Differences in preoperative frailty assessment of surgical candidates by sex, age, and race.

Introduction: Surgical decision-making often relies on a surgeon's subjective assessment of a patient's frailty status to undergo surgery. Certain patient demographics can influence subjective judgment when compared to validated objective assessments. In this study, we explore the relationship between subjective and objective frailty assessments according to patient age, sex, and race. Methods: Patients were prospectively enrolled in urology, general surgery, and surgical oncology clinics. Using a visual analog scale (0-100), operating surgeons independently rated the patient's frailty status. Objective frailty was classified using the Fried Frailty Criteria ranging from 0 to 5. Multivariable proportional odds models were conducted to examine the potential association of factors with objective frailty, according to surgeon frailty rating. Subgroup analysis according to patient sex, race, and age was also performed. Results: Seven male surgeons assessed 203 patients preoperatively with a median age of 65. A majority of patients were male (61 %), white (67 %), and 60 % and 40 % underwent urologic and general surgery/surgical oncology procedures respectively. Increased subjective surgeon rating (OR 1.69; p < 0.001) was significantly associated with the presence of objective frailty. On subgroup analysis, a higher magnitude of such association was observed more in females (OR 1.86; p = 0.0007), non-white (OR 1.84; p = 0.0019), and older (>60, OR 1.75; p = 0.0001) patients, compared to male (OR 1.45; p = 0.0243), non-white (OR 1.48; p = 0.0109) and patients under 60 (OR 1.47; p = 0.0823). Conclusion: The surgeon's subjective assessment of frailty demonstrated tendencies to rate older, female, and non-white patients as frail; however, differences in patient sex, age, and race were not statistically significant.

2018 Leibovich prognostic model for renal cell carcinoma: Performance in a large population with special consideration of Black race.

BACKGROUND: The 2018 Leibovich prognostic model for nonmetastatic renal cell carcinoma (RCC) combines clinical, surgical, and pathologic factors to predict progression-free survival (PFS) and cancer-specific survival (CSS) for patients with clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) histology. Despite high accuracy, <1% of the original cohort was Black. Here, the authors examined this model in a large population with greater Black patient representation. METHODS: By using a prospectively maintained RCC institutional database, patients were assigned Leibovich model risk scores. Survival outcomes included 5-year and 10-year PFS and CSS. Prognostic accuracy was determined using area under the curve (AUC) analysis and calibration plots. Black patient subanalyses were conducted. RESULTS: In total, 657 (29%) of 2295 patients analyzed identified as Black. Declines in PFS and CSS were observed as scores increased. Discrimination for ccRCC was strong for PFS (AUC: 5-year PFS, 0.81; 10-year PFS, 0.78) and for CSS (AUC: 5-year CSS, 0.82; 10-year CSS, 0.74). The pRCC AUC for PFS was 0.74 at 5 years and 0.71 at 10 years; and the AUC for CSS was 0.74 at 5 years and 0.70 at 10 years. In chRCC, better performance was observed for CSS (AUC at 5 years, 0.75) than for PFS (AUC: 0.66 at 5 years; 0.55 at 10 years). Black patient subanalysis revealed similar-to-improved performance for ccRCC at 5 years (AUC: PFS, 0.79; CSS, 0.87). For pRCC, performance was lower for PFS (AUC at 5 years, 0.63) and was similar for CSS (AUC at 5 years, 0.77). Sample size limited Black patient 10-year and chRCC analyses. CONCLUSIONS: The authors externally validated the 2018 Leibovich RCC prognostic model and found optimal performance for ccRCC, followed by pRCC, and then chRCC. Importantly, the results were consistent in this large representation of Black patients. PLAIN LANGUAGE SUMMARY: In 2018, a model to predict survival in patients with renal cell carcinoma (kidney cancer) was introduced by Leibovich et al. This model has performed well; however, Black patients have been under-represented in examination of its performance. In this study, 657 Black patients (29%) were included, and the results were consistent. This work is important for making sure the model can be applied to all patient populations.

Cutaneous Ureterostomy Following Radical Cystectomy for Bladder Cancer: A Contemporary Series.

