bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive accuracy of computer-generated padua nephrometry scores based on continuous variables compared with categorical computer-generated scores and human-generated scores in predicting oncologic and perioperative outcomes.
Authors: Benidir Tarik , Wood Andrew , Abdallah Nour , Remer Erick M. , Campbell Steven , Weight Christopher J.
Published: March 2023

624

Background: The Preoperative Aspects and Dimensions Used for Anatomical Classification (PADUA) score is a validated predictor of a patient’s perioperative outcomes following partial nephrectomy. The use of a fully automated, unbiased and time sensitive PADUA scoring system is a novel concept that may help circumvent PADUA’s widespread adoptability. We sought to automate the scoring of preoperative computed tomography scans (CT) using a machine-learning-generated PADUA score (P-AI). In doing so, we aimed to compare P-AI’s ability to predict meaningful perioperative and oncologic outcomes as compared to human generated PADUA scores using both categorical (P-H) and continuous variables (P-AI+). Methods: 300 patients with pre-operative CT scans were identified from a cohort of 544 consecutive patients undergoing surgical extirpation for suspected renal cancer at a single institution. A deep neural network approach was used to automatically segment kidneys and tumors and geometric algorithms were developed to estimate each component of PADUA based on the segmented regions (P-AI). Tumors were also manually scored by medical personnel blinded to the P-AI (P-H). The ability of P-AI and P-AI+ to predict meaningful perioperative and oncologic outcomes was compared to P-H using logistic regression and receiver operating characteristics (ROC) curve analyses and areas under the curve (AUC). Results: Median age was 60 years, 40% were female. Median tumor size was 4.2 cm, 91.3% had malignant tumors, including 27% and 37% with high-stage and high-grade, respectively. Both P-AI and P-H were able to predict the need for partial nephrectomy (p < 0.001). From an oncologic standpoint, P-AI and P-H were able to predict meaningful oncologic outcomes including the presence of malignancy, high grade and high stage disease (p < 0.004) although the ROC curves were not different from one another). Interestingly, when each PADUA component was left as a continuous rather than ordinal variables (P-AI+), this automated continuous score was able to predict surgical type (AUC 0.88), presence of malignancy (AUC 0.67), indolent tumors (AUC 0.79) and high grade (AUC 0.77)/high stage disease (AUC 0.82), better than both P-AI and P-H. Conclusions: When viewed along a continuous spectrum, AI generated PADUA scores (P-AI+) yields predictive surgical and oncologic outcomes superior to both categorical AI and human generated PADUA scores. If nephrometry can be calculated automatically, there is no longer a need to simplify the equations and the use of an AI generated PADUA scoring system, provides a reliable estimate of meaningful outcomes in a manner that is time sensitive and superior to human expert evaluation. Further prospective work and reproducibility from other centers is encouraged.
Local and systemic therapies for renal cell carcinoma with brain metastases: A single-institution series.
Authors: Ganta Teja , Miller Eric James , Anker Jonathan Forrest , Galsky Matt D. , Tsao Kai
Published: March 2023

627

Background: Current practice guidelines for the management of renal cell carcinoma (RCC) with brain metastases (BM) recommend a multimodal approach with systemic therapy, radiation, and/or surgery. The purpose of this study is to assess treatment patterns and identify prognostic factors for survival in this population. Methods: This retrospective, single-center study evaluated patients with RCC who were diagnosed with metastatic disease between 2015-2020 and were identified to have BM at any point in their care. Fisher's exact test and Mann-Whitney test were used to compare differences among groups. Kaplan-Meier curves were used to estimate time to events from the date of BM diagnosis. Univariate Cox proportional hazards model was used to estimate the effect of factors on survival. Results: 29 patients are included. Median follow-up was 25 months (range: 0.5-73). 16 (55%) patients presented with BM at the time of diagnosis of metastatic disease. 17 (58%) were treated with radiation. 8 (28%) were treated with surgery of which 7 also received radiation. Median overall survival was 10 months (95% CI: 7-not reached). Patients received a median of one (range 0-4) system therapy regimen after diagnosis of BM. 19 (66%) patients were exposed to at least one class of medication therapy for management of BM while 10 (34%) were exposed to two or more classes. 10 patients experienced long term survival (defined as survival ≥12 months). Patients with long term survival were more likely to have received radiation (90% vs 42%; P=0.02). However, use of radiation was not associated with survival (HR 0.47, 95% CI 0.1-1.3). Conclusions: The study is limited by sample size but suggests there is a population of patients with RCC with BM who can experience long term survival. Optimal selection for patients with BM that can be feasibly treated within radiation fields appears favorable. Most patients are not exposed to more than one systemic medication class during their care. Additional research is needed to compare efficacy in BM to guide first line systemic therapy selection. [Table: see text]
Real world outcomes of patients with non-clear cell renal cell carcinoma: A single Asian centre experience.
Authors: Chan Johan W.K. , Peh Daniel , Tan Wei Chong , Tan Hui Shan , Ng Quan Sing , Rajasekaran Tanujaa , Teh Yi Lin , Saw Stephanie , Tan Wan Ling , Lai Gillianne , Jain Amit , Kanesvaran Ravindran
Published: March 2023

