The Current Application and Future Potential of Artificial Intelligence in Renal Cancer.

Artificial intelligence (AI) is the integration of human tasks into machine processes. The role of AI in kidney cancer evaluation, management, and outcome predictions are constantly evolving. We performed a narrative review utilizing PubMed electronic database to query AI as a method of analysis in kidney cancer research. Key search-words included: Artificial Intelligence, Supervised/Unsupervised Machine Learning, Deep Learning, Natural Language Processing, Neural Networks, radiomics, pathomics, and kidney or renal neoplasms or cancer. 72 clinically relevant and impactful studies related to imaging, histopathology, and outcomes were recognized. We anticipate the incorporation of AI tools into future clinical decision-making for kidney cancer.

Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study.

PURPOSE: This study aimed to investigate the prevalence of pathogenic germline variants (PGVs) in hereditary cancer genes utilizing a universal testing approach and to determine the rate of PGVs that would have been missed based on National Comprehensive Cancer Network (NCCN) guidelines in genitourinary (GU) malignancies. MATERIALS AND METHODS: A multisite, single-institution prospective germline genetic test (GGT) was universally offered to patients with new or active diagnoses of GU malignancies (prostate, bladder, and renal) from April 2018 to March 2020 at Mayo Clinic sites. Participants were offered GGT using a next-generation sequencing panel of > 80 genes. Demographic, tumor characteristics, and genetic results were evaluated. NCCN GU cancer guidelines were used to identify whether patients had incremental findings, defined as PGV-positive patients who would not have received testing based on NCCN guidelines. RESULTS: Of 3095 individuals enrolled in the study, 601 patients had GU cancer (prostate = 358, bladder = 106, and renal = 137). The mean enrollment age was 67 years (SD 9.1), 89% were male, and 86% of patients were non-Hispanic White. PGVs were identified in 82 (14%) of all GU patients. PGV prevalence breakdown by cancer type was: 14% prostate, 14% bladder, and 13% renal cancer. Nearly one-third of identified PGVs were high penetrance, and the majority of these (67%) were clinically actionable. Incremental PGVs were identified in 28 (57%) prostate, 15 (100%) bladder, and 14 (78%) renal cancer patients. Of the 82 patients with PGV findings, 29 (35%) had at least 1 relative undergo cascade testing for the familial variant(s) identified. CONCLUSIONS: More than 1 in 8 patients with GU malignancies were found to carry a PGV, with 67% of patients with high-penetrance PGVs undergoing clinically actionable changes. The majority of these PGVs would not have been identified based on current testing criteria. These findings support universal GGT for GU malignancies and underscore its potential to enhance risk assessment and guide precision interventions in urologic oncology.

Robotic-assisted Laparoscopic Repair of Kidney Transplant Ureteral Strictures.

OBJECTIVE: To evaluate outcomes of robotic-assisted transplant ureteral repair (RATUR) for the management of kidney transplant ureteral strictures (TUS). METHODS: We retrospectively analyzed 41 consecutive patients who underwent RATUR for TUS at multiple tertiary referral centers between January 2016 and December 2022. RATUR was performed utilizing a robotic-assisted transperitoneal approach. The primary outcome was stricture recurrence rate and secondary outcomes included postoperative complicate rate, determining factors impacting with allograft functional recovery, and rate of conversion to open surgery. Categorical and continuous variables are displayed as total number (Percentage) or median [Interquartile Range], respectively. Pearson correlation coefficient was utilized to assess categorical variable correlation with creatinine. RESULTS: The median age was 56years [44,66]. The female-to-male ratio was 1.1:1. Approximately 66% of patients were dialysis-dependent prior to kidney transplantation. TUS was identified at a median time of 4months [2, 15.5] following kidney transplant. Median stricture length was 2 cm [1.22, 2.9 cm]. There were no TUS recurrences with a median follow-up of 36months [24,48]. There were 3 Clavien grade 2 and 1 Clavien grade 3 complications (9.5%). No baseline characteristics or preoperative diagnostics were correlated with a long-term decline in renal allograft function. CONCLUSION: RATUR has excellent and durable outcomes with low complication rates. These findings encourage the use of a minimally invasive definitive repair as a first-line treatment option for the management of TUS.

The Impact of Standard vs Early Apical Release Holmium Laser Enucleation of the Prostate Technique on Postoperative Incontinence and Quality of Life.