OBJECTIVE: To report peri-operative outcomes of a contemporary series of bladder cancer patients undergoing radical cystectomy (RC) with cutaneous ureterostomy (CU) urinary diversion at a tertiary referral center. METHODS: We retrospectively identified patients who underwent RC with CU at Mayo Clinic between 2016 and 2021. Clinicopathologic and perioperative characteristics were analyzed using standard descriptive statistics. RESULTS: A total of 31 patients underwent RC with CU at our institution. Median age was 72years and 21 were male. This was highly comorbid cohort (83% had an American Society of Anesthesiologists [ASA] Physical Status Classification System ≥3; median Charlson Comorbidity index= 8). Median time to flatus, tolerating regular diet, and length of stay were 3 (interquartile range [IQR] 3-3), 3 (IQR 3-4), and 4days (IQR 4-7), respectively. A total of 14 patients experienced a high-grade complication (Clavien-Dindo ≥3) within 30days of surgery, and 8 were readmitted. The most common 30-day complication was sepsis, which affected 13% (4/31) of patients. At 90days postsurgery, the readmission rate was 32% (10/31), most commonly for sepsis. Three patients required reoperation within 90days, including one patient who required CU revision due to stomal ischemia. One patient died within this time frame from causes unrelated to bladder cancer. CONCLUSION: In a comorbid, relatively elderly bladder cancer cohort undergoing RC, the use of CU was associated with expeditious surgery and postoperative recovery. CU represents an option for urinary diversion in high-risk patients undergoing RC. Higher rate of postoperative ureteral obstruction can be pre-emptively addressed with chronic stent placement.

Relative impact of lymph-node metastasis and seminal vesical invasion on oncologic outcomes following radical prostatectomy.

BACKGROUND: While both seminal vesicle (SVI) and lymph-node invasion (LNI) have been identified as adverse prognostic variables among men undergoing radical prostatectomy (RP), the relative impact of each of these features on subsequent oncologic outcomes has not been well defined. We assessed the impact of LNI on long-term oncologic outcomes among patients with SVI at RP. METHODS: We reviewed 19,519 patients who underwent RP and identified 2043 with SVI. Metastasis-free (MFS), cancer-specific (CSS), and overall survival (OS) were estimated for patients with SVI, stratified by the presence and number of pelvic lymph node metastases. Cox proportional hazards models were used to evaluate the independent association of the number of metastatic nodes and lymph node density with oncologic outcomes among patients with SVI, controlling for age, year of surgery, margin status, preoperative PSA, pathologic Gleason score, extraprostatic extension, and use of adjuvant therapies. RESULTS: At a median follow up of 12.1 years (IQR 7.0,18.6), 548 patients developed metastatic disease and 1331 died, including 406 who died from prostate cancer (PCa). We found that, among patients with SVI, the presence of a single positive lymph node was not associated with incrementally adverse oncologic outcomes compared to no nodal metastasis at RP, with 10-year MFS, CSS, and OS rates of 81.3% versus 78.3%(p = 0.18), 86.5% versus 89.8%(p = 0.32), and 72.8% versus 76.7%(p = 0.53), respectively. In contrast, on multivariable analyses, the presence of ≥2 metastatic nodes and a 20% lymph-node density cut off remained independently associated with worse survival. CONCLUSIONS: SVI represents an adverse pathologic feature such that the presence of a single positive pelvic lymph node did not further adversely impact prognosis. Meanwhile, a significant number of involved nodes was associated with decreased survival. These findings may aid in risk-stratification as well as clinical trial design for such high-risk patients following surgery.

Creatinine to Cystatin-C Ratio in Renal Cell Carcinoma: A Clinically Pragmatic Prognostic Factor and Sarcopenia Biomarker.

