Risk factors for Gleason score upgrade from prostate biopsy to radical prostatectomy.

Accurate identification of prostate cancer Gleason grade group remains an important component of the initial management of clinically localized disease. However, Gleason score upgrading (GSU) from biopsy to radical prostatectomy can occur in up to a third of patients treated with surgery. Concern for disease undergrading remains a source of diagnostic uncertainty, contributing to both over-treatment of low-risk disease as well as under-treatment of higher-risk prostate cancer. This review examines the published literature concerning risk factors for GSU from time of biopsy to prostatectomy final pathology. Risk factors identified for Gleason upgrading include patient demographic and clinical factors including age, body mass index, race, prostate volume, and biomarker based assays, including prostate-specific antigen (PSA) density, and testosterone values. In addition, prostate magnetic resonance imaging (MRI) findings have also been associated with GSU. Biopsy-specific characteristics associated with GSU include lower number of biopsy cores and lack of targeted methodology, and possibly increasing percent biopsy core positivity. Recognition of risk factors for disease undergrading may prompt confirmatory testing including repeat sampling or imaging. Continued refinements in imaging guided biopsy techniques may also reduce sampling error contributing to undergrading.

Association between pelvic lymph node dissection and survival among patients with prostate cancer treated with radical prostatectomy.

Introduction: Although the clinical benefits of pelvic lymph node dissection (PLND) at the time of radical prostatectomy for prostate cancer remain uncertain, major guidelines recommend PLND based on risk profile. Thus, the objective of this study was to examine the association between PLND and survival among patients undergoing RP stratified by Gleason grade group (GG) with the aim of allowing patients and physicians to make more informed care decisions about the potential risks and benefits of PLND. Materials and methods: From the SEER-17 database, we examined overall (OS) and prostate cancer-specific (PCSS) survival of prostate cancer patients who underwent RP from 2010 to 2015 stratified by GG. We applied propensity score matching to balance pre-operative characteristics including race, age, PSA, household income, and housing status (urban/rural) between patients who did and did not undergo PLND for each GG. Statistical analyses included log-rank test and Kaplan-Meier curves. Results: We extracted a matched cohort from 80,287 patients with GG1-5 who underwent RP. The median PSA value was 6.0 ng/mL, and the median age was 62-years-old. 49,453 patients underwent PLND (61.60%), while 30,834 (38.40%) did not. There was no difference in OS and PCSS between patients who received PLND and those who did not for all Gleason GG (OS-GG1: P = 0.20, GG2: P = 0.34, GG3: P > 0.05, GG4: P = 0.55, GG5: P = 0.47; PCSS-GG1: P = 0.11, GG2: P = 0.96, GG3: P = 0.81, GG4: P = 0.22, GG5: P = 0.14). Conclusions: In this observational study, PLND at the time of RP was not associated with improved OS or PCSS among patients with cGS of 3 + 3, 3 + 4, 4 + 3, 4 + 4, 4 + 5, and 5 + 4. These findings suggest that until definitive clinical trials are completed, prostate cancer patients who have elected RP should be appropriately counseled on the potential risks and lack of proven survival benefit of PLND.

The effect of a fermented soy beverage among patients with localized prostate cancer prior to radical prostatectomy.

