Active Surveillance, Radical Prostatectomy, or Radiation Therapy in Treating Patients With Localized Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

Acitve Monitoring, Radical Prostatectomy, or Radiation Therapy in Treating Patients With Localized Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00632983
• Other study ID #: CDR0000584897
• Secondary ID: SHEFF-PROTECTISR
• Status: Active, not recruiting
• Phase: Phase 3
• First received: March 8, 2008
• Last updated: April 13, 2012
• Start date: June 2001

Study information

• Verified date: October 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radical prostatectomy is surgery to remove the entire prostate. Radiation therapy uses high-energy x-rays or other types of radiation to kill tumor cells. Sometimes the tumor may not need treatment until it progresses. In this case, active surveillance may be sufficient. It is not yet known which treatment regimen is more effective for localized prostate cancer.

PURPOSE: This randomized phase III trial is studying active surveillance to see how well it works compared with radical prostatectomy or radiation therapy in treating patients with localized prostate cancer.

Description:

OBJECTIVES:

• To assess survival of patients with localized prostate cancer at 10 years and 15 years after treatment.

• To investigate 5-year survival, disease progression (i.e., biochemical and clinical), treatment complications, and lower urinary tract symptoms in these patients.

• To investigate the psychosocial impact of case-finding and treatment on these patients, including generic health status, quality of life, and sexual function.

• To estimate the resource use and costs of case-finding, treatment, and follow-up.

• To compare costs and outcomes of treatment in terms of survival and health-related quality of life.

• To collect samples suitable for basic science research (ProMPT study).

OUTLINE: This is a multicenter study. Patients are stratified by age (50-55 vs 56-59 vs 60-65 vs 66-69 years), Gleason score (2-4 vs 5-7 vs 8-10), and average result of Prostate Check Clinic and first biopsy prostate-specific antigen (PSA) tests (< 6 vs 6-9.9 vs ≥ 10 ng/mL). Patients are either randomized to or select 1 of 3 treatment arms.

• Arm I (active monitoring): Patients undergo active monitoring of their disease. Patients are seen by the research nurse 3 months after randomization to fine disease management plan. As part of this process, patients, together with the urologist or research nurse, develop a management plan that includes repeat PSA testing (every 3 months in the first year and then every 6 months thereafter) to detect biochemical progression. Patients also undergo an annual review appointment with an opportunity for digital rectal examination, if indicated (e.g., rise in PSA or new symptoms). PSA levels are monitored and tests repeated as needed. Additional review appointment is arranged with the study urologist for confirmed rising PSA level, apparent symptoms of spreading disease, or concern about the PSA levels. At the review appointment, the study urologist discusses issues raised and current options, including remaining on active monitoring, undergoing re-staging of the cancer, or receiving other treatments, as appropriate.

• Arm II (radical prostatectomy): Patients undergo radical prostatectomy (RP) within 2-12 weeks after study entry. Patients undergo RP and pelvic lymphadenectomy with or without frozen section biopsy of the pelvic lymph nodes prior to prostatectomy. Patients with positive surgical margins may be recommended for adjuvant treatment at the surgeon's discretion.

• Arm III (radical conformal radiotherapy): Patients undergo 3-dimensional conformal radiotherapy for 7.4 weeks (37 fractions). Patients receive neoadjuvant androgen-deprivation therapy comprising luteinizing hormone-releasing hormone (LHRH) agonists once every 4 weeks, beginning prior to the start of radiotherapy and continuing for at least 3-6 months (at least until completion of radiotherapy). Patients also receive cyproterone acetate or equivalent alternative beginning 1 week prior to the first LHRH agonist injection and continuing for at least 3 weeks.

After completion of surgery or radiotherapy, patients are followed according to National Health Service (UK) guidelines every 6-12 months.

All patients complete questionnaires at baseline and periodically during study to provide socio-demographic information (e.g., age, socio-economic status, and ethnicity), as well as clinical information on past or current urinary symptoms, previous PSA tests, anxiety and depression, sexual function, general health status, treatment-related quality of life, and environmental exposures. Resource use and cost-utility analysis is also performed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2050
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 50 Years to 69 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed prostate cancer

• Clinically localized disease

• Stage T1-T2, NX, M0 tumor

• Prostate-specific antigen (PSA) at the Prostate Check Clinic (PCC) in the range of 3.0-19.99 ng/mL

• No skeletal metastases by isotope bone scan (if PCC PSA 10-19.99 ng/mL or Gleason score 8-10)

• Registered with a participating general practice on the date of the PCC

• Registration with another practice after study entry allowed

PATIENT CHARACTERISTICS:

• Life expectancy = 10 years

• Fit for any of the three study treatments

• No concurrent or past malignancies other than a small treated skin cancer

• No serious cardiac or respiratory problems in the past 12 months, including any of the following:

• Stroke

• Myocardial infarction

• Heart failure

• Chronic obstructive pulmonary disease

• Blood-borne infections allowed

PRIOR CONCURRENT THERAPY:

• No prior treatment for prostate malignancy

• No prior kidney dialysis or transplantation

• No bilateral hip replacement

• No previous entry to this study at a prior general practice

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anxiety Disorder
• Anxiety Disorders
• Long-term Effects Secondary to Cancer Therapy in Adults
• Prostate Cancer
• Prostatic Neoplasms
• Sexual Dysfunction
• Urinary Complications

Intervention

Drug:
• cyproterone acetate

• releasing hormone agonist therapy

Other:
• active surveillance

• medical chart review

• questionnaire administration

Procedure:
• assessment of therapy complications

• quality-of-life assessment

• therapeutic conventional surgery

• therapeutic lymphadenectomy

Radiation:
• 3-dimensional conformal radiation therapy

Locations

Country	Name	City	State
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Southmead Hospital	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester General Hospital	Leicester	England
United Kingdom	Freeman Hospital	Newcastle-Upon-Tyne	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	University of Sheffield School of Medicine and Biomedical Sciences	Sheffield	England

Sponsors (1)

Lead Sponsor	Collaborator
Oxford University Hospitals NHS Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (9)

Brindle LA, Oliver SE, Dedman D, Donovan JL, Neal DE, Hamdy FC, Lane JA, Peters TJ. Measuring the psychosocial impact of population-based prostate-specific antigen testing for prostate cancer in the UK. BJU Int. 2006 Oct;98(4):777-82. — View Citation

Collin SM, Metcalfe C, Donovan J, Lane JA, Davis M, Neal D, Hamdy F, Martin RM. Associations of lower urinary tract symptoms with prostate-specific antigen levels, and screen-detected localized and advanced prostate cancer: a case-control study nested wit — View Citation

Lane JA, Howson J, Donovan JL, Goepel JR, Dedman DJ, Down L, Turner EL, Neal DE, Hamdy FC. Detection of prostate cancer in unselected young men: prospective cohort nested within a randomised controlled trial. BMJ. 2007 Dec 1;335(7630):1139. Epub 2007 Nov — View Citation

Lewis SJ, Murad A, Chen L, Davey Smith G, Donovan J, Palmer T, Hamdy F, Neal D, Lane JA, Davis M, Cox A, Martin RM. Associations between an obesity related genetic variant (FTO rs9939609) and prostate cancer risk. PLoS One. 2010 Oct 19;5(10):e13485. doi: — View Citation

Macefield RC, Metcalfe C, Lane JA, Donovan JL, Avery KN, Blazeby JM, Down L, Neal DE, Hamdy FC, Vedhara K; ProtecT Study Group. Impact of prostate cancer testing: an evaluation of the emotional consequences of a negative biopsy result. Br J Cancer. 2010 A — View Citation

Mills N, Donovan JL, Wade J, Hamdy FC, Neal DE, Lane JA. Exploring treatment preferences facilitated recruitment to randomized controlled trials. J Clin Epidemiol. 2011 Oct;64(10):1127-36. doi: 10.1016/j.jclinepi.2010.12.017. Epub 2011 Apr 7. — View Citation

Rowlands MA, Holly JM, Gunnell D, Donovan J, Lane JA, Hamdy F, Neal DE, Oliver S, Smith GD, Martin RM. Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case-control study ProtecT. Cancer Res. 2012 — View Citation

Rowlands MA, Holly JM, Gunnell D, Gilbert R, Donovan J, Lane JA, Marsden G, Collin SM, Hamdy F, Neal DE, Martin RM. The relation between adiposity throughout the life course and variation in IGFs and IGFBPs: evidence from the ProtecT (Prostate testing for — View Citation

Turner EL, Lane JA, Donovan JL, Davis MJ, Metcalfe C, Neal DE, Hamdy FC, Martin RM. Association of diabetes mellitus with prostate cancer: nested case-control study (Prostate testing for cancer and treatment study). Int J Cancer. 2011 Jan 15;128(2):440-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival time as assessed after the first information appointment at 5 years,10 years, and then every 5 years thereafter			No
Secondary	Disease progression as assessed by PSA levels, digital rectal examination, ultrasonography, biopsy, and bone scans at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			No
Secondary	Treatment complications as assessed at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			Yes
Secondary	General health status as assessed by validated instruments, including the SF-12, a subset of the SF-36, and EuroQol EQ-5D at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			No
Secondary	Anxiety, depression, and psychological state as assessed by the Hospital Anxiety and Depression Scale, the Profile of Moods States, and the Impact of Events scale at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			No
Secondary	Urinary symptoms as assessed by the ICSmaleSF questionnaire and the UCLA prostate cancer index at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			No
Secondary	Quality of life as assessed at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			No
Secondary	Sexual function as assessed by the ICSsex questionnaire and the UCLA prostate cancer index at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			No
Secondary	Quality of life related to prostate cancer treatment as assessed by the UCLA prostate cancer index at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			No
Secondary	Qualitative evaluation of outcome as assessed by in-depth interviews with samples of patients in each arm of the trial and also the preference groups at 6 months, 1 year, 5 years, and 10 years and then every 5 years thereafter			No
Secondary	Resource use (NHS, social service, and personal) as assessed by routine hospital and primary care data sources with additional questions in clinical and participant questionnaires			No