Bilateral Versus Unilateral Lymph Node Dissection in High-Risk Prostate Cancer (BALANCE) (BALANCE)

Bilateral or Unilateral Extended Pelvic Lymph Node Dissection in High-Risk Prostate Cancer: The BALANCE Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Procedure: Unilateral Extended Pelvic Lymph Node Dissection; Procedure: Bilateral Extended Pelvic Lymph Node Dissection

• Study Type: Interventional
• Enrollment (Estimated): 820
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chiara Fiameni; Phone Number: +39 011 633 6591; Email: chiara.fiameni@unito.it
• Study Contact Backup: Name: Alessandro Marquis, MD; Phone Number: +39 011 633 6591; Email: alessandro.marquis@unito.it

Study Locations

• Italy
  • Bologna, Italy, 40138
    • Not yet recruiting
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola-Malpighi & University of Bologna
    • Contact: Giovanni Olivieri, MD; Phone Number: +39 0512142373; Email: giovanni.olivieri@aosp.bo.it
    • Principal Investigator: Lorenzo Bianchi, MD
  • Florence, Italy, 50134
    • Not yet recruiting
    • Università degli Studi di Firenze / AOU Careggi
    • Contact: Francesco Sessa, MD; Phone Number: +39 0552758011; Email: francesco.sessa@unifi.it
    • Principal Investigator: Francesco Sessa, MD
  • Foggia, Italy, 71122
    • Not yet recruiting
    • Università degli Studi di Foggia / AO Ospedali Riuniti di Foggia
    • Contact: Ugo Falagario, MD; Phone Number: +39 0881 732111; Email: ugo.falagario@unifg.it
    • Principal Investigator: Ugo Falagario, MD
  • Genova, Italy, 16132
    • Not yet recruiting
    • IRCCS Ospedale Policlinico San Martino & University of Genoa
    • Principal Investigator: Matteo Bauckneht, MD
    • Contact: Francesca Ambrosini, MD; Phone Number: +39 010 555 3473; Email: f.ambrosini@gmail.com
  • Milan, Italy, 20162
    • Not yet recruiting
    • ASST Grande Ospedale Metropolitano Niguarda
    • Contact: Stefano Tappero, MD; Phone Number: +39 02 6444 7896; Email: stefano.tappero@ospedaleniguarda.it
    • Principal Investigator: Paolo Dell'Oglio, MD
  • Milan, Italy, 20141
    • Not yet recruiting
    • IEO, Istituto Europeo di Oncologia
    • Contact: Laura Adamoli, MD; Phone Number: +39 02 57489 1; Email: laura.adamoli@ieo.it
    • Principal Investigator: Ettore Di Trapani, MD
  • Modena, Italy, 41124
    • Not yet recruiting
    • Università degli Studi di Modena / AOU Modena
    • Contact: Natal Rodriguez, MD; Phone Number: +39 059 3962138; Email: natlrodriguez647@gmail.com
    • Principal Investigator: Stefano Puliatti, MD
  • Naples, Italy, 80131
    • Not yet recruiting
    • Istituto Nazionale Tumori, IRCCS, Fondazione "G. Pascale"
    • Contact: Eleonora Monteleone; Phone Number: +39 0815903416; Email: eleonora.monteleone@istitutotumori.na.it
    • Principal Investigator: Gianluca Spena, MD
  • Roma, Italy, 00133
    • Not yet recruiting
    • Università Tor Vergata / Policlinico Tor Vergata
    • Contact: Simone Albisinni, MD; Phone Number: +39 06 2090 2975; Email: simone.albisinni@uniroma2.it
    • Principal Investigator: Simone Albisinni, MD
  • Roma, Italy, 00144
    • Not yet recruiting
    • IFO - Istituti Fisioterapici Ospitalieri
    • Principal Investigator: Giuseppe Simone, MD
    • Contact: Federica Struglia; Phone Number: +39 06 52666217; Email: federica.struglia@ifo.it
  • Roma, Italy, 00168
    • Not yet recruiting
    • Policlinico Universitario Gemelli IRCCS & Università Cattolica del Sacro Cuore
    • Contact: Maria Chiara Sighinolfi, MD; Phone Number: +39 06 3015 5290; Email: mariachiara.sighinolfi@policlinicogemelli.it
    • Principal Investigator: Bernardo Maria Cesare Rocco, MD
  • Torino, Italy, 10126
    • Recruiting
    • AOU Città della Salute e della Scienza di Torino, Ospedale Molinette
    • Contact: Chiara Fiameni; Phone Number: +39 011 633 6591; Email: chiara.fiameni@unito.it
    • Contact: Alessandro Marquis, MD; Phone Number: +39 011 633 6591; Email: alessandro.marquis@unito.it
    • Principal Investigator: Giancarlo Marra, MD
  • Verona, Italy, 37134
    • Not yet recruiting
    • Università degli Studi di Verona / AOU Verona
    • Contact: Sarah Malandra; Phone Number: +39 0458122178; Email: sarah.malandra@univr.it
    • Principal Investigator: Riccardo Bertolo, MD
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Not yet recruiting
      • Humanitas Clinical and Research Centre & Humanitas University
      • Contact: Massimo Lazzeri, MD; Phone Number: +39 0282241; Email: massimo.lazzeri@humanitas.it
      • Principal Investigator: Giovanni Lughezzani, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Unilateral Extended PLND; Extended pelvic lymph node dissection performed only on the side of the dominant prostate cancer lesion during robot-assisted radical prostatectomy.	Procedure: Unilateral 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.
Active Comparator: Bilateral Extended PLND; Extended pelvic lymph node dissection performed bilaterally during robot-assisted radical prostatectomy.	Procedure: Bilateral Extended Pelvic Lymph Node Dissection; Extended pelvic lymph node dissection performed bilaterally according to the study surgical template during robot-assisted radical prostatectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical Recurrence-Free Survival	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	3 years after surgery
PSA Persistence	Postoperative PSA greater than 0.1 ng/mL at 6 weeks after surgery confirmed by an additional PSA measurement performed 2 weeks later.	8 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative Complications	Complications graded using the Clavien-Dindo classification and assessed for likelihood of being related to pelvic lymph node dissection.	Up to 6 months after surgery
Operative Time	Total operative time recorded during robot-assisted radical prostatectomy and pelvic lymph node dissection.	During surgery
Estimated Blood Loss	Intraoperative estimated blood loss.	During surgery
Length of Hospital Stay	Number of days from surgery to discharge from the index hospitalization.	During the index hospitalization, up to 90 days after surgery
Overall Prostate Cancer Quality of Life Score Assessed Using the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP)	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.	1 year after surgery
Treatment-Free Survival	Absence of any salvage local or systemic treatment after surgery.	3 years after surgery
Systemic Treatment-Free Survival	Absence of systemic treatment after surgery.	3 years after surgery
Metastasis-Free Survival	Absence of metastatic disease during follow-up, including PSMA PET assessment when clinically indicated after multidisciplinary discussion.	3 years after surgery
Cost-Effectiveness	Cost-effectiveness assessed as incremental cost per quality-adjusted life year at 1 year after surgery.	1 year after surgery

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Collaborators: AIRC (Italian Association for Cancer Research); Fondazione Ricerca Molinette
• Investigators: Principal Investigator: Giancarlo Marra, MD, Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Radical Prostatectomy; mpMRI; PSMA PET; High-Risk Prostate Cancer; Pelvic Lymph Node Dissection; Unilateral Lymph Node Dissection; Bilateral Lymph Node Dissection
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: BALANCE_UTORINO_2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data sharing plan is currently available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No