The Active Surveillance Study

Официальное название

Active Surveillance Study for Prostate Cancer Management for Men at Higher Genetic Risk Compared With Men at No Known Higher Genetic Risk.

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Active Surveillance
  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

Первичные конечные точки

• To determine the incidence of disease progression of PrCa in the cohorts studied. [Срок оценки: 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. [Срок оценки: The full analysis being completed within one year of date of completion of 5 year follow-up of the last participant.]

Вторичные конечные точки (2)

• To investigate the role of biomarker profiles in men undergoing active surveillance who are also at genetically higher risk for PrCa. [Срок оценки: 5 years]
• To investigate the role of biomarker profiles in men undergoing active surveillance who are also at genetically higher risk for PrCa. [Срок оценки: 5 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Великобритания · 4 центра

• Institute of Cancer Research and Royal Marsden Hospital — Sutton
• North Bristol NHS Trust — Bristol
• The Royal Marsden Hospital — London
• The Royal Marsden Hospital — Sutton

Публикации

• 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 E PMID 27626136
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT05810467 · CCR5747

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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