Advanced Genitourinary Cancers Research Articles

Linking in with advice and supports for men impacted by metastatic cancer: The LIAM Mc trial (NCT05946993).

TPS1646 Background: Multidisciplinary supportive care interventions are key to preventing and managing adverse effects of cancer and its treatment for patients, reducing symptom and psychological burdens and enhancing quality of life (QoL). However, the optimal composition of these interventions for men with genitourinary (GU) cancers is poorly understood. The LIAM Mc Trial is an enhanced supportive care programme, funded by the Irish Cancer Society and designed with the input of patient representatives who highlighted the unmet needs of cancer survivors. An important aspect of the trial is to demonstrate how to improve the survivorship supports and services for underserved communities of men who experience disparities in cancer incidence, prognosis, outcome and QoL, and have not traditionally been the focus of such initiatives. Methods: Using an embedded mixed-method process evaluation this prospective trial aims to assess the feasibility and impact of a holistic 12-week survivorship programme amongst men with advanced GU cancers at an Irish Cancer Centre. The programme involves twice-weekly sessions with input from a dedicated physiotherapist, dietitian, and nurse specialist, along with education sessions from medical social worker and psycho-oncology specialists, and programme oversight provided by medical oncologists. Outcomes are measured at three timepoints; pre-intervention, immediately post-intervention and at 6 months post intervention, and will include EORTC QoL; muscle strength; body composition through bioelectrical impedance analysis and ultrasound; diet quality; cancer related symptom control; cancer related fatigue scores; feasibility outcomes, qualitative interviews and a process evaluation. Any man with a locally advanced or metastatic GU cancer who has recently completed a course of treatment or is stable on active anti-cancer treatment is eligible for the programme. Over the two-year study period the sample size target is 72 participants. The primary endpoint of the study is to evaluate the feasibility of introducing an enhanced supportive care programme as part of routine management for male cancer patients with metastatic disease. Acceptability, satisfaction with the programme and QoL changes are key secondary endpoints. Barriers to participation are also a key outcome under investigation. The study was activated in May 2023 with the first participants enrolled in June 2023. To date 17 men have enrolled with accrual completion anticipated in June 2025. Clinical trial information: NCT05946993 .

(019) Malignant Priapism: Case Report and Update on Management Protocols

Abstract Introduction Malignant priapism is a rare condition characterized by persistent erection resulting from the invasion or metastasis of a primary neoplasm. Penile metastases arise from the genitourinary tract 64% of the time (bladder: 28.6%, prostate: 27.9%, kidney: 6.9%, ureter: 0.5%) with colorectal adenocarcinoma, lung cancer, melanoma, and hematologic diseases comprising the remainder. Malignant priapism is reported to occur in 20-53% of patients with penile metastasis. The mechanism of malignant priapism remains unknown. The most accepted theory is an invasion of the corpus cavernosum as well as associated venous systems with malignant cells. This can occur from either hematogenous or lymphatic spread from the source tumor. Resulting derangement of arterial or veno-occlusive mechanism causes priapism. Both ischemic and non-ischemic priapism can occur. Objective While treatment guidelines for priapism in non-malignant cases have been established, there is currently no guideline for treating malignant priapism. This study aims to present three cases of malignant priapism resulting from advanced genitourinary cancers and evaluate the efficacy of palliative penectomy as a treatment modality for relieving symptoms associated with malignant priapism. Methods We conducted a retrospective analysis of three cases of malignant priapism associated with advanced genitourinary cancers. Data were collected from medical records, including patient demographics, primary tumor characteristics, clinical presentation, treatment modalities, complications, and outcomes. The main treatment approach utilized in all cases was palliative penectomy. Symptom relief and complications were assessed as primary outcomes. Results All three patients presented with progressive penile pain, and imaging studies confirmed the presence of metastatic disease involving the penile structures. Palliative penectomy was performed in all cases, resulting in sustained relief of symptoms. No major complications were reported during the surgical procedures. Follow-up assessments showed improved quality of life in terms of pain relief, but all patients died within a short period following penectomy owing to the advanced predisposing malignancy. (figure 1) Conclusions Treatment of malignant priapism needs to be individualized to the needs of the patient. No matter the primary or secondary nature of the disease, current data suggest that malignant priapism is associated with poor outcomes, and emphasis should be put on palliative care. Although new radiation techniques have shown favorable outcomes, penectomy should be considered the last resort in clinical management. Revisions to the existing management guidelines for priapism are necessary to address its occurrence in malignant contexts. (figure 2) Disclosure No.