632

Background: Non-clear cell RCC (nccRCC) represents a heterogenous group of tumors which is less well studied than clear cell RCC. Clinical data supporting the treatment of nccRCC are still based on phase 2 studies and clinical trials conducted in ccRCC. Little is known about this group of patients in Asia. In this study, we aim to report the real world outcomes of nccRCC patients in a cancer centre in Singapore. Methods: We conducted a retrospective analysis on 81 non-clear cell RCC patients treated at the National Cancer Centre Singapore from 2007-2022. Data on patient demographics, disease characteristics, treatment outcomes and adverse events were collected retrospectively up till March 2022. Overall survival (OS) and progression free survival (PFS) were estimated using the Kaplan-Meier method. Responses to treatment were recorded based on RECIST v1.1 and analyzed using logistic regression. Results: 81 patients were included in this analysis, with a median age at diagnosis of 57 years old. Papillary RCC accounted for 32% (n=26) of the cases, chromophobe RCC was 2% (n=2), unclassified RCC was 28% (n=23), and other subtypes was 20% (n=24). Sarcomatoid features were present in 8% (n=10). Median follow-up time was 24 months. Among this cohort, 73 patients (90%) received tyrosine kinase inhibitors (TKI) alone, 8 patients (9%) had immunotherapy with VEGF TKI while 4 patients (4%) underwent dual checkpoint inhibitors. Median OS for the cohort was 19.4 months, while median PFS was 16 months. Overall disease control rate rate (CR/PR/SD) for first-line treatment was 60%. Comparison of outcomes shown below. Conclusions: This real-world Asian study provides important data regarding clinical outcomes in this rare and heterogeneous group of non-clear cell RCC patients. OS in nccRCC remains inferior to ccRCC and is comparable to data reported in Western populations [Table: see text]
Patient characteristics, treatment patterns and outcomes for patients with renal cell carcinoma in England: A retrospective cohort study using data from the National Cancer Registry and treatment and hospital data.
Authors: Das Prantik , Clark Andrew , Nordstrom Beth , Booth Alison , Dhokia Poonam , Carroll Robert , Vaz Luis
Published: March 2023

639

Background: Renal cell carcinoma (RCC) is the seventh most common cancer in the UK. It is necessary to examine recent treatment trends and outcomes in England to understand the evolving landscape. The primary aim was to describe the demographic and clinical characteristics of patients with RCC, and assess their overall survival (OS) and treatment duration, overall and by subgroups of interest. Secondly, we aimed to understand use of systemic therapies over time. Methods: This was a retrospective cohort study of patients diagnosed with RCC during 2014-2018 using national registry, treatment and hospital data in England. Descriptive statistics were explored with Chi-squared, Fishers exact and Wilcoxon rank sum tests. OS and treatment duration were analysed using Cox regression models to provide hazard ratios (HR) with 95% CI. Kaplan Meier curves were used to compare the proportion of patients alive or on treatment. Results: The cohort included 32,577 individuals; median age at diagnosis 67 years; 36.6% of patients were female; 81.4% exhibited clear cell histology. RCC diagnosed at stage I-III appeared to increase from 61% in 2015 to 68% in 2018. A total of 5,657 patients received at least 1 line of systemic treatment, decreasing to 2,606 and 989 patients for 2 and 3 treatment lines; at 3 months, treatment persisted for 59.9%, 19.0% and 20.5% respectively. In the cohort, 25,566 (78.5%, 95% CI: 78.0–78.9) were alive 1 year from the date of diagnosis and 21,856, (67%, 95% CI: 66.6–67.6) were alive at 3 years. In the subgroup with metastatic disease, 6,786 (37.1%, 95% CI: 35.9–38.2) were alive at 1 year which decreased to 18.0% (95% CI: 17.06–18.92) at 3 years. Among patients with metastatic disease at initial diagnosis, OS was reduced in those with non-clear cell compared to clear cell RCC (HR: 1.19 [95% CI 1.07-1.33]), and those without nephrectomy had a lower probability of survival compared with those who did have a nephrectomy (HR: 2.54, 95% CI: 2.34–2.75). Conclusions: This study presents the most recent and extensive RCC data from England, examining treatment duration, overall survival and patient demographics at presentation, by histology, metastatic status and line of therapy subgroups. These findings could facilitate exploration of potential unmet needs, inequities of treatment or risk factors for patients.
Renal function and survival following treatment for cT1N0 renal cell carcinoma in a veteran population.
Authors: Kumar Abhishek , Salama Joseph Kamel , Boyer Matthew J
Published: March 2023

642

Background: Radical nephrectomy (RN), nephron sparing surgery (NSS) and thermal ablation (TA) are associated with similar oncologic control for early-stage renal cell carcinoma (RCC). However, the potential protective role of nephron sparing treatments on renal function and its impact on non-cancer related mortality remains undetermined. Methods: We employed the national Veterans Affairs Corporate Data Warehouse (CDW) to identify patients diagnosed with cT1N0 RCC between 2000-2018. Laboratory and diagnosis data were used to calculate creatinine clearance and Charlson comorbidity score. Chronic kidney disease (CKD) was defined as creatinine clearance < 60 milliliters per minute. Kaplan-Meier analysis and multivariable Cox regression analysis were used to evaluate overall survival. Results: Overall, there were 8279 Veterans with cT1N0M0 renal cell carcinoma diagnosed between 2000-2018 who received either RN (2946, 36%), NSS (4846, 59%) or TA (487, 6%). Median follow up time was 8 years (90% CI 2-15 years). Patients receiving RN were older than those receiving NSS (median age 64.0 vs 62.6 years, p<0.01) but younger than those receiving TA (median age 67.9 years, p<0.01). Patients receiving RN and TA had more comorbidities than patients receiving NSS (mean Charlson scores 0.76 vs. 1.00 vs. 0.66, p<0.01. More patients among the RN group had CKD before RCC diagnosis than the NSS and TA groups (10% vs. 6% vs. 7%, p<0.01). Among the subset of patients without CKD before treatment, 17% of RN, 8% of NSS, and 11% of TA developed CKD at least 1 year after treatment, (p <0.01). Median OS was 11.5 years with RN, 14.2 years with NSS, and 10.3 years with TA. On multivariable analysis considering age, comorbidities, CKD, race, and year of treatment, compared to RN, NSS was associated with better OS (HR 0.75, p<0.01) with a trend to improved survival with TA (HR 0.88, p=0.08). Conclusions: NSS or TA are associated with less post-operative renal dysfunction than RN in patients treated for cT1N0 RCC in the VAHCS. NSS is associated with improved OS compared to RN. Further studies are warranted to assess the impact of renal dysfunction in this population in relation to oncologic and survival outcomes.
2022 Global patient survey: Reported experience of diagnosis, management, and burden of renal cell carcinomas.
Authors: Giles Rachel H. , Maskens Deborah , Marconi Lorenzo , Martinez Robin , Kastrati Karin , Castro Carlos , Julian Mauro Juan Carlos , Bick Robert , Hickey Margie , Heng Daniel Yick Chin , Larkin James , Bex Axel , Jonasch Eric , Maclennan Sara Jane , Jewett Michael A.S.
Published: March 2023

