OBJECTIVE:Postoperative urinary retention (POUR) commonly occurs following elective lumbar spine surgery. POUR can result in prolonged admission, urinary tract infection (UTI), and patient morbidity. Prophylactic α1-antagonist therapy is often used to reduce the risk of this complication. The aim of this study was to identify the incidence of POUR in this population and determine the effect of prophylactic α1-antagonists using a propensity score (PS)-matched model. METHODS:This retrospective review included patients who underwent elective lumbar spine surgery at a single institution between 2015 and 2021. PSs were generated for the likelihood of receiving prophylactic α1-antagonists immediately after surgery. PS matching was performed using 1:1 nearest-neighbor matching (0.01 caliper) without replacement. From this matched cohort, a random-effects model accounting for variation in surgeon practice was used to assess factors associated with POUR. RESULTS:Overall, 2326 patients were identified and 506 were successfully PS matched. The overall incidence of POUR was 8.8%. Immediately postoperatively, 422 patients (18.1%) received prophylactic α1-antagonist therapy (treatment group) and 1904 patients did not (controls). Prior to matching, there were significant differences between the control and treatment groups. In the multivariable random-effects model of the 506 matched patients, POUR was associated with the use of prophylactic α1-antagonists after surgery (RR 1.94, 95% CI 1.07-3.52), female sex (RR 1.83, 95% CI 1.41-2.39), intraoperative Foley catheter use (RR 0.25, 95% CI 0.12-0.52), the normalized duration of surgery (RR 0.42, 95% CI 0.20-0.88), patient-controlled anesthesia use (RR 2.63, 95% CI 1.47-4.70), and postoperative UTI (RR 3.52, 95% CI 1.34-9.21). CONCLUSIONS:Prophylactic α1-antagonist use immediately after surgery did not reduce POUR, and patients who received prophylaxis were at greater risk of POUR in this large PS-matched analysis. Female sex was associated with a greater incidence of POUR while intraoperative Foley catheter use and a longer operative duration were associated with reduced risk of POUR. Potentially modifiable risk factors, such as patient-controlled anesthesia use and UTI, significantly increased the risk of POUR and thus should be addressed in the early postoperative setting.

To compare the surgical and microbiological characteristics of fracture related infection (FRI) that had union and those requiring additional surgery to promote bone healing. We hypothesized that FRIs with MRSA will have higher risk for reoperation to promote bone healing. This is a retrospective study on 247 patients over 18 who underwent bone fixation for pelvis, upper, and lower extremities fractures between 2013 and 2021 at a level I trauma center. All cases had an FRI and at least 6 months of follow-up after diagnosis. Patients with pathologic fracture due to underlying malignancy and patients with spinal fractures were excluded. We compared surgical and microbiological characteristics of fractures between cases that required reoperation to promote bone healing and those who did not. Of 247 patients, 55 (22.2

Background: Bone-predominant metastatic renal cell carcinoma (mRCC) presents significant clinical challenges due to its associated morbidities and poor prognosis. Optimal first-line treatment remains unclear, largely because these patients are often excluded from clinical trials due to difficulties in measuring bone lesions. Emerging evidence suggests that bone metastases exhibit high angiogenesis gene signatures, potentially predicting favorable responses to tyrosine kinase inhibitors (TKIs). Methods: We conducted a multicenter retrospective analysis of patients with bone-predominant mRCC treated at The Ohio State University Comprehensive Cancer Center and Fred Hutchinson Cancer Center from January 2008 to June 2021. Bone predominance was defined as having a greater number of osseous metastases compared to extra-osseous sites using computed tomography or bone scans. Patients receiving first-line TKIs or immune checkpoint inhibitors (ICIs) were included; those treated with combination TKI-ICI therapies were excluded due to limited numbers. Demographic, clinical, and treatment data were collected. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and compared using the log-rank test. Univariate Cox regression analysis was conducted to identify factors associated with OS. Results: A total of 69 patients with bone-predominant mRCC were identified, with 40 receiving TKIs and 29 receiving ICIs as first-line therapy. Baseline characteristics were comparable between groups. The median OS was significantly longer for patients treated with TKIs compared to those receiving ICIs (41.3 months vs. 19.3 months; log-rank P = 0.036). A trend toward improved median PFS was observed in the TKI group (7.9 months vs. 4.9 months; P = 0.075). Univariate analysis showed that treatment with ICIs was associated with an increased risk of death compared to TKIs (hazard ratio = 1.96; P = 0.040). Objective response rates were higher in the TKI group (22.9% vs. 12.0%), although this difference was not statistically significant (P = 0.332). Conclusions: In this multicenter real-world analysis, first-line treatment with TKIs was associated with significantly improved OS compared to ICIs in patients with bone-predominant mRCC. These findings suggest that TKI-containing regimens may be the preferred front-line therapy for this patient subgroup. Prospective studies are warranted to validate these results and to optimize treatment strategies for bone-predominant mRCC.

