Mittal, Kriti

5045 Background: Radioligand therapy with radium-223 (Rad) and lutetium-177 (Plu) demonstrates notable hematologic toxicities in patients (pts) with prostate cancer (PC), including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Delivery of ionizing radiation to the bone microenvironment is a known risk factor for accelerating clonal hematopoiesis, although the incidence of clonal cytopenias with these agents is not well characterized. We hypothesized that pts treated with Rad and/or Plu would have higher risk of clonal cytopenia of undetermined significance (CCUS) vs matched controls in the “real-world”. Methods: We performed a retrospective study using de-identified aggregate data from the TriNetX US Research Collaborative Network from January 2010 to December 2025. Adult males with PC who received ≥1 administration of Plu and/or Rad were included; pts with prior myeloid malignancy were excluded. Primary outcomes were incidence of CCUS and MDS. Propensity score matching (PSM) was performed based on age, race, prior diagnosis of leukopenia, anemia, thrombocytopenia, or pancytopenia. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. Results: We identified 2,569 pts treated with Plu alone and 2,007 treated with Rad alone and compared them with pts with advanced PC without exposure to either agent (unexposed control) (Table 1). After PSM, the incident risk of CCUS was greater in Rad-exposed pts (RR 2.62, 95% CI 1.45 – 4.73, p < 0.001) while Plu was not associated with a significant increase in CCUS or MDS. Direct comparison after PSM (n=1,433) demonstrated lower risk of pancytopenia (RR 0.46, 95% CI 0.37 – 0.56, p <0.001) and CCUS (RR 0.41, 95% CI 0.20 – 0.81, p =0.008) in Plu vs Rad. In unadjusted analysis, pts receiving both Plu and Rad had increased incidence of CCUS vs Plu alone (RR= 3.64, 95% CI 1.87 - 7.07, p <0.001) and higher risk of MDS vs either agent alone. Conclusions: This “real-world” analysis demonstrates that compared with unexposed controls, Rad – but not Plu – is associated with an increased risk of CCUS. Treatment with Plu and Rad portends a higher risk of CCUS than Plu alone, as well higher risk of MDS than either drug alone. Study limitations include its retrospective nature, missing/ unknown data (e.g. bone marrow and mutation analysis), and potential selection and confounding biases. As treatment sequencing evolves for pts with metastatic PC, further evaluation of clonal hematopoiesis, MDS/AML with adequate sample size and follow up in this population is warranted. ¹⁷⁷Lu-PSMA-617 Exposed(n = 2,569) Unexposed(n =2,569 ) Risk Ratio (95% CI) p -value CCUS 1.03% (26) 0.67% (17) 1.54 (0.84 – 2.82) 0.16 MDS 0.94% (24) 0.55% (14) 1.72 (0.89 – 3.32) 0.10 Radium-223 Exposed(n = 2,007) Unexposed(n = 2,007) Risk Ratio (95% CI) p -value CCUS 1.97% (39) 0.75 (15) 2.62 (1.45 – 4.73) <0.001 MDS 0.85% (17) 0.75% (15) 1.13 (0.57 – 2.26) 0.72

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 .

Circulating tumor DNA (ctDNA) is increasingly being used to monitor minimal residual disease (MRD) in various solid tumors, including urothelial carcinoma (UC). It has emerged as a promising biomarker for MRD and may serve as a valuable tool to guide treatment decisions, particularly in patients at high risk of recurrence after definitive therapy or those experiencing favorable responses to systemic therapy in the setting of locally advanced or metastatic disease. ctDNA technology is largely agnostic to the type of tumor, which can be either hematologic or solid organ malignancies. Its clinical utility requires validation across different tumor types as ctDNA release kinetics and threshold values for testing often vary. Moreover, it is essential to evaluate ctDNA testing across a range of clinical scenarios, including screening, diagnosis, prognosis, and therapeutic decision making. The optimal frequency and duration of testing also need to be defined, particularly in settings such as postdefinitive therapy and ongoing chemotherapy for metastatic disease. In this study, we will summarize the current literature on the role of ctDNA in urothelial cancer. We will discuss the data that inform us of current clinical practice. Furthermore, we will explore evolving developments in the field from other tumor types and potential future directions in UC. Finally, we will highlight selected clinical scenarios for applications of ctDNA testing and its interpretation.

Immunotherapy has significantly affected cancer treatment and survival rates, accompanied by an increase in immune-related adverse events (irAEs) requiring new management strategies. irAEs can affect various organ systems and have varying severity levels, with higher rates observed when combining immune checkpoint inhibitors. National organizations such as ASCO, the National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society for Medical Oncology have created guidelines for managing irAEs. This chapter expands on these guidelines by discussing practical strategies to improve the multidisciplinary management in irAE care, focusing on the who, what, and how to bridge gaps in care and enhance collaboration between academic and community oncology practices. Effective irAE management involves early recognition and guideline-adherent approaches using a multidisciplinary team, including oncologists, other subspecialists, primary care clinicians, and all care team members. Institutions are developing methods to integrate irAE care into clinical workflows, such as incorporating urgent care clinics and e-consults for efficient irAE management and developing hub-and-spoke models to extend specialized care from academic centers to community hospitals for equitable care delivery. Additionally, effective patient education is critical for improving irAE recognition and health literacy. The new ASCO Community of Practice called the Alliance for Support and Prevention of Immune-Related Adverse Events consortium and patient advocacy group Standing Together to Optimize Research, Interventions, and Education in irAEs initiatives aim to advance irAE clinical care, research, and education through global collaboration, standardized data collection, and improved outreach to patients and caregivers.

