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.

GRADE Reporting in Systematic Reviews Published in the Urological Literature (2009-2021).

PURPOSE: We evaluate the reporting of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to rating the certainty of evidence in systematic reviews published in the urological literature. MATERIALS AND METHODS: Based on a predefined protocol, we identified all systematic reviews published in 5 major urological journals from 1998 to 2021 that reported the use of GRADE. Two authors performed study selection and data abstraction independently to assess reporting in accordance with established criteria for applying GRADE. RESULTS: We included 68 of 522 (13.0%) systematic reviews that reported the use of GRADE; the first was published in 2009. Approximately half were published between 2009-2018 (n=36) and the other half between 2019-2021 (n=32). Oncology (24; 35.3%) was the most common clinical topic, and the authors were mostly based in Europe (34; 50%). In their abstract, less than half of all systematic reviews (32; 47.1%) provided any certainty of evidence rating. Only 41 (60.3%) included a tabular result summary in the format of a summary of findings table (24; 35.3%) or evidence profile (17; 25.0%). Few (35.3%) addressed the GRADE certainty of evidence rating in the discussion section. Reporting did not improve over time when comparing the 2 time periods. CONCLUSIONS: Whereas GRADE is increasingly being applied for rating the certainty of evidence, systematic reviews published in the urological literature frequently have not followed established criteria for applying or using GRADE. There is a need for better training of authors and editors, as well as for a GRADE reporting checklist for systematic review authors.

Prognostic Factors for Survival in Patients Undergoing Surveillance After Cytoreductive Nephrectomy.

PURPOSE: The clinical course of patients being placed on surveillance in a cohort of systemic therapy-naïve patients who undergo cytoreductive nephrectomy is not well documented. Thus, we evaluated the clinical course of patients placed on surveillance following cytoreductive nephrectomy and identified predictors of survival. MATERIALS AND METHODS: In this large single-institution study, we retrospectively analyzed metastatic renal cell carcinoma patients who underwent cytoreductive nephrectomy followed by surveillance. Predictors of survival were evaluated using the Kaplan-Meier method with a log-rank test. Patients were risk stratified based on IMDC (International mRCC Database Consortium) and number of metastatic sites (Rini score), with IMDC score ≤1 and ≤2 metastatic organ sites considered favorable risk. Primary end point was systemic therapy-free survival. Secondary end points included intervention-free survival, cancer-specific survival, and overall survival. RESULTS: Median systemic therapy-free survival was 23.6 months (95% CI: 15.1-40.6), intervention-free survival was 11.8 months (95% CI: 8.0-18.4), cancer-specific survival was 54.2 months (95% CI: 46.2-71.4), and overall survival 52.4 months (95% CI: 40.3-66.8). Favorable-risk patients compared to unfavorable-risk patients had longer systemic therapy-free survival (50.6 vs 11.1 months, P < .01), survival (25.2 vs 7.3, P < .01), and cancer-specific survival (71.4 vs 46.2 months, P = .02). CONCLUSIONS: Using risk stratification based on IMDC and number of metastatic sites, surveillance in favorable-risk patients can be utilized for a period without the initiation of systemic therapy. This approach can delay patients' exposure to the side effects of systemic therapy.

Impact of Preoperative Immunonutrition on Perioperative Outcomes following Cystectomy.

