Plain English Summary
Background and study aims
Prostate cancer is the most common cancer in men in the Western world. If prostate cancer is detected when it is at an early stage and not causing any symptoms, treatment is not immediately needed. Instead the patient’s condition is carefully monitored (active surveillance) with blood tests (the PSA test), physical examination of the prostate, and taking a small sample of tissue (a biopsy) from the prostate. There is however a problematic knowledge gap surrounding active surveillance, and the most important piece of evidence missing is when treatment is likely to be needed and beneficial for the patient. Moreover, the optimal follow-up programs are not yet defined. The aim of this study is to compare current practice of active surveillance with a standardised program for follow-up and triggers for treatment. It is believed that standardised criteria for treatment will reduce unnecessary treatment of early stage prostate cancer, without increasing the risk of not being cured in time. Patients can safely be followed-up by nurses, which increase continuity. Standardised, evidence-based active surveillance programs can also decrease inequities of health care in and between countries.
Who can participate?
Scandinavian and British men with untreated low-risk or favourable intermediate-risk prostate cancer, eligible for active surveillance
What does the study involve?
Participants are randomly allocated to one of two equally sized groups. One group is monitored according to current clinical practice at the clinic where the participant is a patient. The other group is monitored according to a standardised program where treatment is initiated only when specific criteria are fulfilled. Both groups undergo a standard set of prostate biopsies and an MRI examination of the prostate upon inclusion in the study, and are then followed in the same way with PSA testing every 6 months, a yearly clinical check-up, and an MRI examination of the prostate every 2 years. In the clinical practice group, further biopsies and tests can be performed according to the urologist’s judgement.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
The study is run from Uppsala University (Sweden), and a number of hospitals in Sweden, Norway, Denmark, Finland and the UK will enrol patients into the study.
When is the study starting and how long is it expected to run for?
June 2016 to October 2030
Who is funding the study?
1. The Swedish Cancer Society
2. Swedish research council
3. Nordic Cancer Union
(updated 11/06/2019, previously: 2. Percy Falk’s Research Foundation 3. Landstinget i Uppsala län)
Who is the main contact?
Professor Anna Bill-Axelson
anna.bill.axelson@surgsci.uu.se
Trial website
Contact information
Type
Public
Primary contact
Dr Ulrika Aberg
ORCID ID
Contact details
Uppsala University
Urology
Dag Hammarskjolds vag 26
Uppsala
75237
Sweden
0046701679744
ulrika.aberg@surgsci.uu.se
Type
Scientific
Additional contact
Prof Anna Bill-Axelson
ORCID ID
Contact details
Uppsala University
Urology
Dag Hammarskjolds vag 26
Uppsala
75237
Sweden
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
NCT02914873
Protocol/serial number
Nil known
Study information
Scientific title
SPCG-17 - Prostate Cancer Active Surveillance Trigger Trial (PCASTT)
Acronym
Study hypothesis
The study hypothesis is that standardized triggers for initiation of curative treatment of men who are in active surveillance will reduce over-treatment without increasing disease progression and prostate cancer mortality.
Ethics approval
Regional Ethical Vetting Board in Uppsala, Sweden, 15/06/2016, ref: 2016/204
Study design
Randomized multi-centre open-label clinical trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet.
Condition
Active surveillance for low-risk and favourable intermediate-risk prostate cancer
Intervention
Current interventions as of 11/06/2019:
Computerized randomisation (1:1) within 12 months from diagnosis of prostate cancer, either to active surveillance according to current practice at the trial centre (reference arm), or to a standardised active surveillance protocol applying specific criteria for initiating curative treatment (experimental arm).
Patients are stratified by centre and Gleason score.
Follow-up in the reference arm (current practice at the trial centre): PSA every 6 months, clinical examination (with PSA test) annually, and MRI (with targeted biopsies at suspicious lesions) every second year. Repeat biopsies and/or other examinations can be initiated according to the urologist’s judgement.
