The Active Surveillance Study

NCT05810467 | Recruiting DMC

• 1 other identifier: CCR5747
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 4

Brief Summary

The Active Surveillance study is a prospective study developed to look at the association of biomarkers with PrCa presentation and progression among men on Active Surveillance and stratify it by their genetic risk. This study will also investigate the incidence and progression by differing genetic risks.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• To determine the incidence of disease progression of PrCa in the cohorts studied.

  Descriptive statistics will be used to determine and compare the characteristics of cancers in each cohort at recruitment. Disease progression will be classified as a Y/N indicator in order to look at the proportion of those progressing in each cohort, using logistic regression to adjust for covariates of interest, such as age at diagnosis, tumour-node-metastasis stage, and Gleason score. Rate ratios for the cumulative incidence of disease progression for any disease, compared between the two cohorts, will be calculated using Poisson regression offset by person-years of follow-up, adjusting for covariates of interest.

  The full analysis being completed within one year of date of completion of 5 year follow-up of the last participant.

• To determine the incidence of aggressiveness of PrCa in the cohorts studied.

  Participants will be defined as experiencing disease progression if they have an upstaging or progression of their disease on MRI or biopsy. i.e., change in MRI or change in Gleason. Rate ratios for the cumulative incidence of aggressive disease (defined as progression on MRI or biopsy that results in the need for active treatment within one year of starting AS), compared between the two cohorts, will be calculated using Poisson regression offset by person-years of follow-up, adjusting for covariates of interest.

  The full analysis being completed within one year of date of completion of 5 year follow-up of the last participant.

Secondary Outcomes (2)

• To investigate the role of biomarker profiles in men undergoing active surveillance who are also at genetically higher risk for PrCa.

  5 years

• To investigate the role of biomarker profiles in men undergoing active surveillance who are also at genetically higher risk for PrCa.

  5 years

Study Arms (2)

Control Arm

Men diagnosed with low-grade PrCa undergoing Active Surveillance and are not known to have an increased genetic risk for PrCa e.g. Men without high-risk mutations or high polygenic risk score (PRS). Men diagnosed with PrCa suitable for Active Surveillance who wish to continue follow up at collaborating hospitals will be offered enrolment in collection and monitoring of various biological samples. These men will act as a control group, as they do not have a known higher genetic risk of PrCa. The control group will have genetic analysis carried out on provided saliva or blood samples. Their family history will be captured. They will be genotyped using the latest technology and at a minimum have PRS testing done. Men may be moved out of the control arm and into the high-risk arm, if identified at a higher genetic risk or as having a strong family history of PrCa for the purposes of the analysis. Any clinically significant genetic results will be discussed with the participants.

Other: Active Surveillance

High-risk Arm

Men who have been diagnosed with low grade PrCa and are undergoing active surveillance who are at genetically higher risk of PrCa defined as: 1. Men of any ancestry with a family history defined as at least one first degree (or second degree if through the female line) relative with PrCa diagnosed at \<70 years (diagnosis verified). 2. Men of Black African or Caribbean ancestry irrespective of family history 3. Men of any ancestry known to carry a mutation in a high-risk gene thought to cause a higher risk of prostate cancer. 4. Men of ancestry with a high genetic risk (common and/or rare variants) for prostate cancer resulting in relative risk (RR) of ≥2.

Other: Active Surveillance

Interventions

Active Surveillance OTHER

Active surveillance (AS) is an accepted management strategy for men diagnosed with low risk PrCa, generally defined as PSA \<10ng/ml and Gleason score of ≤6 and clinical stage T1 to T2a. Occasionally, a minority of men with Gleason 3+4 disease are included, though majority of those included in AS studies have Gleason 3+3 disease or less. Men in AS studies have repeated biopsies based on various criteria including PSA velocity, repeat biopsy at set time points and change noted on digital rectal examination (DRE), biopsy or MRI imaging. Progression of disease has been defined in various ways in different studies, generally, using criteria of Gleason upgrade to greater than Gleason 3+3, evidence of Gleason 4 or Gleason 5 disease, \>50% involvement of any one biopsy core, and greater than 2 cores positive on repeat biopsy. Percentages of men on AS who have upgrade on repeat biopsy have been found to be 19-34%; this may differ in our cohort of men with increased genetic risk for PrCa.

