Prevalence of Dietary Modification and Supplement Use in Patients with Metastatic Renal Cell Carcinoma Receiving Systemic Therapy.

Many patients diagnosed with cancer adopt dietary changes and supplement use, and a growing body of evidence suggests that such modifications can affect outcomes to cancer therapy. We sought to assess the prevalence of these practices and the surrounding physician-patient dialogue among patients with metastatic renal cell carcinoma. An online survey was administered by Kidney Cancer Research Alliance (KCCure), interrogating dietary modification patterns, supplement usage, out-of-pocket expenditure related to supplements, and patients' views toward alternative medicine practices. Patients with metastatic renal cell carcinoma receiving combination therapy were actively solicited. In total, 289 unique responses were collected. The most common first-line treatments were nivolumab/ipilimumab (32.4%) and axitinib/pembrolizumab (13.1%). Within the cohort, 147 (50.9%) started using supplements following diagnosis of renal cell carcinoma; the most utilized supplements were probiotics, cannabidiol (CBD) oil/marijuana, and Vitamin C, reported by 70 (47.6%), 61 (41.4%), and 54 (36.7%), respectively. Dietary modifications following cancer diagnosis were reported by 101 (34.9%) respondents, of which 19.8% followed the Mediterranean diet and 18.8% adopted a ketogenic diet. Most respondents (71.3%) noted that they consistently report supplement usage to their physicians. A substantial proportion of patients with metastatic renal cell carcinoma utilize dietary modification and supplements as an adjunct to antineoplastic therapy. Considering the widespread adoption of these practices and the reported effects on cancer treatment, it is crucial for healthcare providers to engage in discussions with patients regarding supplement use.

Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.

Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab. However, its effect on those receiving tyrosine kinase inhibitor-based combinations is unknown. In this open-label, randomized, investigator-initiated, phase 1 study, 30 participants with locally advanced or mRCC with histological confirmation of clear cell, papillary or sarcomatoid component were randomized in a 2:1 fashion to receive cabozantinib (an inhibitor of vascular endothelial growth factor receptor, MET and AXL) and nivolumab (anti-programmed cell death protein 1) with or without CBM588 as first-line treatment. Metagenomic sequencing was performed on stool samples to characterize their gut microbiome at baseline and 13 weeks into treatment. The primary endpoint was a change in the relative abundance of Bifidobacterium spp.; secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and toxicity profile. The primary endpoint of the study was not met and the addition of CBM588 to cabozantinib and nivolumab did not result in a difference in the relative abundance of Bifidobacterium spp. or alpha diversity (as measured by the Shannon index). However, ORR was significantly higher in participants treated with CBM588 compared to those in the control arm (14 of 19, 74% versus 2 of 10, 20%; P = 0.01). PFS at 6 months was 84% (16 of 19) and 60% (6 of 10) in the experimental and control arms, respectively. No significant difference in toxicity profile was seen between the study arms. Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and nivolumab. Further investigation is needed to confirm these findings and better characterize the underlying mechanism driving this effect.ClinicalTrials.gov identifier: NCT05122546.

Barriers to Clinical Trial Implementation Among Community Care Centers.