653

Background: Kidney cancer (renal cell carcinoma, RCC) has shown a sustained increase in its global prevalence thereby presenting increasing burden to health systems, and most of all, to individual patients and their families. Little is known about the variations in the patient experience and best practices among countries. Although individual national surveys have been held, no conclusions could be drawn about country-level variation in patient experience or best practice. Here, we report on the 3rd biennial Global Patient Survey on the diagnosis, management, and burden of Renal Cell Carcinomas conducted by the International Kidney Coalition (IKCC) and involving its Affiliate Organisations worldwide in 15 languages. The aim of the survey was to improve collective understanding and to contribute toward the reduction of the burden of kidney cancer around the world. Methods: A 35-question survey on the diagnosis, management, and burden of RCC was designed by a multi-country steering committee of patient leaders to identify geographic variations in 6 key dimensions: patient education, experience and awareness, access to care and clinical trials, best practices, quality of life, and unmet psychosocial needs. EAU, ESMO, ASCO and NCCN Guidelines committees provided topics of interest to support evidence-based medicine (eg patient perspective on active surveillance, biopsies, etc) . The survey was distributed to patients with kidney cancer and their caregivers in 15 languages, through social media and IKCC’s 49 Affiliate Organizations and/or allied organizations who are not formal affiliates. It was completed online or in paper form between 26 September 2022 and 31 October 2022. At the time of this abstract submission, the survey was still open for completion. Results: We will present the top-line results of the 2022 survey for the very first time. Survey results will be analyzed using cross-tabulations by an independent third-party organization, and multi-variate analysis of predetermined variable will be performed. The full global report will be presented, as well as individual country reports where at least 100 responses were received. Conclusions: The IKCC and its global affiliates will be using the results to ensure that patients’ voices are heard. Actionable points will suggest future projects. Furthermore, individual countries can use their reports to advance their understanding of patient experiences and to drive improvements in care provision locally.
Is pathological upstaging to T3a renal cell carcinoma associated with a similar prognosis to non-upstaged pathologic T3a disease? A multicenter analysis.
Authors: Nasseri Ryan , Hakimi Kevin , Afari Jonathan , Saidian Ava , Autorino Ricardo , Lane Brian R. , Marchioni Michele , Patil Dattatraya H , Sundaram Chandru , Tanaka Hajime , Porpiglia Francesco , Noyes Sabrina L. , Porter James R , Master Viraj A. , Minervini Andrea , Capitanio Umberto , Montorsi Francesco , Derweesh Ithaar H
Published: March 2023

656

Background: Pathological upstaging to T3a disease may occur following radical (RN) or partial nephrectomy (PN) for patients with T1/T2 renal cell carcinoma (RCC). While a number of studies have demonstrated increased risk of T1/T2 upstaging to pT3a compared to initial staging, a comparison of pathologically upstaged T3a RCC and T3a RCC which was not upstaged has not been performed. We sought to compare survival outcomes and predictors of outcomes in patients who underwent surgical therapy for upstaged T3a RCC versus non-upstaged pT3a RCC. Methods: We conducted a retrospective analysis of a multi-institutional dataset of patients who underwent radical (RN) or partial nephrectomy (PN) with final pathologic stage of pT3a. Patients were classified as being upstaged (US) from cT1 or cT2 or non-upstaged (NUS) with cT3a disease. Primary outcome was Overall Survival (OS)/all-cause mortality (ACM). Secondary outcomes were Cancer-Specific Survival (CSS)/Cancer-Specific Mortality (CSM), and Recurrence-Free survival (PFS)/Recurrence. Multivariable Cox regression analysis (MVA) were conducted for predictors of mortality outcomes and Kaplan Meier Analyses (KMA) were conducted to elucidate survival outcomes comparing US and NUS groups. Results: We analyzed 879 patients [US 691 (cT1 389/cT2 302); NUS 188; median follow-up 48 months). NUS had significantly greater tumor size (9.3 vs. US 7.3 cm, p<0.001), but no difference in positive surgical margins (6.9% vs. 3.9%, p=0.16). MVA for ACM revealed RN (HR 4.35, p<0.001), clear-cell RCC (HR 2.38, p<0.001), and positive surgical margin (HR 2.24, p=0.023) were independently associated, while upstaging status was not (p=0.78). MVA for CSM demonstrated age (HR 1.04, p=0.024) and positive margin (HR 5.28, p=0.029) were independently associated, while upstaging status was not (p=0.14). MVA for recurrence revealed positive margin (HR 6.7, p=0.003) and NUS (HR 3.85, p=0.001) to be associated with increased risk. KMA Comparing NUS and US groups, revealed no difference in 5-year OS (57% NUS vs. US 56%, p=0.38), and worsened 5-year CSS (NUS 66% vs. US 75%, p=0.04) and 5-year RFS (NUS 60% vs. US 84%, p<0.001). Conclusions: Pathologic upstaging to T3a RCC was associated with a lower risk of recurrence compared to non-pathologically upstaged T3a RCC; nonetheless in our analysis upstaging status was not independently associated with increased risk of cancer-specific or overall mortality in T3a RCC. Our findings also highlight the importance of complete surgical resection in the setting of T3a disease and should prompt consideration of intensified follow up, aggressive re-salvage resection and use of adjuvant therapy.
Association of inflammation and depression in renal cell carcinoma.
Authors: Schmeusser Benjamin , Ali Adil , Patil Dattatraya H , Midenberg Eric , Petrinec Benjamin , Bilen Mehmet Asim , Ogan Kenneth , Master Viraj A.
Published: March 2023