BACKGROUND: Fermented soy products have shown to possess inhibitory effects on prostate cancer (PCa). We evaluated the effect of a fermented soy beverage (Q-Can®), containing medium-chain triglycerides, ketones and soy isoflavones, among men with localized PCa prior to radical prostatectomy. METHODS: We conducted a placebo-controlled, double-blind randomized trial of Q-Can®. Stratified randomization (Cancer of the Prostate Risk Assessment (CAPRA) score at diagnosis) was used to assign patients to receive Q-Can® or placebo for 2-5 weeks before RP. Primary endpoint was change in serum PSA from baseline to end-of-study. We assessed changes in other clinical and pathologic endpoints. The primary ITT analysis compared PSA at end-of-study between randomization arms using repeated measures linear mixed model incorporating baseline CAPRA risk strata. RESULTS: We randomized 19 patients, 16 were eligible for analysis of the primary outcome. Mean age at enrollment was 61, 9(56.2%) were classified as low and intermediate risk, and 7(43.8%) high CAPRA risk. Among patients who received Q-Can®, mean PSA at baseline and end-of-study was 8.98(standard deviation, SD 4.07) and 8.02ng/mL(SD 3.99) compared with 8.66(SD 2.71) to 9.53ng/mL(SD 3.03), respectively, (Difference baseline - end-of-study, p = 0.36). There were no significant differences in Gleason score, clinical stage, surgical margin status, or CAPRA score between treatment arms (p > 0.05), and no significant differences between treatment arms in end-of-study or change in lipids, testosterone and FACT-P scores (p > 0.05). CONCLUSIONS: Short exposure to Q-Can® among patients with localized PCa was not associated with changes in PSA levels, PCa characteristics including grade and stage or serum testosterone. Due to early termination from inability to recruit, study power, was not achieved.

A meta-analysis on the use of radiotherapy after prostatectomy: adjuvant versus early salvage radiation.

To determine which method of radiotherapy proves more effective after prostatectomy: Adjuvant (ART) or early salvage (ESRT), we observed the pathologic and adverse risk factors of patients and their results from both treatments, looking specifically at biochemical-free survival rates, metastasis-free survival rates, and overall survival rates. Peer review articles containing their own data collected between 1986 and 2022 were reviewed. We reviewed 67 peer review articles and included 33 that met criteria. Studies focused on the adverse risk factors and the results of patients either before/after receiving adjuvant or early salvage/salvage radiotherapy were included in the analysis. Patient characteristics had an effect on what treatment a patient would receive; if a patient had more than one adverse risk factor such as a high Gleason score, prostate-specific antigen (PSA) level, T-stage, or positive margins, they would receive immediate radiation after prostatectomy, which would classify as ART. If the patient had no adverse risk factors after surgery, they would be placed in an observation period to follow their PSA and overall health, and only if necessary, undergo ESRT. Of the 33 studies, ART was proven to be only slightly more beneficial when relating to biochemical recurrence-free survival while ART and ESRT results were similar in metastasis-free survival and overall survival. ART and ESRT are overall comparable in their patient outcomes, despite their own unique pros and cons. The use of ESRT reduces overtreatment in men who may not experience biochemical recurrence. However, in those with very high-risk pathologic features, a multi-disciplinary approach should be utilized to best determine which mode of radiation therapy after surgery is recommended.

Transcriptomics in RCC.

Improvements in chemistry, molecular biology, genetics, and bioinformatics have allowed broad use of transcriptomic profiling. Understanding the population of ribonucleic acid (RNA) transcripts can provide important clinical information relevant to kidney cancer care. This includes a better understanding of kidney cancer subtype and distinct clusters within these categories. RNA-sequencing (RNA-seq) is typically done on a region within the tumor, which represents thousands to millions of heterogeneous cells and various components of the microenvironment. Computational tools can deconvolute these populations to provide insight into the microenvironment. Specific signatures of hypoxia, proliferation, angiogenesis and immune infiltration can predict response and survival. Prognostic signatures can risk stratify tumors to aid in identification of patients who might derive benefit from adjuvant therapy. As the cost of sequencing continues to decline and improved bioinformatic tools are developed, the barriers to clinical use of transcriptomic data continue to crumble. Here we review the current literature around the use of transcriptomics in kidney cancer diagnosis and management.

Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe.

OBJECTIVE: To improve visualization of upper tract urothelial carcinomas. Previous studies using the novel pH low insertion peptide (pHLIP) variant 3 (Var3) conjugated to indocyanine green (ICG) have demonstrated high sensitivity and specificity for imaging of bladder urothelial carcinoma. Here, we describe a novel approach for the imaging of upper tract urothelial carcinomas using ICG-Var3 pHLIP. METHODS: Twelve ex-vivo upper urinary tract specimens were irrigated with ICG-Var 3 pHLIP for 15 minutes and then examined using a white light laparoscopic camera followed by near infrared fluorescent (NIRF) imaging using a Stryker 1588 AIM imaging system. Standard histopathologic evaluation was performed and findings were correlated with white light and ICG-Var3 NIRF imaging. One patient who underwent radical nephrectomy for renal cell carcinoma was used as a negative control. RESULTS: Nineteen lesions were identified on histopathologic evaluation in 10 patients, including 82% high-grade urothelial carcinoma and 18% low-grade urothelial carcinoma. Nineteen (100%) malignant lesions were identified using NIRF imaging, while 15 (78.9%) lesions were identified using conventional white light examination. The sensitivity of ICG-Var3 pHLIP NIRF imaging was 100% compared to 78.9% white light examination. Both modalities are 100% specific. Benign collecting systems and ureters did not show uptake of the pHLIP construct. CONCLUSION: In this feasibility study, the ICG-Var3 pHLIP imaging agent demonstrated superior diagnostic performance compared to conventional white light examination. While additional studies are required for validation and in-vivo translation, pHLIP-based imaging represents a promising tool to improve the evaluation and management of upper tract urothelial carcinoma.

National trends and economic impact of surgical treatment for benign kidney tumors.

OBJECTIVES: Kidney masses suspicious for malignancy are frequently detected by cross-sectional imaging; however, little is known about the burden of surgical treatment for tumors found to be benign following excision. MATERIAL AND METHODS: We queried the National Inpatient Sample to identify records of individuals who received surgical treatment for renal neoplasms between 2004 and 2014. We characterized temporal treatment trends, patient demographics, treatment related complications, and charges. RESULTS: We identified 7,099 (8.5%) and 76,892 (91.5%) patients who were treated for benign and malignant tumors, respectively. Benign masses accounted for 14.8% of partial and 5.5% of radical nephrectomies. The rates of surgery for benign tumors have remained steady (P = 0.058). The frequency of inpatient death was higher in those with malignant disease (0.63% vs. 0.18%, P < 0.0001). Median length of stay was longer for individuals with malignant renal tumors (4.86 vs. 4.12 days, P < 0.0001). The total discharge bill adjusting for inflation for benign or malignant renal surgery increased each year (R2 = 0.428, R2 = 0.719, P = 0.001, P = 0.0311, respectively). As of 2014, the estimated national inpatient cost of management for benign renal tumors was $153 million dollars ($55,573/individual). CONCLUSIONS: 8.5% of inpatient renal surgical admissions are performed for benign masses. There has been a trend toward decreased operative management for benign renal tumors over time. Surgical management remains a significant economic burden. Efforts to prospectively evaluate modalities for pretreatment identification should be further pursued.

The association of lymph node dissection with 30-day perioperative morbidity among men undergoing minimally invasive radical prostatectomy: analysis of the National Surgical Quality Improvement Program (NSQIP).

BACKGROUND: The incremental morbidity of lymph node dissection (LND) among men undergoing radical prostatectomy remains uncertain. We therefore evaluated  the association of LND with perioperative morbidity among men undergoing minimally invasive radical prostatectomy (MIRP). METHODS: We identified 29,012 men aged 35-89 who underwent MIRP from 2010-2015 in the National Surgical Quality Improvement Program (NSQIP) database, of whom 47% underwent concomitant LND. The associations of LND with 30-day perioperative morbidity and mortality were evaluated using logistic regression, adjusted for patient features. RESULTS: Median age at surgery was 63 (IQR 57, 67) years. There were statistically significant, but clinically insignificant, differences in several baseline characteristics stratified by performance of LND, including older age at surgery (p < 0.001), higher American Society of Anesthesiology (ASA) class (p < 0.001), and longer operative time (p < 0.001) for men who underwent LND. Overall, 30-day complications occurred in 4.3% of patients. There were no statistically significant differences in rates of 30-day complications (4.2 vs. 4.4%, p = 0.44), perioperative blood transfusion (1.7 vs. 1.7%, p = 0.99), hospital readmission (3.6 vs. 4.0%, p = 0.09), reoperation (1.1 vs. 1.1%, p = 0.80), or 30-day mortality (0.1 vs. 0.2%, p = 0.56) between patients who underwent MIRP alone or MIRP with LND, respectively. On multivariable analysis, LND was not significantly associated with an increased risk of perioperative morbidity or 30-day mortality. CONCLUSIONS: LND at the time of MIRP does not appear to be associated with an increased risk of perioperative morbidity.