Importance: While an overwhelming majority of patients diagnosed with cancer express willingness to participate in clinical trials, only a fraction will enroll onto a research protocol. Objective: To identify critical barriers to trial enrollment to translate findings into actionable practice changes that increase cancer clinical trial enrollment. Design, Setting, and Participants: This survey study included designated site contacts at oncology practices with teams who were highly involved with the Association of Community Cancer Centers (ACCC) Community Oncology Research Institute (ACORI) clinical trials activities, all American Society of Clinical Oncology (ASCO)-ACCC collaboration pilot sites, and/or sites providing care to at least 25% African American and Hispanic residents. To determine participation trends among health care practices in oncology-focused research, identify barriers to clinical trial implementation and operation, and establish unmet needs for cancer clinics interested in trial participation, a 34-question survey was designed. Survey questions were defined within 3 categories: cancer center demographic characteristics, clinical trial characteristics, and referral practices. The survey was distributed through email and was open from June 20 through October 5, 2022. Main Outcomes and Measures: Participation in and barriers to conducting oncology trials in different community oncology settings. Results: The survey was distributed to 100 cancer centers, with completion by 58 centers (58%) across 25 states. Fifty-two centers (88%) reported that they conduct therapeutic clinical trials, of which 33 (63%) were from urban settings, 11 (21%) were from suburban settings, and 8 (15%) were from rural settings. Only 25% of rural practices (2 of 8) offered phase 1 trials, compared with 67% of urban practices (22 of 33) (P = .01). Respondents noted challenges in conducting research, including patient recruitment (27 respondents [52%]), limited staffing (27 [52%]), and nonrelevant trials for their patient population (25 [48%]). Among sites not offering therapeutic trials, barriers to research conduct included limited infrastructure, funding, and staffing. Most centers (46 of 58 [79%]) referred patients to outside centers for clinical trial enrollment, particularly in the context of late-stage disease and/or disease progression. Only 17 of these sites (37%) had established protocols for patient follow-up subsequent to outside referral. Conclusions and Relevance: In this national survey study of barriers to clinical trial implementation, most sites offered therapeutic trials, but there were significant disparities in trial availability across care settings. Furthermore, fundamental deficiencies in trial support infrastructure limited research activity, including within programs currently conducting research as well as at sites interested in future clinical research opportunities. These results identify crucial unmet needs for oncology clinics to effectively offer clinical trials to patients seeking care.

CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma.

Therapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70- targeted allogeneic CAR T cells. Significance: Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.

Impact of Synchronous versus Metachronous Metastasis on Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with First-line Immune Checkpoint Inhibitor-based Combinations.

BACKGROUND AND OBJECTIVE: The impact of time of metastasis onset with respect toprimary renal cell carcinoma (RCC) diagnosis on survival outcomes is not well characterized in the era of immune checkpoint inhibitor (ICI)-based combinations. Herein, we assessed differences in clinical outcomes between synchronous and metachronous metastatic RCC (mRCC). METHODS: Data for patients with mRCC treated with first-line ICI-based combination therapies between 2014 and 2023 were retrospectively collected. Patients were categorized as having synchronous metastasis if present within 3 mo of RCC diagnosis; metachronous metastasis was defined as metastasis >3 mo after primary diagnosis. Time to treatment failure (TTF), overall survival (OS), and the disease control rate (DCR) were assessed. KEY FINDINGS AND LIMITATIONS: Our analysis included 223 eligible patients (126 synchronous and 97 metachronous). Median TTF did not significantly differ between the synchronous and metachronous groups (9 vs 19.8 mo; p = 0.063). Median OS was significantly shorter in the synchronous group (28.0 vs 50.9 mo; p = 0.001). Similarly, patients with synchronous metachronous metastasis (58.7% vs. 78.4%; p = 0.002). On multivariable analyses, synchronous metastasis remained independently associated with worse OS and DCR. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this hypothesis-generating study, patients with mRCC with synchronous metastasis who were treated with first-line ICI-based combinations have a poorer OS and worse DCR than those with metachronous mRCC. If these results are externally validated, time to metastasis could be included in prognostic models for mRCC. PATIENT SUMMARY: Our study demonstrates that patients treated with current first-line immunotherapies, who present with metastasis at the initial diagnosis of kidney cancer have worse overall survival compared to those who develop metastasis later. These results can help physicians and patients understand life expectancy.

