The treatment of metastatic renal cell carcinoma (mRCC) has rapidly evolved; however, the progress made in the field is heavily contingent upon timely and efficient accrual to clinical trials. While a substantial proportion of accrual occurs at tertiary care centers, community sites are playing an increasing role in patient recruitment. In this article, we discuss strategies to optimize collaborations between academic and community sites to facilitate clinical research. Further, as the role of biomarker discovery has become increasingly important in tailoring therapy, we will discuss opportunities to bridge diverse accrual sites for the purpose of translational research.

Background: Tertiary cancer centers offer clinical expertise and multi‐modal approaches to treatment alongside the integration of research protocols. Nevertheless, most patients receive their cancer care at community practices. A better understanding of the relationships between tertiary and community practice environments may enhance collaborations and advance patient care.Methods: A 31‐item survey was distributed to community and tertiary oncologists in Southern California using REDCap. Survey questions assessed the following attributes: demographics and features of clinical practice, referral patterns, availability and knowledge of clinical trials and precision medicine, strategies for knowledge acquisition, and integration of community and tertiary practices.Results: The survey was distributed to 98 oncologists, 85 (87%) of whom completed it. In total, 52 (61%) respondents were community practitioners and 33 (38%) were tertiary oncologists. A majority (56%) of community oncologists defined themselves as general oncologists, whereas almost all (97%) tertiary oncologists reported a subspecialty. Clinical trial availability was the most common reason for patient referrals to tertiary centers (73%). The most frequent barrier to tertiary referral was financial considerations (59%). Clinical trials were offered by 97% of tertiary practitioners compared to 67% of community oncologists (p = 0.001). Most oncologists (82%) reported only a minimal‐to‐moderate understanding of clinical trials available at regional tertiary centers.Conclusions: Community oncologists refer patients to tertiary centers primarily with the intent of clinical trial enrollment; however, significant gaps exist in their knowledge of trial availability. Our results identify the need for enhanced communication and collaboration between community and tertiary providers to expand patients’ access to clinical trials.

PURPOSE: Small cell bladder cancer (SCBC) is a rare histologic variant of bladder cancer with an aggressive disease course and poor outcomes. Given its uncommon nature, there is a paucity of high-quality data characterizing genomic drivers of this disease, and most patients are treated with approaches mirroring small cell lung cancer (SCLC). Leveraging the Tempus Lens deidentified clinically annotated genomic data set, we sought to evaluate the mutational landscape of SCBC relative to urothelial carcinoma (UC) and SCLC. METHODS: Somatic pathogenic genomic alterations in patients with SCBC, UC, and SCLC of any stage who underwent blood- or tissue-based genomic profiling through the Tempus assay were cataloged. Baseline clinical and demographic features were compared across histologic groups. Alterations were collated and summarized using descriptive statistics. Pairwise comparisons were performed to assess differences in mutation frequency across pathologic cohorts. RESULTS: In total, 149 SCBC, 4,350 UC, and 1,697 SCLC patients were included in the study. The most common genomic alterations in SCBC were in TP53 (87%), TERT (75%), and RB1 (70%). Among SCBC patients with TP53 mutations, RB1 comutations were observed in 77% of patients. Compared with UC, SCBC patients were significantly enriched for TP53 , RB1 , KMT2D , and KDM6A mutations. Compared with SCLC, SCBC patients were enriched for TERT , ARID1A , and CREBBP mutations, among others ( P < .05). Multiple clinically targetable mutations were observed in SCBC, including PIK3CA (19%), ERBB2/3 (13%), and ALK (10%). Limitations of this study include its retrospective nature. CONCLUSION: This study represents one of the most extensive efforts to characterize SCBC to date, providing a novel understanding of the genomic alterations underlying the disease and revealing actionable mutations that could serve as potential targets for improved clinical outcomes.

