John Sfakianos

The effect of age and gender on bladder cancer: a critical review of the literature

While patient age and gender are important factors in the clinical decision‐making for treating urothelial carcinoma of the bladder (UCB), there are no evidence‐based recommendations to guide healthcare professionals. We review previous reports on the influence of age and gender on the incidence, biology, mortality and treatment of UCB. Using MEDLINE, we searched for previous reports published between January 1966 and July 2009. While men are three to four times more likely to develop UCB than women, women present with more advanced disease and have worse survival rates. The disparity among genders is proposed to be the result of a differential exposure to carcinogens (i.e. tobacco and chemicals) as well as reflecting genetic, anatomical, hormonal, societal and environmental factors. Inpatient length of stay, referral patterns for haematuria and surgical outcomes suggest that inferior quality of care for women might be an additional cause of gender inequalities. Age is the greatest single risk factor for developing UCB and dying from it once diagnosed. Elderly patients face both clinical and institutional barriers to appropriate treatment; they receive less aggressive treatment and sub‐therapeutic dosing. Much evidence suggests that chronological age alone is an inadequate indicator in determining the clinical and behavioural response of older patients to UCB and its treatment. Epidemiological and mechanistic molecular studies should be encouraged to design, analyse and report gender‐ and age‐specific associations. Improved bladder cancer awareness in the lay and medical communities, careful patient selection, treatment tailored to the needs and the physiological and physical reserve of the individual patient, and proactive postoperative care are particularly important. We must strive to develop transdisciplinary collaborative efforts to provide tailored gender‐ and age‐specific care for patients with UCB.

Reflex fluorescence in situ hybridization assay for suspicious urinary cytology in patients with bladder cancer with negative surveillance cystoscopy

To assess the ability of reflex UroVysion fluorescence in situ hybridization (FISH) testing to predict recurrence and progression in patients with non‐muscle‐invasive bladder cancer (NMIBC) with suspicious cytology but negative cystoscopy.

Comparison of Perioperative Outcomes for Epidural Versus Intravenous Patient-controlled Analgesia After Radical Cystectomy

Background and Objectives The use of patient-controlled epidural analgesia after various operations has been associated with an early return of bowel function, thus decreasing patients’ length of stay (LOS). The primary aim of this study was to compare LOS after radical cystectomy between patients who received epidural analgesia versus those who received intravenous patient-controlled analgesia. Our secondary analysis included the assessment of other metrics such as total opioid requirements, pain scores, return of bowel function, and complication rates between the 2 groups. Methods We conducted a retrospective review using the electronic medical records of 308 patients who underwent radical cystectomies at Memorial Sloan Kettering between 2006 and 2011. We aimed to understand if epidural analgesia was associated with a reduced LOS compared with patient-controlled intravenous opioid analgesia. We also aimed to identify performance improvements as a function of epidural analgesia status using various metrics such as pain management, bowel function return, and complication rates. We used both univariate and multivariate analyses to identify if epidural analgesia was associated with meaningful differences in the aforementioned metrics. Results Median age at radical cystectomy, body mass index, sex, American Society of Anesthesiologists score, and T stage were similar for both groups. For our primary objective of LOS, we found no significant difference between the 2 cohorts (8 vs 7 days, P = 0.2). Analysis of our secondary outcome measures revealed that epidural analgesia use was associated with less total opioid requirement for the first 3 postoperative days (PODs) (P = 0.0001). In addition, epidural analgesia was found to be associated with improved postoperative pain scores compared with intravenous patient-controlled analgesia on PODs 1 (P = 0.0001) and 2 (P = 0.004), and there was a slight improvement on POD 3, but this was not significant (P = 0.77). In contrast, we found no difference between pain management types with regard to proportion of patients who experienced a delay in gastrointestinal recovery, fluid bolus requirements within the first 3 perioperative days, rates of infection, pulmonary complications, and grade 3 or greater complications. Conclusions We have demonstrated that, despite significant improvements in initial pain control and less opioid requirement with patient-controlled epidural analgesia, there was no association between analgesic approach and LOS, return of bowel function, or complications.

Genomic differences between black and white patients implicate a distinct immune response to papillary renal cell carcinoma

Significant disparities in survival, incidence and possibly response to current therapies exist between black and white patients with renal cell carcinoma (RCC). Recent genomic evidence to account for these disparities has been reported for clear cell RCC. However, racial disparities at the genomic level for papillary RCC (pRCC) which is a genetically distinct and less responsive histologic subtype of RCC have not been reported. Using The Cancer Genome Atlas (TCGA) data, the present study assessed gene-level expression, somatic mutation and pathway differences between 58 black and 58 white patients with pRCC propensity matched on age, gender and pathologic T stage. Distinct tumor biology with differential expression patterns were observed in black vs. white patients with pRCC. Specifically, significance analysis of microarrays was applied to TCGA gene expression data and identified 163 genes and 120 genes overexpressed in black and white patients, respectively (FDR q<0.05). Gene Set Enrichment Analysis identified 62 gene sets enriched (p<0.10) in blacks. Enrichment of immune immune system pathways were noted in black patients. These included the B cell receptor signaling pathway, the NOD-like receptor signaling pathway and genes involved in defensins. The VEGF pathway was also more significant in black patients. CRYBB2, a gene associated with the WNT pathway was overexpressed in Black patients. While our data requires validation, these findings suggest that race may have implications for distinct immune responses to cancer and that the use of immunotherapies, and VEGFR inhibitors to target these pathways may improve survival in black patients with advanced pRCC.

Reflex fluorescencein situhybridization assay for suspicious urinary cytology in patients with bladder cancer with negative surveillance cystoscopy: Reflex FISH assay for suspicious urinary cytology in patients with bladder cancer

To assess the ability of reflex UroVysion fluorescence in situ hybridization (FISH) testing to predict recurrence and progression in patients with non‐muscle‐invasive bladder cancer (NMIBC) with suspicious cytology but negative cystoscopy.

Moving beyond vascular endothelial growth factor-targeted therapy in renal cell cancer: latest evidence and therapeutic implications:

Renal cell cancer (RCC) continues to be among the most lethal malignancies in the USA. Introduction of anti-vascular epidermal growth factor receptor tyrosine kinase inhibitors over a decade ago resulted in improvement in disease outcomes, but further development of new therapies largely stagnated for many years. More recently, a better understanding of disease biology and treatment-resistance patterns has led to a second renaissance in drug development, with the anti-programmed cell death protein 1 immune checkpoint inhibitor, nivolumab, paving the way for additional therapies entering clinical trial testing in the treatment of RCC.

Dealing with perioperative antiplatelet treatment for transurethral resection of the bladder: primum non nocere

The number of patients receiving antithrombotic treatment is increasing (1), thus increasing the number of patients under anticoagulant or antiplatelet treatment scheduled to undergo endo-urology surgery.

PD65-04 MR/US FUSION GUIDED ULTRA-FOCAL GOLD NANOPARTICLE DIRECTED LASER ABLATION OF PROSTATE TUMORS: RESULTS IN THE FIRST 11 PATIENTS (PHASE I/II TRIAL)

