Prostate Cancer
Conditions
Keywords
Pelvic Lymph Node Dissection, Radical Prostatectomy, PSMA PET, mpMRI, Randomized Controlled Trial, High-Risk Prostate Cancer, Unilateral Lymph Node Dissection, Bilateral Lymph Node Dissection
Brief summary
BALANCE is a multicenter, prospective, randomized controlled trial enrolling men with unilateral high-risk localized prostate cancer identified by prostate biopsy, multiparametric MRI, and PSMA PET imaging. Eligible patients scheduled for robot-assisted radical prostatectomy will be randomized in a 1:1 ratio to undergo either unilateral extended pelvic lymph node dissection or bilateral extended pelvic lymph node dissection. Pelvic lymph node dissection is commonly performed in high-risk prostate cancer for staging purposes, but its therapeutic benefit remains uncertain and the procedure may increase operative time, costs, and postoperative morbidity. Modern imaging techniques may improve the identification of patients with predominantly unilateral disease and support a more selective surgical approach. The co-primary objectives are to compare 3-year biochemical recurrence-free survival and early postoperative PSA persistence between the two surgical strategies. Secondary objectives include comparison of perioperative complications, operative time, blood loss, length of hospital stay, quality of life, long-term oncologic outcomes, and costs. This study is designed to determine whether unilateral extended pelvic lymph node dissection can reduce surgical morbidity while preserving oncologic outcomes in appropriately selected patients with high-risk prostate cancer.
Interventions
PROCEDUREUnilateral Extended Pelvic Lymph Node Dissection
Extended pelvic lymph node dissection performed only on the side of the dominant lesion, as defined by biopsy, multiparametric MRI, and PSMA PET findings.
PROCEDUREBilateral Extended Pelvic Lymph Node Dissection
Extended pelvic lymph node dissection performed bilaterally according to the study surgical template during robot-assisted radical prostatectomy.
Sponsors
University of Turin, Italy
AIRC (Italian Association for Cancer Research)
Fondazione Ricerca Molinette
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants with unilateral high-risk localized prostate cancer scheduled for robot-assisted radical prostatectomy will be randomized in a 1:1 ratio to undergo either unilateral extended pelvic lymph node dissection or bilateral extended pelvic lymph node dissection.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male patients aged 18 years or older * Histologically confirmed unilateral high-risk localized prostate cancer, defined by at least one of the following: ISUP Grade Group 4 or 5; suspicion of at least cT3a disease on multiparametric MRI and/or PSMA PET; or PSA greater than or equal to 20 ng/mL with a unilateral index lesion * Unilateral features of the index lesion defined by biopsy, multiparametric MRI, and PSMA PET * No PSMA PET-positive pelvic lymph nodes contralateral to the dominant side of the prostate cancer * No significant contralateral PSMA uptake on the non-dominant side, defined as lesions with PRIMARY score 3 to 5 * No contralateral index lesion on multiparametric MRI subsequently confirmed by prostate biopsy * No high-risk histology on the side contralateral to the dominant lesion, including ISUP Grade Group greater than 3 or unconventional prostate cancer histology * No frank extracapsular invasion or seminal vesicle invasion on the contralateral side * Up to two positive systematic cores with unfavorable intermediate-risk disease or up to four with favorable intermediate-risk disease are allowed on the contralateral side * A maximum of two pelvic PSMA-positive lymph nodes allowed on the dominant side * Clinically localized disease, defined as less than cT4 on multiparametric MRI and no distant metastases, including no retroperitoneal lymph nodes on PSMA PET * Life expectancy greater than 10 years according to physician judgment * Scheduled for robot-assisted radical prostatectomy and fit for surgery * Written informed consent provided
Exclusion criteria
* Any prostate cancer treatment prior to prostatectomy, including androgen deprivation therapy, neoadjuvant chemotherapy, radiotherapy, or focal ablative therapy * Prior active treatment for prostate cancer * Contralateral ISUP Grade Group 4 to 5 prostate cancer * Contralateral ISUP Grade Group 2 in more than 4 positive cores or ISUP Grade Group 3 in more than 2 positive cores * Contralateral cT3 disease on multiparametric MRI * N1 or M1 disease on PSMA PET or multiparametric MRI, except for up to two positive pelvic lymph nodes on the dominant side * No systematic prostate biopsies performed, with a minimum of 10 cores, and targeted biopsies when a target lesion is present * Other active malignancy * Contraindication to multiparametric MRI and/or PSMA PET * Inability to provide written informed consent * Age younger than 18 years * ASA score greater than 3 * Any contraindication to pelvic lymph node dissection * Severe psychiatric disease * Inadequate hematologic and/or coagulation function * Active infection * Any other serious medical, psychiatric, psychological, familial, or geographic condition that, in the judgment of the investigator, may interfere with staging, treatment, follow-up, compliance, or increase treatment-related risk * Patients with prior malignancy treated with curative intent are eligible only with mandatory approval by the local multidisciplinary tumor board
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical Recurrence-Free Survival | 3 years after surgery | Biochemical recurrence defined as postoperative PSA greater than 0.1 ng/mL with three consecutive rises or initiation of prostate cancer-specific secondary treatment more than 6 months after surgery |
| PSA Persistence | 8 weeks after surgery | Postoperative PSA greater than 0.1 ng/mL at 6 weeks after surgery confirmed by an additional PSA measurement performed 2 weeks later. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic Treatment-Free Survival | 3 years after surgery | Absence of systemic treatment after surgery. |
| Metastasis-Free Survival | 3 years after surgery | Absence of metastatic disease during follow-up, including PSMA PET assessment when clinically indicated after multidisciplinary discussion. |
| Cost-Effectiveness | 1 year after surgery | Cost-effectiveness assessed as incremental cost per quality-adjusted life year at 1 year after surgery. |
| Perioperative Complications | Up to 6 months after surgery | Complications graded using the Clavien-Dindo classification and assessed for likelihood of being related to pelvic lymph node dissection. |
| Operative Time | During surgery | Total operative time recorded during robot-assisted radical prostatectomy and pelvic lymph node dissection. |
| Estimated Blood Loss | During surgery | Intraoperative estimated blood loss. |
| Overall Prostate Cancer Quality of Life Score Assessed Using the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) | 1 year after surgery | Overall prostate cancer-related quality of life assessed using the Expanded Prostate Cancer Index Composite for Clinical Practice questionnaire. The overall score is calculated by summing the five domain summary scores: urinary incontinence, urinary irritation/obstruction, bowel, sexual, and vitality/hormonal. Total scores range from 0 to 60, with higher scores indicating worse symptoms and poorer quality of life. |
| Length of Hospital Stay | During the index hospitalization, up to 90 days after surgery | Number of days from surgery to discharge from the index hospitalization. |
| Treatment-Free Survival | 3 years after surgery | Absence of any salvage local or systemic treatment after surgery. |
Countries
Italy
Contacts
CONTACTChiara Fiameni
CONTACTAlessandro Marquis, MD
PRINCIPAL_INVESTIGATORGiancarlo Marra, MD
Principal Investigator
Outcome results
None listed