PURPOSE: Radical cystectomy (RC) for the management of muscle-invasive bladder cancer remains a morbid procedure with high rates of perioperative complications. The role of preoperative immunonutritional supplementation (pre-INS) in improving post-RC outcomes is promising and needs further validation. MATERIALS AND METHODS: We performed a retrospective review of 204 patients who underwent RC for bladder cancer at a single institution, comparing patients who received oral L-arginine-based pre-INS, and those who did not. Preoperative features, postoperative complications, and readmission data were collected. Outcomes of interest included development of high-grade (Clavien-Dindo III-V) complications, readmission within 30 days, ileus, total parenteral nutrition (TPN) requirement, postoperative infection, and length of stay (LOS). Categorical and continuous outcomes were assessed using Fisher's exact test and Welch T-test, respectively. Multivariable logistic regression (MLoR) analysis was used to identify predictive factors for our outcomes. RESULTS: Patients who received pre-INS had significantly lower odds of requiring postoperative TPN (17.3% vs 35.6%; Fisher p=0.015, OR=0.38) and developing postoperative infection (25% vs 45%; Fisher p=0.003; OR=0.41) but no significant difference in the rates of other outcomes. On MLoR, when adjusting for age, gender, body mass index, Charlson comorbidity index, undergoing neoadjuvant chemotherapy and operative features, pre-INS was a significant predictor of postoperative infection (Fisher p=0.02; OR=0.35) but not for high-grade complications, readmission, ileus, needing TPN or LOS. CONCLUSIONS: Preoperative immunonutrition with an L-arginine-based supplement is associated with significant reduction in postoperative infection, one of the most common complications of RC.

The fate of urological systematic reviews registered in PROSPERO.

PURPOSE: To identify urologic systematic reviews (SRs) registered to PROSPERO that resulted in a publication, and to evaluate their methodological quality and concordance with their stated a priori protocols. METHODS: We searched PubMed to identify urologic SR protocols registered in PROSPERO that resulted in a publication and assessed their methodological quality and protocols in relation to their stated a priori protocols in PROSPERO. RESULTS: Of the 576 urologic SR protocols registered in PROSPERO up to December 2017, 201 (34.9%) resulted in a full SR publication, but only 40 (17.7%) updated their registration record accordingly. Publications were spread over 100 different journals, with a median time-to-publication of 29 months (95% CI 25.0-33.0). The most common topic by far was prostate cancer (59.7%), followed by voiding issues (15.3%), and renal transplantation (15.3%). Only little over half the reviews (52.74%) explicitly stated primary outcome(s) that matched the primary outcome of their corresponding PROSPERO protocol. Notable methodologic deviations from registered protocols included planned restriction on study design (33%), heterogeneity analysis (42%) and planned risk of bias analysis (65.2%). CONCLUSION: SR authors in urology are increasingly using PROSPERO to register their titles, but our findings indicate that registration alone is not a guarantor of a high-quality SR product. There appears to be a critical need to raise the bar for review authors registering protocols in PROSPERO, with an emphasis on transparency in their publication status updates as well as deviations from their a priori protocols.

Gender Equivalence in the Prevalence of Nephrolithiasis among Adults Younger than 50 Years in the United States.

PURPOSE: Although urolithiasis affects each gender, conventional teaching proposes that men are 3 times more likely to have stones. However, clinical practice refutes such a disparity, particularly among working age adults. Small studies have suggested an erosion of this gender gap. Therefore, we examined the relationship between gender and stone prevalence among American adults younger than 50 years. MATERIALS AND METHODS: We analyzed the NHANES (National Health and Nutrition Examination Survey) 2007 to 2012 cohort. Weighted proportions and multivariate logistic regression of the cohort and pertinent subgroups were assessed to determine the prevalence and the odds of nephrolithiasis. RESULTS: The cohort of 17,658 subjects, which was weighted to represent the American population of 218,828,951 adults, was 48.1% male. In our cohort of 8,888 adults weighted to represent 123,976,786 subjects younger than 50 years, which was 49.3% male and 50.7% female, there was no difference in stone prevalence (6.3% in males and 6.4% in females, p = 0.85). On unadjusted logistic regression of those younger than 50 years men were no more likely to report a stone history (OR 0.98, p = 0.85). Multivariate logistic regression adjusting for diabetes, obesity, ethnicity, age, and water, sodium and protein intake confirmed no difference in stone prevalence between the genders (OR 1.1, p = 0.51). CONCLUSIONS: Among adults of working and child rearing ages in the United States the much touted gender disparity in nephrolithiasis is not present. Prior assessments of gender based stone prevalence may have failed to specifically assess this economically critical demographic or there may in fact be an ongoing epidemiological change. Recognition that women are as likely as men to form stones in this cohort suggests the need to better elucidate the pathophysiology of stones in women.