Follow-up in the experimental arm (criteria for intervention): PSA every 6 months, clinical examination (with PSA test) annually, and MRI (with targeted biopsies at suspicious lesions) every second year. Repeat biopsies and/or curative treatment is initiated if specific criteria are fulfilled (see below).
Criteria for repeat biopsies (experimental arm only):
1. A systematic repeat biopsy if PSA density increases to > 0.2 ng/ml/cc
2. MRI progression in men with previously only Gleason grade 3+3 (5 mm or more increase in size in any dimension of a measurable lesion, increase in PI-RADS score to 3-5, high or very-high suspicion of extra-capsular extension or seminal vesicle invasion, or a new lesion with PI-RADS score 3-5)
3. MRI progression in men with Gleason grade 3+4 (5 mm or more increase in size in any dimension of a measurable lesion, or a new lesion with PI-RADS score 3-5)
Criteria for curative treatment (experimental arm only):
1. MRI progression in lesions with confirmed Gleason grade 4 (increase in PI-RADS score to 4 or 5, or high or very-high suspicion of extra-capsular extension or seminal vesicle invasion)
2. Pathological progression (Gleason pattern 5, primary Gleason pattern 4 in any core with 5 mm or more cancer, Gleason 3+4 in 3 or more cores or 30% if more than 10 cores are taken, or Gleason 3+4 in 10 mm or more cancer)
Patients will be followed continuously until initiation of treatment, the event of metastasis, to a break point where active surveillance is considered terminated and watchful waiting starts, or to death of any cause. After the initiation of curative treatment, watchful waiting, or palliative treatment for cancer progression, the patient is followed according to the standard protocol of the participating centre.
Previous interventions:
Computerized randomisation (1:1) within 12 months from diagnosis of prostate cancer, either to active surveillance according to current practice at the trial centre (reference arm), or to a standardised active surveillance protocol applying specific criteria for initiating curative treatment (experimental arm).
Patients are stratified by centre and Gleason score.
Follow-up in the reference arm (current practice at the trial centre): PSA every 6 months, clinical examination (with PSA test) annually, and MRI (with targeted biopsies at suspicious lesions) every second year. Repeat biopsies and/or other examinations can be initiated according to the urologist’s judgement.
Follow-up in the experimental arm (criteria for intervention): PSA every 6 months, clinical examination (with PSA test) annually, and MRI (with targeted biopsies at suspicious lesions) every second year. Repeat biopsies and/or curative treatment is initiated if specific criteria are fulfilled (see below).
Criteria for repeat biopsies (experimental arm only):
1. A systematic repeat biopsy if PSA density increases to > 0.2 ng/ml/cc
2. MRI progression in men with previously only Gleason grade 3+3 (5 mm or more increase in size in any dimension of a measurable lesion, increase in PI-RADS score to 3-5, new suspicion of extra-capsular extension or seminal vesicle invasion, or a new lesion with PI-RADS score 3-5)
3. MRI progression in men with Gleason grade 3+4 (5 mm or more increase in size in any dimension of a measurable lesion, or a new lesion with PI-RADS score 3-5)
Criteria for curative treatment (experimental arm only):
1. MRI progression in lesions with confirmed Gleason grade 4 (increase in PI-RADS score to 4 or 5, or new suspicion of extra-capsular extension or seminal vesicle invasion)
2. Pathological progression (Gleason pattern 5, primary Gleason pattern 4 in any core with 5 mm or more cancer, Gleason 3+4 in 3 or more cores or 30% if more than 10 cores are taken, or Gleason 3+4 in 10 mm or more cancer)
Patients will be followed continuously until initiation of treatment, the event of metastasis, to a break point where active surveillance is considered terminated and watchful waiting starts, or to death of any cause. After the initiation of curative treatment, watchful waiting, or palliative treatment for cancer progression, the patient is followed according to the standard protocol of the participating centre.
Intervention type
Other
Phase
Drug names
Primary outcome measure
The primary outcome is progression-free survival, which is defined as cumulative incidence of PSA relapse after curative treatment and cumulative incidence of androgen deprivation therapy in untreated men.
