Radiodensities of skeletal muscle and visceral adipose tissues are prognostic factors in clear cell renal cell carcinoma.

BACKGROUND: Body composition may be related to survival in clear cell renal cell carcinoma (ccRCC) patients but studies have not simultaneously considered adipose and muscle tissue quantity and radiodensity. METHODS: We analyzed data from 1,022 ccRCC patients who underwent nephrectomy between 2000 -2020 at Memorial Sloan Kettering Cancer Center. Skeletal muscle, visceral adipose, and subcutaneous adipose tissue index (SMI, VATI, SATI respectively; cm2/m2) and radiodensity (SMD, VATD, SATD respectively; Hounsfield Units [HU]) were assessed from non-contrast pre-surgical computed tomography scans; clinical and demographic characteristics were available from the time of surgery. Hazard ratios (HR) and confidence intervals (CI) were estimated for overall (OS) and disease-free survival (DFS) through March 2023 in multivariable models that simultaneously accounted for all body composition measures. RESULTS: Median age was 58 years, 69% were male, and 90% White. There were 169 OS events over 8,392 person-years, and 253 DFS events over 7,753 person-years of follow-up. In adjusted analyses, poor OS was associated with lower SMD (-10 HU, HR (95% CI): 1.37 [1.05, 1.77]), and greater VATD (+10 HU: 1.66 [1.06, 2.59]), with similar findings for DFS. Poor survival was also associated with greater VATI (+40 cm2/m2, OS: 1.32 [0.97, 1.79]; DFS: 1.33 [1.04, 1.71]). Associations with SMD were limited to patients with stage 1/2 disease. CONCLUSIONS: Radiodensities of skeletal muscle and visceral adipose tissue may be novel pre-surgical prognostic factors for ccRCC patients. IMPACT: Findings underscore the importance of evaluating the full range of body composition features simultaneously in multivariable models.

Surgical Outcomes and Genomic Insights of Nonclear Cell Renal Cell Carcinoma With Synchronous and Metachronous Nodal Disease.

INTRODUCTION: Oncological outcomes in patients with nonclear cell renal cell carcinoma (non-ccRCC) treated with surgery for locoregional nodal disease (ND) remain incompletely characterized. The objective was to investigate the characteristics and outcomes of non-ccRCC patients treated with lymph node dissection (LND) and salvage-LND (S-LND). METHODS: A total of 1627 patients underwent nephrectomy for nonmetastatic non-ccRCC at Memorial Sloan Kettering Cancer Center between 2007 and 2023. Histology was grouped as papillary, chromophobe, unclassified, and rare subtypes. Retrospective evaluation identified 2.5% (n = 40) of patients with nodal disease at time of nephrectomy (synchronous-ND) and 1.1% (n = 18) with metachronous nodal disease limited to the retroperitoneum (metachronous-ND). Patients' demographics and tumor characteristics were recorded and evaluated by univariate and multivariate cox regression models. Recurrence-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Patients who underwent tumor DNA sequencing during their clinical course were considered for genomic analysis. RESULTS: OS trended toward longer in metachronous-ND (51 vs 105 months; P = .2), though 23% of patients with synchronous-ND were recurrence-free at 45 months median follow-up. In multivariate analysis, rare histologies were associated with decreased OS (P = .030) and metachronous-ND with improved OS (P = .036). RFS and OS after S-LND was 15 and 96 months, respectively. Late onset of metachronous-ND/recurrence was associated with improved OS (P = .008). Genetic alterations in SETD2, TP53, B2M, and FGFR3 were exclusively seen in synchronous-ND, and tumor mutation burden (TMB) was also higher in patients with synchronous-ND (P = .016). CONCLUSIONS: Patients with metachronous-ND tend to have prolonged OS compared to synchronous-ND, but a substantial portion of patients with synchronous-ND still enter a durable disease-free state following LND. S-LND can likewise provide long-term survival, particularly in patients with longer time to metachronous nodal recurrence. Synchronous-ND was associated with SETD2, TP53, and NF2 alteration as well as higher TMB.