Association of Pregnancy with Stone Formation among Women in the United States: A NHANES Analysis 2007 to 2012.

PURPOSE: Lithogenic urinary changes develop during pregnancy. Such changes may increase stone proclivity thereafter in working and child rearing aged women. However, to our knowledge such an association has not been previously identified. MATERIALS AND METHODS: We analyzed nationally representative data from the 2007 to 2012 NHANES (National Health and Nutrition Examination Survey) to assess the association between pregnancy and nephrolithiasis. RESULTS: The weighted national prevalence of nephrolithiasis among women 50 years or younger was 6.4% (95% CI 5.4-7.6). The prevalence of nephrolithiasis was significantly higher among women who had been pregnant compared with those who had never been pregnant (7.5% vs 3.2%, p = 0.0004). On univariate regression those who had been pregnant had more than twice the odds of having had kidney stones (OR 2.44, 95% CI 1.50-3.98). An increased likelihood of nephrolithiasis in those with a history of pregnancy persisted on multivariable logistic regression adjusting for age, ethnicity, obesity, history of diabetes, gout, hormone use, water intake and high sodium diet (OR 2.13, 95% CI 1.31-3.45). Finally, the adjusted prevalence of nephrolithiasis increased significantly with an increasing number of pregnancies from 5.2% in those with 0 reported pregnancies to 12.4% in those with 3 or more pregnancies (p = 0.001). CONCLUSIONS: Nephrolithiasis is strongly associated with prior pregnancies. Among women of reproductive age the odds of stones are greater than doubled in those who had been pregnant compared with those who had never been pregnant. Nephrolithiasis prevalence also increases with the increasing number of pregnancies. Future investigation and identification of modifiable risk factors among pregnant patients may allow for a reduction in the burden of stone disease in women.

E2F4 regulatory program predicts patient survival prognosis in breast cancer.

INTRODUCTION: Genetic and molecular signatures have been incorporated into cancer prognosis prediction and treatment decisions with good success over the past decade. Clinically, these signatures are usually used in early-stage cancers to evaluate whether they require adjuvant therapy following surgical resection. A molecular signature that is prognostic across more clinical contexts would be a useful addition to current signatures. METHODS: We defined a signature for the ubiquitous tissue factor, E2F4, based on its shared target genes in multiple tissues. These target genes were identified by chromatin immunoprecipitation sequencing (ChIP-seq) experiments using a probabilistic method. We then computationally calculated the regulatory activity score (RAS) of E2F4 in cancer tissues, and examined how E2F4 RAS correlates with patient survival. RESULTS: Genes in our E2F4 signature were 21-fold more likely to be correlated with breast cancer patient survival time compared to randomly selected genes. Using eight independent breast cancer datasets containing over 1,900 unique samples, we stratified patients into low and high E2F4 RAS groups. E2F4 activity stratification was highly predictive of patient outcome, and our results remained robust even when controlling for many factors including patient age, tumor size, grade, estrogen receptor (ER) status, lymph node (LN) status, whether the patient received adjuvant therapy, and the patient's other prognostic indices such as Adjuvant! and the Nottingham Prognostic Index scores. Furthermore, the fractions of samples with positive E2F4 RAS vary in different intrinsic breast cancer subtypes, consistent with the different survival profiles of these subtypes. CONCLUSIONS: We defined a prognostic signature, the E2F4 regulatory activity score, and showed it to be significantly predictive of patient outcome in breast cancer regardless of treatment status and the states of many other clinicopathological variables. It can be used in conjunction with other breast cancer classification methods such as Oncotype DX to improve clinical outcome prediction.

The Interplay Between Adult-Onset Hypogonadism and Prostate Cancer: A Literature Review.