OBJECTIVE: To investigate the difference in postoperative incontinence and quality of life comparing standard vs early apical release (EAR) Holmium Laser Enucleation of the Prostate (HoLEP). METHODS: A retrospective review was performed to identify patients who underwent HoLEP from December 2021 to December 2022 at a single tertiary referral center with two participating consultant urologists. Patients were assessed with questionnaires and evaluated clinically. We performed propensity score matching with a logistic regression and a 1:1 matching method. A propensity score-adjusted logistic regression (PSRM) was performed to compare the pads per day between surgical techniques controlling for age, prostate size, preoperative survey data, uroflow, and postvoid residual. RESULTS: One hundred fourteen patients underwent HoLEP, of which 60 patients were treated with EAR and 54 patients with standard technique. EAR technique demonstrated shorter operative times (P = .046). The EAR cohort demonstrated improved AUASS (P = .034, P = .001), QOL (P = .001, P <.001), and continence rates (P <.001, P <.001) at 6 and 12weeks postoperatively. PSRM showed that the standard HoLEP increased the risk of requiring ≥2 pads per day 4.2x (P = .031, HR 95%, CI=1.16, 15.35) and 8.3x (P <.001, HR 95% CI 3.17, 21.6) at 6 and 12weeks postoperatively. CONCLUSION: EAR technique promoted earlier return of continence and improved quality of life within 6weeks of surgery.

Bacillus Calmette-Guerin (BCG) therapy is safe and effective in non-muscle invasive bladder cancer (NMIBC) patients with immunomodulating conditions.

INTRODUCTION: Bacillus Calmette-Guerin (BCG) is the most effective therapy available to treat high-risk nonmuscle invasive bladder cancer (NMIBC) patients. However, for patients with immunomodulating conditions BCG is a relative contraindication due to efficacy and safety concerns. To our knowledge, no population-level study evaluating the efficacy and safety profile of BCG for immunomodulated patients exists. METHODS: NMIBC patients aged 66 years or older were identified in the Surveillance, Epidemiology, and End Results (SEER) - Medicare database from 1975-2013. All patients completed adequate BCG (at least 5 plus 2 treatments completed within 12 months of diagnosis). Two groups were defined: an immunomodulated population identified by immunomodulating conditions such as solid-organ transplantation, HIV, and autoimmune conditions, and an immunocompetent group. The primary endpoint was 5-year progression-free survival defined as progression to systemic chemotherapy, checkpoint inhibitors, radical or partial cystectomy, metastasis, or cancer-specific death. A safety analysis was performed as a secondary outcome. RESULTS: In a total of 4,277 patients with NMIBC who completed adequate BCG, 606 (14.2%) were immunomodulated. The immunomodulated group was older at diagnosis (P < 0.001), more likely to be female (P < 0.001), more likely to live in a metropolitan area (P < 0.001), and had higher Charlson comorbidity scores (P < 0.001). There were no differences in progression to chemotherapy (P = 0.17), checkpoint inhibitors (P > 0.99), radical cystectomy (P = 0.40), partial cystectomy (P = 0.93), metastasis (P = 0.19), cancer-specific death (P = 0.18) or 5-year total bladder cancer progression (P = 0.30) between the groups. For the safety analysis, rates of disseminated BCG were similar between immunomodulated and immunocompetent patients (0.7% vs. <1.8%, P = 0.51). On multivariable analysis 5-year total bladder cancer progression (HR 1.07 [CI 0.88-1.30]) was similar between the groups. CONCLUSION: Rates of bladder cancer progression and disseminated BCG complications 5-years after BCG therapy were similar regardless of immunomodulation status. These findings suggest that BCG intravesical therapy can be offered to immunomodulated patients with high-risk NMIBC although theoretical infectious complication risks remain.

Low-Value Prostate Cancer Screening Among Young Men With Private Insurance.

INTRODUCTION: No professional society guidelines recommend PSA screening in men younger than age 40; however, data suggest testing occurs at meaningful rates in this age group. The purpose of this study was to identify the rate of PSA testing in men under 40. METHODS: This is a population-based, retrospective cohort study from 2008 to 2017. Using the MarketScan database, rates of testing for the sum of the annual population of men at risk were evaluated. Descriptive statistics and statistical analyses were performed in men continuously enrolled in the database for at least 5 year. Results were stratified by receipt of PSA testing and by age group. The association of diagnoses and Charlson Comorbidity Index with receipt of PSA test was evaluated using multivariable logistic regression models. RESULTS: We identified 3,230,748 men ages 18 to 39 who were enrolled for at least 5 years. The rate of ever receiving PSA testing was 0.6%, 1.7%, 8.5%, and 9.1% in men less than 25, 25 to 29, 30 to 34, and 35 to 39 years, respectively. Multivariable logistic regression showed that relative to all men 18 to 39, patients who received PSA testing had higher odds of a diagnosis of hypogonadism (OR 11.77) or lower urinary tract symptoms (OR 4.19). CONCLUSIONS: This study found a remarkable number of young men receive PSA testing, with a strong association with diagnoses of lower urinary tract symptoms and hypogonadism. Clinicians need to be educated that assessment and management guidelines for other urologic diagnoses now defer PSA testing to prostate cancer screening guidelines.

Impact of choosing wisely on imaging in men with newly diagnosed prostate cancer.

INTRODUCTION: Encouraging the appropriate use of staging imaging in patients with newly diagnosed prostate cancer remains a challenge. Assessing the effects of national efforts may help guide future initiatives in curtailing low-value care. The purpose of this study was to determine the impact of the Choosing Wisely campaign on imaging utilization among men with prostate cancer. METHODS: Surveillance, Epidemiology, and End Results - Medicare data were used to complete a longitudinal population-based study of men diagnosed with prostate cancer from 2007 to 2015. An interrupted time series analysis evaluated the impact of the Choosing Wisely campaign on trends of imaging utilization. RESULTS: From 2007 to 2015 imaging utilization in low-risk patients decreased, with computed tomography (CT) usage declining from 45.0% to 34.4% (P<0.001) and nuclear medicine bone scan (NMBS) from 27.8% to 11.7% (P<0.001). Choosing Wisely likely contributed to an absolute reduction of 2.9% (P=0.03) in utilization of NMBS in the low-risk population. Imaging usage for all modalities increased in the high-risk population, but with 32.8% continuing to not receive guideline-supported imaging. CONCLUSIONS: In 2012, the Choosing Wisely campaign sought to decrease inappropriate staging imaging for men with low-risk prostate cancer and encourage stewardship of medical resources. Overall decreases in staging imaging trends suggest a move towards higher value care. However, this study found that the Choosing Wisely recommendations had a modest impact on utilization of NMBS, but not CT or PET scans. These results may help inform future efforts to promote guideline concordant imaging.

Attenuation of the Induction of TLRs 2 and 4 Mitigates Inflammation and Promotes Neurological Recovery After Focal Cerebral Ischemia.

The intense inflammatory response triggered in the brain after focal cerebral ischemia is detrimental. Recently, we showed that the suppression of toll-like receptors (TLRs) 2 and 4 attenuates infarct size and reduces the expression of pro-inflammatory cytokines in the ischemic brain. In this study, we further examined the effect of unsuppressed induction of TLRs 2 and 4 on the expression of its downstream signaling molecules and pro-inflammatory cytokines 1 week after reperfusion. The primary purpose of this study was to investigate the effect of simultaneous knockdown of TLRs 2 and 4 on M1/M2 microglial polarization dynamics and post-stroke neurological deficits and the recovery. Transient focal cerebral ischemia was induced in young adult male Sprague-Dawley rats by the middle cerebral artery occlusion (MCAO) procedure using a monofilament suture. Appropriate cohorts of rats were treated with a nanoparticle formulation of TLR2shRNA and TLR4shRNA (T2sh+T4sh) expressing plasmids (1 mg/kg each of T2sh and T4sh) or scrambled sequence inserted vector (vehicle control) expressing plasmids (2 mg/kg) intravenously via tail vein immediately after reperfusion. Animals from various cohorts were euthanized during reperfusion, and the ischemic brain tissue was isolated and utilized for PCR followed by agarose gel electrophoresis, real-time PCR, immunoblot, and immunofluorescence analysis. Appropriate groups were subjected to a battery of standard neurological tests at regular intervals until 14 days after reperfusion. The increased expression of both TLRs 2 and 4 and their downstream signaling molecules including the pro-inflammatory cytokines was observed even at 1-week after reperfusion. T2sh+T4sh treatment immediately after reperfusion attenuated the post-ischemic inflammation, preserved the motor function, and promoted recovery of the sensory and motor functions. We conclude that the post-ischemic induction of TLRs 2 and 4 persists for at least 7 days after reperfusion, contributes to the severity of acute inflammation, and impedes neurological recovery. Unlike previous studies in TLRs 2 or 4 knockout models, results of this study in a pharmacologically relevant preclinical rodent stroke model have translational significance.