817 Background: Cancer screening ingastrointestinal (GI) malignancies has translated into an improvement in overall survival due to detection at an earlier stage. The majority of survivors (up to 67%) are over the age of 65. The impact of metabolic profiles on cerebrovascular events amongst this population of cancer survivors is unclear. Methods: Data from the NIS database from 2016 to 2020 were reviewed for patients with seven GI malignancies. Analysis was performed based on the presence or absence of prediabetes using ICD-10 codes. Baseline characteristics, comorbidities, and cerebrovascular outcomes were studied in these 2 cohorts. Results: 1,532,250 hospitalizations of patients with seven GI malignancies, namely colorectal cancer (CRC), pancreatic cancer, hepatocellular carcinoma (HCC), gastric cancer, small intestinal cancer, cholangiocarcinoma, and esophageal cancer, were evaluated and divided into two subgroups: prediabetics (15,610) and non-prediabetics (1,516,640). Prediabetics with GI malignancies as compared to non-prediabetics with GI malignancies were noted to be older (67.7 years vs. 65.64 years), with higher total hospitalization charges (USD 87,267 vs. USD 80,173), greater rates of elective admissions (34.92% vs. 25.89%) but a lower length of stay (6.018 days vs. 6.53 days). Prediabetic patients with GI malignancies were noted to have a higher prevalence of obesity (18.64% vs. 7.69%), dyslipidemia (52.99% vs. 26.16%), and hypertension (49.59% vs. 39.37%). Prediabetics with CRC, as compared to non-prediabetics, had higher adjusted odds ratios (aORs) of occlusion/stenosis of precerebral or cerebral arteries not leading to cerebral infarction, and cerebral infarction, with aORs of 2.03 (95% CI 1.24-3.30, p 0.004), and 1.63 (95% CI 1.01-2.63, p 0.045) respectively. Additionally, prediabetics with pancreatic cancer had a higher aOR of cerebral infarction as compared to non-prediabetics, with aOR of 2.42 (95% CI 1.70-3.44, p<0.001). Conclusions: Prediabetic patients with CRC had higher aORs of cerebral infarction and occlusion/stenosis of precerebral arteries not leading up to cerebral infarction, and prediabetics with pancreatic cancer had twice the risk of cerebral infarction as compared to non-prediabetics. This study highlights the impact of prediabetes, a modifiable risk factor, on cerebrovascular outcomes in patients with GI malignancies.

29 Background: International Medical Graduates (IMGs) comprise over one-third of internal medicine (IM) trainees and practicing oncologists in the United States. We aimed to examine challenges faced by IM IMG residents in pursuing hematology-oncology (HO) fellowship positions. Methods: We conducted a pilot survey using SurveyPluto to assess demographics and evaluate visa related challenges amongst ACGME residents interested in HO. The survey was disseminated through the ASCO IMG Community of Practice (CoP), the Heme-Onc Fellows Mentorship Empowerment (H.O.M.E) group and the IMG Oncologists social media homepage (@IMG_Oncologists). Results: A total of 59 IMG residents completed the survey (20% PGY-1, 36% PGY-2 and 44% PGY-3). The majority of trainees (88%) were from community or university-affiliated community programs. J-1 visa was the most common visa type (67.8%). The visa process was rated as difficult or very difficult by 36% of trainees. Annual visa renewal was required by 51% trainees and 55.9% reported visa related impact on plans for research grant applications (Table). The greatest challenges associated with visa status were disruption of travel plans and inability to unite with family (35.6%); obtaining documentation from home country (33.9%); visa renewal (28.8%) and lack of clarity in visa instructions (27.1%). Among resources that respondents wanted better access to, IMG networking groups (81.4%), legal/financial aids (47.5%), institutional visa seminars (45.8%) and flexibility from their program to visit family overseas (45.8%) were identified as priorities. Conclusions: Visa related barriers pose significant challenges to IMGs interested in HO. Policy changes, advocacy work and additional resources could be beneficial for future IMG oncologists. Challenges associated with visa status for hematology/oncology aspirants. Greatest visa related barriers during training % of respondents (n=59) Documentation from home country 33.9% Disruption in travel plans/ inability to unite with family 35.6% Lack of clarity in renewal instructions/ renewal process post document procurement 55.9% Ability to secure grant affected by visa 22% Non-monetary grant aspects affected by visa 13.6% Did not pursue grants due to visa 20.3% Desired resources during residency Institutional visa seminars 45.8% IMG network groups 81.4% Program flexibility to visit family overseas/ legal and financial aids 45.8%/47.5%