Changes in the Perioperative Management and Outcomes of Patients With Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy at Memorial Sloan Kettering Cancer Center: Over 20 Years of Experience.

INTRODUCTION: We evaluated surgical trends, perioperative management evolution, and oncologic outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a tertiary cancer center over a 24-year period. METHODS: Between 1995 and 2018, we evaluated 743 consecutive patients with UTUC who underwent RNU. Generalized additive models were used to estimate the associations between date of surgery and continuous outcomes using a linear model, dichotomous outcomes using a logit link, categorical outcomes using multinomial models, and 2- and 5-year survival outcomes using Cox proportional hazards models. RESULTS: Over the study period, preoperative diagnostic endoscopic biopsies increased from 10% to 66%, along with the proportion of patients who underwent RNU for high-grade disease from 55% to 91%. The rate of open RNU declined from 100% to 56% with a rise in minimally invasive approaches. Median lymph node yield increased with more retroperitoneal lymph node dissections performed. Neoadjuvant chemotherapy utilization increased with a contemporary utilization rate of 32%, coinciding with an increase in pT0 rate from 2% to 8%. Cancer-specific survival probabilities improved over the study period, while metastasis-free and overall survival remained stable. CONCLUSIONS: We found several changes in treatment patterns and outcomes for patients with UTUC over the past 2 decades. How individual alterations in management factors, such as patient selection, perioperative chemotherapy, lymphadenectomy, and salvage therapies, impact patient outcomes is challenging in the setting of multiple overlapping practice changes for this rare disease and warrants further investigation.

Skeletal muscle and visceral adipose radiodensities are pre-surgical, non-invasive markers of aggressive kidney cancer.

INTRODUCTION: Most studies on body composition in kidney cancer have been conducted among patients with metastatic disease. Given that aggressive tumours can adversely impact body composition and even non-metastatic tumours can be aggressive, we evaluated associations between pre-surgical body composition features and tumour pathological features in patients with non-metastatic clear cell renal cell cancer (ccRCC). METHODS: The Resolve Cohort consists of 1239 patients with non-metastatic ccRCC who underwent nephrectomy at Memorial Sloan Kettering Cancer Center between 2000 and 2020. The cross-sectional areas and radiodensities of skeletal muscle, visceral adipose, and subcutaneous adipose tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. Pearson's correlation coefficients describe inter-relationships among BMI and body composition variables, while odds ratios (OR) and 95% confidence intervals (CI) estimate associations between continuous body composition features (per 1-standard deviation) and advanced stage (Stage III vs. Stages I-II) and high Fuhrman grade (Grades 3-4 vs. 1-2) from multivariable logistic regression models that considered the potential impact of biological sex, contrast enhanced CTs, and early age at onset of ccRCC. RESULTS: The cohort was predominantly male (69%), white (89%), and had a median age of 58. The proportion of patients presenting with advanced stage and high-grade disease were 31% and 51%, respectively. In models that adjusted for demographics and all body composition variables simultaneously, decreasing skeletal muscle radiodensity (i.e., more fat infiltration) but increasing visceral adipose tissue radiodensity (i.e., more lipid depletion) were associated with advanced tumour features. Per 8.4 HU decrease in skeletal muscle radiodensity, the odds of presenting with advanced stage was 1.61 (95% CI: 1.34-1.93). Per 7.22 HU increase in visceral adipose tissue radiodensity, the odds of presenting with advanced stage was 1.45 (95% CI: 1.22-1.74). Skeletal muscle index (i.e., sarcopenia) was not associated with either tumour feature. Similar associations were observed for Fuhrman grade, a more direct marker of tumour aggressiveness. Associations did not differ by sex, contrast use, or age at onset of ccRCC. CONCLUSIONS: Lipid infiltrated skeletal muscle, but lipid depleted visceral adipose tissue were independently associated with advanced tumour features in non-metastatic ccRCC. Findings highlight the importance of evaluating the full range of body composition features simultaneously in multivariable models. Interpreting pre-surgical CTs for body composition for patients may be a novel and non-invasive way to identify patients with aggressive renal tumours, which is clinically relevant as renal biopsies are not routinely performed.