Background: There has been a nearly 4% annual increase in global research output. Publications indexed in Medline (PubMed) alone have increased from 158,922 in 1965 to a staggering 1,063,140 in 2021. A heightened focus in rigor and transparency is needed for proper assessment of quality and applicability to clinical decision making. Consensus generated reporting guidelines such as CONSORT, STROBE, PRISMA have been developed to improve the quality of data reporting. The Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network provides free and easy access to these and other reporting guidelines. They outline the minimum information needed for reviewers and readers to adequately assess studies and have been increasingly adopted in the scientific community. However, their proper use and adherence in the neurosurgical literature has not yet been investigated.

BackgroundThe optimal treatment for metastatic renal cell carcinoma (mRCC) patients who have progressed after both immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) remains uncertain. Lenvatinib and everolimus (LE) are frequently used in combination as salvage therapy because of their different antitumor mechanisms, but efficacy and toxicity data in this setting are lacking.MethodsWe retrospectively reviewed charts from two academic centers for 71 adult mRCC patients who received LE after prior ICI and TKI exposure. We evaluated patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details. Outcomes of interest included objective response rate (ORR), time to treatment failure (TTF), overall survival (OS), ≥grade 3 toxicities, and schedule or dosage changes, which were evaluated using descriptive statistics, chi-square test, Cox proportional hazards model, and the Kaplan–Meier method.ResultsThe median age was 64 (range 31–84). Most patients had clear cell histology (84.5%) and had undergone nephrectomy (80.3%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). The average ORR was 26.8%, while the median TTF was 5.5 months (95% confidence interval [CI], 3.5–7.6) and the median OS was 9 months (95% CI, 7.6–12.9). Intermediate and poor IMDC risks were independently associated with a significantly worse TTF compared to favorable risk (hazard ratio (HR), 3.03, 95% CI, 1.18–7.79), as was ≥4L treatment vs. 2L/3L treatment (HR, 2.02, 95% CI, 1.08–3.8). Of the 71 patients, 57.7% had ≥grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance.ConclusionsLE therapy is feasible but has modest efficacies following ICI/TKI treatment. Patients with favorable risk or treated earlier may have a better treatment response. These observations need to be confirmed in prospective studies.

You have accessJournal of UrologyCME1 Apr 2023PD24-04 OUTCOMES OF DEFERRED CYTOREDUCTIVE NEPHRECTOMY FOLLOWING PRIMARY IMMUNOTHERAPY IN ADVANCED RENAL CELL CARCINOMA: A MULTICENTER ANALYSIS Kevin Hakimi, Ava Saidian, Justine Panian, Pedro Barata, Stephanie Berg, Steven Chang, Renee Saliby, Hannah Dzimitrowicz, Hamid Emamekhoo, Evan Gross, Deepak Kilari, Elaine Lam, Mimi Nguyen, Margaret Meagher, Grant Rauterkus, Vincent D'Andrea, Kendrick Yim, Sarah Psutka, Bicky Thapa, Nicole Weise, Tian Zhang, Rana McKay, and Ithaar Derweesh Kevin HakimiKevin Hakimi More articles by this author , Ava SaidianAva Saidian More articles by this author , Justine PanianJustine Panian More articles by this author , Pedro BarataPedro Barata More articles by this author , Stephanie BergStephanie Berg More articles by this author , Steven ChangSteven Chang More articles by this author , Renee SalibyRenee Saliby More articles by this author , Hannah DzimitrowiczHannah Dzimitrowicz More articles by this author , Hamid EmamekhooHamid Emamekhoo More articles by this author , Evan GrossEvan Gross More articles by this author , Deepak KilariDeepak Kilari More articles by this author , Elaine LamElaine Lam More articles by this author , Mimi NguyenMimi Nguyen More articles by this author , Margaret MeagherMargaret Meagher More articles by this author , Grant RauterkusGrant Rauterkus More articles by this author , Vincent D'AndreaVincent D'Andrea More articles by this author , Kendrick YimKendrick Yim More articles by this author , Sarah PsutkaSarah Psutka More articles by this author , Bicky ThapaBicky Thapa More articles by this author , Nicole WeiseNicole Weise More articles by this author , Tian ZhangTian Zhang More articles by this author , Rana McKayRana McKay More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003302.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Primary systemic therapy in the management of advanced Renal Cell Carcinoma (RCC) has gained increasing traction. We examined the effects of immunotherapy (IO) on the primary tumor, consequent cytoreductive nephrectomy, and short-term oncologic outcomes. METHODS: This was a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO followed by cytoreductive nephrectomy. Disease characteristics between pre- and post-IO groups was assessed using independent sample t-test. The cohort was divided into patients who achieved the Bifecta outcome (complete surgical resection and no post-operative complications) and those who did not achieve Bifecta. Primary outcome was progression-free survival (PFS). Secondary outcomes included change in primary tumor size, tumor thrombus length, and RENAL score following IO treatment. Cox regression multivariable analysis (MVA) was conducted for predictors of survival outcomes. Kaplan-Meier analysis (KMA) assessed PFS in the setting of Bifecta. RESULTS: 56 patients across 9 institutions were analyzed. Median age was 63 years (median follow-up time of 22.5 months). The most common histology was Clear Cell RCC (76.8%). Most patients received nivolumab and ipilimumab (57.1%) and median duration of IO prior to surgery was 8.1 months. IO resulted in significant reductions in median tumor size (9.4 vs 5.9 cm, p<0.001) and tumor thrombus length (6.0 vs. 2.0 cm, p=0.02). Patients saw a significant reduction mean RENAL score (9.2 vs 8.4, p<0.001) as well as a reduction in complex RENAL score (10-12) from 44.6% to 28.6% (p<0.001). Following IO treatment, most patients received open (41.1%) radical nephrectomy (85.7%). 67.9% achieved the novel outcome Bifecta (complete surgical resection and no post-operative complications). MVA noted Bifecta achievement (OR 2.65, p=0.03) as a significant predictor for improved PFS. KMA demonstrated improved 2-year PFS (84% vs 71%, p=0.019) in patients who achieved the Bifecta outcome compared to those who did not. CONCLUSIONS: IO resulted in reductions in tumor size, complexity, and thrombus length. Patients who achieved bifecta displayed improved 2-year PFS. Cytoreductive nephrectomy may be an important tool in the setting of primary IO for advanced RCC. Source of Funding: Stephen Weissman Kidney Cancer Research Fund © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e722 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kevin Hakimi More articles by this author Ava Saidian More articles by this author Justine Panian More articles by this author Pedro Barata More articles by this author Stephanie Berg More articles by this author Steven Chang More articles by this author Renee Saliby More articles by this author Hannah Dzimitrowicz More articles by this author Hamid Emamekhoo More articles by this author Evan Gross More articles by this author Deepak Kilari More articles by this author Elaine Lam More articles by this author Mimi Nguyen More articles by this author Margaret Meagher More articles by this author Grant Rauterkus More articles by this author Vincent D'Andrea More articles by this author Kendrick Yim More articles by this author Sarah Psutka More articles by this author Bicky Thapa More articles by this author Nicole Weise More articles by this author Tian Zhang More articles by this author Rana McKay More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement PDF downloadLoading ...

