The Active Surveillance Study

Recruiting

• Conditions: Prostate Cancer

• Registration Number: NCT05810467
• Lead Sponsor: Institute of Cancer Research, United Kingdom

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.

Detailed Description

This prospective 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. This study will also investigate the incidence and progression by differing genetic risks. The study will review the serial PSA and imaging data for men in AS comparing and contrasting the men of known higher genetic risk for PrCa with those without. Additionally, the study aims to collect samples to investigate the profile of plasma, serum, urine, stool and saliva biomarkers in men at a higher genetic risk of PrCa, who have been diagnosed with low risk PrCa and are undergoing Active Surveillance. It will also review the association of specific genetic profiles and biomarkers (biological samples - plasma, serum, urine, stool and saliva). These markers will be compared and contrasted with samples from men with no known increased genetic risk for PrCa.

The study aims to recruit a total of 200 men with low grade PrCa, aged ≥18 into two cohorts (i.e. men on AS who are known to be at higher genetic risk and those on AS with no known increased genetic risk of PrCa. Patients will be identified through the urology clinics at the Royal Marsden Hospital. These will be men who are already registered at the Royal Marsden Hospital and undergoing active surveillance (as determined by the MDT).

Study Timeline

• Study First Submitted: 2023-03-21
• Study First Submitted QC: 2023-04-11
• Study First Posted: 2023-04-12
• Study Start: 2023-08-22
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-09
• Last Update Posted: 2024-10-11
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 200

Inclusion Criteria

• Men ≥18 years old under the care of the Active Surveillance clinic in the Royal Marsden Hospital (RMH).

• 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 European 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 Caribbean ancestry defined as:

• Both parents and all 4 grandparents from that origin Or (3) Men 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 with a high genetic risk (common and/or rare variants) for PrCa resulting in a RR of ≥2 of PrCa

• Men 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 (see Appendix B)
• Absence of any psychological, familial, sociological, or geographical situation potentially hampering compliance with the study protocol and follow-up schedule.

Exclusion Criteria

• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the incidence of disease progression of PrCa in the cohorts studied.	The full analysis being completed within one year of date of completion of 5 year follow-up of the last participant.	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.
To determine the incidence of aggressiveness of PrCa in the cohorts studied.	The full analysis being completed within one year of date of completion of 5 year follow-up of the last participant.	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.

Secondary Outcome Measures

Name	Time	Method
To investigate the role of biomarker profiles in men undergoing active surveillance who are also at genetically higher risk for PrCa.	5 years	We will focus on metabolites using descriptive statistics and time-to-event analyses to break down the incidence of disease progression in each cohort and determine the association and interaction between higher genetic risk and metabolite levels.

Trial Locations

Locations (1)

Institute of Cancer Research and Royal Marsden Hospital; 🇬🇧 Sutton, Surrey, United Kingdom