Virginia Cancer Institute

33 Background: Historically, PSA DT can be prognostic for metastasis free survival in BCR (as defined on computed tomography (CT) and bone scan). PSA DT is also an important tool in risk stratification in BCR to identify which patients (pts) require therapy (e.g. pts with a PSA DT>6 months). The emerging use of PSMA imaging creates another tool to assess BCR pts, but there is no data on the association of PSA DT and PSMA findings. Methods: NCT05588128 enrolls BCR pts after definitive +/- salvage therapies. Pts must have a PSA>0.5 ng/ml, testosterone >100 ng/dL, and negative CT/bone scans. Lymph nodes (LNs) up to 1.5 cm and prior therapies are permitted. All patients undergo a baseline PSMA PET scan, along with measurement of PSA and PSA DT. Here we describe the relationship between baseline PSA metrics and baseline PSMA imaging findings in patients with BCR. Results: 130 patients are currently evaluable with a median age= 71 years, baseline PSA of 1.95 ng/dL (range: 0.5 to 71) and PSA DT of 10.6 months (range 1.2 to 132) off therapy. Of all participants, 16.9% (n=22) had findings limited to the prostate bed and 34.6% (n=45) had PSMA+ avidity in the prostate bed with other findings. 42.3% (n=55) had PSMA + LNs, and 13.8% (n=18) had PSMA+ bone lesions. Four patients had serosal deposits with PSMA avidity, and one patient had a PSMA+ lung nodule. Conclusions: These data are the first to compare PSMA imaging results with corresponding PSA levels and PSA DT in a large cohort of patients with BCR. Results show that pts with historically favorable/long PSA DT may have high volume/bone+ findings on PSMA. There is no data to suggest treatment escalation is required in BCR pts with high volume PSMA findings, but long/favorable PSA DT. These results highlight the caveats of using PSMA imaging alone to drive treatment decisions in BCR without further data for how baseline PSMA imaging corresponds with long-term outcomes. Clinical trial information: NCT05588128 . PSMA PET+ lesion locations by PSA doubling time in patients with BCR prostate cancer (total n=130). PSA DT # Pts Median PSA PSMA Neg Prostate+ only Lymph Nodes+ ≥ 4 Lymph Nodes+ Bone+ ≥12 mo 52 3.55 9 (17.3%) 16 (30.8%) 24 (46.2%) 12 (23%) 6 (11.5%) 9 to <12 mo 20 1.56 2 (10%) 4 (20%) 11 (55%) 3 (15%) 3 (15%) 6 to <9 mo 17 0.9 5 (29.4%) 0 (0%) 12 (70%) 8 (47.1%) 2 (11.8*) <6 mo 41 2.1 5 (12.2%) 2 (4.9%) 28 (68.3) 15 (36.6) 7 (17.1)

591 Background: We previously reported demographics, race, stage, treatment, and survival patterns in testicular cancer (TC) patients in the U.S. using the National Cancer Database (NCDB) data (Yu et al., JCO:43 (5): Abs 622). We now examine race in a multivariable model to further understand survival outcomes in both seminoma and non-seminoma. Methods: Patient-level data were extracted from NCDB for TC cases diagnosed between 2004 and 2020, including histologic subtypes seminoma (S) and non-seminoma (NS). Statistical analyses involved descriptive statistics, chi-square tests comparing categorical variables, Kaplan-Meier method analyzing overall survival (OS) , and log-rank tests comparing OS across racial/ethnic groups, disease stages, comorbidity scores, facility types, and insurance statuses. Multivariate Cox Proportional Hazards models were used to examine the impact of race, Spanish origin, facility type, Charlson-Deyo Score, Insurance, Stage, Education, and median income on OS. Results: The cohort included 89,550 patients: 81,571 White, 2,860 Black, 3,624 with other races, and 1,495 Unknown. We previously showed that White patients were primarily treated at comprehensive community cancer and academic/research programs, while Black patients were more frequently treated at academic centers. Hispanic patients were underrepresented at academic and comprehensive community cancer programs. Private insurance predominated overall (72%), highest in Whites (72.9%) and lowest in Blacks (54.1%) and Hispanics (48.8%). Medicaid coverage and uninsured status were higher in Black and Hispanic groups. 23589 non-seminoma patients and 18298 seminoma patients were included in the multivariate analyses. Significant factors were worse Charlson-Deyo scores (combined 2&3 vs 0 vs 1) P<0.0001, insurance (combined Medicaid & Medicare & other government vs not insured vs private vs government) P<0.0001, stage (stage I, II, III) P<0.0001, while education (P=0.9044) and median income (P=0.1118) were not significant factors. Conclusions: Race appears to be an important contributing factor to overall survival in non-seminoma patients when accounting for Charlson-Deyo score, stage, and insurance status, but income did not seem to have a significant contributory effect. In multivariate analyses of our TC population overall and specifically in seminoma patients, race appears to have less of an effect on overall survival.