The first analysis for the primary endpoint will be performed 1 year after inclusion of the last patient. Subsequent analyses for primary (and secondary) endpoint will be performed every 3 years. Final outcome at 10 years is cumulative prostate cancer mortality.
Secondary outcome measures
1.Cumulative incidence of pT3 at radical prostatectomy specimens
2. Cumulative incidence of metastasis (will be assessed after each follow-up examination)
3. Cumulative number of treatments with curative intent (mainly radical prostatectomies or local radiotherapy)
4. Cumulative incidence of switch to watchful waiting
5. Quality of life (will be assessed from questionnaires at baseline and every 2 years)
6. Costs
The first analysis for secondary endpoints will be performed 1 year after inclusion of the last patient.
Overall trial start date
15/06/2016
Overall trial end date
31/12/2030
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
The inclusion criteria are:
1. Recently (within 12 months) diagnosed adenocarcinoma of the prostate
2. Tumour stage ≤ T2a, NX, M0 (former MX)
3. PSA <15 ng/ml, PSA density ≤ 0,2 ng/ml/cc
4. Gleason pattern 3+3=6 (any number of cores, any cancer involvement) or Gleason pattern 3+4=7 (<3 cores (or <30 % of cores if more than ten cores are taken), <10 mm cancer in one core)
5. Life expectancy >10 years with no upper age limit
6. Candidate for curative treatment if progression occurs
7. Signed written informed consent
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
2000
Participant exclusion criteria
Participants not fulfilling the inclusion criteria
Recruitment start date
01/10/2016
Recruitment end date
31/12/2022
Locations
Countries of recruitment
Denmark, Finland, Norway, Sweden, United Kingdom
Trial participating centre
Akademiska Hospital
Uppsala
-
Sweden
Trial participating centre
Sahlgrenska University Hospital
Göteborg
-
Sweden
Trial participating centre
Örebro University Hospital
Örebro
-
Sweden
Trial participating centre
Linköping University Hospital
Linköping
-
Sweden
Trial participating centre
Helsinki University Hospital
Helsinki
-
Finland
Trial participating centre
The Royal Marsden Hospital
London
-
United Kingdom
Trial participating centre
King's College Hospital
London
-
United Kingdom
Trial participating centre
Umeå University Hospital
Umeå
-
Sweden
Trial participating centre
Sundsvall Hospital
Sundsvall
-
Sweden
Trial participating centre
Sunderby Hospital
Luleå
-
Sweden
Trial participating centre
Växjö Hospital
Växjö
-
Sweden
Trial participating centre
St Olavs Hospital
Trondheim
-
Norway
Trial participating centre
Vestfold Hospital
Tønsberg
-
Norway
Trial participating centre
Ålesund Hospital
Ålesund
-
Norway
Trial participating centre
Oslo University Hospital
Oslo
-
Norway
Trial participating centre
Guy’s Hospital
London
-
United Kingdom
Trial participating centre
Epsom and St Helier Hospital
Surrey
-
United Kingdom
Trial participating centre
Seinäjoki Central Hospital
Tampere
-
Finland
Trial participating centre
University Hospital of North Norway
Tromsø
-
Norway
Trial participating centre
Odense University Hospital
Odense
-
Denmark
Sponsor information
Organisation
Uppsala University
Sponsor details
Urology Department
Dag Hammarskjolds vag 26
Uppsala
75237
Sweden
Sponsor type
University/education
Website
http://www.surgsci.uu.se/Forskning/Forskningsomraden/Urologi-IKV/prostatacancer-ikv-uu/
Funders
Funder type
Charity
Funder name
Cancerfonden
Alternative name(s)
Swedish Cancer Society
Funding Body Type
unknown
Funding Body Subtype
Location
Funder name
Svenska Forskningsrådet Formas
Alternative name(s)
Svenska Forskningsrådet Formas
Funding Body Type
unknown
Funding Body Subtype
Location
Funder name
Nordic Cancer Union
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
31/12/2031
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2020 protocol in http://dx.doi.org/10.1136/bmjopen-2018-027860 (added 21/09/2020)