Guillen-Rodriguez, José

e17159 Background: Socioeconomic inequality (SI) is a recognized risk factor for negative outcomes in prostate cancer (PCa), influenced by biology, healthcare access, and lifestyle. This study aims to explore the molecular impact of SI on PCa, focusing on targetable and prognostic biomarkers. Methods: We conducted a retrospective analysis of 100 metastatic hormone-sensitive PCa patients (2016-2023), with 97 undergoing next-generation sequencing (NGS). We examined only pathogenic variants alongside clinical variables. The Area Deprivation Index (ADI) assessed neighborhood SI, with higher scores indicating greater disadvantage. Patients were divided into tertiles. Chi-square and Fisher’s exact tests evaluated the relationships between tertiles and genomic alterations, while ordinal logistic regression analyzed outcomes by various stratifications. Results: Of the 97 patients, 29 were in tertile 1, 34 in tertile 2, and 35 in tertile 3. Tertile 1 had a significantly higher percentage of non-Hispanic patients (90%) compared to tertile 2 (62%) and tertile 3 (37%), p=0.0001. Other demographic factors, such as age, comorbidities, and cancer history, showed no significant differences by tertile. Median PSA levels increased from tertile 1 (22 ng/mL) to tertile 3 (95 ng/mL), although this was not statistically significant (p=0.14). Tumor volume and visceral metastasis were notably higher in tertile 3 (p=0.029 and p=0.02). BRCA1/2 mutations were more prevalent in tertile 3 (11%, p=0.03) via liquid biopsy compared to tertiles 1 and 2 (0%). TMPRSS2-ERG fusion mutations were significantly more common in tertile 3 (66.6%) compared to tertile 2 (19.1%) and tertile 1 (14.2%), p=0.009. The association between ADI tertile and TMPRSS2 approached significance when controlled for ethnicity (p=0.061), with Hispanic ethnicity having 3.5 times the odds of the fusion compared to non-Hispanics (p=0.02). Tertile 1 patients were more associated with receiving progressive therapy lines (2L p=0.01, 3L p=0.03, 4L p=0.04), but median time to subsequent treatment at 5 years was similar across tertiles (p=0.84). Conclusions: Higher SI was linked to increased PSA, tumor volume, visceral metastasis risk, and higher prevalence of BRCA1/2 and TMPRSS2-ERG mutations. This study highlights the need for further research on the molecular impacts of SI on adverse PCa outcomes, particularly among Hispanic populations.

Abstract Background: Bladder cancer patients with lower socioeconomic status (SES) often present with more aggressive disease and face poor outcomes, likely due to complex interactions with risk factors linked to lower SES. However, little is known about the effect of low SES on bladder tumor biology at the molecular level. This study sought to characterize better the impact of low SES on the bladder tumor microenvironment. Methods: This is a retrospective analysis of 93 patients (63 male and 30 female) ranging from age 33 to 92 presenting to the University of Arizona Cancer Center with bladder cancer from 2016-2023. Each patient's neighborhood level of SES was scored using the Area Deprivation Index on a scale of 1-100, with 1 representing the highest SES and 100 the least. These patients were then split into tertile 1: 1-33 (T1: N=16), tertile 2: 34-67 (T2: N=43), and tertile 3: 68-100 (T3: N=34), and each patient’s tumor microenvironment and mutational landscape was characterized and compared utilizing NGS (592, NextSeq; WES, NovaSeq) and WTS Sequencing (NovaSeq) (Caris Life Sciences, Phoenix, AZ). Statistical significance was determined using chi-square and Mann-Whitney U (p<0.05). Results: Our study had no significant difference between age, sex, and race between the three tertiles. Hispanic ethnicity was significantly higher in T3 (26.5%) when compared to T2 (7%) and T1 (0%), p=0.013. The frequency of TMB-H (>10 mutations/megabase) was significantly lower in T3 (15.6%) when compared to T2 (51.2%, p=0.02) and T1 (50%, p=0.01). There was significantly less T cell CD8+ infiltration in tertile 3 (0.02%) when compared to T2 (0.43%, p=0.04) and T1 (0.37%, p=0.08), and less dendritic cell infiltration in T3 (0%) when compared to T2 (0.1%, p=0.13) and T1 (0.64%, p=0.008). T regulatory cells were lower in T3 (1.37%) compared to T2 (2.13%, p=0.09) and T3 (2.02%, p=0.24). IHC-PD-L1 and gene expression for immune checkpoint genes, MHC-Class I, and MHC-Class II did not vary significantly between tertiles. KMT2C-mt was highest in T2 (21.1%) compared to T1 (3.12%, p=0.03) and T3 (6.67%). There was no other significant differences in mutation prevalence between the three tertiles. Discussion: In our study, lower SES bladder cancer patients had a lower amount of CD8+ cells, dendritic cell infiltration, and a low frequency of TMB-H, indicating a lower level of adaptive immune response present in the tumor microenvironment. Lower levels of adaptive immune activity have been associated with more aggressive tumor behavior and worse outcomes in bladder cancer patients. These findings provide a partial explanation of the molecular mechanisms underlying the poor prognosis observed in low SES patients with bladder cancer. Larger-scale studies exploring the impact of SES on tumor biology are essential as they hold significant therapeutic and preventive implications. Citation Format: Tom Marco, Kenneth Barker, Jesse Ritter, Numaan Mahmood, Rishab Srivastava, Amith Rao, Isaac Zarif, Ricardo Estrada Mendizabal, Sachin Deshmukh, Edgar Tapia, Jose Guillen-Rodriguez, Juan Chipollini, Alejandro Recio-Boiles. The effects of socioeconomic deprivation on the tumor microenvironment of bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7392.