Analysis of inactivating TSC1 and TSC2 alterations in advanced genitourinary (GU) cancers from a real-world patient population in the Foundation Medicine genomic database.

704 Background: Identification of genetic alterations in cancer via genomic profiling may contribute to better outcomes for patients with advanced GU cancers. Patients with perivascular epithelioid cell tumors in AMPECT (NCT02494570), who had inactivating alterations in the tumor suppressor genes TSC1 or TSC2, critical negative regulators of mTOR activity, had confirmed responses (8/9 patients with inactivating TSC2 alterations and 1/5 patients with inactivating TSC1 alterations) to the mTOR inhibitor nab-sirolimus. PRECISION 1 (NCT05103358), an enrolling tumor-agnostic study, is assessing nab-sirolimus in patients with advanced cancers bearing inactivating TSC1 and/or TSC2 alterations. We used data from a real-world genomic database to enumerate frequencies of TSC1 and TSC2 inactivating alterations in patients with GU cancers. Methods: Next-generation sequencing data from Foundation Medicine’s database of 463,546 patients with advanced cancer (as of March 29, 2022) were analyzed using the FoundationInsights web-based platform to identify inactivating TSC1 or TSC2 alterations in patients with GU cancers. TSC1 or TSC2 alterations were categorized as short variants [base substitutions, insertions and deletions], rearrangements, and copy number deletions. Tumors with these alterations were also evaluated for mutations in other genes, tumor mutational burden (TMB), and microsatellite instability status. Results: Of patients in the database, 9.6% of those with bladder cancer, 5.2% of those with kidney cancer, and 0.7% of those with prostate cancer had inactivating TSC1 or TSC2 alterations. Overall, inactivating TSC1 or TSC2 alterations were present in 1518 of the 36,920 patients with GU cancers. A majority of these 1518 patients (74%) were male and most (78%) were 51–80 years of age at the time the sample was obtained. Of samples with inactivating TSC1 and TSC2 alterations (n=1518), 84.9% were in TSC1 and 15.7% were in TSC2; alterations included short variants (76.7% and 12.2 %), rearrangements (2.4% and 2%), and copy number deletions (5.6% and 1.3%), respectively. TMB was low (<6 mutations/megabase) in 52% of tumors and most (89%) were microsatellite stable. Other commonly mutated genes in this cohort with TSC1 or TSC2 inactivating alterations were TERT (64.4%), TP53 (44.1%), and CDKN2A (40%). Conclusions: Inactivating TSC1 and/or TSC2 alterations commonly occurred in GU cancers. A proportion of GU tumors have a low TMB and/or are microsatellite stable, suggesting that TSC1 and TSC2 inactivating alterations may be driver mutations rather than passenger mutations in those tumors. Therefore, patients with inactivating alterations in TSC1 or TSC2 may benefit from mTOR inhibition via nab-sirolimus. This hypothesis is being tested in the PRECISION 1 study which is open for enrollment of patients with TSC1 or TSC2 alterations.

Immune-related adverse events (irAEs) and the association with clinical outcomes in advanced genitourinary cancers treated with immunotherapy: A systematic review and meta-analysis.