e16520 Background: The optimal treatment for mRCC patients (pts) who have progressed after both ICI and TKI remains uncertain. LE is frequently used as a salvage treatment due to different antitumor mechanisms, but efficacy and toxicity data in this setting are limited. Methods: We retrospectively reviewed charts from two academic centers for 71 adult mRCC pts who received LE after prior ICI and TKI exposure. Collected data included patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details using CTCAEv5. Outcomes were objective response rate (ORR) per RECIST 1.1, median time to treatment failure (mTTF), and toxicity. Descriptive statistics, Cox proportional hazards model and Kaplan-Meier method were utilized. Results: The median age was 64 (range: 31–84). Most pts had clear cell histology (84.5%) and had undergone nephrectomy (75%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). Pts received a median of 3 (range 1-10) prior therapy lines (L) and 42 pts had sequential ICI and TKI, while 29 received ICI/TKI combination therapy. Average ORR was 26.8%, but numerically better when given earlier (2L/3L vs. ≥4L: 28.6% vs. 22%). The mTTF was 5.5 months (m) (95% confidence interval [CI], 3.5–7.6 m), which was not significantly changed by sequential or combinational ICI/TKI treatment exposure. In multivariable Cox analyses, int/poor IMDC risk was associated with a significantly worse TTF compared to favorable risk (HR, 2.2, 95% CI, 1.1-4.1; mTTF: 4.5 vs 12.9 m), and so was ≥4L treatment compared to 2L/3L treatment (HR, 3.2, 95% CI, 1.3-7.6; mTTF: 4.5 vs. 6.6 m). In 57 pts with int/poor IMDC risk, ≥4L treatment was associated with a significantly worse TTF (HR, 2.3, 95% CI, 1.2-4.5; mTTF: 3.6 vs. 6.6 m), while prior nephrectomy was associated with a significantly better TTF (HR, 0.46, 95% CI, 0.22-0.97; mTTF: 5.4 vs. 3.1 m) compared to those without nephrectomy. Of the 71 pts, 64% had ≥ grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance. Conclusions: LE therapy is feasible but has modest efficacy following ICI/TKI treatment. Pts with favorable risk, prior nephrectomy or early salvage may have a better treatment response. These observations need to be confirmed in prospective studies.