INTRODUCTION: Low creatinine to cystatin-C ratio (Cr/Cys-C) may be a biomarker for low-muscle mass. Furthermore, low Cr/Cys-C is associated with decreased overall survival (OS), but to date, has not been examined in patients with renal cell carcinoma (RCC). Our objective is to evaluate associations between low Cr/Cys-C ratio and OS and recurrence-free survival (RFS) in patients with RCC treated with nephrectomy. METHODS: We performed a retrospective review of patients with RCC treated with nephrectomy. Patients with end-stage renal disease and less than 1-year follow up were excluded. Cr/Cys-C was dichotomized at the median for the cohort (low vs. high). OS and RFS for patients with high versus low Cr/Cys-C were estimated with the Kaplan-Meier method, and associations with the outcomes of interest were modeled using Cox proportional Hazards models. Associations between Cr/Cys-C and skeletal muscle mass were assessed with correlations and logistic regression. RESULTS: A total of 255 patients were analyzed, with a median age of 64. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). Low Cr/Cys-C was associated with age, female sex, Eastern Cooperative Oncology Group Performance Status ≥1, TNM stage, and tumor size. Kaplan-Meier and Cox regression analysis demonstrated an association between low Cr/Cys-C and decreased OS (HR = 2.97, 95%CI, 1.12-7.90, P =0.029) and RFS (HR = 3.31, 95%CI, 1.26-8.66, P = .015). Furthermore, a low Cr/Cys-C indicated a 2-3 increase in risk of radiographic sarcopenia. CONCLUSIONS: Lower Cr/Cys-C is associated with inferior oncologic outcomes in RCC and, pending validation, may have utility as a serum biomarker for the presence of sarcopenia in patients with RCC treated with nephrectomy.

Circulating antigen-primed cytotoxic T-cells in patients with renal tumors treated with surgery.

INTRODUCTION: Systemic immunotherapy has changed the paradigm of treatment of advanced renal cell carcinoma, but nephrectomy continues to benefit selected patients. While we continue to identify mechanisms behind drug resistance, the effect of surgery on natural anti-tumor immunity is poorly understood. Specifically, peripheral blood mononuclear cell (PBMC) profile and tumor reactive cytotoxic T lymphocytes changes secondary to tumor resection have not been extensively characterized. Hence, we aimed to evaluate the effect of nephrectomy on PMBC profile and circulating antigen-primed CD8+ T-cells for patients undergoing solid renal mass resection. METHODS: Patients with localized or metastatic solid renal masses who underwent nephrectomy from 2016 to 2018 were enrolled. Blood samples were collected at 3 timepoints for PBMCs analysis (pre-op, 1 day, and 3 months post-op). Flow cytometry was used to identify CD11ahigh CD8+ T lymphocytes that were then further characterized according to the expression of CX3CR1/GZMB, Ki67, Bim, and PD-1. Changes in circulating CD8+ T-cells from pre-op to 1 day and 3 months post-op were evaluated using Wilcoxon signed rank tests. RESULTS: Antigen-primed CX3CR1+GZMB+ T-cells significantly increased by 3 months after surgery among patients with RCC (0.8 × 109 cells; P = 0.01). In contrast, there was a decrease in absolute numbers of Bim+ T-cells at 3 months (-1.9 × 109 cells; P = 0.02). There were no significant absolute changes in PD-1+ (-1.4 × 109; P = 0.7) and CD11ahigh CD8+ T lymphocytes (1.3 × 109; P = 0.9). Ki67+ T-cells decreased by 3 months (-0.8 × 109; P < 0.001). CONCLUSIONS: Nephrectomy is associated with an increase in cytolytic antigen-primed CD8+ T-cells and specific PBMC profile changes. Further studies are warranted to ascertain the role surgery may have in the restoration of anti-tumor immunity.

The Impact of Metastasis Histopathology on Oncologic Outcomes for Patients With Surgically Resected Metastatic Renal Cell Carcinoma.

PURPOSE: Multiple prognostic models exist to assess survival among patients with metastatic clear cell renal cell carcinoma. However, the relative contribution of histopathological features of the metastasis has not been extensively studied. Herein, we compared models using clinical, primary tumor, and metastatic features to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma. MATERIALS AND METHODS: We studied 266 patients who had undergone nephrectomy between 1970 and 2019, and who had a single site of metastasis completely resected. Two versions of the metastatic clear cell renal cell carcinoma score published by Leibovich et al were calculated, using grade and necrosis from the primary tumor and using grade and necrosis from the metastasis. Predictive abilities of these 2 versions and a third model that included metastatic features only were compared using c-indexes from Cox proportional hazards models. RESULTS: A total of 197 patients died from renal cell carcinoma at a median of 2.3 years (IQR 1.1-4.5); median follow-up among survivors was 13.2 years (IQR 10.0-14.5). The Leibovich score using grade and necrosis from the metastasis (c=0.679) had similar predictive ability compared to the original Leibovich score using grade and necrosis from the primary tumor (c=0.675). A third model (c=0.707) demonstrated that metastasectomy within 2 years after nephrectomy, presence of bone metastasis, high grade, and sarcomatoid differentiation in the metastasis were significantly associated with cancer-specific survival. CONCLUSIONS: Scoring algorithms calculated using histopathological features of the metastasis can be used to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma. These findings are of particular importance for instances when primary tumor histopathology is not readily available.