Surgical outcomes of cytoreductive nephrectomy in patients receiving systemic immunotherapy for advanced renal cell carcinoma.

PURPOSE: The use of systemic immune checkpoint blockade before surgery is increasing in patients with metastatic renal cell carcinoma, however, the safety and feasibility of performing consolidative cytoreductive nephrectomy after the administration of systemic therapy are not well described. PATIENTS AND METHODS: A retrospective review of patients undergoing nephrectomy was performed using our prospectively maintained institutional database. Patients who received preoperative systemic immunotherapy were identified, and the risk of postoperative complications were compared to those who underwent surgery without upfront systemic treatment. Perioperative characteristics and surgical complications within 90 days following surgery were recorded. RESULTS: Overall, we identified 220 patients who underwent cytoreductive nephrectomy from April 2015 to December 2022, of which 46 patients (21%) received systemic therapy before undergoing surgery. Unadjusted rates of surgical complications included 20% (n = 35) in patients who did not receive upfront systemic therapy and 20% (n = 9) in those who received upfront systemic immunotherapy. In our propensity score analysis, there was no statistically significant association between receipt of upfront immunotherapy and 90-day surgical complications [odds ratio (OR): 1.82, 95% confidence interval (CI): 0.59-5.14; P = 0.3]. This model, however, demonstrated an association between receipt of upfront immunotherapy and an increased odds of requiring a blood transfusion [OR: 4.53, 95% CI: 1.83-11.7; P = 0.001]. CONCLUSION: In our cohort, there was no significant difference in surgical complications among patients who received systemic therapy before surgery compared to those who did not receive upfront systemic therapy. Cytoreductive nephrectomy is safe and with low rates of complications following the use of systemic therapy.

A comparison of oncologic and functional outcomes in patients with pt3a renal cell carcinoma treated with partial and radical nephrectomy

ABSTRACT Hypothesis: Partial Nephrectomy is oncological safe in patients with pT3a RCC. Purpose: To compare the oncological and functional outcomes of patients with pT3a RCC scheduled for PN and RN. Materials and Methods: We retrospectively reviewed patients with pT3a N0 M0 RCC who underwent partial or radical nephrectomy from 2005 to 2016. Perioperative characteristics, including estimated glomerular filtration rate, tumor size, pathological histology, and RENAL nephrometry score, were compared between patients scheduled for partial or radical nephrectomy. We used multivariable Cox proportional hazards regression models to compare overall survival, cancer-specific survival, and recurrence-free survival between planned procedure type. Results: Of the 589 patients, 369 (63%) and 220 (37%) were scheduled for radical and partial nephrectomy, respectively; 26 (12%) of the scheduled partial nephrectomy cases were intraoperatively converted to radical nephrectomy. After adjusting for tumor size and histology, there were no statistically significant differences in overall survival (hazard ratio 0.66; 95% CI, 0.38-1.13), cancer-specific survival (hazard ratio 0.53; 95% CI, 0.16-1.75), or recurrence-free survival (hazard ratio 0.66; 95% CI, 0.34-1.28) between patients scheduled for partial or radical nephrectomy. Fewer patients scheduled for partial nephrectomy had estimated glomerular filtration rate reductions 3 to 9 months after surgery than patients scheduled for radical nephrectomy. Conclusion: We found no evidence that patients scheduled to undergo partial nephrectomy had poorer oncologic outcomes than patients scheduled to undergo radical nephrectomy. In select patients with pT3a renal cell carcinoma in whom partial nephrectomy is deemed feasible by the surgeon, partial nephrectomy should not be discouraged.