315 Background: PCa has substantial inherited predisposition and certain germline variants like BRCA1/2 , ATM , HOXB13 , and DNA mismatch repair (MMR) genes are associated with an increased risk of PCa. This study follows men without a diagnosis of PCa, with known germline pathogenic/likely pathogenic variant (PV) in BRCA1/2 , DNA MMR genes associated with Lynch syndrome ( MLH1/PMS2 , MSH2 / MSH6 , EPCAM ), HOXB13 , ATM , CHEK2 , PALB2 , TP53 , NBN , RAD51C/D , BRIP1 , and FANCA-FANCM (NCT03805919). Methods: Up to 500 men, ages 30-75 years old (y/o) with a documented PV will enroll. Men undergo biennial mpMRI and annual PSA. Indication for prostate biopsy includes clinical, PSA, and/or MRI findings. Patients are followed at 12-month intervals to determine PSA, PCa diagnosis, and disease/survival status until death. Results: To date, 378 evaluable patients have enrolled: 353 (93%) Caucasian, 11 (3%) Hispanic, 7 (2%) Asian, 4 (1%) African-American, 2 (1%) bi-ethnic. 1 Indian-Asian. Median age was 47 y/o. The most common PV were: 180 (48%) BRCA2 , 94 (25%) BRCA1 , 22 (6%) CHEK2 , and 18 (5%) ATM . PVs in MLH1 / PMS2 , MSH2 / MSH6 , PALB2 , HOXB13 , TP53 , BRIP1 , RAD51D , EPCAM , NBN , and FANCA are &lt;4%. Eight patients carried more than one PV. A total of 782 MRIs were performed: 378 baselines, 228 at year 2, 121 at year 4, 30 at year 6, and 25 clinical. Indication for biopsy was present in 89 (24%) patients with 37 (10%) diagnosed with PCa. Of the 90 biopsies indicated, 1 refused and withdrew and 3 are still pending. Of those with PCa, 22 had BRCA1/2 PVs, 5 had MMR PVs, and 10 had non-MMR PVs. Median age at diagnosis was 62. 24 patients were diagnosed with Grade Group (GG) 1, 8 patients with GG2, 1 patient with GG3, 3 patients with GG4, 1 patient with GG5. 21 opted for active surveillance (AS), 10 opted for prostatectomy, 6 opted for radiation therapy. 5 patients on AS converted to definitive treatment after progression was noted at 1-year follow-up. Conclusions: mpMRI screening in men with PVs is feasible and can be used for early diagnosis, PCa monitoring, and facilitates PCa diagnosis at PSA levels below conventional thresholds. Correlative studies including cfDNA, PBMCs and PRS, are ongoing. Clinical trial information: NCT03805919 . Indication for biopsy. BiopsyPositive BiopsyNegative Biopsy Pending, Refused Total = 89 PSA WNL PSA Elevated PSA WNL PSA Elevated PSA WNL PSA Elevated PIRADS 1 13 0 4 0 9 0 0 PIRADS 2 15 1 3 5 6 0 0 PIRADS 3 23 5 1 11 3 2 1 PIRADS 4 34 <jats:td colspan="1" ro