Subcutaneous emphysema following cystoscopic clot evacuation.

Gross hematuria is a common urologic problem which often requires surgical intervention. While generally a safe procedure, clot evacuation can have serious complications. Here we describe the case of an 85-year-old male who developed extensive subcutaneous emphysema following a small extraperitoneal bladder perforation during a clot evacuation. While our patient did well with expectant management, subcutaneous emphysema can lead to serious complications and any endourologic procedure should be stopped once crepitus is noted.

The role of lymph node dissection in the contemporary management of renal cell carcinoma: A critical appraisal of the evidence.

The role of lymph node dissection (LND) in the management of renal cell carcinoma has been controversial. Older studies provided initial support to a potential survival benefit in resection of lymph node metastases, and several predictive models were developed to identify patients with lymph node involvement. However, the only randomized trial on the subject did not report a survival benefit to LND in the nonmetastatic setting. Several studies have recently reexplored the therapeutic benefit of LND. In both nonmetastatic and metastatic settings, LND does not appear to be associated with a survival benefit. Moreover, it does not appear that LND confers a survival advantage to patients at increased risk of lymph node metastases, such as those with preoperative radiographic lymphadenopathy or across increasing probability of lymph node disease. Among patients with clinically isolated lymph node metastases, the majority develop disease progression following surgical resection, suggesting a high prevalence of occult systemic disease. Lymph node metastases appear to have prognostic value in both nonmetastatic and metastatic settings. LND may, therefore, have an increasingly important staging role in the management of renal cell carcinoma.

Upgrading and upstaging at radical prostatectomy in the post-prostate-specific antigen screening era: an effect of delayed diagnosis or a shift in patient selection?

Prostate cancer management changed in recent times given the recommendation against prostate-specific antigen screening, adherence to active surveillance, and "cytoreductive" surgery. We hypothesized that radical prostatectomy (RP) findings changed as well. All consecutive RPs (n=1348) and first time prostate needle biopsies (n=1719) in a period of 9 years were reviewed. The cohort was separated into 3 groups: (1) from May 2006 to April 2009, (2) from May 2009 to April 2012, and (3) from May 2012 to April 2015. The number of RPs decreased 15% from 551 in group 1 to 476 in group 2 and decreased a further 35% to 311 in group 3. Pure Gleason 6 (grade group 1) decreased from 46% in group 1 to 24% in group 2 (P<.001) to 12% in group 3 (P<.001). Gleason score 4+3=7 (grade group 3) increased from 9.8% in group 1 to 13.4% in group 2 (P=.07) to 20.6% in group 3 (P=.01). Gleason score 8, 9, or 10 (grade groups 4 and 5) increased from 0.9% in group 1 to 8.4% in group 2 (P<.001) to 13.2% in group 3 (P=.04). Pathologic stage pT3 or above increased from 15.5% in group 1 to 29.2% in group 2 (P<.01) to 38.3% in group 3 (P=.01). In needle biopsies, there was no difference in number of cancer diagnoses, number of positive cores, or distribution of grades among 3 groups. More patients with low-risk disease are opting for active surveillance, and patients with high-risk disease are offered cytoreductive surgery. Lack of similar changes in needle biopsies suggests that a decrease in screening is not playing a role in the changes seen at RPs.

The Use of Biomarkers in Prostate Cancer Screening and Treatment.

