Prospective Cohort Study With Collection of Clinical Data, Serum and Plasma of Patients With Prostate Disease
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 1,323
- 试验地点
- 12
- 主要终点
- Group A: Time to prostate cancer (PCa) histological diagnosis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- 未提供
结局指标
主要结局
Group A: Time to prostate cancer (PCa) histological diagnosis
时间窗: At the occurrence of a positive biopsy result or latest 10 years after registration
Time to PCa histological diagnosis will be calculated from the time when patients were assigned into group A until documentation of a positive biopsy result.
Group B2-B3: Interval to biochemical failure (IBF)
时间窗: At 18 months after assigned into Group B2-B3
IBF is defined as the time interval from completion of treatment by patients of group B2 or B3 until biochemical failure (BF). BF is defined by an absolute PSA value superior or equal to the post-treatment PSA nadir + 2 ng/mL.
Group B0: Progression free survival (PFS)
时间窗: At 1 year after assigned into Group B0
PFS will be calculated from the time when patients were assigned into group B0 until first documented event occurred: * three or more positive cores at rebiopsy * Gleason score ≥ 7 at rebiopsy
Group B1: Biochemical relapse free survival
时间窗: At 5 years after assigned into Group B1
Biochemical relapse free survival is calculated from the time when patients were assigned into group B1 until prostate specific antigen (PSA) relapse occurs. PSA relapse is defined as PSA progression after radical prostatectomy (RP) is defined as two consecutive rises with the final PSA value \> 0.1 ng/mL, or three consecutive rises (the first value must be measured earliest 4 weeks after RP).
Group C: Progression free survival (PFS)
时间窗: At progression or latest 10 years after assigned into Group C
PFS is counted from the day the patient entered group C to the day of the first record of either local or regional recurrence, distant recurrence, start of hormonal treatment after biochemical failure, or death due to any cause.
Group E: Overall survival (OS)
时间窗: At death or latest 10 years after assigned into Group E
OS will be calculated from the time when patients were assigned into group E until death from any cause. OS will be censored at the time the patient is last known to be alive if: * the patient is lost to follow-up * or death is not experienced.
Group D: Biochmical prostate specific antigen progression
时间窗: At 6 months after induction of androgen deprivation therapy
The biochemical prostate specific antigen (PSA) progression is calculated from the induction of palliative androgen deprivation therapy (ADT), defined as: * In case PSA levels had not decreased from baseline, under treatment: ≥ 25% increase from baseline (last PSA measurement before treatment start) AND an increase in the absolute PSA value of ≥ 2 ng/mL and presence of castrate level of testosterone. * In case PSA levels decreased from baseline, under treatment: ≥ 25% increase above the nadir AND an increase in the absolute PSA value of ≥ 2 ng/mL and presence of castrate level of testosterone.
次要结局
- Group A, B0-B3, C, D: Overall survival (OS)(At death from any cause or latest 10 years after assigned into the corresponding Group)
- Group B0: Progression free survival (PFS)(At the occurrence of the event or latest 10 year after assigned into Group B0)
- Group B0: Event free survival (EFS)(At the occurrence of the event or latest 10 year after assigned into Group B0)
- Group D: Progression free survival (PFS)(At the occurrence of the event or latest 10 year after assigned into Group D)
- Group E: Progression free survival (PFS)(At the occurrence of the event or latest 10 year after assigned into Group E)
- Group A, B1-B3, C: Time to PCa-specific death(At prostate cancer related death or latest 10 years after assigned into the corresponding Group)