Unilateral versus bilateral extended pelvic lymph node dissection for men with unilateral high‑risk prostate cancer

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

This test checks if removing lymph nodes only on the cancer side instead of both sides can keep cancer control while reducing complications for men with unilateral high-risk prostate cancer undergoing robot-assisted prostate removal.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 820 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: University of Turin, Italy (other)
• Drugs / interventions: chemotherapy
• Locations: 14 sites (Rozzano, Milano and 13 other locations)
• Trial ID: NCT07580196 on ClinicalTrials.gov

What this trial studies

BALANCE is a multicenter, prospective, randomized controlled trial in Italy comparing unilateral versus bilateral extended pelvic lymph node dissection in men with unilateral high-risk localized prostate cancer. Eligible patients are identified by prostate biopsy, multiparametric MRI, and PSMA PET and are randomized 1:1 at the time of planned robot-assisted radical prostatectomy. The co-primary endpoints are 3-year biochemical recurrence-free survival and early postoperative PSA persistence, with secondary endpoints addressing postoperative morbidity and staging outcomes. Modern PSMA PET and mpMRI are used to select patients with predominantly unilateral disease to test whether a selective surgical approach reduces harms without compromising oncologic control.

Who should consider this trial

Good fit: Men aged 18 or older with biopsy-proven unilateral high-risk localized prostate cancer confirmed by mpMRI and PSMA PET, no contralateral PSMA-positive pelvic nodes, and planned robot-assisted radical prostatectomy are ideal candidates.

Not a fit: Patients with bilateral disease, contralateral PSMA-positive nodes, contralateral high-grade histology, extracapsular or seminal vesicle invasion on the non-dominant side, or known metastatic disease are unlikely to benefit from a unilateral approach.

Why it matters

Potential benefit: If successful, the selective unilateral approach could reduce operating time and postoperative complications while preserving long-term cancer control.

How similar studies have performed: Retrospective series and single-center reports suggest selective or image-guided unilateral dissection may lower morbidity without clear oncologic inferiority, but randomized evidence is limited and this randomized comparison is relatively novel.

Eligibility criteria

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

Where this trial is running

Rozzano, Milano and 13 other locations

• Humanitas Clinical and Research Centre & Humanitas University — Rozzano, Milano, Italy (NOT_YET_RECRUITING)
• IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola-Malpighi & University of Bologna — Bologna, Italy (NOT_YET_RECRUITING)
• Università degli Studi di Firenze / AOU Careggi — Florence, Italy (NOT_YET_RECRUITING)
• Università degli Studi di Foggia / AO Ospedali Riuniti di Foggia — Foggia, Italy (NOT_YET_RECRUITING)
• IRCCS Ospedale Policlinico San Martino & University of Genoa — Genova, Italy (NOT_YET_RECRUITING)
• IEO, Istituto Europeo di Oncologia — Milan, Italy (NOT_YET_RECRUITING)
• ASST Grande Ospedale Metropolitano Niguarda — Milan, Italy (NOT_YET_RECRUITING)
• Università degli Studi di Modena / AOU Modena — Modena, Italy (NOT_YET_RECRUITING)
• Istituto Nazionale Tumori, IRCCS, Fondazione "G. Pascale" — Naples, Italy (NOT_YET_RECRUITING)
• Università Tor Vergata / Policlinico Tor Vergata — Roma, Italy (NOT_YET_RECRUITING)
• IFO - Istituti Fisioterapici Ospitalieri — Roma, Italy (NOT_YET_RECRUITING)
• Policlinico Universitario Gemelli IRCCS & Università Cattolica del Sacro Cuore — Roma, Italy (NOT_YET_RECRUITING)
• AOU Città della Salute e della Scienza di Torino, Ospedale Molinette — Torino, Italy (RECRUITING)
• Università degli Studi di Verona / AOU Verona — Verona, Italy (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: Giancarlo Marra, MD — Principal Investigator
• Study coordinator: Chiara Fiameni

Conditions: Prostate Cancer, Pelvic Lymph Node Dissection, Radical Prostatectomy, PSMA PET, mpMRI, Randomized Controlled Trial, High-Risk Prostate Cancer, Unilateral Lymph Node Dissection