e16515 Background: ICIs are an important systemic treatment option for patients with mCCRCC. Sarcopenia, defined as low muscle mass, is associated with inferior outcomes in mCCRCC. However, there is limited data regarding sarcopenia and overall survival (OS) in patients receiving treatment with ICI-based regimens. Our objective was to evaluate associations between sarcopenia and BMI with OS in patients with mCCRCC receiving first line ICIs. Methods: A retrospective review of patients with mCCRCC receiving first line ICI-based therapy at Fred Hutchinson Cancer Center between 1/2015 to 4/2022 was performed. Patients without CT scans within 75 days of treatment initiation were excluded. Skeletal muscle index (SMI) at the level of L3 was measured using validated techniques. Sarcopenia was classified according to an international definition (SMI < 55 cm 2 /m 2 for men and SMI < 39 cm 2 /m 2 for women). BMI was defined as underweight ( < 19 kg/m 2 ), normal (19-24.99kg/m 2 ), overweight (25-29.99 kg/m 2 ), and obese ( > 30 kg/m 2 ). OS was estimated using the Kaplan-Meier method. Associations with OS were evaluated with Cox proportional hazard model analysis. Results: A total of 96 patients (25% female) with a median age of 62 (Interquartile range, IQR 55-68), met inclusion criteria. Due to missing CT images, 9 (9%) patients were excluded. 10 (11%), 43 (49%), and 22 (25%) were International Metastatic RCC Database Consortium (IMDC) favorable, intermediate, and poor risk respectively (12 unknown). Median follow up was 23 months (IQR 12-35). First-line therapy included ICI monotherapy (N = 15), ipilimumab/nivolumab (N = 49) or ICI/VEGF targeted therapy (N = 23). In total, 43 (49%) patients were sarcopenic. Median OS overall was 42.6 months (IQR 15.9-NR). Two-year OS was 57% in sarcopenic vs 76% in non-sarcopenic patients (Log-Rank p = 0.06). On multivariable analysis adjusted for IMDC risk criteria, age, and gender, SMI (continuous) was independently associated with survival (HR 0.94, 95%CI 0.90-0.99, p = 0.03) while BMI was not significantly associated with OS on univariate or multivariable analyses (p > 0.05). Among the 49 patients receiving ipilimumab/nivolumab combination therapy, sarcopenia was significantly associated with decreased 2-year OS (47% vs. 77%, p = 0.02). Across IMDC risk strata, sarcopenia was significantly associated with decreased 2-year OS in the intermediate risk group only (44% vs. 83%, p = 0.01). Conclusions: Sarcopenia, but not BMI, is independently associated with OS among patients with mCCRCC receiving first line ICI-based regimens. This finding is consistent with the literature suggesting that muscle mass measurement provides an important prognostic biomarker for patients with mCCRCC. SMI could inform treatment selection and adoption of muscle measures when risk-stratifying this population should be considered.

OBJECTIVE:The optimal surgical management of Chiari malformation type I (CM-I) remains controversial and heterogeneous. The authors sought to investigate patient-specific, technical, and perioperative features that may affect the incidence of CSF-related complications including pseudomeningocele and CSF leak at their institution. METHODS:The authors performed a single-center, retrospective review of all adult patients with CM-I who underwent posterior fossa decompression. Patient demographics, operative details, and perioperative factors were collected via electronic medical record review. The authors performed Fisher's exact test and independent Student t-tests for categorical and continuous variables, respectively. Univariate regression analysis was performed to determine odds ratios. A multivariable regression analysis was performed for those factors with p < 0.10 or large effect sizes (OR ≥ 2.0 or ≤ 0.50) by univariate analysis. The STROBE guidelines for observational studies were followed. RESULTS:A total of 59 adult patients were included. Most patients were female (78.0%), and the mean body mass index was 32.2 (± 9.0). Almost one-third (30.5%) of patients had a syrinx on preoperative imaging. All patients underwent expansile duraplasty, of which 47 (79.7%) were from autologous pericranium. Arachnoid opening for fourth ventricular inspection was performed in 26 (44.1%) cases. CSF-related complications were identified in 18 (30.5%) of cases. Thirteen (22.0%) patients required readmission and 11 (18.6%) required intervention such as wound revision (n = 5), wound revision with CSF diversion (n = 4), CSF diversion alone (n = 1), or blood patch (n = 1). Three (5.1%) patients required permanent CSF diversion. Male sex (OR 3.495), diabetes mellitus (OR 0.249), tobacco use (OR 2.53), body mass index more than 30 (OR 2.45), preoperative syrinx (OR 1.733), autologous duraplasty (OR 0.331), and postoperative steroids (OR 2.825) were included in the multivariable analysis. No factors achieved significance by univariate or multivariable analysis (all p > 0.05). CONCLUSIONS:The authors report a single-center, retrospective experience of posterior fossa decompression for 59 adults with CM-I. No perioperative or technical features were found to affect the CSF-related complication rate. More standardized practices within centers are necessary to better delineate the true risk factors and potential protective factors against CSF-related complications.

625 Background: Immune checkpoint inhibitor (ICI) based regimens are the standard of care for patients with metastatic renal cell carcinoma (mRCC). In other tumor types such as melanoma, there is evidence that cancer control can persist long after discontinuation of ICI therapy. Outcomes after ICI discontinuation for mRCC are less characterized. Our aim is to characterize the durability of treatment response in mRCC patients who discontinued ICI therapy electively or due to toxicity. Methods: We identified patients with mRCC who responded to nivolumab +/- ipilimumab and then discontinued ICI therapy either for elective reasons or due to toxicity. Patients who discontinued therapy due to progressive disease or who died within 3 months of their last ICI dose were excluded. Complete response (CR) duration was calculated from last ICI dose to the most recent documentation of CR status. Time to progression was defined as the time from last ICI dose to documentation of disease progression or initiation of next-line therapy. Durability of treatment response was calculated from the date of last ICI dose to the most recent follow up date at which sustained response was noted. Results: We identified a total of 56 patients treated with nivolumab +/- ipilimumab therapy who discontinued treatment for toxicity (n=30) or for elective reasons (n=26) and achieved CR or partial response/stable disease (PR/SD). Of the entire cohort, 19 patients (34%) achieved CR, and the majority (95%) were still alive and disease-free with a median follow up of 906 days (range 86-2143 days). Among all patients who discontinued treatment with best response of PR/SD, 49% experienced disease progression, with a median progression-free survival of 382 days (range 77-1267). 42% of patients who stopped ICI electively achieved CR and all (100%) were still alive with sustained CR (median follow-up = 735 days) at data collection. Among those with best response of PR/SD after elective discontinuation, about half (53%) maintained disease control while the rest had disease progression or death (47%). Conclusions: Patients with mRCC who achieve CR with nivolumab +/- ipilimumab and then subsequently discontinue therapy for reasons other than disease progression have excellent long-term cancer outcomes. Recurrence and subsequent progression are rare in this group. These results are similar to the durability of ICI treatment response observed in complete responders in melanoma. Outcomes were less favorable for patients who obtained PR/SD as best response prior to ICI discontinuation, although some patients had ongoing and durable cancer control for up to several years. More research is indicated to ascertain which disease/patient features predict long-term disease control after ICI discontinuation in patients who respond favorably to ICI therapy.

Background: Brain tumors are the most common solid tumors and the leading cause of cancer-related deaths in children. Incidence in the USA has been on the rise for the last 2 decades. While therapeutic advances in diagnosis and treatment have improved survival and quality of life in many children, prognosis remains poor and current treatments have significant long-term sequelae. Summary: There is a substantial need for the development of new therapeutic approaches, and since the introduction of immunotherapy by immune checkpoint inhibitors, there has been an exponential increase in clinical trials to adopt these and other immunotherapy approaches in children with brain tumors. In this review, we summarize the current immunotherapy landscape for various pediatric brain tumor types including choroid plexus tumors, embryonal tumors (medulloblastoma, AT/RT, PNETs), ependymoma, germ cell tumors, gliomas, glioneuronal and neuronal tumors, and mesenchymal tumors. We discuss the latest clinical trials and noteworthy preclinical studies to treat these pediatric brain tumors using checkpoint inhibitors, cellular therapies (CAR-T, NK, T cell), oncolytic virotherapy, radioimmunotherapy, tumor vaccines, immunomodulators, and other targeted therapies. Key Messages: The current landscape for immunotherapy in pediatric brain tumors is still emerging, but results in certain tumors have been promising. In the age of targeted therapy, genetic tumor profiling, and many ongoing clinical trials, immunotherapy will likely become an increasingly effective tool in the neuro-oncologist armamentarium.

Background Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO). Materials and Methods This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs. Results Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9). Conclusions IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era.

Background/Objectives: Postoperative pseudomeningocele (PMC) and CSF leak are not uncommon complications following posterior fossa and posterolateral skull base surgeries. These complications can result in significant patient morbidity and cost, possibly requiring readmission and further surgery for definitive management. No previous authors have attempted to devise a perioperative risk score to stratify patient risk for these adverse events. Our objectives were to (1) identify patients most at risk for postoperative PMC/CSF leak, (2) determine which patients are likely to require permanent CSF diversion, and (3) develop and optimize a perioperative model and clinical score to stratify patients' risk for PMC/CSF leak.

Primary systemic therapy in the management of advanced Renal Cell Carcinoma (RCC) has gained increasing traction. We examined immunotherapy (IO) followed by cytoreductive nephrectomy (CRN) in 56 patients with mostly favorable/intermediate IMDC risk. IO significantly reduced tumor /thrombus size, complexity, and clini-cal/pathologic stage. A quality CRN (negative margins and without complications) following IO demonstrated improved 2-year progression-free survival.Background: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). Methods: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) follow-ing surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multi-variable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. Results: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size ( P < .001), thrombus size ( P = .02), and RENAL score ( P < .001); 38 (67.9%) patients were clinically downstaged on imaging ( P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery ( P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). Conclusions: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.Clinical Genitourinary Cancer, Vol. 21, No. 6, 694-702 (c) 2023 Elsevier Inc. All rights reserved.

Background: Cytoreductive nephrectomy (CN) for the treatment of metastatic renal cell carcinoma (mRCC) was called into question following the publication of the CARMENA trial. While previous retrospective studies have supported CN alongside targeted therapies, there is minimal research establishing its role in conjunction with immune checkpoint inhibitor (ICI) therapy. Objective: To evaluate the association between CN and oncological outcomes in patients with mRCC treated with immunotherapy. Materials and methods: A multicenter retrospective cohort study of patients diagnosed with mRCC between 2000 and 2020 who were treated at the Seattle Cancer Care Alliance and The Ohio State University and who were treated with ICI systemic therapy (ST) at any point in their disease course. Overall survival (OS) was estimated using Kaplan Meier analyses. Multivariable Cox proportional hazards models evaluated associations with mortality. Results: The study cohort consisted of 367 patients (CN+ST n = 232, ST alone n = 135). Among patients undergoing CN, 30 were deferred. Median survivor follow-up was 28.4 months. ICI therapy was first-line in 28.1%, second-line in 17.4%, and third or subsequent line (3L+) in 54.5% of patients. Overall, patients who underwent CN+ST had longer median OS (56.3 months IQR 50.2-79.8) compared to the ST alone group (19.1 months IQR 12.8-23.8). Multivariable analyses demonstrated a 67% reduction in risk of all-cause mortality in patients who received CN+ST vs. ST alone (P < 0.0001). Similar results were noted when first-line ICI therapy recipients were examined as a subgroup. Upfront and deferred CN did not demonstrate significant differences in OS. Conclusions: CN was independently associated with longer OS in patients with mRCC treated with ICI in any line of therapy. Our data support consideration of CN in well selected patients with mRCC undergoing treatment with ICI.(c) 2022 Elsevier Inc. All rights reserved.

334 Background: IO, either as combination therapy in the frontline or monotherapy in the second line, has improved outcomes for patients with advanced RCC. With the movement away from upfront CN, limited data are available on the outcomes of patients who receive IO with delayed CN. In this study, we characterized the pathologic and survival outcomes for patients who received IO followed by CN. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO combination or monotherapy followed by CN. An IRB-approved and HIPAA-compliant registry was used to collect data from the electronic medical record. Our primary endpoint was the degree of pathologic downstaging comparing baseline clinical T stage to pathologic T stage following IO. Secondary endpoints included investigator assessed response using RECIST principals, progression-free survival (PFS), and overall survival (OS). Results: We identified53 patients with advanced RCC across 9 institutions who were eligible for the study. The median age was 63 years, 72% were white, and 60% were male. 81% of patients had clear cell histology, 11% had sarcomatoid differentiation, and 75% presented with de novo metastatic disease. Baseline IMDC risk is as follows: 4% favorable, 55% intermediate, and 26% poor risk with 15% unknown. 23% had bone metastases and 23% had liver metastases at baseline. Lines of therapy prior to CN was 1 line in 74% of patients, 2 lines in 25%, and 3 lines in 2%. For the line of IO therapy immediately preceding CN, 49% received nivolumab+ipilimumab, 30% received IO monotherapy, and 21% received combination IO/VEGF therapy. The median duration of therapy prior to surgery was 11.3 months (range 0.38-47.8). 28% of patients discontinued treatment after CN for observation. Best overall response prior to CN was stable disease in 25% of patients, partial response in 60%, and progressive disease in 4% with 11% unknown. Following receipt of IO-based treatment, 38% of patients exhibited downstaging from the baseline clinical T stage to the CN pathological T stage (Table). 11% of patients had no residual disease at CN. For pathologic outcomes, 85% of patients had negative margins, 75% had necrosis present, and the median tumor size at CN was 6.5 cm. The median PFS was 11.3 months and median OS was 25.7 months for the overall cohort. Conclusions: IO-based strategies demonstrate efficacy in the renal primary in patients with advanced RCC. T stage downstaging was demonstrated in 38% of patients with 11% having a complete pathologic response in the renal primary following IO administration. Biomarker studies on baseline and CN tissue will further elucidate molecular predictors of response and resistance to IO therapy.[Table: see text]

