SPCG17: Prostate Cancer Active Surveillance Trigger Trial

Study Overview
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Brief Summary
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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
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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 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: A systematic repeat biopsy if PSA density increases to > 0.2 ng/ml/cc, and then at every 0.1 ng/ml/cc increase 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 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: 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 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.

Official Title
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SPCG17: Prostate Cancer Active Surveillance Trigger Trial (PCASTT)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Procedure: Active surveillance


Participation Criteria
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Eligibility Criteria
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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 0.2 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
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Current practice for active surveillance<br>In this arm, patients are monitored according to current practice for active surveillance at the trial centre. Repeat biopsies (and/or other examinations) and curative treatment are performed according to the urologist's judgement. | Procedure: Active surveillance<br>* Active monitoring of prostate cancer and curative treatment if there are signs of tumor progression.<br>|
| Experimental: Standardized triggers for treatment<br>In this arm, patients are monitored according to a standardized active surveillance protocol with specific triggers for treatment. Repeat biopsies and curative treatment are only initiated if/when specific criteria are fulfilled. | Procedure: Active surveillance<br>* Active monitoring of prostate cancer and curative treatment if there are signs of tumor progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival is defined as cumulative incidence of PSA relapse following curative treatment and cumulative incidence of androgen therapy in untreated men. | Median 10 years follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of pT3 at radical prostatectomy specimens | Occurrence of confirmed pT3 in radical prostatectomy specimens according to the pathology report | Median 10 years follow-up | 
| Cumulative incidence of metastases | Occurrence of distant metastasis (suspected or confirmed) during follow-up | Median 10 years follow-up | 
| Cumulative number of treatments with curative intent (mainly radical prostatectomies or local radiotherapy) | Occurrence of radical prostatectomies or local radiotherapy (with or without adjuvant androgen deprivation therapy) | Median 10 years follow-up | 
| Cumulative incidence of switch to watchful waiting | Occurrence of conversions from active surveillance to watchful waiting during follow-up | Median 10 years follow-up | 
| Quality of life | Assessed by questionnaire | Median 10 years follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, active surveillance, standardised treatment triggers, MRI, randomized