The Role of Gut Microbiome in the Pathogenesis and the Treatment of Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic condition characterized by inflammation of the gastrointestinal tract. Its exact cause is unknown, but it's thought to result from a dysregulated immune response influenced by various factors, including changes in the intestinal microbiota, diet, lifestyle, and genetics. The gut microbiome, consisting of diverse microorganisms, plays a crucial role in maintaining physiological balance, with its disruption leading to inflammatory responses typical of IBD. Treatments primarily aim at symptom control, employing immunomodulators, corticosteroids, and newer approaches like probiotics, prebiotics, fecal transplants, and dietary modifications, all focusing on leveraging the microbiota's potential in disease management. These strategies aim to restore the delicate balance of the gut microbiome, typically altered in IBD, marked by a decrease in beneficial bacteria and an increase in harmful pathogens. This review underscores the importance of the gut microbiome in the pathogenesis and treatment of IBD, highlighting the shift towards personalized medicine and the necessity for further research in understanding the complex interactions between the gut microbiota, immune system, and genetics in IBD. It points to the potential of emerging treatments and the importance of a multifaceted approach in managing this complex and challenging disease.

Outcomes of Patients with Brain Metastases from Renal Cell Carcinoma Receiving First-line Therapies: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Patients with brain metastases (BrM) from renal cell carcinoma and their outcomes are not well characterized owing to frequent exclusion of this population from clinical trials. We analyzed data for patients with or without BrM using the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). A total of 389/4799 patients (8.1%) had BrM on initiation of systemic therapy. First-line immuno-oncology (IO)-based combination therapy was associated with longer median overall survival (OS; 32.7 mo, 95% confidence interval [CI] 22.3-not reached) versus tyrosine kinase inhibitor monotherapy (20.6 mo, 95% CI 15.7-24.5; p = 0.019), as were intensive focal therapies with stereotactic radiotherapy or neurosurgery (31.4 mo, 95% CI 22.3-37.5) versus whole-brain radiotherapy alone or no focal therapy (16.5 mo, 95% CI 10.2-21.1; p = 0.028). On multivariable analysis, IO-based regimens (HR 0.49, 95% CI 0.25-0.97; p = 0.040) and stereotactic radiotherapy or neurosurgery (HR 0.48, 95% CI 0.29-0.78; p = 0.003) were independently associated with longer OS, as was IMDC favorable or intermediate risk (HR 0.40, 95% CI 0.24-0.66; p < 0.001). Intensive systemic and focal therapies were associated with better prognosis in this population. Further studies should explore the clinical effectiveness of multimodal strategies. PATIENT SUMMARY: In a large group of patients with advanced kidney cancer, we found that 8.1% had brain metastases when starting systemic therapy. Patients with brain metastases had significantly poorer prognosis than those without brain metastases. Receipt of combination immunotherapy, stereotactic radiotherapy, or neurosurgery was associated with longer overall survival.

Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Characterization of Patients with Metastatic Renal Cell Carcinoma Undergoing Deferred, Upfront, or No Cytoreductive Nephrectomy in the Era of Combination Immunotherapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: The role of cytoreductive nephrectomy (CN) has not yet been well characterized in the era of combination immunotherapy. OBJECTIVE: To evaluate characteristics and outcomes for patients with metastatic renal cell carcinoma (mRCC) who received immuno-oncology (IO)-based combination therapy according to CN status. DESIGN, SETTING, AND PARTICIPANTS: Using the International mRCC Database Consortium (IMDC), patients with mRCC who received frontline IO-based combinations were included. Upfront CN was defined as CN up to 3 mo before diagnosis of metastatic disease but before systemic therapy initiation. Deferred CN was defined as CN after systemic therapy initiation. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) from initiation of systemic therapy was estimated via Cox proportional-hazards regression. A 12-mo landmark time and a time-varying covariate for CN status were used to mitigate potential bias. RESULTS AND LIMITATIONS: Of the 385 patients eligible for landmark analysis, 24, 182, and 179 underwent deferred CN, upfront CN, and no CN, respectively. Patients in the no CN subgroup were older (63 yr vs 57 yr in the deferred CN subgroup and 60 yr in the upfront CN subgroup; p = 0.001) and a higher proportion had bone metastases (44% vs 26% in the deferred CN subgroup and 23% in the upfront CN subgroup; p < 0.001). A lower proportion of patients in the upfront CN subgroup had IMDC poor risk (23% vs 43% in the no CN subgroup and 47% in the deferred CN subgroup; p < 0.001). On multivariable analysis, CN receipt was an independent favorable prognostic factor (hazard ratio 0.45, 95% confidence interval 0.26-0.78; p = 0.005). The study is limited by the lack of randomization and its retrospective nature. CONCLUSIONS: Despite changes in practice patterns with the advent of novel therapeutic agents, CN may still serve as an effective surgical intervention in carefully selected patients. PATIENT SUMMARY: For patients with metastatic kidney cancer, surgery to remove the primary tumor was traditionally the treatment of choice, but immunotherapy drugs are now another option for these patients. We analyzed data for contemporary patients with metastatic kidney cancer who received combination immunotherapy as their first treatment. We found that in selected patients receiving immunotherapy, surgery to remove the primary tumor as well can result in better prognosis.