431 Background: The approval of several immune checkpoint inhibitors (ICIs) for the treatment of advanced genitourinary cancers has resulted in a significant revolution in the management of urological tumors. This study investigated the profile of the irAEs and evaluated the association between irAEs and clinical outcomes in the patients with advanced genitourinary cancers treated with ICIs. Methods: We conducted a comprehensive search of online databases up to April 2023 to identify eligible studies. We extracted the type, grade, and frequency of irAEs, the hazard ratios(HRs) and corresponding 95% confidence intervals (95%CIs) for overall survival (OS) and progression-free survival (PFS), raw data or the odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) for objective response rate (ORR) and disease control rate (DCR). RevMan5.3 software was used to calculate pooled results. Results: A total of 21 studies with 4779 patients were included. Of those, 13 studies investigated renal cell carcinoma (RCC), 6 studies investigated urothelial carcinoma (UC), and 2 investigated mixed population with RCC or UC. The pooled overall incidence was 29.0% (95%CI: 28.0%-30.0%) for any-grade irAEs in RCC and UC and 13.0% (95%CI: 11.0%-14.0%) for grade ≥3 irAEs. Furthermore, the HRs for OS and PFS in advanced genitourinary cancer patients with versus without irAEs were 0.45 (95%CI: 0.40-0.51, p < 0.001) and 0.41 (95%CI: 0.31-0.55, p < 0.001), respectively. The ORs for overall ORR and DCR in advanced genitourinary cancer patients with irAEs versus without irAEs were 3.65 (95%CI: 3.03-4.39, p < 0.001) and 4.19 (95%CI: 2.94-5.97, p < 0.001), respectively. In the subgroup analysis, we also observed a positive association between the occurrence of irAEs and improved treatment outcomes in UC and RCC, respectively. Specifically, patients with skin irAEs showed a better OS, patients with skin irAEs and thyroid disfunction were associated with better PFS. Conclusions: Our study provides a comprehensive overview of irAEs in advanced genitourinary cancers treated with immunotherapy. Our findings suggest that the occurrence of irAEs could be a favorable prognostic factor for advanced genitourinary cancer patients treated with ICIs.

Analysis of Health-Related Quality of Life Reporting in Phase III RCTs of Advanced Genitourinary Tumors

Background: As recommended in the European Society for Medical Oncology (ESMO) guidelines, assessment of health-related quality of life (HRQoL) should be a relevant endpoint in randomized controlled trials (RCTs) testing new anticancer therapies. However, previous publications by our group and others revealed a frequent underestimation and underreporting of HRQoL results in publication of RCTs in oncology. Herein, we systematically reviewed HRQoL reporting in RCTs testing new treatments in advanced prostate, kidney and urothelial cancers and published between 2010 and 2022. Methods: We searched PubMed RCTs testing novel therapies in genitourinary (GU) cancers and published in fifteen selected journals (Annals of Oncology, BMC Cancer, British Journal of Cancer, Cancer Discovery, Clinical Cancer Research, Clinical Genitourinary cancer, European Journal of Cancer, European Urology, European Urology Oncology, JAMA, JAMA Oncology, Journal of clinical Oncology, Lancet, Lancet Oncology and The New England Journal of Medicine). We excluded trials investigating exclusively best supportive care or behavioral intervention, as well as subgroup or post hoc analyses of previously published trials. For each RCT, we investigated whether HRQoL assessment was performed by protocol and if results were reported in the primary manuscript or in a secondary publication. Results: We found 85 eligible trials published between 2010 and 2022. Only 1/85 RCTs (1.2%) included HRQoL among primary endpoints. Of note, 25/85 (29.4%) RCTs did not include HRQoL among study endpoints. HRQoL results were non-disclosed in 56/85 (65.9%) primary publications. Only 18/85 (21.2%) publications fulfilled at least one item of the CONSORT-PRO checklist. Furthermore, 14/46 (30.4%) RCTs in prostate cancer, 12/25 (48%) in kidney cancer and 3/14 (21.4%) in urothelial cancer reported HRQoL data in primary publications. Next, HRQoL data were disclosed in primary manuscripts of 12/32 (37.5%), 5/13 (38.5%), 5/16 (31.3%) and 5/15 (33.3%) trials evaluating target therapies, chemotherapy, immunotherapy and new hormonal agents, respectively. Next, we found that HRQoL data were reported in 16/42 (38%) and in 13/43 (30.2%) positive and negative trials, respectively. Finally, the rate of RCTs reporting HRQoL results in primary or secondary publications was 55.3% (n = 47/85). Conclusions: Our analysis revealed a relevant underreporting of HRQoL in RCTs in advanced GU cancers. These results highlight the need to dedicate more attention to HRQoL in RCTs to fully assess the value of new anticancer treatments.

