Condition category
Cancer
Date applied
05/09/2016
Date assigned
20/09/2016
Last edited
21/09/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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, 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. The Percy Falk Research Foundation
3. Uppsala läns landsting

Who is the main contact?
Associate 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

Dr Anna Bill-Axelson

ORCID ID

Contact details

Uppsala University
Urology
Dag Hammarskjolds vag 26
Uppsala
75237
Sweden

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

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

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 multiparametric 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 multiparametric 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 measures

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

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

31/12/2020

Locations

Countries of recruitment

Denmark, Finland, Sweden, United Kingdom

Trial participating centre

Akademiska Hospital
Uppsala, Sweden

Trial participating centre

Sahlgrenska University Hospital
Göteborg, Sweden

Trial participating centre

Karolinska University Hospital
Solna, Sweden

Trial participating centre

Danderyd Hospital
Danderyd, Sweden

Trial participating centre

Ryhov Hospital
Jönköping, Sweden

Trial participating centre

Skåne University Hospital
Malmö, Sweden

Trial participating centre

Örebro University Hospital
Örebro, Sweden

Trial participating centre

Östersund Hospital
Östersund, Sweden

Trial participating centre

Linköping University Hospital
Linköping, Sweden

Trial participating centre

Helsinki University Hospital
Helsinki, Finland

Trial participating centre

Aarhus University Hospital
Aarhus, Denmark

Trial participating centre

The Royal Marsden Hospital
London, UK

Trial participating centre

King's College Hospital
London, UK

Sponsor information

Organisation

Anna Bill-Axelson

Sponsor details

Uppsala University
Urology
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

The Swedish Cancer Society

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Percy Falk’s Research Foundation

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Landstinget i Uppsala län

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes