(UroToday.com) The 2025 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Annual Symposium held in San Francisco, CA was host to a urothelial carcinoma trials in progress poster session. Dr. Guillaume Grisay presented the ongoing EORTC GUCG 2418 platform trial – STARBURST: strategies for treatment adaptation following re-evaluation of the bladder after using primary neoadjuvant systemic therapies.
Dr. Grisay noted that the standard treatment for patients with muscle-invasive bladder cancer (MIBC) typically consists of neoadjuvant systemic therapy (NAT) followed by radical cystectomy (RC) or trimodal therapy (TMT). Currently, patients are not routinely re-assessed following NAT administration and proceed directly to local treatment, resulting in a missed opportunity for patients with complete or near complete responses who may benefit from bladder sparing strategies. On the other hand, for the non-responders, it is a missed opportunity to implement further escalation strategies with additional systemic therapy.
Unfortunately, several studies have shown an insufficient concordance between the clinical and pathological staging of MIBC, highlighting the inadequacy of current methods for clinical staging post-NAT. The STARBURST project aims to refine the bladder cancer treatment landscape via two successive steps:
- The EORTC GUCG 2418 STARBURST-1 (SB-1) study aims to develop and validate a clinical multimodal signature to enhance the prediction of systemic treatment responses.
- STARBURST-2 (SB-2) will be developed as a risk-adapted strategy trial based on post-NAT response status. This strategy will consist of omitting the local treatment in responders and substituting it with intravesical or systemic treatments and, in non-responders, replacing it with an immediate systemic escalation.
In this report, Dr. Grisay presented the study methodology of SB-1.
SB-1 is a prospective, single arm phase II trial of 237 patients with newly diagnosed MIBC (pT2-4aN0-1M0). All patients will be treated with standard of care (SOC) NAT followed by RC. All patients will be assessed before NAT by a cystoscopy, urine cytology, bladder multiparametric MRI (mpMRI; NacVI-RADS score), and blood and urine samples (ctDNA. utDNA, multiplex urine molecular biomarkers). After completing NAT, all patients will be reassessed with a cystoscopy (+/- biopsy), a bladder mpMRI, and urinary and blood markers.
The primary endpoints of SB-1 are to prospectively validate:
- The accuracy of the NacVI-RADS score to predict pathological complete responses, defined as the absence of residual disease on cystectomy specimen (i.e., pT0)
- The accuracy of the NacVI-RADS score to predict pathological near complete responses, defined as the absence of muscle invasive disease on cystectomy specimen (i.e., ypT0/a/1)
- To predict the absence of muscle invasive disease (ypT2 vs ypT0/a/1), assessed using the negative predictive value (NPV), positive predictive value (PPV), and receiver operating curves (ROC). Kappa score agreement between the MRI staging and RC pathological staging will also be addressed.
Secondary endpoints include the assessment of new biomarkers, including blood circulating tumor DNA (ctDNA), urine tumor DNA (utDNA), urine multiplex biomarkers, pathomics, radiomics, and molecular alterations that could predict the pathological response.
Dr. Grisay concluded as follows:
- The current standard of care, which involves NAT followed by RC without standardized reassessment, may overlook the potential for tailored treatment plans based on individual patient responses.
- The EORTC GUCG 2418 - STARBURST-1 project offers a unique opportunity to define and validate clinical multimodal signature of response to NAT properly and further offer patients downstream risk-adapted strategies.
- STARBURST-1 will be run in the SPECTA Platform. The SPECTA platform is supported by Alliance Healthcare. Alliance Healthcare will become Cencora.
Presented by: Guillaume Grisay, MD, Department of Medical Oncology, Centre Hospitalier Jolimont-Lobbes, Lobbes, Belgium
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.