Access to Care and Healthcare Quality Metrics for Patients with Advanced Genitourinary Cancers in Urban versus Rural Areas.

Compared to the urban population, patients in rural areas face healthcare disparities and experience inferior healthcare-related outcomes. To compare the healthcare quality metrics and outcomes between patients with advanced genitourinary cancers from rural versus urban areas treated at a tertiary cancer hospital, in this retrospective study, eligible patients with advanced genitourinary cancers were treated at Huntsman Cancer Institute, an NCI-Designated Comprehensive Cancer Center in Utah. Rural-urban commuting area codes were used to classify the patients' residences as being in urban (1-3) or rural (4-10) areas. The straight line distances of the patients' residences from the cancer center were also calculated and included in the analysis. The median household income data were obtained and calculated from "The Michigan Population Studies Center", based on individual zip codes. In this study, 2312 patients were screened, and 1025 eligible patients were included for further analysis (metastatic prostate cancer (n = 679), metastatic bladder cancer (n = 184), and metastatic renal cell carcinoma (n = 162). Most patients (83.9%) came from urban areas, while the remainder were from rural areas. Both groups had comparable demographic profiles and tumor characteristics at baseline. The annual median household income of urban patients was $8604 higher than that of rural patients (p < 0.001). There were fewer urban patients with Medicare (44.9% vs. 50.9%) and more urban patients with private insurance (40.4% vs. 35.1%). There was no difference between the urban and rural patients regarding receiving systemic therapies, enrollment in clinical trials, or tumor genomic profiling. The overall survival rate was not significantly different between the two populations in metastatic prostate, bladder, and kidney cancer, respectively. As available in a tertiary cancer hospital, access to care can mitigate the difference in the quality of healthcare and clinical outcomes in urban versus rural patients.

Utility of circulating tumor DNA in monitoring treatment response to immune checkpoint inhibitors in patients with advanced genitourinary cancers.

721 Background: Current methodologies for monitoring treatment response are largely based on conventional scans and/or tumor biopsies, which may be limited in their ability to accurately assess disease burden at the molecular level. Circulating tumor DNA (ctDNA) detection in blood has emerged as a prognostic and predictive biomarker and has shown to better assess treatment response in patients receiving immune checkpoint inhibitors (ICI). We conducted a prospective, pilot study to investigate the concordance of serial ctDNA detection and dynamics with radiographic response in patients with advanced GU malignancies undergoing ICI-based treatment. Methods: Twenty patients with histologically confirmed advanced GU malignancies (renal, urothelial, and prostate) were enrolled in the prospective study. All eligible patients received ICI treatment for at least 12 weeks and were followed by serial collection of blood samples every 6-8 weeks until disease progression. Conventional scans were performed approximately every 12 weeks until disease progression. Overall response rate (ORR) by investigator was reported and associated with ctDNA detection. Results: ctDNA analysis was performed on 122 plasma samples obtained from 20 patients (N=15 renal cell carcinoma; N=4 urothelial carcinoma; N=1 prostate cancer). Prior therapies to ICI-based treatment included chemotherapy (10%), hormonal therapy (5%) and anti-VEGF (5%). After study enrollment, patients received anti-PD-1 (95%), anti-CTLA-4 (30%) or anti-PD-L1 (5%) with an ORR of 70% as best response. With a median follow-up of 19 months (range: 4-48), progressive disease was observed in 7 patients. Nineteen patients had longitudinal plasma samples available and ctDNA detection at any time point was 45% (9/20). The overall concordance between ctDNA dynamics and radiographic response at 12 weeks was observed in 89% (17/19) of patients. Of these 17 concordant patients, one patient showed transient ctDNA positivity followed by clearance at the last two timepoints on treatment. The two patients with discordant results included the ones with CNS-only metastasis (ctDNA negative). Of the 7 patients who progressed on ICI, ctDNA was detected in five (71%); the remaining two had CNS-only metastases. The last patient had a single time point available on treatment that showed ctDNA-positivity and passed away 7 weeks after molecular evidence of disease. Conclusions: In this study, serial collection of blood samples for ctDNA analysis to monitor response to ICI-based therapiesin patients with advanced GU tumors was feasible. There was a high concordance rate between radiological imaging and ctDNA data, especially in extra-CNS disease. Further studies are needed to validate ctDNA as a tool to aid disease monitoring in patients treated with ICI.

Access to Care and Health Care Quality Metrics in Urban Versus Rural Patients With Advanced Genitourinary Cancers

Access to Care and Health Care Quality Metrics in Urban Versus Rural Patients With Advanced Genitourinary Cancers

A retrospective study to evaluate the efficacy and safety of SARS-CoV-2 vaccine in patients with advanced genitourinary cancers

BackgroundCOVID-19 vaccination is one of the pivotal key tools against the ongoing pandemic, but its acceptance relies on efficacy and safety data among various populations, including patients with cancers. However, there is limited data on seroconversion rates, efficacy, and safety of the COVID-19 vaccine in patients with cancer. Breakthrough infections after vaccination have also been reported, which could further strengthen the refusal behavior of specific populations to be immunized. Our objective was to investigate the efficacy and safety of COVID-19 vaccination in real-world patients with advanced genitourinary cancers. Methods and resultsA retrospective study of the 738 patients with advanced metastatic genitourinary malignancy was conducted at our genitourinary oncology clinic from October 2020 to September 2021, out of which 462 patients (62.6%) were vaccinated. During the study period, two vaccinated, and six unvaccinated patients tested positive for SARS-CoV-2 (breakthrough infection rate: 0.4% vs. 2.2%, p = 0.027). Vaccine protection against infection was 81.8% (95% CI: 0.04–0.98). One vaccinated and 4 unvaccinated patients were hospitalized due to COVID-19 (0.2% vs. 1.4%, p = 0.048). Vaccine effectiveness in preventing hospitalization was 85.7% (95% CI: 0.02–1.33). Within one month of vaccination, 1.5% of patients (n = 7) had emergency visits, 0.8% (n = 4) were hospitalized for any reason, and of these, 3 (0.6%) experienced a delay in the receipt of their cancer therapy. ConclusionIn our hypothesis-generating data among patients with advanced genitourinary cancers, COVID-19 vaccination was efficacious and safe and was rarely associated with treatment disruptions. These data should help improve the acceptance of the COVID-19 vaccine in the general population and patients with cancer. The vaccine effectiveness in our patients is comparable with existing published data without cancer.

O9-1 Updated analysis of circulating tumor DNA in advanced genitourinary cancers: SCRUM-Japan MONSTAR SCREEN Project

Circulating tumor DNA (ctDNA) is a promising resource to detect and monitor molecular characteristics of tumors. In the present study, we precisely determined mutational status of plasma ctDNA in patients with genitourinary (GU) cancers.

CONTINUUM: A pilot care transition intervention for hospitalized patients with advanced cancer.