Racial and ethnic differences in perceptions of germline or somatic DNA sequencing among patients with advanced prostate, urothelial, or kidney cancer.

We sought to determine racial and ethnic differences in perceptions (quality of communication, expectations, and concerns) of germline or somatic DNA sequencing (genomic profiling). Patients with prostate, urothelial, or kidney cancer were surveyed using a questionnaire that assessed previous experience, beliefs, expectations, and concerns regarding genomic profiling. Descriptive statistics and chi-square tests were used to identify factors associated with patients' perceptions of genomic profiling. A total of 150 consecutive patients were enrolled. The majority were male (74%) with a mean age of 68 years old. Most patients underwent somatic testing (54%), 24% undertook germline testing, and 21% undertook both tests. Significant differences were found across racial and/or ethnicity concerning factors that could have influenced patients' decision to pursue genomic profiling, including ability to guide the type of treatment (White: 54.1% vs. other ethnic groups: 43.9%, p = 0.04) and potential to improve treatment response (White: 10.1% vs. other ethnic groups: 22.0%, p = 0.04). Other ethnic group of patients were more concerned about learning that the cancer was less treatable or aggressive (43.8% vs. 27.7%, p = 0.01) and anxious about what would be learnt from genomic profiling (34.4% vs. 21.3, p = 0.01) as compared to White patients. Our findings reinforce the importance of developing culturally tailored education to help patients participate actively in decisions about genomic profiling.

Characterization of papillary and clear cell renal cell carcinoma through imaging mass cytometry reveals distinct immunologic profiles.

Objective: To characterize and further compare the immune cell populations of the tumor microenvironment (TME) in both clear cell and papillary renal cell carcinoma (RCC) using heavy metal-labeled antibodies in a multiplexed imaging approach (imaging mass cytometry). Materials and methods: Formalin-fixed paraffin-embedded (FFPE) baseline tumor tissues from metastatic patients with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were retrospectively requisitioned from an institutional biorepository. Pretreated FFPE samples from 33 RCC patients (10 ccRCC, 23 pRCC) were accessioned and stained for imaging mass cytometry (IMC) analysis. Clinical characteristics were curated from an institutional RCC database. FFPE samples were prepared and stained with heavy metal-conjugated antibodies for IMC. An 11-marker panel of tumor stromal and immune markers was used to assess and quantify cellular relationships in TME compartments. To validate our time-of-flight (CyTOF) analysis, we cross-validated findings with The Cancer Genome Atlas Program (TCGA) analysis and utilized the CIBERSORTx tool to examine the abundance of main immune cell types in pRCC and ccRCC patients. Results: Patients with ccRCC had a longer median overall survival than did those with pRCC (67.7 vs 26.8 mo, respectively). Significant differences were identified in the proportion of CD4+ T cells between disease subtypes (ccRCC 14.1%, pRCC 7.0%, p<0.01). Further, the pRCC cohort had significantly more PanCK+ tumor cells than did the ccRCC cohort (24.3% vs 9.5%, respectively, p<0.01). There were no significant differences in macrophage composition (CD68+) between cohorts. Our results demonstrated a significant correlation between the CyTOF and TCGA analyses, specifically validating that ccRCC patients exhibit higher levels of CD4+ T cells (ccRCC 17.60%, pRCC 15.7%, p<0.01) and CD8+ T cells (ccRCC 17.83%, pRCC 11.15%, p<0.01). The limitation of our CyTOF analysis was the large proportion of cells that were deemed non-characterizable. Conclusions: Our findings emphasize the need to investigate the TME in distinct RCC histological subtypes. We observed a more immune infiltrative phenotype in the TME of the ccRCC cohort than in the pRCC cohort, where a tumor-rich phenotype was noted. As practical predictive biomarkers remain elusive across all subtypes of RCC, further studies are warranted to analyze the biomarker potential of such TME classifications.

Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma.

BACKGROUND: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings. METHODS: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression. RESULTS: Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios [HR] 3.61, 95% CI 1.96-6.66, P ≤ .01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P = .01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff. CONCLUSION: Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC.

Association Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma.

BACKGROUND: Preclinical evidence demonstrating circadian rhythmicity within the immune system provides a rationale for hypothesis that immune checkpoint inhibitor (ICI) infusion time-of-day may serve as an actionable mechanism to improve outcomes. Herein, we explore the association between ICI time of infusion (TOI) and outcomes in metastatic renal cell carcinoma (mRCC). METHODS: Data from patients with mRCC who received nivolumab or nivolumab/ipilimumab, in first- or second-line were retrospectively collected. Patients who received < 20% of infusions after 16:30 were assigned to the early TOI sub-cohort, while the rest were assigned to the late TOI sub-cohort. Clinical outcomes were compared across the 2 groups. RESULTS: Among 135 patients included, 89 (65.9%) and 46 (34.1%) were assigned to early and late TOI sub-cohorts, respectively. Baseline characteristics were comparable across the 2 sub-cohorts. Objective response rate (ORR) was 36.0% with early TOI versus 29.5% with late TOI (P = .157). Median time to treatment failure (TTF) was 9.5 months in the early TOI sub-cohort versus 4.6 months in the late TOI sub-cohort with a hazard ratio (HR) of 1.405 (95% CI, 0.919-2.149; P = .11) in univariate analysis and 1.694 (95% CI, 1.064-2.698; P = .026) in multivariate analysis. Higher cut offs allocating patients into the late TOI sub-cohort yielded an incremental increase in the HR for TTF and overall survival (OS) that reached statistical significance. CONCLUSIONS: In patients with mRCC, early TOI yielded a numerical increase in ORR, TTF and OS, with the TTF difference reaching significance in multivariate analysis. Prospective randomized studies are warranted to examine the impact of chronomodulation on outcomes with ICIs in mRCC.

Changes in Perception of Cure Among Patients With Genitourinary Cancers Initiating Immune Checkpoint Inhibitors: A Longitudinal Study.

BACKGROUND: We explored changes in perceptions of cure among patients with genitourinary (GU) cancers starting Immune checkpoint inhibitors (ICIs) therapy. MATERIALS AND METHODS: This longitudinal study assessed patients before starting therapy and 3-months later with a questionnaire that included patient perceptions of ICIs and the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale. General linear modeling was used to investigate changes in expectation of cure over time, and chi-square tests were used to determine the association between expectation of cure and perceptions of ICIs and anxiety. RESULTS: A total of 45 patients were recruited (73% male, 84% diagnosed with renal cell carcinoma). The proportion of patients who possessed an accurate expectation of cure increased over time (55.6%-66.7%, P = .001). An accurate expectation of cure was associated with lower rates of anxiety over time. Patients with inaccurate expectation of cure reported more severe side effects and worse self-reported ECOG score at the follow-up assessment (P = .04). CONCLUSION: We found that patients with GU metastatic cancer treated with ICI therapy have increasingly accurate expectations of cure over time. Accurate expectation of cure is associated with decreased anxiety. Further research is needed to fully explore this dynamic over time and help inform interventions that can help patients develop accurate expectations.

