SPCG-17 - when to treat men who are in active surveillance for prostate cancer, a randomized study comparing current practice with standardized triggers for initiation of curative treatment
| ISRCTN | ISRCTN64382660 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN64382660 |
| ClinicalTrials.gov number | NCT02914873 |
- Submission date
- 05/09/2016
- Registration date
- 20/09/2016
- Last edited
- 06/12/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
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 December 2040
Who is funding the study?
1. The Swedish Cancer Society
2. Swedish research council
3. Nordic Cancer Union
Who is the main contact?
Professor Anna Bill-Axelson
anna.bill.axelson@uu.se
Contact information
Public
Uppsala University, Urology
Dag Hammarskjolds vag 26
Uppsala
75237
Sweden
| Phone | 0046701679744 |
|---|---|
| ulrika.aberg@uu.se |
Scientific
Uppsala University, Urology
Dag Hammarskjolds vag 26
Uppsala
75237
Sweden
Study information
| Study design | Randomized multi-centre open-label clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | SPCG-17 - Prostate Cancer Active Surveillance Trigger Trial (PCASTT) |
| Study objectives | 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(s) | Regional Ethical Vetting Board in Uppsala, Sweden, 15/06/2016, ref: 2016/204 |
| Health condition(s) or problem(s) studied | 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 |
| Primary outcome measure | Current primary outcome measure as of 15/12/2024: The primary outcome is disease progression, defined as 1) cumulative incidence of PSA relapse after curative treatment or 2) cumulative incidence of androgen deprivation therapy in untreated men still in active surveillance. The first analysis for the primary endpoint will be performed 1 year after inclusion of the last patient into the study. Subsequent analyses for primary (and secondary) endpoints will be performed every 3 years. Previous 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 | Current secondary outcome measure as of 15/12/2024: 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. Prostate cancer mortality 6. Quality of life (will be assessed from questionnaires at baseline and every 2 years) 7. Costs The first analysis for secondary endpoints will be performed 1 year after inclusion of the last patient. Previous secondary outcome measure as of 15/12/2024: 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 study start date | 15/06/2016 |
| Completion date | 31/12/2040 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Male |
| Target number of participants | 2000 |
| Total final enrolment | 2009 |
| Key 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 |
| Key exclusion criteria | Participants not fulfilling the inclusion criteria |
| Date of first enrolment | 01/10/2016 |
| Date of final enrolment | 30/09/2024 |
Locations
Countries of recruitment
- Denmark
- England
- Finland
- Norway
- Sweden
- United Kingdom
Study participating centres
SE-752 37
Sweden
SE-413 45
Sweden
SE-701 85
Sweden
SE-581 85
Sweden
FI-00029
Finland
SW3 6JJ
United Kingdom
SE5 9RS
United Kingdom
SE-901 85
Sweden
SE-851 86
Sweden
SE-971 80
Sweden
SE-351 85
Sweden
NO-7006
Norway
NO-3116
Norway
NO-6026
Norway
NO-0424
Norway
SE1 9RT
United Kingdom
KT18 7EG
United Kingdom
FI-33014
Finland
NO-9038
Norway
DK-5000
Denmark
-
Denmark
Woolwich
London
SE18 4QH
United Kingdom
Bedford
MK42 9DJ
United Kingdom
Croydon
CR7 7YE
United Kingdom
Sponsor information
University/education
Urology Department
Dag Hammarskjolds vag 26
Uppsala
75237
Sweden
| Website | http://www.surgsci.uu.se/Forskning/Forskningsomraden/Urologi-IKV/prostatacancer-ikv-uu/ |
|---|---|
"ROR" |
https://ror.org/048a87296 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Swedish Cancer Society
- Location
- Sweden
Government organisation / National government
- Alternative name(s)
- Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, Swedish Research Council Formas, Formas
- Location
- Sweden
No information available
Results and Publications
| Intention to publish date | 31/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 22/08/2019 | 21/09/2020 | Yes | No |
Editorial Notes
06/12/2024: Contact details updated.
05/12/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 31/12/2024 to 30/09/2024.
2. The overall study end date was changed from 31/12/2034 to 31/12/2040.
3. Total final enrolment added.
15/01/2024: 1. The overall study end date was changed from 31/12/2033 to 31/12/2034.
2. The primary outcome measure was changed.
3. The secondary outcome measure was changed.
4. A study website was added.
5. Study contact email was updated.
07/12/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2022 to 31/12/2024.
2. The overall end date was changed from 31/12/2030 to 31/12/2033.
3. The intention to publish date
4. The plain English summary was updated to reflect these changes.
5. The trial participating centres Rigshospitalet, Queen Elizabeth Hospital, Bedford Hospital, Croydon University Hospital were added.
19/10/2020: Internal review.
21/09/2020: The following changes were made to the trial record:
1. The trial participating centres "Epsom Hospital", and "The University of North Norway" were removed.
2. The trial participating centres , "Seinäjoki Central Hospital", "University Hospital of North Norway", "Odense University Hospital", and "Epsom and St Helier Hospital" were added.
3. Demark was added as a country of recruitment.
4. A study contact was updated.
5. The plain English summary was updated accordingly.
6. Publication reference added.
11/03/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/12/2020 to 31/12/2022.
2. The trial participating centre University of North Norway was added.
06/01/2020: Internal review.
11/06/2019: The following changes were made to the trial record:
1. The funders were changed from "Percy Falk’s Research Foundation and Landstinget i Uppsala län" to "Svenska Forskningsrådet Formas (Swedish research council) and Nordic Cancer Union".
2. The countries of recruitment were changed: "Denmark" was removed and "Norway" was added.
3. The plain English summary was updated to reflect these changes.
4. The ClinicalTrials.gov number was added.
5. The interventions were changed.
6. The trial participating centres were changed: "Karolinska University Hospital; Danderyd Hospital; Ryhov Hospital; Skåne University Hospital; Östersund Hospital; Aarhus University Hospital" were removed. "Umeå University Hospital; Sundsvall Hospital; Sunderby Hospital; Växjö Hospital; St Olav's Hospital; Vestfold Hospital; Ålesund Hospital; Oslo University Hospital; Guy’s Hospital; Epsom Hospital" were added.
01/11/2017: Internal review.