Prostate cancer screening and diagnosis has been guided by prostate-specific antigen levels for the past 25 years, but with the most recent US Preventive Services Task Force screening recommendations, as well as concerns regarding overdiagnosis and overtreatment, a new wave of prostate cancer biomarkers has recently emerged. These assays allow the testing of urine, serum, or prostate tissue for molecular signs of prostate cancer, and provide information regarding both diagnosis and prognosis. In this review, we discuss 12 commercially available biomarker assays approved for the diagnosis and treatment of prostate cancer. The results of clinical validation studies and clinical decision-making studies are presented. This information is designed to assist urologists in making clinical decisions with respect to ordering and interpreting these tests for different patients. There are numerous fluid and biopsy-based genomic tests available for prostate cancer patients that provide the physician and patient with different information about risk of future disease and treatment outcomes. It is important that providers be able to recommend the appropriate test for each individual patient; this decision is based on tissue availability and prognostic information desired. Future studies will continue to emphasize the important role of genomic biomarkers in making individualized treatment decisions for prostate cancer patients.

Endourologic and Open Ureterolithotomy and Common Sheath Reimplant for Large Bladder and Distal Ureteral Calculi.

A twenty-eight-year-old female with a history of suprapubic pain and recurrent urinary tract infections presents for urology referral with a kidney, ureter, and bladder radiograph showing a 4.4 cm bladder calculus and 6.5 cm distal left ureteral stone. She underwent effective cystolitholapaxy of the bladder stone. Endourologic attempt (left ureteroscopy) was unsuccessful because of ureteral stone burden. Findings at ureteroscopy revealed a duplicated system on the left with the lower pole moiety joining just proximal to the ureteral orifice. The stone was found to be in the upper pole moiety ureter. An open ureterolithotomy was performed with intraoperative ureteroscopic laser lithotripsy and common sheath ureteral reimplant. Furthermore, a previously placed stent was found to be encrusted at the time of the ureterolithotomy. Effective ureteroscopy and lasering were performed through the ureterotomy up to the renal pelvis of the upper pole ureter.

Targeted imaging of urothelium carcinoma in human bladders by an ICG pHLIP peptide ex vivo.

Bladder cancer is the fifth most common in incidence and one of the most expensive cancers to treat. Early detection greatly improves the chances of survival and bladder preservation. The pH low insertion peptide (pHLIP) conjugated with a near-infrared fluorescent dye [indocyanine green (ICG)] targets low extracellular pH, allowing visualization of malignant lesions in human bladder carcinoma ex vivo. Cystectomy specimens obtained after radical surgery were immediately irrigated with nonbuffered saline and instilled with a solution of the ICG pHLIP construct, incubated, and rinsed. Bladders were subsequently opened and imaged, the fluorescent spots were marked, and a standard pathological analysis was carried out to establish the correlation between ICG pHLIP imaging and white light pathological assessment. Accurate targeting of bladder lesions was achieved with a sensitivity of 97%. Specificity is 100%, but reduced to 80% if targeting of necrotic tissue from previous transurethral resections or chemotherapy are considered as false positives. The ICG pHLIP imaging agent marked high-grade urothelial carcinomas, both muscle invasive and nonmuscle invasive. Carcinoma in situ was accurately diagnosed in 11 cases, whereas only four cases were seen using white light, so imaging with the ICG pHLIP peptide offers improved early diagnosis of bladder cancers and may also enable new treatment alternatives.

Intravesical Hemostatic Clip Migration After Robotic Prostatectomy: Case Series and Review of the Literature.