The interplay between endogenous testosterone (Te) and prostate cancer (PCa) has long been recognized, with androgen deprivation therapy (ADT) being a cornerstone of advanced and metastatic PCa management. However, the association between Te levels and PCa risk remains complex and not fully understood. This review delves into the complex relationship between adult-onset hypogonadism (AOH) and PCa, shedding light on the complexities surrounding PCa risk and disease aggressiveness. Despite the significant prevalence of PCa among men, particularly as they age, and the emergence of AOH as a prevalent health concern, data regarding their association remains heterogeneous and inconsistently documented. While some studies suggest a potential correlation between low Te levels and decreased PCa detection rates, others indicate a higher risk of aggressive pathological features, primarily observed in prostatectomy cohorts. It's noteworthy that there's evidence indicating hypogonadal men might face an increased risk of reclassification during active surveillance (AS) of low-risk disease. This is supported by the observation of elevated rates of disease upgrading in historical cohorts of low-risk prostatectomies. These contradictory findings are poorly reflected in treatment guidelines. Further research is imperative to comprehensively understand the clinical and associative correlations between AOH and PCa risk and biology, thereby informing more effective management strategies in the future.

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.

"Shared decision-making" for prostate cancer screening: Is it a marker of quality preventative healthcare?

BACKGROUND: "Shared decision-making" (SDM) is a cornerstone of prostate cancer (PCa) screening guidelines due to tradeoffs between clinical benefits and concerns for over-diagnosis and over-treatment. SDM requires effort by primary-care-providers (PCP) in an often busy clinical setting to understand patient preferences with the backdrop of patient risk factors. We hypothesized that SDM for PCa screening, given its prominence in guidelines and practical challenges, may be associated with quality preventative healthcare in terms of other appropriate cancer screening and encouragement of other preventative health behaviors. METHODS: From the 2020 Behavioral Risk Factor Surveillance Survey, 50-75 year old men who underwent PSA screening were assessed for their participation in SDM, PCa and colorectal cancer (CRC) screening, and other preventative health behaviors, like vaccination, exercise, and smoking status. Adjusted odds ratio of likelihood of PSA testing as a function of SDM was calculated. Likelihoods of SDM and PSA testing as a function of preventative health behaviors were also calculated. RESULTS: Screening rates were 62 % for PCa and 88 % for CRC. Rates of SDM were 39.1 % in those with PSA screening, and 16.2 % in those without. Odds of PSA screening were higher when SDM was present (AOR = 2.68). History of colonoscopy was associated with higher odds of SDM (AOR = 1.16) and PSA testing (AOR = 1.94). Health behaviors, like regular exercise, were associated with increased odds of SDM (AOR = 1.14) and PSA testing (AOR = 1.28). History of flu vaccination (AOR = 1.29) and pneumonia vaccination (AOR = 1.19) were associated with higher odds of SDM. Those who received the flu vaccine were also more likely to have PSA testing (AOR = 1.36). Smoking was negatively associated with SDM (AOR = 0.86) and PSA testing (AOR = 0.93). Older age was associated with higher rates of PSA screening (AOR = 1.03, CI = 1.03-1.03). Black men were more likely than white men to have SDM (AOR = 1.6, CI = 1.59 - 1.6) and decreased odds of PSA testing (AOR = 0.94, CI = 0.94 - 0.95). CONCLUSIONS: SDM was associated with higher odds of PSA screening, CRC screening, and other appropriate preventative health behaviors. Racial disparities exist in both SDM and PSA screening usage. SDM may be a trackable metric that can lead to wider preference-sensitive care and improved preventative care.

Assessment of mechanical bowel preparation prior to nephrectomy in the minimally invasive surgery era: insights from a national database analysis in the United States.