658

Background: Patients with cancer experience depression at higher rates, which is associated with worse outcomes and quality of life. In renal cell carcinoma (RCC) specifically, depression is particularly prevalent. Aside from the emotional distress of a cancer diagnosis, a biologic basis for cancer associated depression is inflammation, which is highly associated with RCC as well as worse outcomes. Here, we aim to assess the association between inflammation and major depression, measured by a score of 10+ on the Patient Health Questionnaire (PHQ-8), in patients undergoing nephrectomy for nonmetastatic RCC. Methods: A retrospective review of prospectively administered PHQ-8 surveys in patients that underwent nephrectomy for nonmetastatic RCC was conducted. Patients with available preoperative PHQ-8 within 180 days before surgery were included. Association of major depression on PHQ-8 with patient/tumor characteristics were determined by Generalized chi-square test or Fisher’s exact test for categorical variables and Wilcoxon rank-sum test for continuous variables. Multivariable logistic regression was used to determine variables significantly associated with major depression on PHQ-8, including pre-operative C-Reactive Protein (CRP) independently and combined with American Joint Committee on Cancer (AJCC) staging for RCC. Results: 224 patients were analyzed, with 67% being male. Median age and BMI was 64 and 29.0, respectively. 65.2% of patients were white, and 28.6% were black. Histologically, most patients had clear cell RCC (67.4%). AJCC staging was 52.2% stage I, 5.36% stage II, and 42.41% stage III. 30.4% had an elevated CRP (>10mg/L). Median PHQ-8 score was 4, with 42 (18.8%) of patients screening positive for major depression on PHQ-8 (10+). Multivariable regression models showed elevated CRP alone (OR 2.74, 95% CI 1.02-7.40, p=0.047) and in-combination with AJCC stage I-II (OR=8.13, 95% CI 1.99-33.27, p=0.004) and III (OR=4.82, CI 1.11-20.88, p=0.035) as a predictor of major depression on PHQ-8. Conclusions: In this study of patients with nonmetastatic RCC, elevated CRP (>10mg/L) was an independent predictor of major depression on PHQ-8. [Table: see text]
Impact of age on functional decline following radical nephrectomy: Analysis of the International Marker Consortium for Renal Cancer (INMARC).
Authors: Nguyen Mimi , Walia Arman , Saidian Ava , Wang Luke , Hakimi Kevin , Meagher Margaret , Cerrato Clara , Shah Aastha , Liu Franklin , Dhanji Sohail , Patil Dattatraya H , Fujii Yasuhisa , Derweesh Ithaar H
Published: March 2023

664

Background: Radical nephrectomy (RN) is a mainstay of management of localized renal cancer >4 cm. RN is associated with renal functional decline, however impact of age on functional decline is unclear. We investigated impact of age on post RN function, focusing on decline to moderate and severe chronic kidney disease (CKD). Methods: This was a retrospective analysis of patients who underwent RN. Patients were stratified by age (<50, 50-70 and >70 years). Primary outcome was development of denovo CKD-S 3b [estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2)]. Secondary outcomes included denovo CKD-S 3a (eGFR<60) and denovo CKD-S 4 (eGFR<30). Multivariable logistic regression analysis (MVA) was utilized to identify risk factors for renal functional decline. Linear regression was utilized to identify risk factors for increasing DeGFR. Kaplan-Meier analysis (KMA) was utilized to evaluate functional outcomes for different age groups Results: We analyzed 2436 patients (<50 years, n=513; 50-70 years, n=1344; >70, n=579; median follow-up 31.9 months). On MVA, increasing age was an independent risk factor for CKD-S 3a (HR=3.4-9.4, p<0.001), CKD-S 3b (HR=3.4-7.7, p<0.001), and denovo CKD-S 4 (HR=1.96, p=0.027). On linear-regression analysis, increasing age was significantly correlated with increased delta eGFR (β=-0.212, p<0.001). KMA Comparing <50, 50-70 and >70 demonstrated age-associated declines in 5-year freedom from denovo CKD-S 3a (73.9%; 50-70 53.7%; and >70 37.06%, respectively, p<0.001), denovo CKD-S 3b (92.7%; 71.8%; and 55.5%, p<0.001) and denovo CKD-S 4 (93.7%; 89.8%; and >70 81.2%, p<0.001). Conclusions: Increasing age is a risk factor for progressive and clinically significant renal functional decline after RN. Prioritization for nephron-sparing management may be considered when indicated and oncologically safe and feasible in elderly patients to reduce potential risk of sequelae of functional decline. [Table: see text]
Overall survival, efficacy, and safety outcomes beyond front-line modern therapies in metastatic clear-cell renal cell carcinoma.
Authors: Kreutzfeldt Jordyn , Obeng-Kusi Mavis , Estrada-Mendizabal Ricardo J. , Choi Briana M , Abraham Ivo , Recio-Boiles Alejandro
Published: March 2023

667

Background: Due to the ever-changing front-line landscape therapeutic options for m-ccRCC, the second-line (2L) treatment decision remains challenging due to limited information comparing each of the options. We present a survival, efficacy, and safety comparison of the 2L treatment regimens based on the most recent drug approvals for m-ccRCC. Methods: Inclusion criteria for our NMA included phase II/III RTCs that evaluated 2L and beyond for metastatic ccRCC. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and severe adverse events (SAE) hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (CI) of the treatment differences were abstracted. The p-scores were used to rank treatments. Data were analyzed in a fixed effects model using the netmeta package in R v.1.5-0. Results: Nine studies with 10 therapies included demonstrated some level of efficacy over placebo (Table). Pairwise comparisons using the NMA matrix revealed no differential OS benefit between axitinib (A), cabozantinib (C), lenvatinib+everolimus (LE), and nivolumab (N). Other regimens had no OS benefit when compared to placebo. Table was ordered based on p-score ranking the certainty that one treatment is better than another averaged over all competing treatments for OS. Placebo represents the reference of 1. Conclusions: LE had the lowest safety profile, although did prove to have the best OS and efficacy based on PFS/ORR. C and N, both had significant improvement in OS and efficacy over placebo with lower rates of SAEs compared to LE. Therefore, while further direct comparison studies are warranted to inform clinical practice, for now, we rely on the limitations inherent in indirect treatment comparisons of a NMA. [Table: see text]
Phase II trial of intermittent therapy in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with front-line ipilimumab and nivolumab (Ipi/Nivo).
Authors: George Laeth , Wei Wei , Diaz-Montero C. Marcela , Martin Allison , Vyas Neil , Basu Arnab , Beckermann Katy , Nizam Amanda , Wee Christopher Eing , Gilligan Timothy D. , Gupta Shilpa , Rini Brian I. , Ornstein Moshe Chaim
Published: March 2023

672

Background: The combination of ipilimumab and nivolumab (Ipi/Nivo) is approved for patients (pts) with treatment-naïve, intermediate- and poor-risk metastatic renal cell carcinoma (mRCC), but duration of therapy and safety/efficacy of re-induction at progression is unknown. A phase II trial of intermittent Ipi/Nivo with re-induction at progression was conducted (NCT03126331). Methods: Patients with treatment-naïve mRCC were treated with induction Ipi/Nivo followed by up to 24 weeks (+/- 8 weeks) of maintenance Nivo. Pts who achieved a complete response (CR) or partial response (PR) were eligible for inclusion and entered a treatment-free observation period. Pts were restaged every 12 weeks. Pts with no disease progression (PD) remained off therapy. Upon PD, pts were re-challenged with 2 doses of Ipi/Nivo every 3 weeks, with 1 or 2 more doses at physician discretion. The study objectives were to estimate success rate of observation in pts who achieve a CR/PR (defined by 50% of CR/PR pts sustaining a treatment-free interval of at least 9 months), and to assess toxicity in pts undergoing re-induction. The study was closed early given poor accrual in the rapidly changing mRCC treatment landscape. Results: Nine pts were included; 89% male, median age 57, 78% prior nephrectomy, 67% clear-cell histology, all had KPS ≥ 80%, and 78% were intermediate-risk by IMDC criteria. All pts had 4 doses of induction Ipi/Nivo. Response to Ipi/Nivo and Nivo maintenance prior to enrollment was 33% CR and 67% PR. Most (78%) pts patients have remained off therapy, with a median treatment-free interval (TFI) of 34.3 months (range, 8.7-41.8). The success rate of 0.78 (95% CI: 0.40-0.97) exceeded the pre-specified threshold of 50%. Two pts had PD off therapy (3 and 8 months after therapy cessation; both with best initial response of PR). Both received 2 cycles of re-induction Ipi/Nivo. No grade 3 or greater toxicities occurred with re-induction, but both pts developed PD at their first scans after re-induction. Conclusions: This pilot prospective study demonstrates that patients with a radiographic response to Ipi/Nivo can have prolonged treatment-free intervals. Further studies of de-escalation strategies are warranted. Correlative investigations for this trial are ongoing. Clinical trial information: NCT03126331 .
Survival outcomes of metastasis-directed therapy for solitary sites of metastatic clear cell renal cell carcinoma.
Authors: Lewis Akeem Ronell , Lohse Christine M. , Lyon Timothy D. , Cheville John , Leibovich Bradley C. , Sharma Vidit , Costello Brian Addis
Published: March 2023

