Clinical trial NCT04024475: Prostate Cancer Biobank
Official title: Prospective Cohort Study With Collection of Clinical Data, Serum and Plasma of Patients With Prostate Disease
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Prostatic Neoplasms
Keywords: Radical prostatectomy
Metastatic castration resistant prostate cancer
Oligometastatic prostate cancer
Radiotherapy
Prostate cancer screening
Prostate-specific antigen (PSA)
Prostate cancer (PCa)
Opportunistic screening
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
Collaborators: name: ProteoMediX AG
name: Cantonal Hospital of St. Gallen
First posted: 2019-07-18
Enrollment: 1323
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: See description under "Groups/Cohorts"

Brief summary: Carcinoma of the prostate is the second most commonly diagnosed cancer and occurs predominantly in older men - almost two-thirds of those affected are over 65 years of age. In a significant proportion of patients, the disease is harmless and progresses only very slowly. As a result, there is a risk of overdiagnosis and overtreatment. The main diagnostic tool for prostate cancer is the prostate-specific antigen (PSA) test, but its specificity is minimal. It is important to look for other biological characteristics (biomarkers) that provide pointers to the need for a diagnosis and treatment. Even after treatment and in advanced stages of disease, decisions are often difficult, because it is not necessarily clear which patient needs a specific treatment.

In this study, a multicenter biobank of patient sera, plasma and tissue is being established together with information of relevance to the disease, in order to provide a basis for the testing of biomarkers. The aim is to identify markers that offer diagnostic and treatment-selective pointers and thus make a decisive contribution to the optimum care of patients.

Detailed description: Background \& Rationale:

Prostate Cancer (PCa) occurs mainly in older men, nearly two thirds are diagnosed in men aged 65 or older. However, in a substantial subset of patients, the disease will be slow-growing and harmless. This highlights one of the major issues with PCa screening and diagnosis: the risks of over-detection and overtreatment, i.e. to diagnose and invasively treat indolent cancers that may lead to reduced quality of life without increasing overall survival.

The main diagnostic tool for PCa is the systematic screening for PSA (prostate-specific antigen), despite the low specificity of PSA and the unclear cut-off value, resulting in a large proportion of unnecessary biopsies with potential side effects. Additionally, as screening addresses a healthy population and screened men may suffer from disadvantages, such as unnecessary biopsies, screening in PCa remains controversial.

Besides the dilemmas in PCa screening, there are several additional important clinical questions that deserve further investigation and better risk-adapted patient stratification as follows: 1) active treatment versus deferred therapy in the heterogeneous group of patients with localized PCa; 2) treatment intensification for locally-advanced, high-risk prostate cancers with significant risk of PCa-related deaths; 3) optimal approach for patients with high risk of local recurrence post-radical prostatectomy; 4) treatment of patients with rising PSA (biochemical relapse) after curative treatment (either radical prostatectomy or RT); 5) a better understanding of oligometastatic disease and; and 6) treatment of patients with castration-resistant prostate cancer (CRPC).

PCa is characterized by a wide spectrum of molecular and phenotypic characteristics. PCa patients are currently grouped in different risk categories, illustrating particular features of a heterogeneous disease. On one side, many patients present benign disease, such as benign prostate enlargement caused by prostate hyperplasia and, on the other side, progressively malignant PCa, ranging from localized, locally-advanced, metastatic and castrate-resistant disease.

For the purpose of this study, we established 5 groups and their corresponding subgroups, as follows:

A) Opportunistic screening and benign prostate syndrome (BPS) with prostate biopsy; B) Localized and locally advanced prostate cancers treated with curative intent; C) Biochemical relapse after RP; D) Metastatic advanced PCa without curative treatment but hormone sensitive disease, treated with ADT (medical or surgical); E) Metastatic castration resistant prostate cancer (mCRPC).

Currently a comprehensive biobank in the field of urogenital disease, driven by a multidisciplinary panel (composed by specialists from the following fields: urology, medical oncology, radio-oncology and pathology), does not exist in Switzerland.

Such biobank (together with the corresponding clinical data) would enable researchers and clinicians alike to discover and validate diagnostic, prognostic and predictive PCa biomarkers, which are currently highly needed.

Importantly, the biobank shall consist of specific sample sets related to the different stages of PCa development (including screened healthy men and newly diagnosed patients). Ultimately, this comprehensive project will allow addressing some of the urgent questions in different stages of PCa.

Objective:

To create a novel and comprehensive plasma and serum biobank of about 55000 samples (derived from about 1540 patients) accompanied by the corresponding clinical data. This will enable us to explore and validate different diagnostic, prognostic and predictive biomarkers regarding prostate disease.