Low Skeletal Muscle as a Risk Factor for Worse Survival in Nonmetastatic Renal Cell Carcinoma with Venous Tumor Thrombus.

BACKGROUND: Renal cell carcinoma (RCC) with tumor thrombosis often requires nephrectomy and tumor thrombectomy. As an extensive and potentially morbid operation, patient preoperative functional reserve and body composition is an important consideration. Sarcopenia is a risk factor for increased postoperative complications, systemic therapy toxicity, and death solid organ tumors, including RCC. The influence of sarcopenia in RCC patients with tumor thrombus is not well defined. This study evaluates the prognostic ability of sarcopenia regarding surgical outcomes and complications in patients undergoing surgery for RCC with tumor thrombus. METHODS: We retrospectively analyzed patients with nonmetastatic RCC and tumor thrombus undergoing radical nephrectomy and tumor thrombectomy. Skeletal muscle index (SMI; cm2/m2) was measured on preoperative CT/MRI. Sarcopenia was defined using body mass index- and sex-stratified thresholds optimally fit via a receiver-operating characteristic analysis for survival. Associations between preoperative sarcopenia and overall (OS), cancer-specific survival (CSS), and 90-day major complications were determined using multivariable analysis. RESULTS: 115 patients were analyzed, with median (IQR) age and body mass index of 69 (56-72) and 28.6 kg/m2 (23.6-32.9), respectively. 96 (83.4%) of the cohort had ccRCC. Sarcopenia was associated with shorter median OS (P = .0017) and CSS (P = .0019) in Kaplan-Meier analysis. In multivariable analysis, preoperative sarcopenia was prognostic of shorter OS (HR = 3.38, 95% confidence interval [CI] 1.61-7.09) and CSS (HR = 5.15, 95% CI 1.46-18.18). Notably, 1 unit increases in SMI were associated with improved OS (HR = 0.97, 95% CI 0.94-0.999) but not CSS (HR = 0.95, 95% CI 0.90-1.01). No significant relationship between preoperative sarcopenia and 90-day major surgical complications was observed in this cohort (HR = 2.04, 95% CI 0.65-6.42). CONCLUSION: Preoperative sarcopenia was associated with decreased OS and CSS in patients surgically managed for nonmetastatic RCC and VTT, however, was not predictive of 90-day major postoperative complications. Body composition analysis has prognostic utility for patients with nonmetastatic RCC and venous tumor thrombus undergoing surgery.

A Novel PD-L1 Antibody Promotes Antitumor Function of Peripheral Cytotoxic Lymphocytes after Radical Nephrectomy in Patients with Renal Cell Carcinoma.

The intrinsic and acquired resistance to PD-1/PD-L1 immune checkpoint blockade is an important challenge for patients and clinicians because no reliable tool has been developed to predict individualized response to immunotherapy. In this study, we demonstrate the translational relevance of an ex vivo functional assay that measures the tumor cell killing ability of patient-derived CD8 T and NK cells (referred to as "cytotoxic lymphocytes," or CLs) isolated from the peripheral blood of patients with renal cell carcinoma. Patient-derived PBMCs were isolated before and after nephrectomy from patients with renal cell carcinoma. We compared the efficacy of U.S. Food and Drug Administration (FDA)-approved PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab) and a newly developed PD-L1 inhibitor (H1A Ab) in eliciting cytotoxic function. CL activity was improved at 3 mo after radical nephrectomy compared with baseline, and it was associated with higher circulating levels of tumor-reactive effector CD8 T cells (CD11ahighCX3CR1+GZMB+). Treatment of PBMCs with FDA-approved PD-1/PD-L1 inhibitors enhanced tumor cell killing activity of CLs, but a differential response was observed at the individual-patient level. H1A demonstrated superior efficacy in promoting CL activity compared with FDA-approved PD-1/PD-L1 inhibitors. PBMC immunophenotyping by mass cytometry revealed enrichment of effector CD8 T and NK cells in H1A-treated PBMCs and immunosuppressive regulatory T cells in atezolizumab-treated samples. Our study lays the ground for future investigation of the therapeutic value of H1A as a next-generation immune checkpoint inhibitor and the potential of measuring CTL activity in PBMCs as a tool to predict individual response to immune checkpoint inhibitors in patients with advanced renal cell carcinoma.

Mayo Adhesive Probability Score Does Not Have Prognostic Ability in Locally Advanced Renal Cell Carcinoma.

Nephrectomy remains standard treatment for renal cell carcinoma (RCC). The Mayo Adhesive Probability (MAP) score is predictive of adherent perinephric fat and associated surgical complexity, and is determined by assessing perinephric fat and stranding. MAP has additionally predicted progression-free survival (PFS), though primarily reported in stage T1-T2 RCC. Here, we examine MAP's ability to predict overall survival (OS) and PFS in T3-T4 RCC. From our prospectively maintained RCC database, patients that underwent radical nephrectomy (2009-2016) with available abdominal imaging (<90 days preop) and T3/T4 RCC underwent MAP scoring. Survival analyses were conducted with MAP scores as individual (0-5) and dichotomized (0-3 vs 4-5) using Kaplan-Meier method. Multivariable Cox proportional hazard regression models for PFS and OS were built with backward elimination. 141 patients were included. 134 (95%) and 7 (5%) had pT3 and pT4 disease, respectively. 46.1% of patients had an inferior vena cava thrombus. Mean MAP score was 3.22±1.52, with 75 (53%) patients having a score between 0-3 and 66 (47%) having a score of 4-5. Both male gender (p=0.006) and clear cell histology (p=0.012) were associated with increased MAP scores. On Kaplan-Meier and multivariable analysis, no significant associations were identified between MAP and PFS (HR=1.01, 95% CI 0.85-1.20, p=0.93) or OS (HR=1.01, 95% CI 0.84-1.21, p=0.917). In this cohort of patients with locally advanced RCC, high MAP scores were not predictive of worse PFS or OS.

Antibody-Based Therapeutics for the Treatment of Renal Cell Carcinoma: Challenges and Opportunities.

Renal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicity profile and survival outcomes, key concerns such as patient selection, treatment sequencing, and intrinsic and acquired resistance remain unresolved. Emerging options such as antibody-based therapeutics (eg, anti-CD70, anti-CA9, and anti-ENPP3) are being explored in clinical trials for patients with cancer resistant or refractory to current immunotherapies. Despite positive results for hematological cancers, breast cancer, and more recently bladder cancer, most antibody-based therapies failed to improve the outcomes in patients with advanced RCC. This underscores the need to understand the underlying causes of failed responses to this treatment class, which will ultimately support the rational design of more effective and tolerable treatments. In this review, we summarize the evolving landscape of RCC therapeutics and describe recent clinical trials with emerging antibody-based therapeutics. We also describe the challenges that need to be overcome for the successful creation of therapeutic antibodies for treating RCC.

Race-free renal function estimation equations and potential impact on Black patients: Implications for cancer clinical trial enrollment.

BACKGROUND: Black patients face disparities in cancer outcomes. Additionally, Black patients are more likely to be undertreated and underrepresented in clinical trials. The recent recommendation to remove race from the estimated glomerular filtration rate (eGFR) results in lower eGFR values for Black patients. The ramifications of this decision, both intended and unintended, are still being elucidated in the medical community. Here, the authors analyze the removal of race from eGFR for Black patients with cancer, specifically with respect to clinical trial eligibility. METHODS: In a cohort of self-identified Black patients who underwent nephrectomy at a tertiary referral center from 2009 to 2021 (n = 459), eGFR was calculated with and without race in commonly used equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] and Modification of Diet in Renal Disease [MDRD]). The distribution of patients and changes within chronic kidney disease stages with different equations was considered. Theoretical exclusion at commonly observed clinical trial eGFR points was then simulated on the basis of the utilization of the race coefficient. RESULTS: The median eGFR from CKD-EPI was significantly higher with race (76 ml/min/1.73 m2 ) than without race (66 ml/min/1.73 m2 ; p < .0001). The median eGFR from MDRD was significantly higher with race (71.0 ml/min/1.73 m2 ) than without race (58 ml/min/1.73 m2 ; p < .0001). Observing results in the context of common clinical trial cutoff points, the authors found that 13%-22%, 6%-12%, and 2%-3% more Black patients would fall under common clinical trial cutoffs of 60, 45, and 30 ml/min, respectively, depending on the equation used. A subanalysis of stage III-IV patients only was similar. CONCLUSIONS: Race-free renal function equations may inadvertently result in increased exclusion of Black patients from clinical trials. This is especially concerning because of the underrepresentation and undertreatment that Black patients already experience. PLAIN LANGUAGE SUMMARY: Black patients experience worse oncologic outcomes and are underrepresented in clinical trials. Kidney function, as estimated by glomerular filtration rate equations, is a factor in who can and cannot be in a clinical trial. Race is a variable in some of these equations. For Black patients, removing race from these equations leads to the calculation of lower kidney function. Lower estimated kidney function may result in more black patients being excluded from clinical trials. The inclusion of all races in clinical trials is important for offering best care to everyone and for making results from clinical trials applicable to everyone.