390 Background:The concept of primary systemic therapy has gained increasing traction in the management of metastatic and locally advanced Renal Cell Carcinoma (RCC). Most series have evaluated the use of tyrosine-kinase inhibitors, however, with the emergence of immune checkpoint inhibitor therapy as first line agents in advanced RCC, further assessment of efficacy is warranted. We examined the effects of immunotherapy (IO) combinations on the primary tumor and consequent surgical quality and short-term oncological outcomes. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO followed by Radical (RN) or partial nephrectomy (PN). Primary outcome was achievement of Bifecta (composite outcome of complete resection and no 30-day post-operative complications). Predictors for achievement of Bifecta were assessed with logistic regression multivariable analysis. Secondary outcomes were change in maximal tumor dimension, RENAL nephrometry score and disease progression. Kaplan-Meier analysis was used to assess progression-free survival (PFS) for Bifecta and non-Bifecta patients. Results: We identified 52 patients with advanced RCC across 9 institutions who were eligible. The median age was 63 years and 60.4% were males. Median tumor size at diagnosis was 9.3 cm. 19.6% had T4 disease and 75% had AJCC Stage IV disease. IO treatment resulted in significant reductions in median tumor size (-25.4%; 9.7 cm vs. 7.3cm p = 0.0129) and RENAL nephrometry score (9 to 8, p = 0.032). 43 (83%) of patients underwent RN and (9) 17% had PN. Median tumor size was smaller for PN (8 vs. 4.1 cm, p < 0.001), and 30 day complication rates were higher (p = 0.024). Bifecta was achieved in 39 patients [33/42 (78.6%) RN and 6/9 (67%) PN, p = 0.264). Predictors for achievement of Bifecta were younger age (OR 1.06, p = 0.01), increasing reduction in tumor size (OR 1.187, p < 0.001), and shorter time between therapy and surgery (OR 1.07, p < 0.001). Kaplan-Meier analysis demonstrated longer median time to progression in the Bifecta-positive group compared to patients who failed to achieve Bifecta (75 vs. 30 months, p = 0.04). Conclusions: Pre-surgical therapy resulted in tumor size and complexity reduction. Tumor size reduction was predictive for achievement of Bifecta, which was associated with improved short term oncological outcomes. To our knowledge, this is the first series evaluating the effect of neoadjuvant systemic therapy on the primary tumor prior to surgical intervention.

CONCLUSIONS: There was a moderate agreement between IMDC and MSKCC score groups ccmRCC patients treated with TKI. OS and PFS were not impacted by disagreement between the score. Despite the preferred role of the IMDC for risk strati fi cation, results of studies using the MSKCC score can be used for comparison of results in research and the clinical setting.

e16567 Background: ICI/TKI combinations are a new standard of care for the initial treatment (tx) of mRCC. Efficacy and toxicity of such combination regimens beyond the first-line (1L) setting remain unknown. Methods: We retrospectively reviewed charts for adult patients (pts) receiving an ICI/TKI combination in any line of tx for mRCC of any histology at one of two academic centers as of May 1, 2020. ICIs included pembrolizumab (Pm), nivolumab (Ni), ipilimumab (Ip), or avelumab (Av); TKIs included sunitinib (Su), axitinib (Ax), pazopanib (Pz), lenvatinib (Ln), or cabozantinib (Ca). Clinical data including pt demographics, histology, International mRCC Database Consortium (IMDC) risk group, tx history, and ICI/TKI tx and toxicity details were recorded. Outcomes included objective response rate (ORR), median progression-free survival (mPFS), and safety, analyzed via descriptive statistics and the Kaplan-Meier method. Results: Of 85 pts, 69 (81%) were male and 67 (79%) had clear cell histology. IMDC risk was favorable (24%), intermediate (54%), poor (20%), and unknown (2%). 39% had ICI/TKI tx in the 1L setting. ICI/TKI regimens included Pm/Ax (33%), Ni/Ca (25%), Ni/Ax (20%), Av/Ax (11%), Ni/Ip/Ca (8%), Ni/Su (2%), and Ni/Ln (1%). ORR and mPFS stratified by line of tx and prior tx are shown in the table. Of 52 pts who received ICI/TKI tx as salvage (after 1L), 52% had a grade 3 or higher (≥G3) adverse event (AE), of which the most common were anorexia (13.5%), diarrhea and hypertension (11.5% each), and fatigue (9.6%). 65% of pts on salvage ICI/TKI tx stopped tx for progression/death, while 16% stopped tx for ≥G3 AE. ≥G3 AE rates by line of tx were 62.5% (2L), 50% (3L), and 45% (≥4L). Conclusions: ICI/TKI combination therapy is effective and safe beyond the 1L setting. Prior tx history appears to impact efficacy but has less of an effect on safety/tolerability. These observations will need to be confirmed in prospective studies.[Table: see text]