674

Background: Metastasis directed therapy (MDT) is associated with improved cancer-specific survival and delay in use of systemic therapy for metastatic clear cell RCC (mccRCC). Although the benefits of MDT may differ based on organ site of metastasis due to differences in disease biology, survival based on site of metastasis remain underexplored. We aim to evaluate survival outcomes of patients who underwent MDT for solitary sites of mccRCC. Methods: The Mayo Clinic Nephrectomy Registry was queried to identify adults undergoing radical or partial nephrectomy for unilateral, sporadic ccRCC from 2000 to 2019 with a single site of metastasis treated with MDT including complete metastasectomy or radiation, in lieu of systemic therapy. Overall and cancer-specific survival were estimated using the Kaplan-Meier method, with the duration of follow-up calculated from the date of metastasis to the date of death or last follow-up. Associations with time to death from RCC were evaluated using Cox proportional hazards regression models and summarized with hazard ratios and 95% confidence intervals (CIs). Results: In this cohort of 207 mccRCC patients, 152 underwent complete metastasectomy and 55 underwent radiation. 133 died at a median of 2.7 years (IQR 1.2-4.7) following metastasis, including 105 who died from RCC at a median of 2.2 years (IQR 1.0-3.9). The median duration of follow-up for the 74 patients who were still alive at last follow-up was 8.1 years (IQR 3.7-12.1). Overall survival rates (95% CI) at 2, 4, 6, 8, and 10 years following metastasis were 73% (69-79), 54% (48-62), 45% (38-52), 37% (30-44), and 32% (26-40), respectively; cancer-specific survival rates were 75% (69-81), 56% (50-64), 47% (41-55), 44% (37-52), and 42% (35-50), respectively. Age, poor performance status, presence of synchronous metastasis and asynchronous metastasis <1 year from nephrectomy, tumor size, and bone metastasis were associated with death from RCC (table). Conclusions: These findings provide useful survival benchmarks to patients who are considering MDT as a therapeutic option. In addition, synchronous and asynchronous metastasis <1 year from nephrectomy, poor performance status, and bone metastasis are significantly associated with worse survival from mccRCC. [Table: see text]
A phase II trial of combination of PD-1 immune checkpoint inhibition with all-lesion stereotactic radiation (SBRT) in oligometastatic renal cell carcinoma (omRCC).
Authors: Liu Jing , Zou Benkui , Zhang Chao , Zhu Kunli , Feng Rui , Xu Lei , Dou Xue , Shi Pengyue , Zhang Yun , Yue Jinbo
Published: March 2023

677

Background: Although systemic therapy has recently made strides, the 5-year survival rate of mRCC patients is still low — around 10%. Through the abscopal effect, SBRT can improve the antitumor immunity of PD-1 immune checkpoint inhibition (ICI) in metastatic RCC. OmRCC patients have a low tumor load and a favorable prognosis, so more active treatment strategies are needed. It might work even better when all lesions of omRCC are controlled by SBRT. The study aims to evaluate whether the antitumour immunity can be enhanced by combination of ICI and all-lesion SBRT for omRCC. Methods: Patients with progression disease after ≤ 2 prior anti-angiogenic therapies and with ≤ 5 lesions located in ≤ 3 non-brain metastatic sites may all suitable for SBRT are included. Tislelizumab was given as 200 mg in intravenously on day 1, Q3W, until PD or unacceptable toxicity. Hypofractionated radiation at a dose and schedule of 5-8 Gy×3-10 fractions were performed according to lesion site, size and organs at risk individually. SBRT of first lesion were applied after 7 days from the first infusion of Tislelizumab. SBRT of other lesions were performed sequentially during the intervals of Tislelizumab. The primary objective is Objective Response Rate (ORR) according to RECIST v1.1. Secondary endpoints are progression free survival (PFS), overall survival (OS) and safety profile. An exploratory project also identifies molecular basis of synergistic effect of SBRT and immunotherapy, potential mechanisms of ICI resistance. Results: Fifteen patients were enrolled from May 2021 to May 2022. Totally 36 lesions were radiated, including 10 lung lesions (63 Gy/9 fractions), 10 bone lesions (24-40 Gy/5-8 fractions), 7 lymph nodes (30-50 Gy/6-10 fractions), 4 kidney lesions (40 Gy/5 fractions), and 5 other lesions. ORR were 33.3% for patients (CR=0, PR=5, SD=7, PD=2, not evaluable=1) and 27.8% for lesions (CR=2, PR=8, SD=11, PD=3, not evaluable=12). The most common treatment-related toxicities include fatigue (20%), hypothyroidism (20%), and pneumonia (13.3%), all with G1-2. One patient suffered G3 treatment-related hematologic toxicity. There were no treatment related deaths. Median PFS and OS were not reached. Conclusions: The combination of all-lesion SBRT with ICI is feasible and associated with an accepted safety profile. Encouraging antitumor activity was observed warranting further investigations. Clinical trial information: ChiECRCT20210046 .
Barriers to guideline-concordant use of bone modifying agents for prostate cancer.
Authors: Mitchell Aaron Philip , Persaud Sonia , Chimonas Susan , Salner Andrew L. , Palyca Paul , Farooki Azeez , Ostroff Jamie S. , Morris Michael J.
Published: March 2023

68

Background: NCCN Guidelines recommend the use of bone-modifying agents (BMAs) to prevent skeletal-related events (SRE) for patients with castrate-resistant prostate cancer (CRPC) and bone metastasis, but not for castrate-sensitive prostate cancer (CSPC). Prior studies have identified both underuse of BMAs for CRPC and overuse for CSPC, but the clinical circumstances underlying these apparent gaps in care are unknown. Methods: Qualitative interview study, with physicians who treat prostate cancer within an academic cancer center and an affiliated network of community-based practices. Using a semi-structured interview guide, an experienced moderator probed participants’ experiences and perceptions around NCCN Guidelines recommendations, guideline adherence and non-adherence, and barriers to adherence. Interviews also probed participants’ views of potential interventions to promote guideline-concordant BMA use. Participants used Likert-scale items to rate the likely effectiveness of each intervention in influencing BMA practice patterns. They also identified the 3 most helpful interventions for reducing BMA underuse and overuse separately. Results: 19 physicians were invited, of whom 15 agreed to participate; 1 physician did not respond to some questions as outside scope of practice. All were aware of the recommendation for use of BMAs in CRPC. 14% (2/14) were unaware of the recommendation against BMA use for CSPC; an additional 29% (4/14) believed that BMA use could be appropriate for CSPC depending on the burden of bony metastatic disease. 36% (5/14) were unaware of recommendations for baseline DEXA scan and BMA for patients with low bone mineral density. The most commonly reported barriers (occurring “often” or “sometimes”) to BMA use for CRPC were obtaining dental clearance (11/15) and insufficient time in clinic (6/15). The interventions perceived as most helpful to reduce underuse for CRPC were dental navigation (11/15) and EMR-based guidance (9/15). The interventions identified as most helpful to reduce overuse for CSPC were peer-to-peer education (14/15) and EMR-based guidance (13/15). Conclusions: Among physicians treating prostate cancer in our study, there was incomplete awareness of guideline recommendations for screening and treatment of low bone mineral density, and against BMA use for SRE prevention in CSPC. Dental navigation, peer-to-peer education, and EMR-based guidance were preferred implementation strategies to reduce underuse and overuse of BMAs.
Clinical characteristics and outcomes of SARS-CoV-2 infection in patients with genitourinary cancer.
Authors: Kenny Dorothy , Wang Jue
Published: March 2023

7

Background: Cancer patients have increased risk for severe outcomes related to SARS-CoV-2 infection (COVID-19), due to their increased vulnerability to infection, older age, and comorbidities in comparison to the general population. While multiple studies have been completed examining outcomes of COVID-19 infection in cancer patients overall, there has been limited investigation into the outcomes of COVID-19 infection in patients with genitourinary (GU) cancers. Methods: We completed a single institution retrospective study to examine the outcomes of adults with GU cancers and COVID-19 infection from March 10, 2020 to June 15, 2022. Baseline data included age, sex, BMI, type of malignancy, cancer status (stable or progressive disease, in remission), current and previous anticancer therapy received, and comorbidities. Results: Eighty-four patients with a GU cancer diagnosis and laboratory-confirmed SARS-CoV-2 infection were identified. Seventy-nine (94%) were male and the median age was 64 years (range 24-91). Forty-four (52%) were non-Hispanic white, 28 (33%) were Hispanic, and 11 (13%) were African-American. Prostate cancer was the most common (n = 45), followed by renal cell carcinoma (n = 20), testicular (n = 9), bladder (n = 6), and penile cancer (n = 3). Eight patients had ≥2 episodes of COVID-19 infection. Sixty-three percent of patients were unvaccinated at the time of infection, while 37% of patients had breakthrough infection. Hospitalization was required for 39.3% (n = 33), with 4.8% (n = 4) requiring ICU admission. Of the patients requiring hospitalization, 26.2% (n = 22) died. Hospitalization was associated with having ≥2 comorbidities (OR 18.6 [95% CI, 3.1-111.8], p<0.01) and receiving active cancer treatment (OR 12.4 [95% CI, 1.92-79.7], p< 0.01). Mortality was associated with advanced age (OR 21.7 [95% CI, 1.40-341.7], p=0.03) and ≥2 comorbidities (OR 19.2 [95% CI, 3.02-122.5], p=0.02). Vaccination was negatively associated with both hospitalization (OR 0.04 [95% CI, 0.02-0.91], p=0.04) and mortality (OR 0.14 [95% CI, 0.02-0.84], p=0.03). Conclusions: Among patients with GU cancer, advanced age and comorbidities are associated with adverse outcomes of COVID-19 infection; vaccination is protective. With the emergence of variants and waning immunity of vaccines, our findings highlight the importance of development and implementation of enhanced mitigation strategies in cancer patients, especially those undergoing active cancer treatment.
Dynamic and immunocytochemistry analysis of circulation tumor cells (CTCs) in blood samples from patients with advanced ccRCC starting first-line treatment in a Brazilian Cancer Center.
Authors: Tariki Milena Shizue , Carreta Ruano Anna Paula , Torres Jacqueline Aparecida , Braun Alexcia Camila , Costa Daniela JF , Torrezan Giovana Tardin , Carraro Dirce Maria , da Costa Walter Henriques , Chinen Ludmilla T.D.
Published: March 2023

704

Background: Treatment of advanced clear cell renal carcinoma (ccRCC) improved dramatically in the last 20 years, but biomarkers development lagged behind. Circulating tumor cell (CTC) is used as a prognostic and predictive tool in many solid tumors but is poorly studied in ccRCC. Objective: Our aim was to evaluate CTC counts in serial blood samples from patients with advanced ccRCC that started first-line treatment and analyze the protein expression of PBRM1, BAP1, PD-L1 and CD133 in these cells. Methods: Blood samples (10mL) were collected in EDTA tubes at three different timepoints, 30 days apart, after treatment start. We used a filtration technique (ISET system, Rarecells/France) to isolate and collect CTCs. Protein expression was evaluated by immunocytochemistry. Results: Twelve patients were included. All had detectable CTCs at baseline (1st blood draw), with a median of 1.5 CTCs/mL. Patients with CTCs above the median had ≥2 metastatic sites (p=0.015) and worse progression free survival (PFS) (19.7 vs 31.1 months, p=0.35), although the difference was not statistically different. Favorable CTCs kinetics at the time of first follow-up (2nd blood draw) indicated better PFS (24.76 months) versus unfavorable (6.65 months; p=0.014). PBRM-1, BAP-1 and PD-L1 expression in CTCs was associated with better overall survival (OS), although without statistical significance. CD133 expression in CTCs at baseline was associated with worse OS (p=0.08). Conclusions: CTCs isolation was feasible in advanced ccRCC patients starting first-line treatment and were frequently detected by ISET method. CTC counts at baseline and at 30 days after treatment initiation had prognostic implication, as well as its dynamic evaluation after 30 days of treatment with a favorable kinetics associated with better outcome.
Molecular characteristics of advanced clear cell renal cell carcinoma (ccRCC) harboring TERTmutations.
Authors: Mar Nataliya , Jaeger Ellen B. , Ashok Arya , Rezazadeh Arash
Published: March 2023

