Diagnostic miRNA Signatures in Paired Tumor, Plasma, and Urine Specimens From Renal Cell Carcinoma Patients.

BACKGROUND: The incidence of patients diagnosed with renal cell carcinoma (RCC) is increasing. There are no approved biofluid biomarkers for routine diagnosis of RCC patients. This retrospective study aims to identify cell-free microRNA (cfmiR) signatures in urine samples that can be utilized as biomarkers for early diagnosis of sporadic RCC patients. METHODS: Tissue, plasma, and urine samples (n = 221) from 56 sporadic RCC patients and respective normal healthy donors were profiled for 2083 microRNAs (miRs) using the next-generation sequencing-based HTG EdgeSeq miR Whole Transcriptome Assay. DESeq2 (FC |1.2|, false discovery rate <0.05) was performed to identify differentially expressed miRs. Data from RCC tissue samples of The Cancer Genome Atlas database were used for miR validation. RESULTS: We found a 10-miR signature that distinguished RCC tissues from remote normal kidney tissue or benign kidney lesion samples. Additionally, we identified subtype-specific miRs (miR-122-5p, miR-210-3p, and miR-21-3p) and miRs specific for all RCC subtypes (miR-106b-3p, miR-629-5p, and miR-885-5p). We observed that miR-155-5p was associated with tumor size. Using The Cancer Genome Atlas data sets, we validated the miRs found in RCC tissue samples. In plasma or urine analysis, we found cfmiRs that were consistently and significantly upregulated in RCC tissue samples. A 15-cfmiR signature was proposed in urine samples of RCC patients, of which miR-1275 was consistently upregulated in tissue, plasma, and urine samples. CONCLUSIONS: This integrative study found diagnostic miRs/cfmiRs for RCC patients, which were validated using The Cancer Genome Atlas data sets. Distinctive cfmiR signatures found in urine may have clinical utility for the diagnosis of RCC.

Advances in chemoablation in upper tract urothelial carcinoma: overview of indications and treatment patterns.

Localized upper tract urothelial carcinoma (UTUC) is a difficult disease for clinicians to treat, due to the multitude of oncological and patient factors to consider. Despite the challenges of diagnostic staging, endoscopic management, and disease recurrence, there is still a need for local therapeutic options that do not subject patients to the morbidities of radical nephroureterectomy (RNU). Intraluminal chemotherapies have allowed for improved oncological control in patients with low-grade disease receiving renal-sparing treatment approaches. This narrative review discusses the treatment modalities available for localized low-grade UTUC, with a focus on the current status of chemoablation. The OLYMPUS trial was a pivotal study that lead to the Food and Drug Administration (FDA) approval of UGN-101 (mitomycin-C) in April 2020 for the treatment of low-grade UTUC, and intraluminal chemotherapy is now a widely used modality for managing this disease. The trial reported a complete response (CR) rate of 59%, and an estimated treatment durability of 82% at 1 year. However, a concern was the reported 44% ureteral stricture rate using the retrograde approach. More research is currently underway to determine the ideal instillation method for intraluminal therapies (e.g., retrograde vs. antegrade). Lastly, we discuss upcoming treatment options. Newer novel agents like padeliporfin vascular targeted photodynamic (VTP) therapy (brand name TOOKAD) are currently being studied, which will in hope provide additional treatment options for UTUC patients.

Characterization of Lymph Node Tumor Burden in Node-Positive Prostate Cancer Patients after Robotic-Assisted Radical Prostatectomy with Extended Pelvic Lymph Node Dissection.

BACKGROUND: Prostate cancer (PCa) nodal staging does not account for lymph node (LN) tumor burden. The LN anatomical compartment involved with the tumor or the quantified extent of extranodal extension (ENE) have not yet been studied in relation to biochemical recurrence-free survival (BRFS). METHODS: Histopathological slides of 66 pN1 PCa patients who underwent extended pelvic lymph node dissection were reviewed. We recorded metrics to quantify LN tumor burden. We also characterized the LN anatomical compartments involved and quantified the extent of ENE. RESULTS: The median follow-up time was 38 months. The median number of total LNs obtained per patient was 30 (IQR 23-37). In the risk-adjusted cox regression model, the following variables were associated with BRFS: mean size of the largest LN deposit per patient (log2: adjusted hazard ratio (aHR) = 1.91, p < 0.001), the mean total span of all LN deposits per patient (2.07, p < 0.001), and the mean percent surface area of the LN involved with the tumor (1.58, p < 0.001). There was no significant BRFS association for the LN anatomical compartment or the quantified extent of ENE. CONCLUSION: LN tumor burden is associated with BRFS. The LN anatomical compartments and the quantified extent of ENE did not show significant association with BRFS.

Route of Administration for UGN-101 and Impact on Oncological and Safety Outcomes.

BACKGROUND: UGN-101 can be used for chemoablation of low-grade upper tract urothelial carcinoma (UTUC). The gel can be administered via a retrograde route through a ureteral catheter or an antegrade route via a nephrostomy tube. OBJECTIVE: To report outcomes of UGN-101 by route of administration. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of 132 patients from 15 institutions who were treated with UGN-101 for low-grade UTUC via retrograde versus antegrade administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survival outcomes are reported per patient. Treatment, complications, and recurrence outcomes are reported per renal unit. Statistical analysis was performed for primary endpoints of oncological response and ureteral stricture occurrence. RESULTS AND LIMITATIONS: A total of 136 renal units were evaluated, comprising 78 retrograde and 58 antegrade instillations. Median follow-up was 7.4 mo. There were 120 cases (91%) of biopsy-proven low-grade UTUC. Tumors were in the renal pelvis alone in 89 cases (65%), in the ureter alone in 12 cases (9%), and in both in 35 cases (26%). Seventy-six patients (56%) had residual disease before UGN-101 treatment. Chemoablation with UGN-101 was used in 50/78 (64%) retrograde cases and 26/58 (45%) antegrade cases. A complete response according to inspection and cytology was achieved in 31 (48%) retrograde and 30 (60%) antegrade renal units (p = 0.1). Clavien grade 3 ureteral stricture occurred in 21 retrograde cases (32%) and only six (12%) antegrade cases (p < 0.01). Limitations include treatment bias, as patients in the antegrade group were more likely to undergo endoscopic mechanical ablation before UGN-101 instillation. CONCLUSIONS: These preliminary results show a significantly lower rate of stricture occurrence with antegrade administration of UGN-101, with no apparent impact on oncological efficacy. PATIENT SUMMARY: We compared results for two different delivery routes for the drug UGN-101 for treatment of cancer in the upper urinary tract. For the antegrade route, a tube is inserted through the skin into the kidney. For the retrograde route, a catheter is inserted past the bladder into the upper urinary tract. Our results show a lower rate of narrowing of the ureter (the tube draining urine from the kidney into the bladder) using the antegrade route, with no difference in cancer control.

Imaging After Ureteroscopy: Practice Patterns, Patient Adherence and Impact on Subsequent Management in an Urban Academic Hospital System.

OBJECTIVE: To evaluate practice patterns of post-ureteroscopy (URS) imaging, to assess predictors of imaging order, type and completion, and to analyze impact on patient management. METHODS: We conducted a retrospective review of patients who underwent URS for nephrolithiasis at a single institution between May, 2020 to May, 2021. Patient demographic, clinical and operative characteristics were reviewed, and surgeons' years in practice. Post-URS imaging studies less than 6 months post-operative were reviewed. Changes in patient management were defined as additional imaging tests ordered or subsequent unplanned surgery. Patient, provider and surgical variables were compared between those who had imaging ordered and those who did not. RESULTS: A total of 289 patients underwent URS. About 234 (81.0%) had post-operative imaging ordered; 147 (62.8%) completed them. Baseline demographics, stone and surgical variables were similar among those who did and did not have imaging ordered and among patients who completed imaging and did not. Pre-operative hydronephrosis was associated with ordering of post-operative imaging (OR = 4.08, P = .01). Urologists in practice less than 5 years were more likely to order post-operative imaging compared to those in practice for more than 5 years (<5: 90.6%, 15+: 53.7%; P <.001). Management changed for 52 of 147 (35.4%) patients who completed imaging; additional imaging was ordered for 38 patients (25.9%) and a second, unplanned surgery was performed for 14 (9.5%). CONCLUSION: The main predictive factor of ordering post-URS imaging was surgeons' time in practice and pre-operative hydronephrosis. Post-operative imaging changed management in 35.4% of patients. We recommend the development of guidelines encouraging routine imaging for patients following ureteroscopy.

Methodology for triage of urologic surgical cases in the setting of a pandemic.

BACKGROUND: The first wave of the COVID-19 pandemic in March 2020 forced our healthcare system in the Bronx, New York to cancel nearly all scheduled surgeries. We developed a framework for prioritizing postponed urologic surgeries that was utilized once cases were permitted to be rescheduled. As many parts of our country experience first and second waves of this pandemic, our framework may serve as a resource for other centers experiencing restrictions on the scheduling of elective urologic surgeries. METHODS: As the COVID-19 pandemic started and peaked in New York, almost all of our scheduled urologic surgeries were cancelled. Each Urologist was asked to rank his/her cancelled surgeries by priority (Level 1-least urgent; Level 2-moderately urgent; Level 3-most urgent). A committee of Urologists assigned a subclass to Level 3 and 2 cases (3a-least urgent; 3b-moderately urgent; 3c-most urgent; 2a-lower priority; 2b-higher priority). The committee then reviewed cases by urgency to derive a final priority ranking. RESULTS: A total of 478 total urologic surgeries were canceled and categorized: 250 Level 1, 130 Level 2, 98 Level 3 (73 adult, 25 pediatric). Level 3c involved renal cell carcinoma ≥ T2b, high-grade bladder urothelial carcinoma, adrenal mass/cancer > 6 cm, testicular cancer requiring radical orchiectomy, and penile cancer. Level 3b involved T2a renal masses requiring nephrectomy, while high-risk prostate cancer and symptomatic nephrolithiasis were classified as 3a. Level 2 included testicular cancer requiring retroperitoneal lymph node dissection and complicated benign prostatic hyperplasia. Surgeries for urologic reconstruction, non-complicated nephrolithiasis, erectile dysfunction, and urinary incontinence were considered Level 1. CONCLUSIONS: Our disease-specific approach to surgical rescheduling offers appropriate guidance for triaging urologic surgeries. Our system can provide guidance to other institutions as COVID-19 cases surge in different regions and with the growing second wave.

Multi-parametric MRI findings of granulomatous prostatitis developing after intravesical bacillus calmette-guérin therapy.

PURPOSE: To evaluate the multi-parametric MRI (mpMRI) findings in patients with biopsy-proven granulomatous prostatitis and prior Bacillus Calmette-Guérin (BCG) exposure. MATERIALS AND METHODS: MRI was performed in six patients with pathologically proven granulomatous prostatitis and a prior history of bladder cancer treated with intravesical BCG therapy. Multi-parametric prostate MRI images were recorded on a GE 750W or Philips Achieva 3.0 Tesla MRI scanner with high-resolution, small-field-of-view imaging consisting of axial T2, axial T1, coronal T2, sagittal T2, axial multiple b-value diffusion (multiple values up to 1200 or 1400), and dynamic contrast-enhanced 3D axial T1 with fat suppression sequence. RESULTS: Two different patterns of MR findings were observed. Five of the six patients had a low mean ADC value <1000 (decreased signal on ADC map images) and isointense signal on high-b-value imaging (b = 1200 or 1400), consistent with nonspecific granulomatous prostatitis. The other pattern seen in one of the six patients was decreased signal on the ADC map images with increased signal on the high-b-value sequence, revealing true restricted diffusion indistinguishable from aggressive prostate cancer. This patient had biopsy-confirmed acute BCG prostatitis. CONCLUSIONS: Our study suggests that patients with known BCG exposure and PI-RADS v2 scores ≤3, showing similar mpMRI findings as demonstrated, may not require prostate biopsy.

Smoking-related genitourinary cancers: A global call to action in smoking cessation.

Smoking is a known modifiable risk factor in the development of genitourinary malignancies. Although the association has long been supported by numerous research studies, the impact of smoking cessation on the decreased risk of genitourinary malignancies is less well studied. PubMed databases were searched using the terms smoking, smoking cessation, bladder cancer, kidney cancer, prostate cancer, penile cancer, testicular cancer, their synonyms, and also targeted manual searches to perform a literature review in order to summarize the benefits of cessation on disease progression and patient outcomes including survival and morbidities. Our review yielded substantial evidence highlighting the improved outcomes observed in those diagnosed with bladder, renal, and prostate cancers. The risk of bladder cancer is reduced by up to 60% in those who were able to quit for 25 years and the risk of kidney malignancy was reduced by 50% in those who abstained from smoking for 30 years. A similar trend of reduced risk was observed for prostate cancer with those who quit for more than 10 years, having prostate cancer mortality risks similar to those that never smoked. Although the data were encouraging for bladder, renal, and prostate malignancies, there are comparatively limited data quantifying the benefits of smoking cessation for penile and testicular cancers, highlighting an opportunity for further study. The role of urologists and their impact on their patients' likelihood to quit smoking shows more than half of urologists never discuss smoking cessation upon diagnosis of a malignancy. Most urologists said they did not provide cessation counseling because they do not believe it would alter their patients' disease progression. Studies show urologists have more influence at changing their patients' smoking behaviors than their primary care physicians. The diagnosis of cancer may lead to a teachable moment resulting in increased smoking quit rates. Furthermore, implementing a brief 5-minute clinic counseling session increases quit attempts and quit rates. Diagnosis of genitourinary cancers and the following appointments for treatment provide a unique opportunity for urologists to intervene and affect the progression and outcome of disease.