Clinical trial NCT02914873: SPCG17: Prostate Cancer Active Surveillance Trigger Trial
Official title: SPCG17: Prostate Cancer Active Surveillance Trigger Trial (PCASTT)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prostate Cancer
Keywords: prostate cancer
active surveillance
standardised treatment triggers
MRI
randomized
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2016-09-26
Enrollment: 2000
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A large proportion of men with prostate cancer are overdiagnosed and overtreated mainly due to PSA testing. Active surveillance (AS) aims to reduce these harms by recommending curative treatment only when and if signs of tumor progression occur. There are however a number of uncertainties in AS, the most important being when to initiate treatment. The investigators are therefore starting a large randomized multicenter trial testing the safety of a standardized active surveillance protocol with specified triggers for repeat biopsies and initiation of curative treatment. The standardized protocol is compared with current practice for active surveillance. The primary aim of the study is to reduce overtreatment and subsequent side effects, without increasing the risk of disease progression or prostate cancer mortality.

Detailed description: STUDY HYPOTHESIS

The study hypothesis is that standardized triggers for initiation of curative treatment of men who are in active surveillance will reduce overtreatment without increasing disease progression and prostate cancer mortality.

STUDY DESIGN

Randomized multi-centre open-label clinical trial

INTERVENTIONS

Computerized randomisation (1:1) within 12 months from diagnosis of prostate cancer, either to active surveillance according to current clinical practice at the trial centre (reference arm), or to a standardised active surveillance protocol applying specific criteria for repeat biopsies and the initiation of curative treatment (experimental arm). Patients are stratified by centre and Gleason score.

Follow-up both groups: PSA every 6 months, clinical examination (with PSA test) annually, and MRI every second year.

Repeat biopsies (reference arm): Current practice

Repeat biopsies (experimental arm), standardised triggers:

1. A systematic repeat biopsy if PSA density increases to \> 0.2 ng/ml/cc, and then at every 0.1 ng/ml/cc increase
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, a new lesion with PI-RADS score 3-5, or high or very high suspicion of extra-capsular extension or seminal vesicle invasion
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

Curative treatment (reference arm): Current practice

Curative treatment (experimental arm), standardised triggers:

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. For men who discontinue active surveillance, the follow-up and management continue according to standard clinical practice but with annual reporting in the study.

Eligibility criteria: Inclusion Criteria:

* Recently (within 12 months) diagnosed adenocarcinoma of the prostate
* Tumor stage less than or equal to T2a, NX, M0
* PSA less than 15 ng/ml, PSA density less than or equal to 0.20 ng/ml/cc
* Gleason pattern 3+3=6 (any number of cores, any cancer involvement)
* Gleason pattern 3+4=7 (less than 3 cores (or less than 30% of cores if more than 10 cores are taken), less than 10 mm cancer in one core)
* Life expectancy more than 10 years with no upper age limit
* Candidate for curative treatment if progression occurs
* Signed written informed consent

Exclusion Criteria:

* none

Primary outcomes:
measure: Progression-free survival
timeFrame: Median 10 years follow-up
Secondary outcomes:
measure: Cumulative incidence of pT3
timeFrame: Median 10 years follow-up
measure: Cumulative incidence of metastases
timeFrame: Median 10 years follow-up
measure: Cumulative number of treatments with curative intent (mainly radical prostatectomies or local radiotherapy)
timeFrame: Median 10 years follow-up
measure: Cumulative incidence of switch to watchful waiting
timeFrame: Median 10 years follow-up
measure: Prostate cancer mortality
timeFrame: Median 10 years follow-up
measure: Quality of life
timeFrame: Median 10 years follow-up
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Tampere
country: Finland
facility: Seinäjoki Central Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North Norway
city: Trondheim
country: Norway
facility: St Olavs University Hospital
city: Tønsberg
country: Norway
facility: Hospital of Vestfold
city: Ålesund
country: Norway
facility: Ålesund Regional Hospital
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Luleå
country: Sweden
facility: Sunderby Regional Hospital
city: Sundsvall
country: Sweden
facility: Sundsvall Regional Hospital
city: Umeå
country: Sweden
facility: Umeå University Hospital
city: Uppsala
country: Sweden
facility: Akademiska University Hospital
city: Växjö
country: Sweden
facility: Växjö Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
city: Bedford
country: United Kingdom
facility: Bedford Hospital
city: Croydon
country: United Kingdom
facility: Croydon University Hospital
city: London
country: United Kingdom
facility: Epsom and St Helier Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: London
country: United Kingdom
facility: Queen Elisabeth Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Uppsala University
name: Anna Bill-Axelson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ahlberg MS, Adami HO, Beckmann K, Bertilsson H, Bratt O, Cahill D, Egevad L, Garmo H, Holmberg L, Johansson E, Rannikko A, Van Hemelrijck M, Jaderling F, Wassberg C, Aberg UWN, Bill-Axelson A. PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design. BMJ Open. 2019 Aug 22;9(8):e027860. doi: 10.1136/bmjopen-2018-027860.