Background:

Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments.

Objectives:

To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50–69 years.

Design:

A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up.

Setting:

Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK.

Participants:

Between 2001 and 2009, 228,966 men aged 50–69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment.

Interventions:

The interventions were active monitoring, radical prostatectomy and radical radiotherapy.

Trial primary outcome measure:

Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants.

Secondary outcome measures:

Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes.

Results:

There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy’s impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy).

Limitations:

A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed.

Conclusions:

At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years.

Trial registration:

Current Controlled Trials ISRCTN20141297.

Funding:

This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

Article history

The research reported in this issue of the journal was funded by the HTA programme as project number 96/20/99. The contractual start date was in June 2001. The draft report began editorial review in March 2018 and was accepted for publication in November 2018. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors

Malcolm Mason reports personal fees from Sanofi (Paris, France), Bayer (Leverkusen, Germany) and Janssen Pharmaceutica (Beerse, Belgium) outside the submitted work. Derek Rosario reports grants from Bayer and personal fees from Ferring Pharmaceuticals (Saint-Prex, Switzerland) outside the submitted work. Jane Blazeby was a member of the following during the project: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Clinical Trials and Evaluation Committee (2009–2013), HTA NIHR Obesity (2010–2012), Commissioning Board for HTA Surgery Themed Call Board and the NIHR Clinical Trials Unit (CTU) Standing Advisory Committee (2015–2019). Jenny Donovan was a member of the following during the project: HTA Commissioning Board (2006–12), Rapid Trials and Add-on Studies Board (2012), NIHR Senior Investigator panel (2009–12) and NIHR Health Services and Delivery Research board (Deputy Chairperson) (2010–11). Freddie C Hamdy was a member of the following during the project: HTA Commissioning Board (2007–12) and HTA Surgery Themed Call Board (2012–13). J Athene Lane was a member of the following during the project: CTUs funded by NIHR (2017 to present). Chris Metcalfe was a member of the following during the project: CTUs funded by NIHR (2010 to present). Tim Peters was a member of the following during the project: HTA Medicines for Children Themed Call (2005–6) and NIHR CTU Standing Advisory Committee (2008–14). John Staffurth reports support for travel to conferences and attendance on an advisory board from Bayer. Emma L Turner reports grants from Cancer Research UK (London, UK) during the conduct of the study.