Purpose: This study was performed to evaluate the association between mechanical bowel preparation (MBP) and perioperative outcomes following nephrectomy in the minimally invasive surgery (MIS) era. Methods: All partial and radical nephrectomies between 2019 and 2021 from the National Surgical Quality Improvement Program database were evaluated. Thirty-day perioperative outcomes were compared between groups where MBP was performed vs. not, in both the MIS and open surgery (OS) cohorts. A propensity score matching technique was utilized within MIS cases to control for covariates. The chi-square and t tests were used to determine significance. Results: A total of 11,869 cases met the inclusion criteria and were included in the analysis. Of these, 8,204 (69.1%; comprising 65.3% robotic and 34.7% laparoscopic) underwent MIS, while 3,655 (30.9%) underwent OS. The rate of MBP was higher in the MIS group (16.0% vs. 10.0%, p < 0.001). Within the MIS group, MBP was associated with reduced rates of postoperative ileus (0.9% vs. 1.9%, p = 0.02), while other complications were comparable. Propensity score matching showed no association between MBP and postoperative ileus. However, a lower rate of 30-day readmission in the MBP group became statistically significant (4.4% vs. 6.4%, p = 0.01). Conversely, patients in the MBP group also demonstrated higher rates of pneumonia (1.29% vs. 0.46%, p = 0.002) and pulmonary embolism (0.6% vs. 0%, p < 0.001) after matching. Conclusion: MBP practice prior to nephrectomy is infrequent in both OS and MIS cases, with minor differences in perioperative outcomes for patients undergoing MIS. Routine MBP should continue to be excluded from the standard of care for nephrectomy in the MIS era.

Quantification of Gleason Pattern 4 Metrics Identifies Pathologic Progression in Patients With Grade Group 2 Prostate Cancer on Active Surveillance.

BACKGROUND: During active surveillance (AS) for Grade Group (GG) 2 prostate cancer, pathologic progression to GG3 on surveillance biopsy is a trigger for intervention. However, this ratio of GP3:GP4, may be obscured by increases of relatively indolent disease. We aimed to explore changes in GP4 quantity during AS and propose alternative definitions for progression based on GP4 changes. DESIGN, SETTING, AND PARTICIPANTS: We assessed patients enrolled on AS between November 2014 and March 2020 with GG2 disease on diagnostic biopsy and subsequent surveillance biopsy approximately 1 year later. Outcome measures included change in overall %GP4 and total length GP4 (mm). RESULTS AND LIMITATIONS: 61 patients met the inclusion criteria, the median change in total length of GP4 and %GP4 was -0.12 mm (IQR -0.31, 0.09) and -2.5% (IQR -8.6, 0.0), respectively. Excluding the 35 patients with no evidence of GP4 on surveillance biopsy, median change in total GP4 length and %GP4 was 0.19 mm (IQR -0.04, 0.67) and 1.2% (IQR -1.6, 6.6), respectively. Three patients progressed to GG3 disease on surveillance biopsy, one of whom had only a small increase in %GP4. Conversely, an additional 2 patients who did not meet the criterion for GG3 had a large increase (> 1 mm) in total GP4 length. CONCLUSIONS: Presence of GG3 disease on surveillance biopsy as a trigger for treatment in men on AS is of questionable use alone; we suggest including other measures that do not depend on a ratio, such as an increase in total GP4 length.

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.

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.

Current and Future Biomarkers in the Management of Renal Cell Carcinoma.

Renal cell carcinoma biomarkers include serum, urine, liquid, and tissue biomarkers. There is currently an ongoing search for predictive biomarkers in the detection, recurrence, and treatment of renal cell carcinoma. Emerging signatures in the transcriptomic and translational biomarker space seem promising, although additional work is needed to validate candidates in a larger and more generalizable patient population.

Evolution of the HIF targeted therapy in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, affecting hundreds of thousands of people worldwide and can affect people of any age. The pathogenesis of ccRCC is most commonly due to biallelic loss of the tumor suppressor gene VHL. VHL is the recognition subunit of an E3-ubiquitin-ligase-complex essential for degradation of the hypoxia-inducible factors (HIF) 1α and 2α. Dysfunctional degradation of HIF results in overaccumulation, which is particularly concerning with the HIF2α subunit. This leads to nuclear translocation, dimerization, and transactivation of numerous HIF-regulated genes responsible for cell survival and proliferation in ccRCC. FDA-approved therapies for RCC have primarily focused on targeting downstream effectors of HIF, then incorporated immunotherapeutics, and now, novel approaches are moving back to HIF with a focus on interfering with upstream targets. This review summarizes the role of HIF in the pathogenesis of ccRCC, novel HIF2α-focused therapeutic approaches, and opportunities for ccRCC treatment.