374 Background: Treatment with N/I with the addition of CBM588, a live bacterial product comprised primarily of Clostridium butyricum, improved PFS and RR versus N/I alone when used as first line treatment for patients with mRCC (Meza et al ASCO 2021). Increased abundance of certain bacterial species in the gut microbiome have been associated with the development of treatment related adverse events (TREAs) in lung cancer patients receiving immunotherapy (Chau et al BMC Cancer 2021). However, this association has not yet been delineated in the setting of mRCC. Here, we present results of an exploratory analysis assessing the differences in stool microbiome composition between patients who experienced grade (G) 3/4 TREAs and those who did not. Methods: Patients were randomized 2:1 to receive N/I with or without CBM588. Stool collection for bacteriomic profiling was planned at baseline and after 12 weeks of therapy for all randomized patients. Whole metagenome sequencing was performed using previously published methods (Dizman et al Cancer Med 2021) and differences in microbiome composition were measured based on the occurrence of G 3/4 TREAs. Results: 30 patients were enrolled and 29 included in the study. At the time of data cutoff (April 15, 2021) the median follow up was 12.2 months (95% confidence intervals [CI], 10.6-13.8). Grade 3/4 TRAEs were experienced in 52, 50, and 53% of patients in the overall cohort, control, and intervention arms, respectively (p = NS). Among the most common G 3/4 TRAEs, subjects experienced fatigue, diarrhea, and hyperglycemia. Patients with a complete set of stool samples were included for the microbiome analysis (n = 26). In patients who experienced G 3/4 TRAEs, a significantly greater baseline abundance of Escherichia coli, Klebsiella spp. and Blautia spp. (p = 0.02, 0.03, 0.05) were seen when compared to those not experiencing G 3/4 TRAEs. In contrast, Bacteroides intestinalis and B. thetaiotamicron, were observed in significantly higher abundances in baseline stool specimens of patients who did not experience G 3/4 TREAs (p = 0.03 for both). No significant differences were seen for any of these species at the 12-week timepoint. Conclusions: We are among the first to investigate the differences in baseline stool microbiome in mRCC patients experiencing G 3/4 TRAEs while receiving immunotherapy. Our results suggest that certain taxa of bacteria are predictors of the development of serious TRAEs. Larger cohorts are needed to corroborate these findings. Clinical trial information: NCT03829111.

PURPOSE: The impact of insurance status on survival outcomes in patients receiving first-line systemic therapy for metastatic renal cell carcinoma (mRCC) has not been explored. Herein, we aimed to determine whether insurance status affects progression-free survival (PFS) and overall survival (OS) in this setting. METHODS: Patients diagnosed with mRCC between 1990 and 2022 from two National Cancer Institute–designated cancer centers with available insurance information were retrospectively identified using institutional databases. Patients were stratified by primary insurance type and secondary insurance status. PFS and OS were estimated by the Kaplan-Meier method and compared on the basis of insurance status using log-rank tests. Univariable and multivariable models were used to examine the impact of insurance status on survival outcomes. RESULTS: Of the 645 patients evaluated, 344 (53.3%), 250 (38.8%), and 51 (7.9%) had primary Medicare, private insurance, and Medicaid/no insurance, respectively. Compared with the Medicaid/no insurance group, patients with primary Medicare had significantly better PFS (hazard ratio [HR], 0.698 [95% CI, 0.502 to 0.971], P = .033), whereas patients with private insurance had similar PFS (HR, 1.017 [95% CI, 0.737 to 1.404], P = .917). Having secondary coverage was associated with significantly better PFS, but not OS, compared with primary coverage alone (HR, 0.812 [95% CI, 0.674 to 0.978], P = .028; HR, 1.025 [95% CI, 0.822 to 1.279], P = .824, respectively). Medicare was associated with lower risk of death compared with Medicaid/no insurance (HR, 0.495 [95% CI, 0.336 to 0.730], P < .001), whereas no significant difference in OS between private and Medicaid/no insurance groups was observed (HR, 0.955 [95% CI, 0.660 to 1.382], P = .807). CONCLUSION: In patients with mRCC, Medicare was associated with significantly better survival outcomes compared with Medicaid/no insurance and having secondary insurance was associated with better PFS compared with primary insurance alone. These results contribute to understanding cancer-related disparities and provide valuable data for devising solutions to address health care inequities.