Examining Exclusion Criteria in Advanced Prostate Cancer Clinical Trials: An Assessment of recommendations From the American Society Of Clinical Oncology and Friends of Cancer Research.

PURPOSE: Eligibility criteria illustrate the characteristics of the study population and promote the safety of participants. However, overreliance on restrictive eligibility criteria may limit the generalizability of outcomes. As a result, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) issued statements to curtail these challenges. In this study, we aimed to assess restrictiveness in eligibility criteria across advanced prostate cancer clinical trials. MATERIALS AND METHODS: We identified all phase I, II, and III advanced prostate cancer clinical trials between June 30, 2012, and June 30, 2022, through Clinicaltrials.gov. We evaluated whether a clinical trial excluded, conditionally included, or did not report 4 common criteria: brain metastases, prior or concurrent malignancies, HIV infection, and hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. Performance status (PS) criteria were recorded based on the Eastern Cooperative Oncology Group (ECOG) scale. RESULTS: Out of 699 clinical trials within our search strategy, 265 (37.9%) trials possessed all the required data and were included in our analysis. The most common excluded condition of our interest was brain metastases (60.8%), followed by HIV positivity (46.4%), HBV/HCV positivity (46.0%), and concurrent malignancies (15.5%). Additionally, 50.9% of clinical trials only included patients with ECOG PS 0 to 1. HIV and HBV/HCV infection were exclusion criteria of 22 (80.8%) and 19 (73.1%) immunotherapy trials, respectively. CONCLUSION: Patients with brain metastases, prior or concurrent malignancies, HIV infection, HBV/HCV infection, or low-functioning PS were overly restricted from participating in advanced prostate clinical trials. Advocating for broader criteria may ameliorate generalizability.

Ultrasensitive Circulating Tumor DNA Pilot Study Distinguishes Complete Response and Partial Response With Immunotherapy in Patients With Metastatic Renal Cell Carcinoma.

PURPOSE: Circulating tumor DNA (ctDNA) has been validated across multiple indications in the adjuvant and surveillance settings. We evaluated whether targeted digital sequencing (TARDIS) may distinguish a partial response (PR) from a complete response (CR) among patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: Eligible patients had mRCC that yielded a PR or CR to ICI therapy. Peripheral blood was obtained at a single time point for ctDNA analysis. TARDIS was used for quantification of average variant allele fractions (VAFs). Our primary objective was to determine the association between VAFs and depth of response (PR v CR). A secondary objective was to determine whether VAFs were associated with disease progression. RESULTS: Twelve patients were analyzed, nine of whom achieved a PR (75%). Patients received either nivolumab monotherapy (50%) or nivolumab plus ipilimumab (50%). ctDNA analysis incorporated an average of 30 patient-specific mutations (range, 19-35); average coverage depth was 103,342 reads per target. TARDIS quantified a significant difference in VAFs between PR and CR (median, 0.181% [IQR, 0.077%-0.420%] v 0.007% [IQR, 0.0%-0.028%], respectively [P = .014]). Of the 12 patients in the series, six patients demonstrated radiographic progression subsequent to ctDNA assessment. Patients who progressed on subsequent scans had significantly higher ctDNA than those who maintained their response (median, 0.362% [IQR, 0.181%-2.71%] v 0.033% [IQR, 0.007%-0.077%], respectively [P = .026]). CONCLUSION: In this pilot study, TARDIS accurately differentiated PR from CR among patients with mRCC receiving immunotherapy, and also prospectively identified patients at risk for subsequent progression. Given these findings, we envision subsequent studies that validate these results and investigate the utility of this assay to discern appropriate candidates for discontinuation of immunotherapy.

Twelve-Month Follow-up of the Immune Response After COVID-19 Vaccination in Patients with Genitourinary Cancers: A Prospective Cohort Analysis.