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I (MP14)1 Sep 2021MP14-08 A MULTICENTER ASSESSMENT OF SURVIVAL IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA (mRCC) WHO RECEIVED IMMUNE CHECKPOINT INHIBITOR THERAPY (ICI) WITH OR WITHOUT CYTOREDUCTIVE NEPHRECTOMY (CN) Evan Gross, Mingjia Li, Ming Yin, Delaney Orcutt, Duncan Hussey, Elliot Trott, Joel Kramer, Kaylee Oliva, John Gore, George Schade, Daniel Lin, Scott Tykodi, Evan Hall, John Thompson, Anish Parikh, Yuanquan Yang, Katharine Collier, Abdul Miah, Sherry Mori-Vogt, Megan Hinkley, Amir Mortazavi, Paul Monk, Edmund Folefac, Steven Clinton, and Sarah Psutka Evan GrossEvan Gross More articles by this author , Mingjia LiMingjia Li More articles by this author , Ming YinMing Yin More articles by this author , Delaney OrcuttDelaney Orcutt More articles by this author , Duncan HusseyDuncan Hussey More articles by this author , Elliot TrottElliot Trott More articles by this author , Joel KramerJoel Kramer More articles by this author , Kaylee OlivaKaylee Oliva More articles by this author , John GoreJohn Gore More articles by this author , George SchadeGeorge Schade More articles by this author , Daniel LinDaniel Lin More articles by this author , Scott TykodiScott Tykodi More articles by this author , Evan HallEvan Hall More articles by this author , John ThompsonJohn Thompson More articles by this author , Anish ParikhAnish Parikh More articles by this author , Yuanquan YangYuanquan Yang More articles by this author , Katharine CollierKatharine Collier More articles by this author , Abdul MiahAbdul Miah More articles by this author , Sherry Mori-VogtSherry Mori-Vogt More articles by this author , Megan HinkleyMegan Hinkley More articles by this author , Amir MortazaviAmir Mortazavi More articles by this author , Paul MonkPaul Monk More articles by this author , Edmund FolefacEdmund Folefac More articles by this author , Steven ClintonSteven Clinton More articles by this author , and Sarah PsutkaSarah Psutka More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001995.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of CN in the treatment of mRCC has been questioned with the recent approval of novel systemic therapy (ST) agents and the results of the CARMENA trial. Our objective was to compare overall survival (OS) between patients with mRCC treated with ICI therapy with CN vs. ST alone. METHODS: We performed a retrospective review of patients diagnosed with mRCC (2000-2020) and treated with ICI therapy at the Seattle Cancer Care Alliance or at the Ohio State University. Kaplan-Meier and Cox Proportional hazards were used to assess associations between CN and OS adjusting for relevant confounding covariates. Median follow-up in survivors was 29 months. RESULTS: The cohort consisted of 367 patients treated with ICI (CN: n=231, ST: n=136). ICI receipt was front line (1L) in 28.1%, 2nd line (2L) in 17.4%, 3rd or subsequent line (3L+) in 54.5%. IMDC risk classification in CN was Favorable, Intermediate or Poor in 5.6%, 65.4%, and 16.5%, respectively, compared with 2.9%, 65.4%, and 29.4% in ST (p= .01). Patients had one site of metastasis in CN: 49.8% vs. ST: 34.6% (p=.002). CN occurred a median of 0.9 months (IQR 0.4 – 1.9) after mRCC diagnosis. Median time from diagnosis to ICI receipt in CN was 1L: 2.6 months (2.0 – 4.0), 2L: 11.5 (5.9 – 19.7), and 3L+ was 22.1 (15.2 – 60.4) compared to 1.6 (1.0 – 2.5), 6.3 (3.5 – 19.5), and 30.1 (11.9 – 36.0) respectively in ST patients. In patients undergoing CN and 1L ICI, 19.2% had complete response, 27.6% partial response, 23.4% stable disease, and 19.2 had progressive disease vs. 0%, 26.8%, 17.9%, and 32.1% respectively in ST patients (p=.003). Median OS was CN: 56 months (95% confidence interval [CI], 50–77) vs. ST: 19 months (95% CI 12 – 23, p<.0001). On multivariable analysis, CN was associated with improved OS (HR 0.35, p<.0001, Figure). CONCLUSIONS: In this retrospective multicenter cohort of patients with mRCC who received ICI, CN was associated with improved OS compared with ST alone. Although this retrospective study is subject to significant imbalances in prognostic factors, these results support research to identify predictors for improved outcomes with CN and the potential utility of CN in carefully selected patients. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e255-e255 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Evan Gross More articles by this author Mingjia Li More articles by this author Ming Yin More articles by this author Delaney Orcutt More articles by this author Duncan Hussey More articles by this author Elliot Trott More articles by this author Joel Kramer More articles by this author Kaylee Oliva More articles by this author John Gore More articles by this author George Schade More articles by this author Daniel Lin More articles by this author Scott Tykodi More articles by this author Evan Hall More articles by this author John Thompson More articles by this author Anish Parikh More articles by this author Yuanquan Yang More articles by this author Katharine Collier More articles by this author Abdul Miah More articles by this author Sherry Mori-Vogt More articles by this author Megan Hinkley More articles by this author Amir Mortazavi More articles by this author Paul Monk More articles by this author Edmund Folefac More articles by this author Steven Clinton More articles by this author Sarah Psutka More articles by this author Expand All Advertisement PDF downloadLoading ...