Prospective Study on the Role of Radical Prostatectomy in Oligo-metastatic Hormone-sensitive Prostate Cancer in Patients on Androgen Deprivation Therapy
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Overall Survival
Study Overview
Brief Summary
MAZINGA is a prospective, single-group pilot study evaluating disease control after robot-assisted radical prostatectomy with extended pelvic lymph-node dissection in men with oligometastatic hormone-sensitive prostate adenocarcinoma who have received androgen-deprivation therapy for at least 6 months and achieved a serum prostate-specific antigen (PSA) level below 4 ng/mL. Eligible participants have no more than five bone metastases confined to the spine and/or pelvis, no visceral or retroperitoneal lymph-node metastases, and no bulky pelvic lymph nodes.
All participants undergo surgery and continue androgen-deprivation therapy as prescribed by their treating oncologist. PSA and serum testosterone are assessed for 24 months. Contrast-enhanced computed tomography plus whole-body bone scintigraphy, or prostate-specific membrane antigen positron emission tomography according to the imaging approach used at staging and clinical judgment, is performed every 6 months. The study evaluates overall survival, progression-free survival, pathological and PSA responses, quality of life, serum biomarkers, urinary complications, and conversion to open surgery.
Detailed Description
Radical prostatectomy is being investigated as a cytoreductive treatment in selected men with oligometastatic hormone-sensitive prostate cancer who respond to androgen-deprivation therapy (ADT). MAZINGA is a prospective, single-centre, single-group pilot study designed to obtain preliminary estimates of survival and treatment response after the addition of radical prostatectomy to ongoing ADT.
Eligible participants have acinar prostate adenocarcinoma, no more than five bone metastases confined to the spine and/or pelvis, no visceral or retroperitoneal nodal metastases, no bulky pelvic nodes greater than 3 cm, an Eastern Cooperative Oncology Group performance status of 0 or 1, and a PSA level below 4 ng/mL after at least 6 months of ADT. Participants undergo robot-assisted laparoscopic radical prostatectomy with modified extended bilateral pelvic lymph-node dissection. ADT is continued according to the treating oncologist.
PSA and serum testosterone are measured at months 1 and 3 and every 3 months thereafter through month 24. Contrast-enhanced computed tomography of the chest and abdomen plus whole-body bone scintigraphy are performed every 6 months through month 24; PSMA PET may be used instead according to the imaging modality used at staging and clinical judgment. EPIC-CP and IPSS questionnaires are administered at months 3 and 12. After month 24, survival status is assessed every 6 months.
The planned convenience sample is 30 participants. Baseline characteristics and biomarker data are summarised descriptively, and survival outcomes are estimated using Kaplan-Meier methods. Radiological response is planned to be assessed according to RECIST version 1.1; the operational definition across the permitted imaging modalities must be confirmed before release.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 41 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent and consent for the use of personal data.
- •Male sex and age greater than 40 years.
- •Histologically or cytologically confirmed acinar adenocarcinoma of the prostate.
- •Oligometastatic bone disease with no more than 5 metastatic bone lesions, none located outside the spine or pelvis. [Confirm the intended threshold because the protocol also states <5.]
- •No retroperitoneal lymph-node metastases and no visceral metastases.
- •No bulky pelvic lymph-node metastases greater than 3 cm.
- •Eligible for radical prostatectomy and lymphadenectomy.
- •Eastern Cooperative Oncology Group performance status 0 or
- •Life expectancy of at least 1 year.
- •Receiving androgen-deprivation therapy for at least 6 months.
- •Serum PSA below 4 ng/mL after at least 6 months of androgen-deprivation therapy.
- •White blood cell count at least 3,000/mm³ and/or absolute granulocyte count at least 1,000/mm³.
- •Platelet count at least 100,000/mm³.
- •Haemoglobin at least 10 g/dL.
- •Serum creatinine no more than 1.5 times the upper limit of normal.
- •Aspartate aminotransferase less than 2.5 times the upper limit of normal.
- •Alanine aminotransferase less than 2.5 times the upper limit of normal.
- •Total bilirubin no more than 1.5 times the upper limit of normal, except in participants with documented Gilbert syndrome.