1534 Background: Patients with advanced cancer are frequently hospitalized and experience burdensome transitions of care after discharge. Interventions to address patients’ symptoms, support medication management, and ensure continuity of care after discharge are lacking. We sought to demonstrate the feasibility and acceptability of CONTINUUM (CONTINUity of care Under Management by video visits) for this population. Methods: We conducted a single-arm pilot trial (n = 54) of CONTINUUM at Massachusetts General Hospital (MGH). The intervention consisted of a video visit with an oncology nurse practitioner (NP) within 3 business days of hospital discharge to address symptoms, medication management, hospitalization-related issues, and care coordination. Prior to discharge, we enrolled English-speaking adults with advanced breast, gastrointestinal, genitourinary, or thoracic cancers experiencing an unplanned hospitalization who were receiving ongoing oncology care at MGH and being discharged home without hospice services. We defined the intervention as feasible if ≥70% of approached and eligible patients enrolled and if ≥70% of enrolled patients completed the intervention within 3 business days of discharge. At 2 weeks after discharge, patients rated the ease of use of the video technology and stated whether they would recommend the intervention. NPs completed post-intervention surveys to assess fidelity to the intervention protocol. Results: From 01/07/21 to 05/28/21, we enrolled 54 patients (77.3% of patients approached). Of the enrolled patients (median age = 65.0 years; 59.3% and 22.2% had advanced gastrointestinal or thoracic cancers, respectively), 83.3% of enrolled patients received the intervention within 3 business days of discharge. Patient rating of the ease of use of video technology was a mean of 7.8 out of 10, with 71.4% stating they “agreed” or “strongly agreed” that they would recommend the intervention. NP post-intervention surveys revealed that visits focused on symptom management (85.7%), followed by addressing post-hospital care issues (69.0%). At 30 day follow up, 38.8% were readmitted within 30 days of discharge, and 12.2% died within 30 days of discharge. Conclusions: We found that CONTINUUM, which consists of an NP-delivered video visit soon after hospital discharge addressing patients’ symptoms, medications, and care coordination, represents a feasible and acceptable approach to provide post-discharge care for hospitalized patients with advanced cancer. Future studies will test the efficacy of the intervention for reducing hospital readmissions. Clinical trial information: NCT04640714.

PD59-11 ASSOCIATION BETWEEN IMMUNE-RELATED ADVERSE EVENTS AND CLINICAL OUTCOMES IN ADVANCED GENITOURINARY CANCERS TREATED WITH IMMUNOTHERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS

You have accessJournal of UrologyCME1 May 2022PD59-11 ASSOCIATION BETWEEN IMMUNE-RELATED ADVERSE EVENTS AND CLINICAL OUTCOMES IN ADVANCED GENITOURINARY CANCERS TREATED WITH IMMUNOTHERAPY: A SYSTEMATIC REVIEW AND META-ANALYSIS Junru Chen, Yaowen Zhang, Yuchao Ni, Guangxi Sun, and Hao Zeng Junru ChenJunru Chen More articles by this author , Yaowen ZhangYaowen Zhang More articles by this author , Yuchao NiYuchao Ni More articles by this author , Guangxi SunGuangxi Sun More articles by this author , and Hao ZengHao Zeng More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002644.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Several immune checkpoint inhibitors (ICIs) have been approved for the treatment of advanced genitourinary cancers. However, there is an unmet need to identify predictors for the efficacy of ICIs. In this study, we conducted a systemic review and meta-analysis to evaluate the association between immune-related adverse events (irAEs) and clinical outcomes in advanced genitourinary cancers treated with immunotherapy. METHODS: Databases of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched for eligible studies. Raw data for objective response rate (ORR), number of patients, hazard ratios (HRs), and corresponding 95% confidence intervals (95%CIs) for progression-free survival (PFS) and overall survival (OS) were extracted. Meta-analysis was performed using Review Manager 5.3. RESULTS: A total of 10 studies involving 2933 patients were included, in which 6 studies reported data of renal cell carcinoma (RCC), 3 reported data of urothelial carcinoma (UC), and 1 reported data of mixed population with RCC or UC. Overall, patients with irAEs were associated with significantly higher ORR (odds ratio [OR]: 3.37; 95%CI: 2.69–4.23; P<0.00001), longer PFS (HR: 0.39; 95%CI: 0.31–0.50; P<0.00001), and OS (HR: 0.50; 95%CI: 0.42–0.59; P<0.00001) in patients with advanced genitourinary cancers. More specifically, similar results were observed in patients with RCC that irAEs predicted better ORR (OR: 3.89; 95%CI: 2.36–6.40; P<0.00001), PFS (HR: 0.39; 95%CI: 0.30–0.50; P<0.00001), and OS (HR: 0.48; 95%CI: 0.35–0.65; P<0.00001). For patients with UC, irAEs were associated with higher ORR (OR: 3.15; 95%CI: 2.41–4.12; P<0.00001) and improved PFS (HR: 0.41; 95%CI: 0.18–0.93; P=0.03), while the relationship between the presence of irAEs and OS was not statistically significant (HR: 0.28; 95%CI: 0.06–1.26; P=0.10). CONCLUSIONS: IrAEs were associated with better clinical outcomes in patients with advanced genitourinary cancers receiving ICIs, especially in patients with RCC. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1023 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Junru Chen More articles by this author Yaowen Zhang More articles by this author Yuchao Ni More articles by this author Guangxi Sun More articles by this author Hao Zeng More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP12-02 PROSPECTIVE EVALUATION OF CIRCULATING TUMOR DNA (ctDNA) IN DETECTING EARLY PROGRESSION ON IMMUNE CHECKPOINT INHIBITORS IN PATIENTS WITH ADVANCED GENITOURINARY CANCERS

