Active Surveillance Study for Prostate Cancer Management for Men at Higher Genetic Risk Compared With Men at No Known Higher Genetic Risk.
概览
- 阶段
- 不适用
- 干预措施
- Active Surveillance
- 疾病 / 适应症
- Prostate Cancer
- 发起方
- Institute of Cancer Research, United Kingdom
- 入组人数
- 200
- 试验地点
- 4
- 主要终点
- To determine the incidence of disease progression of PrCa in the cohorts studied.
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: 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.
干预措施: Active Surveillance
结局指标
主要结局
To determine the incidence of disease progression of PrCa in the cohorts studied.
时间窗: 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.
时间窗: 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.
次要结局
- To investigate the role of biomarker profiles in men undergoing active surveillance who are also at genetically higher risk for PrCa.(5 years)