INTRODUCTION AND OBJECTIVES: Gold Nanoparticles (GNP) mediated laser ablation has been shown to be biocompatible and safe for the treatment of focal cancer. Herein, we report the first 11 cases in the world using GNP-directed focal laser ablation of prostate tumors using ultrasound (US) and MR/US fusion technology (NCT NCT02680535). METHODS: All patients were diagnosed with Gleason 7 or less prostate cancer with biopsy proven MR visible lesions and no disease other than appreciated on the MRI. Patients underwent ultra-focal laser ablation of the tumors using GNP with MR/US fusion guidance. Following infusion of intravenous GNP on Day 0, trans-perineal laser catheters were placed into the prostate lesions for GNP excitation/tumor ablation under MR/US fusion guidance using an electromagnetictracked MR/US fusion device (UroNav, Invivo Gainesville FL). At 48 hours post-ablation, the patient is imaged, followed by re-imaging and MR/US fusion guided biopsy (FBx) at 3 months. All patient demographics, clinical variables, and complications were recorded. RESULTS: To date, 11 patients (mean age: 69.6 yrs; range 5879 yrs) have been enrolled in the trial. All patients were diagnosed with Gleason < 7. All patients had a solitary lesion with mean tumor volume 0.73 mL (range 0.6-1.87 cc). A single patient did not tolerate the cold IV infusion of the gold nano particles and was not able to undergo ablation the following day. 8 of 10 patients have completed the 3 month followup targeted biopsy as primary endpoint. Mean pre-treatment PSA was 7.84 ng/mL (range 5.5-12.3 ng/mL). Mean post-treatment PSA was 3.9 ng/mL (range 1.5-6.1 ng/mL; 50% reduction). Five out of eight patients (62.5%) did not have any cancer detected on follow up biopsy. Only 1 out of 8 patients had clinically significant cancer as per Delphi consensus criteria (Gleason score >6 or cancer > 3mm at Gleason score 6). CONCLUSIONS: Recent trends toward less invasive image guided therapies have been seen as investigators pursue focal targeted therapies. This report is the first in-man demonstration of MR/US guided ultra-focal laser ablation of prostate tumors using GNP.

Current Role of Checkpoint Inhibitors in Urologic Cancers

Harnessing the host immune system to combat genitourinary cancers has key theoretical advantages over other anticancer strategies including specificity and memory which should translate to favorable tolerability and response durability in the clinic. Indeed, key examples of the potential for immunotherapeutic treatment of solid tumors are derived from data in genitourinary cancers including Bacillus Calmette-Guerin for urothelial cancer, sipuleucel-T for prostate cancer, and interleukin-2 for renal cancer. Despite these successes, developing effective immunotherapeutic strategies for the treatment of cancer has largely been hampered by an incomplete understanding of tumor immunobiology and mechanisms of immune resistance. In just a few years since entering the clinic, immune checkpoint blockade has dramatically changed the landscaped of treatment for genitourinary cancer and has secured a place as a standard pillar of treatment. Further iterative bench-bedside-bench research is anticipated to extend the benefits of immunotherapeutic-based approaches to additional patients.

Genomic Characterization of Upper-Tract Urothelial Carcinoma in Patients With Lynch Syndrome

Purpose Patients with Lynch syndrome (LS) have a significantly increased risk of developing upper-tract urothelial carcinoma (UTUC). Here, we sought to identify differences in the patterns of mutational changes in LS-associated versus sporadic UTUCs. Patients and Methods We performed targeted sequencing of 17 UTUCs from patients with documented LS-associated germline mutations (LS-UTUCs) using the Memorial Sloan Kettering Integrated Molecular Profiling of Actionable Cancer Targets targeted exon capture assay and compared the results with those from a recently characterized cohort of 82 patients with sporadic UTUC. Results Patients with LS-UTUC were significantly younger, had had less exposure to tobacco, and more often presented with a ureteral primary site compared with patients with sporadic UTUC. The median number of mutations per tumor was significantly greater in LS-UTUC tumors than in tumors from the sporadic cohort (58; interquartile range [IQR], 47-101 v 6; IQR, 4-10; P < .001), as was the MSIsensor score (median, 25.1; IQR, 17.9-31.2 v 0.03; IQR, 0-0.44; P < .001). Differences in the genetic landscape were observed between sporadic and LS-associated tumors. Alterations in KMT2D, CREBBP, or ARID1A or in DNA damage response and repair genes were present at a significantly higher frequency in LS-UTUC. CIC, NOTCH1, NOTCH3, RB1, and CDKN1B alterations were almost exclusive to LS-UTUC. Although FGFR3 mutations were identified in both cohorts, the R248C hotspot mutation was highly enriched in LS-UTUC. Conclusion LS- and sporadic UTUCs have overlapping but distinct genetic signatures. LS-UTUC is associated with hypermutation and a significantly higher prevalence of FGFR3 R248C mutation. Prospective molecular characterization of patients to identify those with LS-UTUC may help guide treatment.