BACKGROUND: Vaccinations against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had a transformative impact on morbidity and mortality. However, the long-term impact of vaccination on patients with genitourinary cancers is currently unknown. MATERIALS AND METHODS: This study aimed to assess seroconversion rates in patients with genitourinary cancers receiving COVID-19 vaccination. Patients with prostate cancer, renal cell carcinoma, or urothelial cancer who had not been vaccinated for COVID-19 were included. Blood samples were obtained at baseline and after 2, 6, and 12 months of one dose of an FDA-approved COVID-19 vaccine. Antibody titer analysis was performed using the SCoV-2 Detect IgG ELISA assay, and the results were reported as immune status ratio (ISR). A paired t-test was used for comparison of ISR values between timepoints. In addition, T-cell receptor (TCR) sequencing was performed to assess for differences in TCR repertoire 2 months after vaccination. RESULTS: Out of 133 patients enrolled, 98 baseline blood samples were collected. At 2-, 6-, and 12-month time points 98, 70, and 50 samples were collected, respectively. Median age was 67 (IQR, 62-75), with the majority of patients diagnosed with prostate (55.1%) or renal cell carcinoma (41.8%). Compared to baseline (0.24 [95% CI, 0.19-0.31]) a significant increase in the geometric mean ISR values was observed at the 2-month timepoint (5.59 [4.76-6.55]) (P < .001). However, at the 6-month timepoint, a significant decrease in the ISR values was observed (4.66 [95% CI, 4.04-5.38]; P < .0001). Notably, at the 12-month timepoint, the addition of a booster dose resulted in an absolute increase in the ISR values compared to those who did not receive a booster dose (P = .04). CONCLUSIONS: Only a minority of patients with genitourinary cancers did not ultimately achieve satisfactory seroconversion after receiving commercial COVID-19 vaccination. Cancer type or treatment rendered did not appear to affect the immune response mounted after vaccination.

The Gut Microbiome and Metastatic Renal Cell Carcinoma.

The introduction of targeted therapy (TT) and immuno-oncology (IO) agents have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). However, despite the significant improvements in survival and clinical response yielded by these agents, a significant percentage of patients still experience progressive disease. Evidence now suggests that microorganisms living in the gut (i.e., the gut microbiome) could be used as a biomarker for response and may also have utility in increasing response to these treatments. In this review, we present an overview of the role of the gut microbiome in cancer and its potential implications in the treatment of mRCC.

Genomic and Transcriptomic Predictors of Response from Stereotactic Body Radiation Therapy in Patients with Oligoprogressive Renal Cell Carcinoma.

Stereotactic body radiation therapy (SBRT) has been shown to be safe and effective for delaying systemic treatment change among patients with metastatic renal cell carcinoma (mRCC). In this study, we sought to assess the genomic signatures of patients with mRCC who underwent SBRT for oligoprogression. A total of 30 patients with oligoprogressive disease were identified, the majority of whom had clear cell renal cell carcinoma (83.3%) and were receiving first-line treatment (53.3%). Genomic and transcriptomic sequencing were available in 20 and 16 patients, respectively. Duration of systemic treatment (DOT) was categorized as that prior (DOT[P]) and subsequent (DOT[S]) to radiation treatment. The median DOT(P) and DOT(S) were 15.1 and 18.3 mo, respectively, with a median DOT(S)/DOT(P) ratio of 1.4. Patients who had a DOT(S)/DOT(P) ratio of ≥1 had increased expression in pathways related to cell proliferation and development. In contrast, among patients with a ratio of ≤1, the reactive oxygen species pathway was enriched. This study highlights the potential role of genomics and transcriptomics to refine radiation treatment selection in patients with mRCC. PATIENT SUMMARY: In this study, we looked at mutations and genomic expressions among kidney cancer patients who responded better to stereotactic body radiotherapy. We found that enriched expression of certain pathways might play a role in response to radiotherapy.