Salvage radical prostatectomy.

PURPOSE OF REVIEW: Salvage radical prostatectomy (sRP) is underutilized because of fear of historical high rates of peri-operative morbidities. However, there has been significant improvements in complication rates as well as oncologic outcomes in the recent years. RECENT FINDINGS: Complication rates have significantly declined for both open and robotic approach in the past decade. Rectal injury is now reported around 2%, which is down from 30% in the historic series. Similarly, the current risk of major vascular injury is low. About 75% of patients report social continence (up to one pad per day). However, erectile function recovery remains poor and patients should be counselled accordingly. Long-term durable oncologic response is achievable with 10-year recurrence-free survival reported in about 40-50% of well selected patients. SUMMARY: Recent improvements in oncologic and peri-operative outcomes make sRP a desirable option for local control. sRP treats the whole gland as opposed to focal therapies and allows for pelvic lymph node dissection and removal of seminal vesicles, which can be sanctuary site of disease. In experienced hands, regardless of the surgical approach, sRP can achieve a durable response resulting in delaying or avoiding androgen deprivation therapy and its associated morbidities.

Inguinal lymph node dissection in the era of minimally invasive surgical technology.

BACKGROUND: Inguinal lymph node dissection (ILND) is an essential step in both treatment and staging of several malignancies including penile and vulvar cancers. Various open, video endoscopic, and robotic-assisted techniques have been utilized so far. In this review, we aim to describe available minimally invasive surgical approaches for ILND, and review their outcomes and complications. METHODS: The PubMed, Wiley Online Library, and Science Direct databases were reviewed in February 2020 to find relevant studies published in English within 2000-2020. FINDINGS: There are different minimally invasive platforms available to accomplish dissection of inguinal nodes without jeopardizing oncological results while minimizing postoperative complications. Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy are safe and achieve the same nodal yield, a surrogate metric for oncological adequacy. When compared to open technique, Video Endoscopic Inguinal Lymphadenectomy and Robotic Video Endoscopic Inguinal Lymphadenectomy may offer faster postoperative recovery and fewer postoperative complications including wound dehiscence, necrosis, and infection. The relatively high rate and severity of postoperative complications hinders utilization of recommended ILND for oncologic indications. Minimally invasive approaches, using laparoscopic or robotic-assisted platforms, show some promise in reducing the morbidity of this procedure while achieving adequate short and intermediate term oncological outcomes.

Prognostic Value of Sarcopenia and Albumin in the Surgical Management of Localized Renal Cell Carcinoma.