INTRODUCTION: The Weck Hem-o-lok™ Ligating clip is a routinely used hemostatic tool in robotic and laparoscopic surgery. It has been the practice in our institution to use such clips for hemostasis of the vascular bundles during robotic prostatectomy. Migration of such clips has been reported in the literature as single case reports. In this study, we present a case series of intravesical Weck clip extrusions presenting as bladder calculi. Such events have led to a change in our practice, and more research is needed to assess the impact of this change. MATERIALS AND METHODS: A retrospective chart review was conducted over the period 2006-2011. Patients included in the study required cystoscopic intervention for removal of encrusted or impacted Weck clips. Primary data points included type of intervention required, time to presentation, and number of presentations. Postoperative anastomotic leak, duration of postoperative hospital stay, and initial operative time were also investigated. RESULTS: Out of 570 total men undergoing robotic-assisted laparoscopic radical prostatectomy (RALRP), eight required return to the operating room for clip extraction (1.4%). Extraction methods included laser lithotripsy, blunt litholapaxy, and grasper extraction. Men experiencing clip migration were hospitalized for a longer period of time (7.6 days vs. 2.1 days, P < .01) and they required more blood transfusions (1.4 units vs. 0.05 units, P < .01) than men who did not experience clip migration. The most common site for clip intrusion was the bladder neck. Average time to presentation was 1.75 years. DISCUSSION: Weck clip migration is a recognized complication of robotic-assisted radical prostatectomy. Men with recurrent urinary tract infection, bothersome voiding symptoms, or hematuria following RALRP should be considered for cystoscopic evaluation. Increased length of hospital stays and the need for a larger volume blood transfusion following prostatectomy were significant predictors of clip migration. More research is needed to determine if implemented changes to our surgical technique have mitigated these risks.

Partial Nephrectomy for Small Renal Masses: Do Teaching and Nonteaching Institutions Adhere to Guidelines Equally?

INTRODUCTION: The American Urological Association (AUA) guidelines recommend partial nephrectomy (PN) as the gold standard for treatment of small renal masses (SRMs). This study examines the change in utilization of partial and radical nephrectomies at teaching and nonteaching institutions from 2003 to 2012. MATERIALS AND METHODS: The data sample for this study came from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 2003 to 2012. International Classification of Diseases, Ninth Revision and Clinical Modification codes were used to identify patients undergoing PN and radical nephrectomy for renal masses limited to the renal parenchyma. Teaching hospitals were defined, but not limited to any institution with an American Medical Association-approved residency program. Linear regression, bivariate, multivariate, and odds ratio analysis were used to demonstrate statistical significance. RESULTS: 39,685 patients were identified in teaching hospitals, and 22,239 were identified in nonteaching hospitals. Prior to the 2009 AUA guidelines, cumulative rates of PN were 33% vs 20% in teaching vs nonteaching hospitals (p < 0.0001) compared with postguideline rates of 48% vs 33% in teaching vs nonteaching hospitals (p < 0.0001). CONCLUSIONS: During the 10-year study period, the use of PN to treat SRMs has significantly increased in both teaching hospitals and in nonacademic centers; however, these changes are occurring at a slower rate in nonteaching hospitals.

c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme.

Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism of progression from well-differentiated to dedifferentiated liposarcoma. To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c-Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c-Jun amplification. c-Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well-differentiated components (59%), but only in the minority of pure well-differentiated liposarcomas (27%). When c-Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c-Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c-Jun in c-Jun-amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c-Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation.

A prostatic intraepithelial neoplasia-dependent p27 Kip1 checkpoint induces senescence and inhibits cell proliferation and cancer progression.

Transgenic expression of activated AKT1 in the murine prostate induces prostatic intraepithelial neoplasia (PIN) that does not progress to invasive prostate cancer (CaP). In luminal epithelial cells of Akt-driven PIN, we show the concomitant induction of p27(Kip1) and senescence. Genetic ablation of p27(Kip1) led to downregulation of senescence markers and progression to cancer. In humans, p27(Kip1) and senescence markers were elevated in PIN not associated with CaP but were decreased or absent, respectively, in cancer-associated PIN and in CaP. Importantly, p27(Kip1) upregulation in mouse and human in situ lesions did not depend upon mTOR or Akt activation but was instead specifically associated with alterations in cell polarity, architecture, and adhesion molecules. These data suggest that a p27(Kip1)-driven checkpoint limits progression of PIN to CaP.