Clinical trial NCT02454543: Impact of Radical Prostatectomy as Primary Treatment in Patients With Prostate Cancer With Limited Bone Metastases
Official title: Multicentric, Prospective, Randomized Controlled Trial Comparing Best Systemic Therapy (BST) With Radical Prostatectomy or BST Alone in the Management of Men With Pauci-metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Prostate Cancer
Keywords: metastatic
prostatectomy
androgen deprivation
best systemic therapy
Lead sponsor: Martini-Klinik am UKE GmbH
Sponsor class: OTHER
Collaborators: name: Förderverein Hilfe bei Prostatakrebs e.V.
First posted: 2015-05-27
Enrollment: 452
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to investigate, the effect of radical prostatectomy with extended lymphadenectomy on cancer-specific survival, time to castration-resistance, time to progression and quality of life in patients with a limited bone metastatic prostate cancer. In addition the influence of patient- and disease-related factors on clinical outcome (prognostic effect) and on the comparison therapy (predictive effect) will be examined.

Amendment05: Due to the slow tumor biology of prostate cancer, the follow-up period of 5 years is not sufficient to reach the primary endpoint of the study. For this reason, the follow-up is extended for a further 5 years with 2 visits per year.

Detailed description: More recent data has shown that performing local therapy with lymphogenic metastatic prostate cancer has resulted in a definite benefit in cancerspecific and overall survival. The analysis of this data has led to a change of paradigm in the treatment of lymphogenic metastatic prostate cancer (Isbarn Deutsches Ärzteblatt 2013). Patients with low lymphogenic metastatic load and low comorbidity are therefore frequently given local therapy. In a retrospective review of patients with lymphogenic metastatic prostate cancer, who were either treated by means of best systemic therapy or best systemic therapy plus radical prostatectomy, a highly significant benefit is shown for the patient group which received surgery (Engel et al., Eur Urol 2012). The 5 and 10 year overall survival rate in this cohort was 84% and 64% respectively following RP and in the other cohort with best systemic therapy without RP 60% and 28% respectively.

Our own working group was able to confirm this clear survival benefit in the lymphogenic metastatic stage for patients who received surgery: in a matched pair analysis the clinically progression-free survival rate after 5 and 10 years was 77% and 61% respectively after additional RP and 61% and 31% respectively with best systemic therapy alone (p=0.005). The same trend was found for cancer-specific survival (84% and 76% with additional RP versus 81% and 46% with best systemic therapy alone (p=0.001) (Steuber et al., BJUI 2011).

The impressive improvements in the survival rates of lymphogenic metastatic prostate cancer through local therapy compared with best systemic therapy alone suggests that patients with distant metastases could potentially also benefit from local therapy. Besides possible effects on tumour control, the RP could also be beneficial with regard to a local progression of the prostate cancer (rectal infiltration, infiltration of the bladder). This could lead to an improvement in the quality of life in the course of the disease. On the other hand, radical prostatectomy is associated with potential side-effects (e.g. urinary incontinence in approximately 5 - 10% of patients as well as possible general side-effects, such as thrombosis, embolism, impaired wound healing etc.), which can lead to a loss in terms of quality of life.

Eligibility criteria: Patients with locally resectable intermediate and high-risk prostate cancer which has been confirmed by biopsy according to D'Amico criteria (intermediate risk: PSA 10-20 ng/ml, cT2b-c, Gleason score 7; high risk: PSA \>20 ng/ml, \>cT2c, Gleason score 8-10) with clinical evidence of bone metastases in imaging tests can be included. Necessary radiotherapy of the bone metastases as required is also permitted prior to inclusion in the study.

In line with the results from the recent CHAARTED and STAMPEDE studies (Sweeny et al., 2015, James et al 2015), early treatment with taxanes may be used in both the standard treatment arm as well as in the intervention arm where the prostatektomie is performed. The period 6 months from the initial diagnosis to randomization and possibly three months from randomization to surgery must be complied with.

Inclusion criteria

1. Patients with newly diagnosed prostate cancer which has been confirmed by histological examination (within the last 6 months prior to randomization)
2. At least one and at most 5 bone metastases in imaging tests (bone scintigraphy, CT, MRT or PET) at diagnosis with no evidence of visceral metastasis. Patients with evidence of lymph node metastasis (N1) are allowed
3. PSA ≤ 200 ng/ml at diagnosis (without ADT)
4. Asymptomatic or mild symptomatic disease
5. Locally resectable tumour stage
6. ECOG Performance Score 0-1
7. Submission of the patient's written declaration of informed consent following explanation
8. Age ≥ 18 - ≤ 75 years
9. Full legal capacity and compliance of the Patient

Exclusion Criteria:

* Contraindications to radical prostatectomy (Local non-resectable disease, increased anesthetic risk due to comorbidities)
* Detection of more than 5 bone metastases
* Pain management with opioid analgetics
* Evidence of visceral metastases or brain metastases
* Neuroendocrine and / or small cell differentiation in histology of the biopsy
* Charlson Comorbidity Index \> 2
* ECOG Performance Score \> 1
* Myocardial infarction or stroke within the last 6 months
* Existing major cardiovascular (grade III - IV according to NYHA), pulmonary (pO2 \<60 mmHg), renal, hepatic or hematopoietic disease (e.g. severe bone marrow aplasia)
* Severe psychiatric disorders persons housed on judicial or administrative arrangement in an institution
* Simultaneous participation in another clinical trial with interventional character of the metastatic prostate cancer

Primary outcomes:
measure: Cancer specific survival
timeFrame: 10 years
Secondary outcomes:
measure: Developement of castration-resistance measured by PSA value
timeFrame: 10 years
measure: Overall survival
timeFrame: 10 years
measure: Progression-free survival
timeFrame: 10 years
Other outcomes:
measure: Quality of Life measured by the EPIC-26
timeFrame: 10 years
Locations:
city: Hamburg
country: Germany
facility: Markus Graefen
state: Nein
Study officials:
affiliation: Martini-Klinik am UKE GmbH
name: Markus Graefen, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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