Control Arm; High-risk Arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Assigned male at birth.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Control group (i.e., no known high PrCa risk): 100 men * Men at genetically higher PrCa risk: 100 men

You may qualify if:

• Men ≥18 years old under the care of an Active Surveillance clinic.
• Known diagnosis of PrCa, deemed suitable for Active surveillance at multi-disciplinary meeting (MDT).
• Men at genetically higher PrCa risk who are either:
• (1) Men of any ancestry with a positive family history of PrCa defined as:
• Having a first degree relative (or second degree if through female line) with histologically or death certificate proven PrCa diagnosed at \<70 years
• Having two relatives on the same side of the family with histologically or death certificate proven PrCa where at least one is diagnosed at \<70 years
• Having three relatives on the same side of the family with histologically or death certificate proven PrCa diagnosed at any age
• Or (2) Men of Black African or Black African-Caribbean ancestry defined as:
• Both parents and all 4 grandparents from that origin Or (3) Men of any ancestry with a pathogenic mutation in a gene thought to cause a higher risk of prostate cancer: (including BRCA1, BRCA2, ATM, PALB2, MLH1, MSH2, MSH6, CHEK2 and other DNA repair gene mutations as listed in appendix A) Or (4) Men of any ancestry with a high genetic risk (common and/or rare variants) for PrCa resulting in a RR of ≥2 of PrCa
• Men of any ancestry with no known high risk genetic factors who have been diagnosed with low grade PrCa and deemed suitable for Active Surveillance at multi-disciplinary meeting (control group) as defined in the 4 criteria above.
• Who performance status 0-2
• Absence of any psychological, familial, sociological, or geographical situation potentially hampering compliance with the study protocol and follow-up schedule.

You may not qualify if:

• No PrCa diagnosis
• PrCa diagnosis that is not deemed suitable for active surveillance at multi-disciplinary meeting
• Any significant psychological conditions that may be worsened or exacerbated by participation in the study

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Royal Marsden NHS Foundation Trust: collaborator
• North Bristol NHS Trust: collaborator

Study Sites (4)

Institute of Cancer Research and Royal Marsden Hospital

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

North Bristol NHS Trust

Bristol, BS10 5NB, United Kingdom

NOT YET RECRUITING

The Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

RECRUITING

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

RECRUITING

Related Publications (5)

• Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1415-1424. doi: 10.1056/NEJMoa1606220. Epub 2016 Sep 14.

  PMID: 27626136 BACKGROUND

• Tseng KS, Landis P, Epstein JI, Trock BJ, Carter HB. Risk stratification of men choosing surveillance for low risk prostate cancer. J Urol. 2010 May;183(5):1779-85. doi: 10.1016/j.juro.2010.01.001. Epub 2010 Mar 20.

  PMID: 20304433 BACKGROUND

• Bokhorst LP, Valdagni R, Rannikko A, Kakehi Y, Pickles T, Bangma CH, Roobol MJ; PRIAS study group. A Decade of Active Surveillance in the PRIAS Study: An Update and Evaluation of the Criteria Used to Recommend a Switch to Active Treatment. Eur Urol. 2016 Dec;70(6):954-960. doi: 10.1016/j.eururo.2016.06.007. Epub 2016 Jun 19.

  PMID: 27329565 BACKGROUND

• Porten SP, Whitson JM, Cowan JE, Cooperberg MR, Shinohara K, Perez N, Greene KL, Meng MV, Carroll PR. Changes in prostate cancer grade on serial biopsy in men undergoing active surveillance. J Clin Oncol. 2011 Jul 10;29(20):2795-800. doi: 10.1200/JCO.2010.33.0134. Epub 2011 May 31.

  PMID: 21632511 BACKGROUND

• Berglund RK, Masterson TA, Vora KC, Eggener SE, Eastham JA, Guillonneau BD. Pathological upgrading and up staging with immediate repeat biopsy in patients eligible for active surveillance. J Urol. 2008 Nov;180(5):1964-7; discussion 1967-8. doi: 10.1016/j.juro.2008.07.051. Epub 2008 Sep 17.

  PMID: 18801515 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

This study will look at the association of biomarkers with PrCa presentation and progression among men on Active Surveillance and stratify it by their genetic risk. It will also investigate the incidence and progression by differing genetic risks. The study will review serial PSA, biomarkers and imaging data for men in AS comparing and contrasting those of known higher genetic risk for PrCa with those without a known higher genetic risk. Samples will be collected to investigate the association of genetic profiles and biomarkers from biological samples including plasma, serum, urine, stool, and saliva in these two groups.

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Study Officials

• Ros A Eeles, FRCP, FRFR

  Institute of Cancer Research and Royal Marsden Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eva McGrowder, PhD

CONTACT

02087224483; eva.mcgrowder@icr.ac.uk

Elizabeth K Bancroft, PhD

CONTACT

02087224483; elizabeth.bancroft@icr.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 12, 2023
• Study Start: August 22, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

GB (4)