48 Background: The incidence of stage IV prostate cancer in the United States has risen over the past decade, possibly reflecting changes in PSA screening guidelines. Recent studies have also shown increasing implementation of active surveillance in the initial management of intermediate-risk prostate cancer. However, the impact of these practice changes on trends in advanced disease remains unclear. We evaluated temporal trends in diagnosis, treatment, and survival among men with advanced-stage prostate cancer using the NCDB. Methods: The NCDB (2010–2021) was queried for demographics, comorbidities, PSA, Gleason score, stage, and treatment. Multivariable logistic regression assessed associations with stage IV diagnosis over time. Propensity score modeling balanced treatment (Tx) versus no treatment/active surveillance (nTx/AS) groups based on age, race, region, facility type, insurance, income, education, and PSA. Results: The overall NCDB cohort (n= 1424835), which included patients across all stages, comprised 79.8% White, 15.4% Black, and 4.9% Hispanic men. The median age at diagnosis was 66 years, with a median PSA of 4.4 ng/ml. After inverse probability weighting (IPW), overall survival (OS) was modestly improved in the nTx group compared to the Tx group (HR 0.96; 95% CI 0.93–0.99). However, among patients with stage III–IV disease, the nTx group had markedly worse OS compared with those who underwent Tx (HR, 2.45; 95% CI, 2.33–2.58). For men diagnosed with stage IV prostate cancer, multivariable logistic regression showed that the likelihood of presenting with metastatic disease increased significantly over time. The odds of a stage IV diagnosis rose from 2011 (OR 1.03; 95% CI 1.00–1.07) to 2021 (OR 2.48; 95% CI 2.41–2.56; p &lt; 0.001). Subgroup analysis of men with stage IV prostate cancer found that 77.4% were White, 17.4% Black, and 6.5% Hispanic, with a median age of 69 years and PSA 42.8 ng/mL. Those managed with nTx/AS were older (78 vs 69 years), had higher PSAs (95.7 vs 41.2 ng/mL), were less often treated at research and academic centers (26% vs 40%), and more frequently insured by Medicare (71% vs 56%). Conclusions: The proportion of stage IV prostate cancer diagnoses has significantly increased over the past decade. Among men with advanced-stage (III–IV) disease, OS was significantly improved in those who received active treatment, underscoring the importance of assessing factors that influence withholding treatment. Untreated patients were older, had higher PSA, and were less often managed at academic or research hospitals.

Same-day, colocated multidisciplinary clinics (MDCs) aim to expedite complex cancer care, yet their added value over sequential referral remains uncertain. We systematically reviewed comparative studies to assess their effects on treatment decisions, timelines, guideline adherence, and survival in newly diagnosed solid tumors. We searched MEDLINE, Embase, and CENTRAL through April 15, 2025, for studies comparing MDCs with routine care. Eligible studies involved same-day, on-site evaluation by ≥2 oncology specialties and at least one clinical or patient-centered outcome. Risk of bias was assessed with Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). Twenty-seven observational cohorts (>18,000 patients) met inclusion criteria: 17 studies (63%) were rated serious risk of bias and 10 (37%) were rated critical risk on ROBINS-I. Across studies, MDCs shortened the diagnosis-to-treatment interval and improved guideline concordance. A pooled analysis of two comparable cohorts showed that therapy began 9.5 days sooner (95% CI, -16.2 to -2.7 days; I2 = 0%). Guideline adherence averaged 91% with MDCs versus 68% with routine pathways. Eleven series reported management change rates of 24%-52%, most often escalation to multimodality therapy or evidence-based de-escalation. Patient-reported satisfaction exceeded 90% in all five studies capturing this outcome, and two economic analyses documented reduced diagnostic expenditures without shifting cost to patients. A random-effects meta-analysis of two risk-adjusted cohorts showed improved overall survival (pooled hazard ratio, 0.77 [95% CI, 0.68 to 0.87]; τ2 = 0.004; I2 = 51%). Observational evidence suggests that same-day MDCs compress care timelines, raise guideline adherence, and may improve survival, while maintaining high patient satisfaction and neutral out-of-pocket costs. Randomized or quasi-experimental designs are needed to confirm causality and identify the clinic features that drive benefit.