Eligibility criteria: Inclusion Criteria:

* Written informed consent for storage of liquid samples and referencing of biopsy(-ies) in the biobank, and for clinicopathological data collection, for translational research purposes.

Criteria for entering diagnostic group A

* Patient scheduled for prostate biopsy for any reason

Criteria for entering group B

Subgroup B0 (active surveillance, closed group):

* Patient under active surveillance for localized PCa

All of the following criteria should be fulfilled:

* clinical stage T1/T2
* PSA ≤ 10 ng/ml
* PSA density \< 0.2 ng/ml per milliliter
* biopsy Gleason score ≤ 6
* one or two positive biopsy cores

Subgroups B1-B3 (treatment with curative intent):

* Patient under treatment for localized PCa with either radical prostatectomy or RP followed by (adjuvant) external beam radiation (B1), or external beam radiation therapy without (B2) or with ADT (B3).

Criteria for entering diagnostic group C

* Patient underwent RP
* Patient with biochemical relapse: PSA progression after RP is defined as two consecutive rises with final PSA value \> 0.1 ng/mL, or three consecutive rises (the first value must be measured earliest 4 weeks after radical prostatectomy).
* Patient is candidate for salvage RT with or without combined systemic therapy.

Criteria for entering diagnostic group D

* Metastatic PCa without curatively intended treatment, but hormone sensitive disease, treated with ADT (medical or surgical) with or without additive treatments, such as docetaxel or short term course of Bicalutamide or continuous Bicalutamide.
* Oligometastatic PCa: N1 or M1a/b disease detected on PET or whole body MRI presenting ≤5 synchronous lesions (bone and/or lymph nodes), under active surveillance, or treated with chemotherapy, treated with focal RT (i.e. SBRT), treated with surgery or other treatments; ADT can be combined, but it is not necessarily required for oligometastatic patients.

Criteria for entering diagnostic group E (metastatic castration resistant PCa)

* Patient with mCRPC defined by: progressive disease after surgical castration or under medical ADT and suppressed testosterone levels.
* Oligometastatic PCa: N1 or M1a/b disease detected on PET or whole body MRI presenting ≤5 synchronous lesions (bone and/or lymph nodes), under active surveillance, or treated with chemotherapy, treated with focal RT (i.e. SBRT), treated with surgery or other treatments; ADT can be combined, but it is not necessarily required for oligometastatic patients.

Exclusion criteria:

* Other concurrent active malignancy.
* Psychiatric disorder precluding understanding of information on study related topics and giving informed consent.
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and follow-up.

Primary outcomes:
measure: Group A: Time to prostate cancer (PCa) histological diagnosis
timeFrame: At the occurrence of a positive biopsy result or latest 10 years after registration
measure: Group B0: Progression free survival (PFS)
timeFrame: At 1 year after assigned into Group B0
measure: Group B1: Biochemical relapse free survival
timeFrame: At 5 years after assigned into Group B1
measure: Group B2-B3: Interval to biochemical failure (IBF)
timeFrame: At 18 months after assigned into Group B2-B3
measure: Group C: Progression free survival (PFS)
timeFrame: At progression or latest 10 years after assigned into Group C
measure: Group D: Biochmical prostate specific antigen progression
timeFrame: At 6 months after induction of androgen deprivation therapy
measure: Group E: Overall survival (OS)
timeFrame: At death or latest 10 years after assigned into Group E
Secondary outcomes:
measure: Group A, B0-B3, C, D: Overall survival (OS)
timeFrame: At death from any cause or latest 10 years after assigned into the corresponding Group
measure: Group A, B1-B3, C: Time to PCa-specific death
timeFrame: At prostate cancer related death or latest 10 years after assigned into the corresponding Group
measure: Group B0: Progression free survival (PFS)
timeFrame: At the occurrence of the event or latest 10 year after assigned into Group B0
measure: Group B0: Event free survival (EFS)
timeFrame: At the occurrence of the event or latest 10 year after assigned into Group B0
measure: Group D: Progression free survival (PFS)
timeFrame: At the occurrence of the event or latest 10 year after assigned into Group D
measure: Group E: Progression free survival (PFS)
timeFrame: At the occurrence of the event or latest 10 year after assigned into Group E
Other outcomes:
Locations:
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Fribourg
country: Switzerland
facility: Hopital Fribourgeois HFR
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaires Genève HUG
city: Lugano
country: Switzerland
facility: Clinica Luganese
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Thun
country: Switzerland
facility: Spital STS AG
Study officials:
affiliation: Cantonal Hospital of St. Gallen
name: Daniel Engeler, MD
role: STUDY_CHAIR
References: