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Background: MRI fusion prostate biopsy has improved the detection of clinically significant prostate cancer (CSC). Continued refinements in predicting the pre-biopsy probability of CSC are essential for optimal patient counseling. We investigated potential factors related to improved cancer detection rates (CDR) of CSC in patients with PI-RADS ≥ 3 lesions. Methods: The pathology of 980 index lesions in 980 patients sampled by transrectal mpMRI-targeted prostate biopsy across four medical centers between 2017–2020 was reviewed. PI-RADS lesion distribution included 291 PI-RADS-5, 374 PI-RADS-4, and 315 PI-RADS-3. We compared CDR of index PI-RADS ≥ 3 lesions based on location (TZ) vs. (PZ), PSA density (PSAD), and history of prior negative conventional transrectal ultrasound-guided biopsy (TRUS). Results: Mean age, PSA, prostate volume, and level of prior negative TRUS biopsy were 66 years (43–90), 7.82 ng/dL (5.6–11.2), 54 cm3 (12–173), and 456/980 (46.5%), respectively. Higher PSAD, no prior history of negative TRUS biopsy, and PZ lesions were associated with higher CDR. Stratified CDR highlighted significant variance across subgroups. CDR for a PI-RADS-5 score, PZ lesion with PSAD ≥ 0.15, and prior negative biopsy was 77%. Conversely, the CDR rate for a PI-RADS-4 score, TZ lesion with PSAD < 0.15, and prior negative biopsy was significantly lower at 14%. Conclusions: For index PI-RADS ≥ 3 lesions, CDR varied significantly based on location, prior history of negative TRUS biopsy, and PSAD. Such considerations are critical when counseling on the merits and potential yield of prostate needle biopsy.

Imaging for prostate cancer defines the extent of disease. Guidelines recommend against imaging low-risk prostate cancer patients with a computed tomography (CT) scan or bone scan due to the low probability of metastasis. We reviewed imaging performed for men diagnosed with low-risk prostate cancer across the Pennsylvania Urologic Regional Collaborative (PURC), a physician-led data sharing and quality improvement collaborative. The data of 10 practices were queried regarding the imaging performed in men diagnosed with prostate cancer from 2015 to 2022. The cohort included 13,122 patients with 3502 (27%) low-risk, 2364 (18%) favorable intermediate-risk, 3585 (27%) unfavorable intermediate-risk, and 3671 (28%) high-risk prostate cancer, based on the AUA guidelines. Amongst the low-risk patients, imaging utilization included pelvic MRI (59.7%), bone scan (17.8%), CT (16.0%), and PET-based imaging (0.5%). Redundant imaging occurred in 1022 patients (29.2%). There was variability among the PURC sites for imaging used in the low-risk patients, and iterative education reduced the need for CT and bone scans. Approximately 15% of low-risk patients had staging imaging performed using either a CT or bone scan, and redundant imaging occurred in almost one-third of men. Such data underscore the need for continued guideline-based education to optimize the stewardship of resources and reduce unnecessary costs to the healthcare system.

Bladder cancer can often exhibit genomic and morphological heterogeneity. Here, the authors use genomics analysis to show lineage plasticity of bladder cancers with squamous differentiation, and identify key transcription factors related to this morphological and immune heterogeneity.

Abstract Human cancers display a restricted set of expression profiles, despite diverse mutational drivers. This has led to the hypothesis that select sets of transcription factors act on similar target genes as an integrated network, buffering a tumor’s transcriptional state. Noninvasive papillary urothelial carcinoma (NIPUC) with higher cell cycle activity has higher risk of recurrence and progression. In this paper, we describe a transcriptional network of cell cycle dysregulation in NIPUC, which was delineated using the ARACNe algorithm applied to expression data from a new cohort (n = 81, RNA sequencing), and two previously published cohorts. The transcriptional network comprised 121 transcription factors, including the pluripotency factors SOX2 and SALL4, the sex hormone binding receptors ESR1 and PGR, and multiple homeobox factors. Of these 121 transcription factors, 65 and 56 were more active in tumors with greater and less cell cycle activity, respectively. When clustered by activity of these transcription factors, tumors divided into High Cell Cycle versus Low Cell Cycle groups. Tumors in the High Cell Cycle group demonstrated greater mutational burden and copy number instability. A putative mutational driver of cell cycle dysregulation, such as homozygous loss of CDKN2A, was found in only 50% of High Cell Cycle NIPUC, suggesting a prominent role of transcription factor activity in driving cell cycle dysregulation. Activity of the 121 transcription factors strongly associated with expression of EZH2 and other members of the PRC2 complex, suggesting regulation by this complex influences expression of the transcription factors in this network. Activity of transcription factors in this network also associated with signatures of pluripotency and epithelial-to-mesenchymal transition (EMT), suggesting they play a role in driving evolution to invasive carcinoma. Consistent with this, these transcription factors differed in activity between NIPUC and invasive urothelial carcinoma.

Background: Prostate needle biopsy (PNB) remains the referent standard for diagnosing prostate cancer. Contemporary data highlight an increase in PNB-related infections particularly when performed transrectally. Non-infectious complications, however, may similarly contribute to biopsy-related morbidity. We review the incidence and predictors of non-infectious complications following transrectal PNB in a large statewide quality registry. Methods: Transrectal ultrasound-guided prostate needle biopsies performed between 2015 and 2018 were retrospectively reviewed. The incidence and distribution of non-infectious complications were annotated. Clinical, demographic, and biopsy variables of interest were evaluated by logistic regression for potential association with specific types of non-infectious complications. Results: Of 8,102 biopsies, 277 (3.4%) biopsies had reported post-procedure complications including 199 (2.5%) non-infectious and 78 (0.9%) infectious. Among the non-infectious complications, the most common events included urinary or rectal bleeding (74; 0.9%), urinary retention (70, 0.9%), vasovagal syncope (13, 0.2%), and severe post-operative pain (10, 0.1%). Approximately 56% of these non-infectious complications required an Emergency Department visit (111/199) and 27% (54/199) hospital admission for monitoring. Increasing transrectal ultrasound prostate volume was associated with post-procedure urinary retention (Odds ratio (OR) 1.07, 1.02–1.11, p = 0.002). No specific variables noted association with post-biopsy bleeding. Conclusion: Non-infectious complications occurred 2.5 times more often than infectious complications following transrectal ultrasound prostate needle biopsies. Larger prostate size was associated with a greater risk of post-procedure urinary retention. These data originating from experience from over 100 urologists across different health systems provide an important framework in counseling patients regarding expectations following transrectal prostate biopsy.

Background: The 2017 AUA White Paper on prevention of prostate needle biopsy (PNB) complications highlights an algorithm for reducing procedural related infections. The incorporation of topical rectal antiseptic (TRS) at time of transrectal PNB is listed as one such modality. We present data on over 1000 transrectal PNB procedures to determine the impact of TRS on 1) infectious complications and 2) use of augmented procedural antibiotics. Methods: The records of 1181 transrectal PNB procedures performed over a 10-year period were reviewed. In 2013, TRS with either 10% povidone iodine or 4% chlorhexidine was more regularly incorporated into PNB procedures. Clinical and procedural factors were analyzed for association with post-procedure infections. Infectious complications outcomes were compared in patients receiving TRS (n = 566) versus those who had not (n = 615). Results: A total of 990 men underwent 1181 transrectal PNB procedures. Median age of the cohort was 63 years with a median PSA of 7 ng/dL. Of them, 86% of the men were Caucasian, 28% had undergone at least one prior biopsy, 14% were diabetic, and 6% had prior hospitalization within 6 months of the procedure. Five hundred sixty-six patients (48%) received TRS at time of biopsy. Perioperative IV adjunctive antibiotics were used less frequently in patients receiving TRS (13.4% vs. 28.6%, p

Abstract Muscle-invasive bladder cancers are characterized by their distinct expression of luminal and basal genes, which could be used to predict key clinical features such as disease progression and overall survival. Transcriptionally, FOXA1, GATA3, and PPARG are shown to be essential for luminal subtype-specific gene regulation and subtype switching, while TP63, STAT3, and TFAP2 family members are critical for regulation of basal subtype-specific genes. Despite these advances, the underlying epigenetic mechanisms and 3D chromatin architecture responsible for subtype-specific regulation in bladder cancer remain unknown. Result We determine the genome-wide transcriptome, enhancer landscape, and transcription factor binding profiles of FOXA1 and GATA3 in luminal and basal subtypes of bladder cancer. Furthermore, we report the first-ever mapping of genome-wide chromatin interactions by Hi-C in both bladder cancer cell lines and primary patient tumors. We show that subtype-specific transcription is accompanied by specific open chromatin and epigenomic marks, at least partially driven by distinct transcription factor binding at distal enhancers of luminal and basal bladder cancers. Finally, we identify a novel clinically relevant transcription factor, Neuronal PAS Domain Protein 2 (NPAS2), in luminal bladder cancers that regulates other subtype-specific genes and influences cancer cell proliferation and migration. Conclusion In summary, our work identifies unique epigenomic signatures and 3D genome structures in luminal and basal urinary bladder cancers and suggests a novel link between the circadian transcription factor NPAS2 and a clinical bladder cancer subtype.

Multiple molecular profiling methods are required to study urothelial non-muscle-invasive bladder cancer (NMIBC) due to its heterogeneity. Here the authors integrate multi-omics data of 834 NMIBC patients, identifying a molecular subgroup associated with multiple alterations and worse outcomes.

Background: The United States Preventative Services Task Force (USPSTF) guideline on Prostate Specific Antigen (PSA)-based prostate cancer screening evolved both in 2008 (Grade I for men 75 years) and in 2012 (Grade D for all ages). Materials and methods: A statewide cancer registry operated by the Pennsylvania Department of Health was accessed to analyze over a 15-year period prostate cancer rates across different categories including age, stage, and geographic distribution. Results: Local prostate cancer rates decreased significantly when comparing before and after USPSTF's guideline changes: 2002–2008 vs. 2009–2012 vs. 2013–2016 (p 70 years), the implications of the aforementioned observations on mortality outcomes merit further follow-up.

Nationwide databases have implicated an increased incidence of renal cell carcinoma (RCC). The Pennsylvania (PA) Cancer Registry was queried to better define incidence, geographic distribution, and statewide trends of new RCC cases over a 27-year period. JoinPoint Trend Analysis Software modeled average annual percent changes (APCs) in age-adjusted rates (AAR). Maps plotting county-level incidence rates and stage distribution of disease across the state in 5-year time intervals were created using R 4.0.2 software. Overall, 59,628 cases of RCC were recorded in PA from 1990 to 2017. Eighty six percent of patients were >50 years of age, 61% were males, and 89% were Caucasian. Stage distribution using the SEER staging system included 64% local, 17% regional, and 16% distant. Over the study interval, AAR of all RCC cases increased from 9.9 to 18.0 patients per 100,000 population with an APC of 2.3% (p < 0.01). AAR of local disease increased from 5.4 to 12.7 patients per 100,000 population with an APC of 3.2% (p < 0.01). AAR of regional disease also increased from 1.9 to 2.9 patients per 100,000 population with an APC of 1.0% (p = 0.01). Younger patients (

Abstract Background Advances in systemic targeted therapies afford treatment opportunities in patients with metastatic renal cell carcinoma (RCC). Elderly patients with metastatic RCC present a subpopulation for consideration owing to competing causes of mortality and benefits seen with new therapeutic agents. We investigate treatment patterns for elderly patients with stage IV RCC and determine factors associated with not receiving treatment. Methods The Surveillance Epidemiology and End Results (SEER) Medicare linked data set contained 949 stage IV RCC patients over age 65 diagnosed between 2007 and 2011. Treatment approach was modeled using multinomial logistic regression. Landmark analysis at 6 months accounted for early death as a potential explanation for no treatment. Results Of the 949 patients with stage IV RCC, 26.2% received surgery and 34.1% received systemic therapy within 6 months of diagnosis. Among our entire cohort, over half (51.2%) had no evidence of receiving surgery or systemic therapy. Among the 447 patients who survived at least 6 months, 26.6% did not receive treatment during this time. Older patients and those with a higher Charlson Comorbidity Index (CCI) had lower odds of being treated with surgery, systemic therapy, or both. Conversely, married patients had higher odds of receiving these therapies. These associations were largely sustained in the 6-month landmark analyses. Conclusions Elderly patients with metastatic RCC present a unique subpopulation for consideration owing to competing causes of mortality. Many elderly patients with stage IV RCC did not receive surgery or systemic therapy up to 6 months from diagnosis. Several clinical and demographic factors were associated with this observation. Further investigation is needed to understand the rationale underlying the underutilization of systemic therapy in elderly patients.

Management of residual or recurrent disease following thermal ablation of renal cortical tumors includes surveillance, repeat ablation, or surgical extirpation. We present a multicenter experience with regard to the management of this clinical scenario. Prospectively maintained databases were reviewed to identify 1265 patients who underwent cryoablation (CA) or radiofrequency ablation (RFA) for enhancing renal masses. Disease per-sistence or recurrence was classified into one of the three categories: (i) residual disease in ablation zone; (ii) recurrence in the ipsilateral renal unit; and (iii) metastatic/extra-renal disease. Seventy seven patients (6.1%) had radiographic evidence of disease persistence or recurrence at a median interval of 13.7 months (range, 1–65 months) post-ablation. Distribution of disease included 47 patients with residual disease in ablation zone, 29 with ipsilateral renal unit recurrences (all in ablation zone), and one with metastatic disease. Fourteen patients (18%) elected for surveillance, and the remaining underwent salvage ablation (n = 50), partial nephrectomy (n = 5), or radical nephrectomy (n = 8). Salvage ablation was successful in 38/50 (76%) patients, with 12 failures managed by observation (3), tertiary ablation (6), and radical nephrectomy (3). At a median follow-up of 28 months, the actuarial cancer-specific survival and overall survival in this select cohort of patients was 94.8 and 89.6%, respectively.

Background: To evaluate early consequences of 2012 United States Preventive Services Task Force (USPSTF) recommendations for decreased prostate-specific antigen (PSA) screening on prostate biopsy characteristics and prostate cancer presentation. Materials and methods: A single tertiary-care institution, multisurgeon, prospectively maintained database was queried for patients undergoing prostate biopsy from October 2005 to September 2016. Patient demographics, biopsy characteristics, and extent of disease were reported. Patient cohorts before and after USPSTF recommendations were compared using two-sample t test, Chi-square test, and Wilcoxon rank sum test with significance at P

Cellular and molecular heterogeneity within tumors has long been associated with the progression of cancer to an aggressive phenotype and a poor prognosis. However, how such intratumoral heterogeneity contributes to the invasiveness of cancer is largely unknown. Here, using a tumor bioengineering approach, we investigate the interaction between molecular subtypes within bladder microtumors and the corresponding effects on their invasiveness. Our results reveal heterogeneous microtumors formed by multiple molecular subtypes possess enhanced invasiveness compared to individual cells, even when both cells are not invasive individually. To examine the molecular mechanism of intratumoral heterogeneity mediated invasiveness, live single cell biosensing, RNA interference, and CRISPR-Cas9 gene editing approaches were applied to investigate and control the composition of the microtumors. An agent-based computational model was also developed to evaluate the influence of NOTCH1 variation on DLL4 expression within a microtumor. The data indicate that intratumoral variation in NOTCH1 expression can lead to upregulation of DLL4 expression within the microtumor and enhancement of microtumor invasiveness. Overall, our results reveal a novel mechanism of heterogeneity mediated invasiveness through intratumoral variation of gene expression.

Low-attenuation renal lesions on non-contrast computed tomography (CT) are often considered to be benign cysts without need for further imaging. However, the papillary subtype of renal cell carcinoma (RCC) may have similar radiographic charac-teristics. A single-center retrospective review was therefore performed to identify extirpated papillary RCC (pRCC) specimens with correlation made to preoperative tumor imaging characteristics. A total of 108 pRCC specimens were identified of which 84 (27 type I, 17 type 2, 40 unspecified) had CT imaging available for review. Non-contrast CT was available for 73 tumors with 16 (22%) demonstrating Hounsfield units (HU) measurements fewer than 20 at baseline without differences between papillary subtypes. Mean attenuation following contrast administration was similar between papillary subtypes (45 HU for type 1 pRCC and 49 HU for type 2). This study highlights that pathologically proven pRCC is a heterogeneous entity in terms of density on preoperative CT imaging. A non-contrast CT scan with HU fewer than 20 may not be an adequate evaluation for incidental renal masses, as over 1 in 5 pRCCs demonstrate lower attenuation than this cutoff. Further study is needed to identify the appropriate role of ancillary imaging in the workup of seemingly benign-appearing renal lesions.

The standard diagnostic procedure for prostate cancer (PCa) is transrectal ultrasound (TRUS)-guided needle biopsy. However, due to the low sensitivity of TRUS to cancerous tissue in the prostate, small yet clinically significant tumors can be missed. Magnetic resonance imaging (MRI) with TRUS fusion biopsy has recently been introduced as a way to improve the identification of clinically significant PCa in men. However, the spatial errors in coregistering the preprocedural MRI with the real-time TRUS causes false negatives. A real-time and intraprocedural imaging modality that can sensitively detect PCa tumors and, more importantly, differentiate aggressive from nonaggressive tumors could largely improve the guidance of biopsy sampling to improve diagnostic accuracy and patient risk stratification. In this work, we seek to fill this long-standing gap in clinical diagnosis of PCa via the development of a dual-modality imaging device that integrates the emerging photoacoustic imaging (PAI) technique with the established TRUS for improved guidance of PCa needle biopsy. Unlike previously published studies on the integration of TRUS with PAI capabilities, this work introduces a novel approach for integrating a focused light delivery mechanism with a clinical-grade commercial TRUS probe, while assuring much-needed ease of operation in the transrectal space. We further present the clinical potential of our device by (i) performing rigorous characterization studies, (ii) examining the acoustic and optical safety parameters for human prostate imaging, and (iii) demonstrating the structural and functional imaging capabilities using deep-tissue-mimicking phantoms. Our TRUSPA experimental studies demonstrated a field-of-view in the range of 130 to 150 degrees and spatial resolutions in the range of 300 μm to 400 μm at a soft tissue imaging depth of 5 cm.

As a rare disease, the management of upper tract urothelial carcinoma (UTUC) continues to evolve. While radical nephroureterectomy remains the gold standard, there is a growing desire to pursue nephron-sparing approaches through endoscopic management, particularly for low-risk disease or in the setting of imperative indications. A particular challenge for those undertaking endoscopic management is appropriate grading and staging of tumors, and thereby appropriate patient selection. In this review we will cover the current state of diagnostics for UTUC as well as highlight the challenges in accurate diagnosis. Additionally, we will focus on emerging technologies to aid in optimizing diagnostic accuracy in UTUC. This will include discussion of narrow band imaging, photodynamic diagnosis, optical coherence tomography, and confocal laser endomicroscopy.

Purpose To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes. Materials and Methods Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. Results The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06). Conclusions Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC.

Since the inception of laparoscopic surgery, there has been an ongoing effort to develop an even more ‘minimally invasive’ approach to surgery. A novel example of such advancement can be found in laparoendoscopic single-site (LESS) surgery. Performing surgery through a single site of access holds the promise of decreased morbidity, lower blood loss, shorter convalescence, and improved cosmesis. Given the nonextirpative nature of the pyeloplasty procedure, this patient cohort has proven to be the ideal candidates for LESS surgery. The driving force behind adaptation of this newer technique can be attributed to innovations in access sites and devices, instrumentation, optics, and robotic-based assistance. There are now several studies in the published literature demonstrating the feasibility and efficacy of LESS pyeloplasty in both children and adults. Although comparative studies have failed to demonstrate any objective advantage of the LESS pyeloplasty operation, it is important to realize that LESS surgery is still a fairly new technique. Further technological developments and additional studies will ultimately define its role in the field of urologic surgery, and subsequently, its application for the pyeloplasty procedure.