Ballas, Leslie

TPS913 Background: A subset of patients with MIBC who receive neoadjuvant therapy (NAT) prior to radical cystectomy (RC) have a pathologic complete response (pCR) at the time of RC. With pCR rates of 22-42% in patients with MIBC following NAT (+/- ICI), whether a subset of patients with good clinical response to NAT can avoid RC is an important unanswered question, especially with the development of more active systemic therapies. HCRN 16-257 evaluated maintenance nivolumab in lieu of cystectomy in patients with MIBC who experienced clinical complete response (cCR) following neoadjuvant GC and nivolumab. The cCR rate was 48%, but 8/33 (24%) patients who elected bladder preservation subsequently underwent cystectomy for local disease recurrence. The RETAIN trial also evaluated omission of local therapy following neoadjuvant therapy with a 2-year bladder preservation rate in patients with ≤T1 disease following NAC of 54% (22/41). Of the 9/25 (36%) patients on that trial developed metastatic disease, 8/9 developed localized disease before metastasizing. These data illustrate the critical role that local therapy plays in patients with MIBC. For this reason, we believe that radiotherapy to the bladder combined with ICI will improve bladder intact event-free survival (BI-EFS). This trial also allows for patients to opt for bladder preservation based on a good clinical response to NAT. Methods: This is a single arm, phase 2 trial (NCT07061964) evaluating risk-adapted bladder preservation therapy for patients with MIBC following NAT. NAT consists of any NCCN guideline concordant therapy for MIBC. Patients with cT2-T4aN0M0 MIBC who complete NAT will be eligible if they have ≤T1 disease on post-NAT TURBT, confirmed by biopsies of prior tumor sites and systematic sampling (left/right lateral walls, dome, posterior wall, trigone). Patients will receive 55 Gray (Gy) in 20 fractions of radiotherapy (RT) to the bladder with 1 year of pembrolizumab. The primary objective is to evaluate whether 3-year BI-EFS is at least 70% in participants with < = T1 (without multifocal CIS) following NAT and RT with 1 year of pembrolizumab. Secondary objectives include local muscle invasive recurrence-free survival, metastasis-free survival (MFS), overall survival (OS), the rate of salvage cystectomy, and evaluation of the frequency and severity of toxicities in participants who receive RT and pembrolizumab. Plasma and urine will be banked for future correlative studies. S2427 was activated in September 2025 with an accrual goal of 111 patients. Clinical trial information: NCT07061964 .

TPS283 Background: There is no clear standard of care for biochemically recurrent prostate cancer (PCa) with positron emission tomography (PET)-detected oligometastases and normal conventional imaging (CIM). Phase II trials show that stereotactic ablative body radiotherapy (SABR) to oligometastases may delay cancer progression and initiation of androgen deprivation therapy (ADT) and its untoward effects. ADT with radiation prolongs survival in locally advanced PCa and in CIM metastatic PCa. However, there is a knowledge gap about timing and benefit vs toxicity of ADT with SABR in early oligometastatic PCa. NRG GU011 (PROMETHEAN) is a randomized phase II trial of SABR with or without relugolix for early PET-detected recurrent oligometastatic PCa. This study aims to evaluate the impact of relugolix, a novel oral gonadotropin-releasing hormone receptor antagonist, when combined with SABR to oligometastases. Relugolix allows for rapid testosterone recovery and is associated with fewer cardiovascular events when compared to leuprolide and is hypothesized to have low late ADT toxicity. GU011 will provide patients and their physicians data on the relative risks and benefits of early or delayed ADT in this setting. Methods: NRG-GU011 NCT# 05053152 is a randomized phase II double-blinded, placebo-controlled trial with randomization to SABR + 6 months placebo vs SABR + 6 months relugolix. Eligible patients have biochemical recurrence after prior curative intent radiation or surgery for localized PCa, PSA < 10 ng/mL, negative CIM and 1-5 PET-evident metastases (≥1 extrapelvic). SABR is delivered in 1-5 fractions to BED >100 Gy1.5, followed by placebo or relugolix 120mg daily for 6 months. Patients will then be followed with imaging at time of biochemical recurrence. The planned sample size of 260 patients (130 per arm) will provide 85% power to detect a hazard ratio of 0.65 for radiographic progression-free survival (rPFS), based on a one-sided test at alpha 0.10. Planned enrollment is predicted at 8 patients per month with an estimated study completion date of late 2026. The primary endpoint is CIM rPFS. Secondary endpoints include PET-based rPFS, sexual and hormonal quality of life (QoL) assessed by EPIC-26, other QoL measures from EQ5D-5L, EORTC QLQ-30 and PROMIS Fatigue, and between-group comparisons of time to salvage therapy, castration-resistance, local progression (SABR-targeted lesion), biochemical progression, distant metastases, prostate cancer-specific mortality, metastasis-free survival, and overall survival. We also aim to determine adverse event rates for both treatment arms and evaluate genomic and blood markers of treatment response. This study opened in December 2021. Clinical trial information: NCT05053152 .