706

Background: There is a large unmet need for identifying prognostic and predictive biomarkers in advanced RCC. TERT is a catalytic subunit of the telomerase enzyme and TERT promoter mutations lead to increased telomerase activity, which promotes tumorigenesis by preventing telomere shortening. Emerging data suggests a correlation between TERT promoter mutations (pTERTmut) and improved responses to immune checkpoint inhibitors in urothelial carcinoma (UC), while there is paucity of such data in RCC. This study aims to analyze the immune biomarker environment and co-mutational landscape in TERT mutated versus wild-type RCC. Methods: A retrospective analysis of patients with advanced ccRCC who completed sequencing with the Tempus xT assay (DNA-seq of 648 genes at 500x coverage, full transcriptome RNA-seq) was performed. De-identified data was analyzed for presence of pTERTmut, all other TERT mutations (otherTERT), and TERT wildtype (wtTERT). Companion alterations and immune biomarkers were compared between these three groups. Results: A total of 866 samples was analyzed, with 58% from primary renal lesions and 42% from a metastatic site. The frequency of all TERT mutations was 8.2% (71/866). pTERTmut was present in 5.6% (28/502) of primary and 5.5% (20/364) of metastatic sites, while otherTERT was present in 3.0% (15/502) of primary and 2.2% (8/364) of metastatic sites. Tumor mutational burden (TMB) was performed in 764 samples and only 0.4% had TMB greater than 10 m/MB, all of which were wtTERT. Median TMB was 2.08 m/MB across all samples, with 1.91 m/MB in pTERTmut, 1.72 m/MB in otherTERT, and 2.31 m/MB in wtTERT. Only 0.2% of 834 samples harbored MSI-high and 1.4% of 295 samples were mismatch repair deficient (dMMR), all of which were wtTERT. PD-L1 status was available in 439 samples, with 14% scored as positive (PD-L1+) with a combined positive score >10. Of PD-L1+, 4.8% was in pTERTmut, 3.2% in otherTERT, and 92.1% in wtTERT. Neoantigen tumor burden of all non-silent mutations was evaluated in 698 samples, with a median value of 2.11 in pTERTmut, 1.58 in otherTERT, and 2.11 in wtTERT. PBRM1 co-mutations were noted in 22.9% of samples with pTERTmut, 21.7% in otherTERT, and 33.2% in wtTERT. Additional RCC co-mutations are listed in the table. RCC mRNA and UC cohort data analysis is in progress. Conclusions: This is the largest analysis of the molecular and immune landscape of TERT mutated ccRCC. Interestingly, this dataset showcases that traditional immune biomarkers (TMB, MSI, dMMR, and PD-L1) do not appear to be highly prevalent in RCC and their use in clinical practice may be limited. Further investigation into the TERT biomarker candidate is warranted. [Table: see text]
Characteristics and outcomes of T1a renal cell carcinoma presenting with metastasis.
Authors: Wang Luke , Puri Dhruv , Liu Franklin , Dhanji Sohail , Meagher Margaret F , Shah Aastha , Ghassemzadeh Saeed , Javier-Desloges Juan , Bagrodia Aditya , Rose Brent Shane , Murphy James Don , Derweesh Ithaar H , McKay Rana R.
Published: March 2023

734

Background: T1a renal cell carcinoma (RCC) is associated with excellent cure rates. However, a small fraction present with metastasis. We sought to determine the clinical characteristics, variables associated with synchronous metastasis, and survival outcomes in patients with pT1a and cT1a RCC using the National Cancer Database (NCDB). We secondarily evaluated whether surgery impacted risk of all cause mortality in cT1a RCC with synchronous lung and bone metastasis. Methods: From 2004 to 2019, all cases of RCC in patients age ≥18 were extracted from NCDB. pT1a and cT1a RCC were characterized as those 1) with no metastasis at diagnosis, 2) with synchronous metastasis [pT1aNxM1 at diagnosis]. Impact of surgery on all cause mortality was not evaluated for cT1a with synchronous metastasis to liver and brain due to low sample sizes. Results: The table describes selected characteristics of the cohorts. On multivariable logistic regression, diagnosis of pT1a with synchronous metastasis was associated with age (OR 1.02), male sex (OR 1.64), tumor size (OR 1.84), cN1 (OR 1.08), sarcomatoid (OR 5.50), tumor grade (OR 2.84) (p<0.005 for these variables); and inversely with diagnosis in 2016-2019 (OR 0.66, p=0.044) and papillary histology (OR 0.45, p<0.001). On multivariable Cox regression of the cT1a cohort, ACM was associated with Charlson score (HR 1.50, p<0.001), metastasis to >1 site (HR 2.48, p=0.032), and inversely with radical (HR 0.42, p<0.001) and partial nephrectomy (HR 0.31, p<0.001). In cT1a with lung metastasis, partial (HR 0.06, p=0.049) and radical nephrectomy (HR 0.17, p=0.006) was inversely associated with ACM, while surgery of distant site was not. In cT1a with bone metastasis, partial (HR 0.21, p<0.001) and radical nephrectomy (HR 0.32, p<0.001) were the only variables inversely associated with ACM. 5-year overall survival for pT1a with synchronous metastasis is 39.4%; for cT1a with synchronous metastasis is 20.9%. Conclusions: Known prognostic features were associated with synchronous metastasis in T1a RCC. Surgical resection of primary site may impact risk of all cause mortality in select cases of synchronous metastatic disease. [Table: see text]