast MRI scans; genetic testing; and PSA blood testing in comparison with a control group that will follow the standard National Health Service screening process (that does not include routine PSA testing).

Stage 2 of TRANSFORM will include up to 300,000 participants and evaluate the most efficacious option(s) from stage 1, as well as any potential harms. Participants included in the study will be followed for at least 10 years, and the researchers anticipate releasing the first phase of results at approximately three years into the trial.

Best practice in screening

Conventional screening and early detection methods generally include digital rectal examination (DRE) and PSA testing. However, previous research has suggested that DRE as a stand-alone screening method, or in combination with PSA monitoring, may be less effective than originally thought, and a recent study by the Comprehensive Cancer Centre Vienna of the Medical University of Vienna and Vienna General Hospital, Austria, has reinforced these suggestions.

The comprehensive review and meta-analysis, which was published online in January 2024 in European Urology Oncology, analysed and combined data from eight different studies, achieving a total sample population of 85,738 participants.²

Primary endpoints were the positive predictive value (PPV) and cancer detection rate (CDR) of DRE. Secondary endpoints included the PPV and CDR of both PSA alone and in combination with DRE. The results suggest that DRE alone, or in combination with PSA, is not more effective in the early detection of prostate cancer compared to PSA testing alone. In particular, DRE alone showed a lower CDR compared to the PSA test.

“The validity of rectal examination in detecting prostate cancer is not particularly impressive, suggesting that it may not be necessary to perform this examination routinely as part of screening in the absence of clinical symptoms and signs,” said leader of the international study Dr Shahrokh Shariat, Head of the Department of Urology at Medical University of Vienna and University Hospital Vienna.

“The continuous improvement of prostate cancer screening methods remains of paramount importance to protect the health and wellbeing of men worldwide. We certainly hope that by removing this barrier, more men will go for prostate cancer screening.” The data are expected to widen the discussion about the benefits of DRE in the early detection of prostate cancer.

Active surveillance

Many patients with low-risk prostate cancer require no active treatment and are managed with active surveillance instead. A new study examined the rates of active surveillance use and evaluated the factors associated with selecting this management strategy over surgery or radiation.

The findings revealed the strongest determinant of active surveillance uptake was a urologist’s recommendation to choose this option. The study was published online in January 2024 in Cancer, the peer-reviewed journal of the American Cancer Society.³

Dr Jinping Xu, Wayne State University, Detroit, Michigan, US, and her colleagues analysed data from metro-Detroit, Michigan, and Georgia cancer registries, focusing on patient self-reported information related to black and white patients who were newly diagnosed with low-risk prostate cancer from 2014-to-2017.

The American investigation did have a deliberate focus on underserved black patients due to the current deficit of data within this cohort.

Among 1,688 patients, 57 per cent chose active surveillance (51 per cent of black patients and 61 of white patients) over other treatments. The strongest determinant of uptake was a urologist’s recommendation to choose this option.

Other factors linked with the decision to undergo active surveillance included a shared patient-physician treatment decision and greater knowledge about prostate cancer.

Conversely, men were less likely to try active surveillance if their considerations were strongly influenced by the desire to achieve a ‘cure’, if they expected to ‘live longer’ with treatment, or if they perceived that their low-risk prostate cancer diagnosis was more ‘serious’.

Education and interventions for patients, and especially urologists that address these factors, may increase the use of recommended active surveillance among individuals with low-risk prostate cancer, according to the researchers.

“I am glad to see that the majority of our study participants selected active surveillance, which indicates that acceptance has improved over the last decade; however, there is room for greater acceptance.

Our study findings shed new light on potentially modifiable factors that can help further increase active surveillance use among patients with newly diagnosed low-risk prostate cancer to avoid unnecessary invasive treatment and improve their quality-of-life,” said Dr Xu.

Social support and clinical outcomes

Findings published online in Cancer Epidemiology, Biomarkers, and Prevention⁴ in January 2024 have highlighted the importance of social support in overall survival for men with advanced prostate cancer. The study investigated the associations of marital status and living arrangements with overall survival among 2,119 participants with advanced prostate cancer.

All participants were enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) – which contains patients with advanced prostate cancer (metastatic hormone-sensitive prostate cancer and castration-resistant prostate cancer) from 16 countries – and had been recruited between July 2017 and January 2023.

Researchers found that married participants had better overall survival than unmarried participants. Widowed participants had the worst survival compared with married individuals.

Reducing radiotherapy time

A major breakthrough at The Royal Marsden could safely cut radiotherapy treatment time by 75 per cent. The PACE-B clinical trial, which was led by Prof Nicholas van As, Medical Director and Consultant Clinical Oncologist at The Royal Marsden, London, UK, found just five sessions of higher-dose stereotactic body radiotherapy (SBRT) performed as well as conventional radiotherapy treatment in men whose prostate cancer had not spread.

Data showed that 96 per cent of patients who received SBRT remained cancer-free after five years, compared to 95 per cent for patients treated with conventional radiotherapy.

The findings could potentially reduce a patient’s treatment time to less than one-quarter of the period currently required. Prof van As said he expected the trial to be “practice changing”. The findings were presented at the American Society for Therapeutic Radiation and Oncology conference in San Diego, in October 2023, and published in the International Journal of Radiation, Oncology, Biology, Physics.⁵