MP12-02 PROSPECTIVE EVALUATION OF CIRCULATING TUMOR DNA (ctDNA) IN DETECTING EARLY PROGRESSION ON IMMUNE CHECKPOINT INHIBITORS IN PATIENTS WITH ADVANCED GENITOURINARY CANCERS

HSR22-151: Access to Care and Health Care Quality Metrics in Urban Versus Rural Patients With Advanced Genitourinary Cancers

HSR22-151: Access to Care and Health Care Quality Metrics in Urban Versus Rural Patients With Advanced Genitourinary Cancers

Changes in perception of immunotherapy over time among patients with advanced genitourinary cancers.

328 Background: Previous studies have shown that a significant proportion of patients with metastatic genitourinary cancers harbor inaccurate expectations of cure prior to starting treatment with immunotherapy. This study sought to compare changes in perceptions of immunotherapy reported before, and three months after, the start of therapy, as well as treatment side-effects and quality of life. Methods: This longitudinal study enrolled patients diagnosed with advanced genitourinary cancers (bladder, renal, and prostate cancers) prior to commencing immunotherapy. Patients’ perceptions were assessed prior to starting treatment (T0) and three months later (T1). Patients responded to the same survey at both time points assessing expectations of side effects, clinical outcomes (expectation of cure) and quality of life (Functional Assessment of Chronic Illness Therapy-General). Results: Among the 30 patients enrolled, the median age was 67 years old (range, 44-91); most were male (70%), married (80%), and well-educated (70%). Renal cell carcinoma (70%) was the most common form of cancer. Before starting immunotherapy (T0), patients expected (1) fewer side effects (83%) compared with other types of cancer treatment, (2) great efficacy in preventing tumor progression (90%). and (3) increased survival (90%). Notably, the expectation of cure with immunotherapy treatment had changed over time (T0 = 24% vs T1 = 7%; P = 0.001) and overall quality of life had increased (median at T0 = 90 vs T1 = 98; P = 0.01). Three months into treatment (T1), patients perceived themselves as less active (T0 = 70% vs T1 = 63%; P = 0.02), however just 16% reported severe side effects, including fatigue (10%) and diarrhea (10%). In general, patients were satisfied with the management of these side effects (60%). The majority of patients perceived improvement in their condition (50%) and were satisfied with their treatment (60%). Conclusions: This longitudinal study suggests that inaccurate perceptions of cure with immunotherapy may recede over time, with an increased proportion of patients estimating a more accurate (and lower) chance of cure after 3 months of treatment. Patients also reported improved quality of life despite these adjusted expectations of cure.

Characteristics associated with common reasons to pursue genomic profiling among patients with metastatic genitourinary cancers.

