Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

BACKGROUND: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS). OBJECTIVE: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021. INTERVENTION: SRS for RCC BMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death. RESULTS AND LIMITATIONS: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041). CONCLUSIONS: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting. PATIENT SUMMARY: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.

Investigation of Disparity of Urologic Fellowship Match Rates by Gender and US Versus International Medical Graduates Over the Past Decade.

OBJECTIVE: To investigate the influence of postgraduate medical education (US vs international) and gender on applicant matching for postgraduate training across different urologic sub-specialties. METHODS: Match statistics of 5 societies that participated in the AUA fellowship match between 2010 and 2024 were retrospectively reviewed. Societies included: Endourology Society (EUS), Society for Urological Oncology (SUO), American Society of Andrology (ASA), Society of Genitourinary Reconstructive Surgeons (GURS), and Society of Pediatric Urology (SPU). Candidates were classified based on gender (male/female) and their postgraduate medical education: local graduates from the United States or Canada (US/Ca) and international medical graduates (IMGs). The match odds were analyzed using the Chi-square test, while trends were assessed through the Mann-Kendall test. RESULTS: Overall, 2439 applicants applied for 1627 programs from 2010 to 2024, comprising 1998 males (81.8%), 399 females (16.4%), and 42 undisclosed (1.7%). There were 1486 US/Ca graduates (60.8%) and 953 IMGs (39.2%). Around 1471 (60.6%) applicants were matched with a program, compared to 958 (39.4%) unmatched. The likelihood of US/Ca graduates matching (83.8%) was significantly higher than IMGs (23.3%), OR= 17.5, 95% CI: (14.3, 21.5), P <.001. IMGs had the highest match rate with GURS (33.8%, 47/118) and the lowest with SPU (7%, 1/14). Female applicants had a significantly higher chance of matching 324/399 (81.2%) than male applicants 1139/1998 (57%), OR= 3.26, 95% CI: (2.5, 4.3), P <.001. US/Ca-to-IMGs ratios and the male-to-female ratios were stable throughout the match years. CONCLUSION: Compared to IMGs, U.S./Ca graduates had remarkably higher matching rates. Matching outcomes were also significantly better for female applicants. Further assessment of international involvement and diversity in urological subspecialty roles is warranted.

Consistent predictive ability of prostate-specific antigen density prediction model for clinically significant prostate cancer across age strata.

BACKGROUND: Prebiopsy prostate-specific antigen density (PSAD) is a well-known predictor of clinically significant prostate cancer (csPCa). Since prostate-specific antigen (PSA) and prostate volume (PV) increase normally with aging, PSAD thresholds may vary. The purpose of the study was to determine if PSAD was predictive of csPCa in different age strata. METHODS: We retrospectively reviewed our institutional database for patients who underwent multiparametric magnetic resonance imaging (MRI) between January 2016 and December 2021. We included patients who had post-MRI prostate biopsies. Based on age, we divided our cohort into four subgroups (groups 1-4): <55, 55-64, 65-74, and ≥75 years old. PSAD accuracy was estimated by the area under the curve (AUC) as a predictive model for differentiating csPCa between the groups. CsPCa was defined as a Gleason Grade Group 2 or higher. Three different PSAD thresholds (0.1, 0.15, and 0.2) were tested across the groups for sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV). Chi-square and analysis of variance tests were used for bivariate analysis. All analys were completed using R 4.3 (R Core Team, 2023). RESULTS: Among 1913 patients, 883 (46.1%) had prostate biopsies. In groups 1, 2, 3, and 4, there were 62 (7%), 321 (36.4%), 404 (45.8%), and 96 (10.9%) patients, respectively. Median PSA was 5.6 (interquartile range 3.4-8.1), 6.2 (4.8-9), 6.8 (5.1-9.7), and 9 (5.6-13), respectively (p < 0.01). Median PV was 42.3 (30-62), 51 (36-77), 55.5 (38-85.9), and 59.3 (42-110) mL, respectively (p < 0.01). No difference was observed in median PSAD between age groups 1-4 (0.1 [0.07-0.16], 0.11 [0.08-0.18], 0.1 [0.07-0.19], and 0.1 [0.07-0.2]), respectively (p = 0.393). CsPCa was diagnosed in 241 (27.3%) patients, of which 10 (16.1%), 65 (20.2%), 121 (30%), and 45 (46.7%) were in groups 1-4, respectively (p < 0.001). For groups 1-4, the PSAD AUC for predicting csPCa was 0.75, 0.68, 0.71, and 0.74. While testing PSAD threshold of 0.15 across the different age groups (1-4), the PPV vs. NPV was 39.1 vs. 93.2, 33.6 vs. 87, 50.9 vs. 80.8, and 66.1 vs. 64.7, respectively. CONCLUSIONS: PSAD prediction model was found to be similar among different age groups. In young patients, PSAD had a high NPV but low PPV. With increasing age, the opposite trend was observed, likely due to higher disease prevalence. While PSAD thresholds may be less useful in older patients to rule out higher-grade prostate cancer, the clinical consequences of these diagnoses require a case-by-case evaluation.

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.

2022 WUOF/SIU International Consultation on Urological Diseases: Genetics and Tumor Microenvironment of Renal Cell Carcinoma.

Renal cell carcinoma is a diverse group of diseases that can be distinguished by distinct histopathologic and genomic features. In this comprehensive review, we highlight recent advancements in our understanding of the genetic and microenvironmental hallmarks of kidney cancer. We begin with clear cell renal cell carcinoma (ccRCC), the most common subtype of this disease. We review the chromosomal and genetic alterations that drive initiation and progression of ccRCC, which has recently been shown to follow multiple highly conserved evolutionary trajectories that in turn impact disease progression and prognosis. We also review the diverse genetic events that define the many recently recognized rare subtypes within non-clear cell RCC. Finally, we discuss our evolving understanding of the ccRCC microenvironment, which has been revolutionized by recent bulk and single-cell transcriptomic analyses, suggesting potential biomarkers for guiding systemic therapy in the management of advanced ccRCC.