The Active Surveillance Study (AS)

Institute of Cancer Research, United Kingdom

Status: Enrolling

Conditions: Prostate Cancer

Treatments: Other: Active Surveillance

Study type: Observational

Funder types: Other

Identifiers

NCT05810467

CCR5747

Details and patient eligibility

About

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.

Full 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 a known higher genetic risk. Additionally, the study aims to collect samples to investigate the profile of plasma, serum, urine, stool, and saliva (or DNA from blood) 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 - where possible, DNA from blood will be used instead of saliva samples). 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 urology clinics at the Royal Marsden Hospital and North Bristol NHS Trust. These will be men who are already registered at either the Royal Marsden Hospital or North Bristol NHS Trust and undergoing active surveillance (as determined by the MDT) will be given a patient information sheet. This explains the study in lay terms and gives the contact details for the relevant research team.

Enrollment: 200 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• 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.

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

Trial design

200 participants in 2 patient groups

Control Arm

Description:

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.

Treatment:

Other: Active Surveillance

High-risk Arm

Description:

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.

Treatment:

Other: Active Surveillance