327 Background: Patients with cancer may possess limited knowledge of emerging modalities in oncology, including genomic profiling (GP) tests, which can create barriers to shared decision making. Effective provider communication can address such barriers but little is understood regarding patients’ perceptions of GP. Methods: In this cross-sectional study, patients who were diagnosed with advanced genitourinary cancers (bladder, renal, and prostate cancers), and were referred for GP responded to a survey to assess reasons to pursue such testing. Clinicopathologic characteristics were collected via chart review. Kolmogorov-Smirnov tests were used to assess associations between reasons to pursue GP and patient characteristics. Results: Data was obtained from a sample of 126 patients (gender: 75% M, 25% F; average age: 67; marital status: 78% married; education: 76% some college; histology: 67% renal cell carcinoma, 19% urothelial, and 14% prostate). The most common reasons to pursue GP by patient response were: to guide treatment (73%), to improve treatment response (32%), to follow physician’s indication (27%), to predict treatment response (23%), to learn about their disease (19%), and to contribute to the science (12%). Notably, older age was significantly associated with three reasons (guide treatment, P = 0.001; physician’s indication, P = 0.03; contribute to the science, P = 0.001). No association was found among younger patients. A higher level of education was associated with the desire to guide treatment (P = 0.001). In contrast, a lower level of education was associated with physician’s indication (P = 0.002). Conclusions: This study highlights important associations between reasons to pursue GP and age and level of education. Differing strategies for information delivery could be considered when communicating GP benefits to older patients and to patients with lower levels of education.

Genomic classification of clinically advanced major genito-urinary cancers (GUca) based on methylthioadenosine phosphorylase (MTAP) genomic loss.

164 Background: Novel treatments for clinically advanced GUca including castrate resistant prostate ca (PC), bladder urothelial ca (BUC) and clear cell renal ca (ccRCC) are widely needed. Recently, the targeting of cancer cells with arginine accumulation caused by MTAP loss has emerged as a new synthetic lethality-based anti-cancer program. Methods: 8,436 mCRPC, 2,683 BUC and 841 ccRCC underwent hybrid-capture based comprehensive genomic profiling (CGP) to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 tumor cell expression was determined by IHC (Dako 22C3). Results: 1.3% of PC, 24.2% of BUC and 5.5% of ccRCC featured MTAP loss. There were no significant age or gender differences associated with MTAP loss. CDKN2A/B loss ranged from 94% in ccRCC to &gt; 99% in PC and BUC. The GA/tumor frequencies were similar when CDKN2A/B GA are excluded. In PC, GA in TP53, PTEN and BRCA1 were more frequent, while GA in AR, CDK12, RB1 and BRCA2 were less frequent in cases with MTAP loss. In BUC, GA in TSC1 and FGFR3 were more frequent and GA in RB1and TP53 were less frequent in cases with MTAP loss. In ccRCC, GA in NF2 were more frequent in cases with MTAP loss, while GA in VHL and PBRM1 were less frequent in cases with MTAP loss. “Targetable” kinase GA were rare in all groups, except for FGFR3 GA in MTAP loss BUC. Immunotherapy (IO) putative biomarkers varied among tumors, with MSI-high status less frequent and TMB ≥ 10 mut/Mb more frequent in BUC MTAP-intact than BUC with MTAP loss. PD-L1 expression was similar except for high PD-L1 expression more frequent in MTAP-intact BUC. Conclusions: When compared with PC and ccRCC, the clinical development of novel drugs, such as PRMT5 and MTA2 inhibitors in GUca will likely be focused on BUC given the 24% frequency of MTAP loss in that tumor type. CGP of PC, BUC and ccRCC reveal significant differences in GA in MTAP-intact and tumors with MTAP loss, which may impact future combinatorial clinical trial designs.[Table: see text]

A0386 - Association between immune-related adverse events and clinical outcomes in advanced genitourinary cancers treated with immunotherapy: A systematic review and meta-analysis

A0386 - Association between immune-related adverse events and clinical outcomes in advanced genitourinary cancers treated with immunotherapy: A systematic review and meta-analysis

1564MO Characterization of COVID-19 vaccination response by antibody (Ab) titer and T-cell receptor (TCR) sequencing in patients (pts) with advanced genitourinary (GU) cancers

Preliminary studies have characterized potential adverse effects associated with COVID-19 vaccination in pts with cancer. However, biological characterization of vaccine response has yet to be performed.

617P Genomic profiling of circulating tumor DNA in advanced genitourinary cancer patients: SCRUM-Japan MONSTAR SCREEN Nationwide Cancer Genome Screening Project

Circulating tumor DNA (ctDNA) is an emerging resource for the diagnosis and prognosis of various types of cancer. However, characteristics and clinical utility of ctDNA is still largely unknown, especially in patients with genitourinary (GU) cancers.