INTRODUCTION: A universally accepted model for preoperative surgical risk stratification in localized RCC patients undergoing nephrectomy is currently lacking. Both the evaluation of body composition and nutritional status has demonstrated prognostic value for patients with cancer. This study aims to investigate the potential associations between sarcopenia and hypoalbuminemia and survival outcomes in patients with localized kidney cancer treated with partial or radical nephrectomy. MATERIALS AND METHODS: We retrospectively analyzed 473 patients with localized RCC managed with radical and partial nephrectomy. Skeletal muscle index (SMI) was measured from preoperative CT and MRI. Sarcopenic criteria were created using BMI- and sex-stratified thresholds. Relationships between sarcopenia and hypoalbuminemia (Albumin <3.5 g/dL) with overall (OS), recurrence-free (RFS), and cancer-specific survival (CSS) were determined using multivariable and Kaplan-Meier analysis. RESULTS: Of the 473 patients, 42.5% were sarcopenic and 24.5% had hypoalbuminemia. Sarcopenia was significantly associated with shorter OS (HR=1.51, 95% CI 1.07-2.13), however, was nonsignificant in the RFS (HR = 1.33, 95% CI 0.88-2.03) and CSS (HR=1.66, 95% CI 0.96-2.87) models. Hypoalbuminemia predicted shorter OS (HR=1.76, 95% CI 1.22-2.55), RFS (HR=1.86, 95% CI 1.19-2.89), and CSS (HR=1.82, 95% CI 1.03-3.22). Patients were then stratified into low, medium, and high-risk groups based on the severity of sarcopenia and hypoalbuminemia. Risk groups demonstrated an increasing association with shorter OS (all p<0.05). Reduced RFS was observed in the medium risk-hypoalbuminemia (HR=2.18, 95% CI 1.16-4.09) and high-risk groups (HR=2.42, 95% CI 1.34-4.39). Shorter CSS was observed in the medium risk-hypoalbuminemia (HR=2.31, 95% CI 1.00-5.30) and high-risk groups (HR=2.98, 95% CI 1.34-6.61). CONCLUSION: Localized RCC patients with combined preoperative sarcopenia and hypoalbuminemia displayed a two to a three-fold reduction in OS, RFS, and CSS after nephrectomy. These data have implications for guiding prognostication and treatment election in localized RCC patients undergoing extirpative surgery.

Clinic friendly estimation of muscle composition: Preoperative linear segmentation shows overall survival correlated with muscle mass in patients with nonmetastatic renal cell carcinoma.

Purpose: Sarcopenia is associated with decreased survival and increased complications in patients with renal cell carcinoma. Readily identifying patients with low muscle composition that may experience worse outcomes or would benefit from preoperative intervention is of clinical interest. Traditional body composition analysis methods are resource intensive; therefore, linear segmentation with routine imaging has been proposed as a clinically practical alternative. This study assesses linear segmentation's prognostic utility in nonmetastatic renal cell carcinoma. Materials and Methods: A single institution retrospective analysis of patients that underwent nephrectomy for nonmetastatic renal cell carcinoma from 2005-2021 was conducted. Linear segmentation of the bilateral psoas/paraspinal muscles was completed on preoperative imaging. Total muscle area and total muscle index associations with overall survival were determined by multivariable analysis. Results: 532 (388 clear cell) patients were analyzed, with median (IQR) total muscle index of 28.6cm2/m2 (25.8-32.5) for women and 33.3cm2/m2 (29.1-36.9) for men. Low total muscle index was associated with decreased survival (HR=1.96, 95% CI 1.32-2.90, p<0.001). Graded increases in total muscle index were associated with better survival (HR=0.95, 95% CI 0.92-0.99, p=0.006). Conclusions: Linear segmentation, a clinically feasible technique to assess muscle composition, has prognostic utility in patients with localized renal cell carcinoma, allowing for incorporation of muscle composition analysis into clinical decision-making. Muscle mass determined by linear segmentation was associated with overall survival in patients with nonmetastatic renal cell carcinoma.

Extramammary Paget's disease: Updates in the workup and management.

Objective: Extramammary Paget's disease (EMPD) is a rare cutaneous malignant disease. Due to its rarity, there is a paucity of data regarding best treatment strategy. EMPD primarily affects apocrine gland-bearing skin areas such as the vulva, scrotum, and penis. Our objective was to provide a present-day rationale for diagnosis, pathogenesis, and treatment of EMPD with a focus on recent progress in workup and management of the disease. Methods: Literature on EMPD until February 2022 was assessed through PubMed, MEDLINE databases, and Google scholar. A narrative review of the most relevant articles was provided. Results: EMPD usually presents with indolent growth while usually being diagnosed primarily as carcinoma in situ. The foundation of EMPD treatment centers around prompt and accurate diagnosis, wide local or Mohs micrographic surgical excision with proper management towards the margin status, and careful consideration for lymphadenectomy in patients with regionally positive disease. Conventional chemotherapies are alternative treatments modality for patients with distant metastases; however, they sometimes have suboptimal efficacy. At present, there is no agreement regarding adjuvant or systemic therapies, although recent studies have shown several insights into the molecular pathogenesis, tumor biology, and genomics of the development and advancement of EMPD, which may lead to novel and targeted treatment approaches for metastatic EMPD in the future. Conclusion: Patients with EMPD should seek care from physicians with expertise in disease management and patient counseling. These patients should be surveilled with close follow-up to evaluate them for disease recurrence or progression. Global collaborations with groups such as the Global Society for Rare Genitourinary Tumors, and especially patient support groups are crucial in designing clinical trials to help elucidate more robust data in this orphan disease.

