"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.

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.

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.

Adverse pathologic features impact survival outcomes for small renal masses following nephrectomy.

PURPOSE: While most small renal masses (SRM) < 4 cm have an excellent prognosis following resection, the impact of adverse T3a pathologic features on oncologic outcomes of SRMs remains unclear. We sought to compare clinical outcomes for surgically resected pT3a versus pT1a SRMs at our institution. MATERIALS AND METHODS: We retrospectively reviewed records of patients who underwent radical or partial nephrectomy (RN, PN) for renal tumors <4 cm at our institution between 2010 and 2020. We compared features and outcomes of pT3a vs pT1a SRMs. Continuous and categorical variables were compared using Student's t and Pearson's chi-squared tests, respectively. Postoperative outcomes of interest including overall, cancer-specific, and recurrence-free survival (OS, CSS, and RFS) were analyzed using Kaplan-Meier method, Cox proportional hazard regression, and competing risk analysis. Analyses were performed using R statistical package (R Foundation, v4.0). RESULTS: We identified 1,837 patients with malignant SRMs. Predictors of postoperative pT3a upstaging included higher renal score, larger tumor size, and presence of radiologic features concerning for T3a disease (odds ratio [OR] = 5.45, 95% confidence interval [CI] 3.92-7.59, P < 0.001). On univariable modeling, pT3a SRMs had higher positive margin rates (9.6% vs 4.1%, P < 0.001), worse OS (hazard ratio [HR] = 2.9, 95% CI 1.6-5.3, P = 0.002), RFS (HR 9.32, 95% CI 2-40.1, P = 0.003), and CSS (HR = 3.6, 95% CI 1.5-8.2, P = 0.003). On multivariable modeling, pT3a status remained associated with worse RFS (HR = 2.7, 95% CI 1.04-7, P = 0.04), but not OS (HR 1.6, 95% CI = 0.83-3.1, P = 0.2); multivariable modeling was deferred for CSS due to low event rates. CONCLUSIONS: Adverse T3a pathologic features portend worse outcomes for SRMs, highlighting the crucial role of pre-operative planning and case selection. These patients have relatively poor prognosis, and should be monitored more closely and counseled for consideration of adjuvant therapy or clinical trials.

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.

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.

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.

Radiogenomics in Clear Cell Renal Cell Carcinoma: A Review of the Current Status and Future Directions.

Radiogenomics is a field of translational radiology that aims to associate a disease's radiologic phenotype with its underlying genotype, thus offering a novel class of non-invasive biomarkers with diagnostic, prognostic, and therapeutic potential. We herein review current radiogenomics literature in clear cell renal cell carcinoma (ccRCC), the most common renal malignancy. A literature review was performed by querying PubMed, Medline, Cochrane Library, Google Scholar, and Web of Science databases, identifying all relevant articles using the following search terms: "radiogenomics", "renal cell carcinoma", and "clear cell renal cell carcinoma". Articles included were limited to the English language and published between 2009-2021. Of 141 retrieved articles, 16 fit our inclusion criteria. Most studies used computed tomography (CT) images from open-source and institutional databases to extract radiomic features that were then modeled against common genomic mutations in ccRCC using a variety of machine learning algorithms. In more recent studies, we noted a shift towards the prediction of transcriptomic and/or epigenetic disease profiles, as well as downstream clinical outcomes. Radiogenomics offers a platform for the development of non-invasive biomarkers for ccRCC, with promising results in small-scale retrospective studies. However, more research is needed to identify and validate robust radiogenomic biomarkers before integration into clinical practice.

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.

Innovations in Disposable Technologies for Stone Management.

Disposable stone retrieval devices are an inherent element of modern-day stone management. Efforts are being made in several different areas to improve the efficiency of stone removal. Ureteral access sheaths with pressure control features as well as suction capabilities are being explored as one such mechanism. Additional efforts are being made to improve stone basket design, grasping capabilities, and deployment mechanisms. Finally, bioadhesives are being developed to potentially improve the capability to extract otherwise difficult small stone fragments and debris from the kidney.

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.