- •Available and willing to attend all protocol-specified follow-up visits.
Exclusion Criteria
- •Special histological subtypes of prostate carcinoma
- •PSA greater than 100 ng/mL at diagnosis before starting androgen-deprivation therapy.
- •Visceral metastases or retroperitoneal lymph-node metastases.
- •Pelvic lymph-node metastases greater than 3 cm.
- •More than 5 metastatic bone lesions or bone metastases outside the spine or pelvis.
- •Concomitant treatment with other antineoplastic agents, including investigational endocrine therapies.
- •Hypogonadism or severe androgen deficiency defined as serum testosterone below 100 ng/dL.
- •History of pituitary or adrenal insufficiency.
- •Concomitant or planned treatment with medicines that affect androgen metabolism, including spironolactone, ketoconazole, finasteride or dutasteride.
- •Active malignancy or malignancy diagnosed within the previous 5 years, except basal-cell carcinoma of the skin.
- •Uncontrolled arterial hypertension, defined as systolic blood pressure at least 160 mmHg or diastolic blood pressure at least 95 mmHg. Participants with a history of hypertension are eligible if blood pressure is controlled with antihypertensive treatment.
- •Severe uncontrolled concomitant disease or medical condition, including active uncontrolled infection.
- •Clinically significant cardiovascular disease, including myocardial infarction or an arterial thrombotic event within the previous 6 months, severe or unstable angina, symptomatic cardiac arrhythmia or arrhythmia requiring treatment, recent deep-vein thrombosis, pulmonary embolism, cerebrovascular event or ischaemic event.
- •Acute or chronic hepatitis.
- •Dementia or psychiatric illness that limits compliance with study requirements or may prevent understanding or signing the informed-consent form.
- •Previous finasteride or dutasteride treatment discontinued less than 6 months before enrolment.
Arms & Interventions
Arm 1: Radical Prostatectomy Plus Ongoing Androgen-Deprivation Therapy
Participants who have received at least 6 months of androgen-deprivation therapy and achieved a PSA level below 4 ng/mL undergo robot-assisted laparoscopic radical prostatectomy with modified extended bilateral pelvic lymph-node dissection. Androgen-deprivation therapy is continued according to the treating oncologist
Intervention: Robot-Assisted Radical Prostatectomy With Extended Pelvic Lymph-Node Dissection (Procedure)
Outcomes
Primary Outcomes
Overall Survival
Time Frame: From the date of radical prostatectomy until death from any cause, assessed up to 5 years after radical prostatectomy.
Overall survival is defined as the time from the date of radical prostatectomy to death from any cause. Participants who are alive at the time of analysis will be censored at the last date on which they were known to be alive
Progression-Free Survival
Time Frame: From the date of radical prostatectomy until the first documented radiological disease progression or death from any cause, whichever occurs first, assessed up to 24 months after radical prostatectomy.
Time from radical prostatectomy to radiological disease progression or death in the absence of documented progression. Radiological progression will be assessed according to the protocol-defined imaging criteria.
Secondary Outcomes
- Expanded Prostate Cancer Index Composite for Clinical Practice Total and Domain Scores(At 3 months and 12 months after radical prostatectomy.)
- International Prostate Symptom Score Total Score(At 3 months and 12 months after radical prostatectomy.)
- Pathological Complete Response Rate(At radical prostatectomy (Day 0))
- PSA Response Rate(From the baseline sample to From the baseline sample to 5 years from last prostatectomy)
- Serum Testosterone Concentration(Screening and 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after radical prostatectomy)
- Serum Alkaline Phosphatase Concentration(Screening and 1, 6, 12, 18 and 24 months after radical prostatectomy)
- Serum C-Terminal Telopeptide Concentration(assessment schedule through 24 months from prostatectomy)
- Incidence of Postoperative Upper and Lower Urinary Tract Complications(From surgery through 24 months after radical prostatectomy)
- Conversion to Open Surgery(During surgery (Day 0))
- Radiological Response to Androgen-Deprivation Therapy(From pre-ADT baseline imaging to preoperative screening after at least 6 months of androgen-deprivation therapy)