Data regarding covariates significantly associated with sarcopenia and varying albumin statuses in patients with renal cell carcinoma.

Poor functional, nutritional, and muscle status is a significant negative predictor for surgical and survival outcomes in patients with cancer, including renal cell carcinoma. This dataset displays results from preoperative muscle composition analysis and albumin levels in a large cohort (n = 473) of patients undergoing surgery for renal cell carcinoma. Data was obtained from retrospective review of prospectively maintained databases and retrospective image analysis. The optimal cut-point for skeletal muscle index (sarcopenia) was determined by a receiver operatic characteristic analysis to optimally stratify cohort, adjusting for BMI and sex. A threshold value of 3.5 g/dL was used to categorize normal versus low serum albumin. Patients were stratified into low risk (non-sarcopenic and normal albumin), medium risk (non-sarcopenic and low albumin, or sarcopenic and normal albumin), and high risk (sarcopenic and low albumin) groups. This data could potentially be used in future studies to determine other relationships between nutrition and musculature in renal cell carcinoma patients.

Compliance with Percutaneous Tibial Nerve Stimulation at a Tertiary Academic Center versus a County Hospital.

OBJECTIVES: To compare percutaneous tibial nerve stimulation (PTNS) compliance rate at a safety-net versus tertiary academic hospital and assess the impact of social determinants on compliance. METHODS: Retrospective cohort study of 133 patients at Grady Memorial Hospital and Emory Clinic from May 2015 to March 2020 who had refractory overactive bladder (OAB) and were prescribed PTNS. RESULTS: Grady patients were younger (age 58.7±11.6 versus 70.7±13.5), predominantly male (52% versus 22%), and predominately African American (80% versus 34%). Compliance rate for PTNS was 55% at Emory and 70% at Grady. In the multivariable model including sex, race, insurance status, income level, and baseline voiding symptoms, Grady patients had 5.31 times the odds of compliance (p=.02). CONCLUSIONS: Compliance rate at a safety-net hospital was greater and was not affected by demographic and socioeconomic variables. These results support offering PTNS as standard of care to a predominantly Black population with refractory OAB.

Utility of ultrasonography in preoperative assessment of tumor thrombi in kidney cancer.

INTRODUCTION: This study examined the clinical accuracy of ultrasonography compared to magnetic resonance imaging (MRI) and intraoperative findings for evaluation of tumor thrombi level in patients with renal cell carcinoma. MATERIALS AND METHODS: We retrospectively identified 38 patients at our institution who underwent both ultrasonography and MRI before undergoing open radical nephrectomy with tumor thrombectomy between 2010 and 2019. We compared tumor thrombus level findings of both ultrasonography and MRI, as well as the diagnostic accuracy of each to intraoperative findings. Agreement between ultrasonography, MRI, and surgery was tested with kappa. Logistic regression models identified factors that predict a mismatched thrombus level between an imaging modality and surgical findings. RESULTS AND CONCLUSIONS: Tumor thrombus levels determined by ultrasonography matched with MRI in 26 (68.4%) cases. Compared to operative findings, ultrasonography accurately identified the cephalad extent of thrombi in 30 (79.0%) cases, under-staged five (13.2%) cases, and over-staged three (7.9%). Magnetic resonance imaging agreed with operative findings in 30 (79.0%) cases, under-staged five (13.2%) and over-staged three (7.9%) cases. On univariable regression assessment, M1 stage was predictive of a mismatched result between MRI and surgery (OR: 6.0, 95% CI: 1.02-35.3, p = 0.047), but this association did not hold-up in a multivariable model. Ultrasonography and magnetic resonance imaging identified the preoperative tumor thrombus level at a rate of 79%. Ultrasonography is an effective preoperative imaging modality for evaluating tumor thrombi associated with kidney cancer, notably as an adjunct to magnetic resonance imaging.