Individuals with primary brain tumors and their caregivers experience substantial psychological distress, yet positive psychological outcomes, such as post-traumatic growth (PTG), remain understudied. This study aimed to assess the prevalence and profile of PTG among primary brain tumor patients and caregivers, examine associations with demographic, medical, and psychological variables, and inform future neuro-oncology interventions. In this prospective cross-sectional study, 141 participants (96 patients, 45 caregivers) completed validated surveys assessing PTG, depression, anxiety, and death anxiety. Participants were recruited via online neuro-oncology support and advocacy groups. PTG was measured using the Post-Traumatic Growth Inventory (PTGI). PTG profiles were examined using descriptives and associations between PTG and patient/caregiver characteristics, tumor-related medical variables, and psychological distress were examined using t-tests, ANOVAs, and Pearson correlations. 70% of patients and 48.8% of caregivers reported moderate-to-high PTG. Appreciation of Life was the most frequently endorsed subscale in both groups. Patients with high-grade tumors exhibited significantly higher PTG than those with low-grade tumors; caregivers of patients with left-hemisphere tumors trended toward higher PTG. PTG was positively associated with death anxiety in patients but unrelated to depression or generalized anxiety in either group. Despite significant distress, many patients and caregivers experience PTG following a brain tumor diagnosis, particularly in appreciating life. These findings highlight the potential for psychosocial and palliative interventions to harness PTG through meaning-making and existential engagement.

The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of four cohorts of patients with ATM-altered tumors treated with olaparib are reported: colorectal cancer (CRC), lung cancer (LC), pancreatic cancer (PC), and other solid tumors (histology-pooled, HP). Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were OR, progression-free survival, overall survival, duration of response or SD, and safety. Patients with CRC (n = 30), LC (n = 20), PC (n = 28), or other advanced cancers (n = 38) with ATM alterations were enrolled. The DC rates were 23% (one-sided 90% CI, 8 to 100; P = .38), 45% (one-sided 90% CI, 32 to 100; P = .0004), 28% (one-sided 90% CI, 14 to 100; P = .14), and 25% (one-sided 90% CI, 16 to 100), respectively. The null hypothesized 15% DC rate was rejected for the LC and HP cohorts but not the CRC and PC cohorts. Twenty of 116 patients (17%) experienced treatment-related grade 3 adverse events (AE) or serious AEs. Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complexes and amplified expression of SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) complexes that drive an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program. The small molecule SUMOylation inhibitor, TAK-981, de-SUMOylates the cBAF/PBAF component, SMARCE1, stabilizing and restoring cBAF on chromatin, shifting SS models away from SS18::SSX-driven transcription. The result is DNA damage, cell death and tumor inhibition across both human and mouse SS tumor models. TAK-981 synergizes with cytotoxic chemotherapy through increased DNA damage, leading to tumor regression. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX transcriptome, identifying an unappreciated role of SUMOylation in SS and a subsequent therapeutic vulnerability.

Abstract Background: While HPV vaccination and Pap screening have advanced cervical cancer (CCa) prevention, high-grade squamous intraepithelial lesions (HSIL) remain common, particularly among individuals with metabolic comorbidities such as diabetes and hypercholesterolemia. Statins, commonly used for lipid control, possess anti-inflammatory and antiproliferative properties that may offer protective effects against cervical dysplasia. We evaluated whether statin use is associated with reduced HSIL risk and explored whether effects vary by comorbidity and race. Patients and Methods: We retrospectively analyzed electronic health records and billing data from 2,378 non-Latina/e (nL) Black and nL-White patients diagnosed with LSIL or HSIL between 2014 and 2021 at a large academic medical center. Logistic regression assessed associations between statin use, comorbidity profiles (diabetes and hypercholesterolemia), race, and HSIL, adjusting for potential confounders. Interaction terms were tested to evaluate effect modification. Results: Statin users had significantly lower odds of HSIL than nonusers (adjusted OR=0.48, p&amp;lt;0.0001), despite being older and more likely to have comorbidities. Predicted HSIL probabilities ranged from 4% to 20% in statin users versus 13% to 29% in nonusers. The lowest risk was observed among diabetic women on statins—particularly non-Latina Black women—suggesting a possible synergistic protective effect in metabolically vulnerable populations. Yet, only 35% of patients with hypercholesterolemia were prescribed statins. Conclusions/Impact: Statin use was associated with substantially lower HSIL risk, particularly among patients with diabetes. These findings support further investigation of statins as a potential low-cost chemopreventive tool for cervical dysplasia, especially in populations with metabolic dysfunction. Citation Format: Purvika Gautam, Jinlei Zhao, Chelsea Levi, Shreya Raman, Bianca D. Owens, Jerome F. Strauss III, Katherine Y. Tossas. Potential protective effect of statins against HSIL in women with metabolic comorbidities [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B137.