Faysal A. Yafi

Contemporary outcomes of 2287 patients with bladder cancer who were treated with radical cystectomy: a Canadian multicentre experience.

Study Type – Therapy (case series)

Impact of tumour location versus multifocality in patients with upper tract urothelial carcinoma treated with nephroureterectomy and bladder cuff excision: a homogeneous series without perioperative chemotherapy

Study Type – Prognosis (case series)

Is the performance of urinary cytology as high as reported historically? A contemporary analysis in the detection and surveillance of bladder cancer

OBJECTIVES The goal of this study was to evaluate sensitivity and specificity of urine cytology during a contemporary period at our institution in comparison with historical analysis and other reported urinary biomarkers. MATERIALS AND METHODS Data from 1,114 consecutive patients corresponding to 3,251 specimens (2,979 cytologic and 272 histologic specimens) between January 2006 and July 2006 were retrieved. Subsequent cytologic and surgical specimen reports were examined with a minimum 2-year follow-up period. Collected parameters included the date of collection, reason for urinary evaluation, type of specimen, and tumor grade. Atypical diagnosis was considered negative. RESULTS On cytologic examination, 71% of specimens were benign, 23% atypical, and 6% suspicious or positive for urothelial carcinoma. Reason for collection was surveillance in 61% and new symptoms in 28%. Depending on the tumor grade, sensitivity results ranged from 10% for low-grade to 51% for high-grade tumors. Importantly, specificity of urine cytology ranged from 83% to 88% (depending on the type of urine collection and type of clinical presentation). Anticipatory positive rate was 44% after a median time of 15 months. Specificity of other reported urinary markers ranges from 40% to 90%. CONCLUSION Our institutions experience with regard to specificity of urine cytology is lower than reported historically. Whether this is a consequence of heterogeneous study designs and parameters is open to debate. As the anticipatory positive rate was high, close surveillance remains recommended in patients with positive urine cytology and negative workup. Other institutions are encouraged to evaluate whether there remains a significant advantage for urine cytology over other urinary marker assays within their own clinical setting.

Surveillance guidelines based on recurrence patterns after radical cystectomy for bladder cancer: the Canadian Bladder Cancer Network experience

Study Type – Prognosis (cohort)

Prognostic factors and outcome in patients with T1 high-grade bladder cancer: can we identify patients for early cystectomy?

Study Type – Therapy (case series)

Adjuvant chemotherapy for upper-tract urothelial carcinoma treated with nephroureterectomy: Assessment of adequate renal function and influence on outcome

OBJECTIVES Upper-tract urothelial carcinoma (UTUC) is associated with poor outcomes. Our aim was to assess adequacy of renal function and evaluate the role of adjuvant chemotherapy (AC) in patients with UTUC treated by radical nephroureterectomy (RNU) in a universal health care system. MATERIALS AND METHODS Retrospective data from 1,029 patients treated with RNU across 10 Canadian academic centers were collected. Tested variables included various clinico-pathological parameters, the use of perioperative chemotherapy, preoperative and postoperative creatinine values, and estimated glomerular filtration rates (eGFR). Univariable and multivariable Cox regression models addressed overall survival and disease-specific survival after surgery. Kaplan-Meier survival curves were used to compare outcomes in patients who received or did not receive AC. RESULTS Median age of patients was 70 years with a median follow-up of patients who were alive of 26 months. The median preoperative and postoperative eGFR rates were 59 mL/min/1.73 m(2) and 47 mL/min/1.73 m(2), respectively. Using a cutoff eGFR of 60, 49% of all the patients and 48% of the patients with ≥ pT3 or pTxN+ or both diseases would have been eligible for cisplatin-based chemotherapy preoperatively and only 18% and 21% of the patients, respectively remained eligible postoperatively. Of the patients who received AC, 75% had an eGFR<60. On multivariate analysis, AC was not prognostic for improved overall survival or disease-specific survival. CONCLUSIONS Chronic kidney disease is common in patients with UTUC. Following RNU, 57% of the high-risk patients with good preoperative renal function became ineligible for cisplatin-based chemotherapy. Use of AC did not translate into improved survival. Whether this is due to inherent biases of retrospective analysis, limited efficacy of AC in patients with UTUC, or use of suboptimal regimen or dose because of poor postoperative renal function requires further evaluation.

Relevance of the mammalian target of rapamycin pathway in the prognosis of patients with high-risk non–muscle invasive bladder cancer☆☆☆

High-risk non-muscle invasive bladder cancer (NMIBC) is associated with higher rates of recurrence and progression. Molecular markers within aberrant signaling pathways in cancer need further evaluation of their role as prognostic indicators and potential future targets for prevention of recurrence. Our objective was to investigate the role of the mammalian target of rapamycin (mTOR) signaling pathway on the stage and outcome of patients with high-risk NMIBC. Tissue microarrays were built from archival bladder tumor specimens (n = 142). Various clinicopathologic variables were collected retrospectively from patients treated with transurethral resection. Immunohistochemical staining was performed for phosphatase and tensin homolog, phosphorylated Akt, phosphorylated mTOR, phosphorylated S6 (p-S6), eukaryotic translation initiation factor 4E-binding protein-1, and p27. Multivariate analysis using Cox regression models addressed recurrence-free survival (RFS), progression-free survival, and worsening-free survival. In multivariate analysis, p-S6 was an independent predictor of shorter RFS (hazard ratio, 3.55; 95% CI, 1.31-9.64). Expression of p27 was inversely correlated with RFS (hazard ratio, 0.27; 95% CI, 0.10-0.74). Low levels of phosphatase and tensin homolog expression were associated with worsening-free survival (P < .03). None of the markers showed correlation with progression-free survival. Our results demonstrate that activation of the mTOR pathway, as assessed by p-S6 and expression of p27, might be used to provide prognostic information, particularly as a predictor of recurrence among patients with high-risk NMIBC.

The Effect of Duration of Penile Traction Therapy in Patients Undergoing Intralesional Injection Therapy for Peyronie's Disease

PURPOSE The concomitant use of penile traction therapy with interferon α-2b has been previously described. We present an update on our clinical experience to assess the benefit and duration of daily traction. MATERIALS AND METHODS A retrospective review of patients who underwent interferon α-2b therapy between 2001 and 2012 was performed. Charts were reviewed and data collected regarding various patient demographics, vascular parameters, objective length and curvature measurements, and use of penile traction therapy. Penile traction therapy was further stratified according to duration of daily use. RESULTS A total of 112 patients underwent a median of 12 interferon α-2b injections (range 6 to 24). Daily use of penile traction therapy was reported by 31% of patients. There were no differences in patient demographics, initial vascular status, pretreatment stretched penile length, erect circumference and curvature between patients who followed a penile traction therapy regimen and those who did not. Overall, the use of penile traction therapy did not effect change in penile circumference (with therapy +3.2 mm [SD 6.5] vs no therapy +2.1 mm [SD 7.4], p=0.45), change in curvature (with therapy -8.1 degrees [SD 16.0] vs no therapy -9.9 degrees [SD 11.8], p=0.49) or change in stretched penile length (with therapy +2.4 mm [SD 0.9] vs no therapy +1.3 mm [SD 0.8], p=0.56). Men who used penile traction therapy 3 or more hours per day gained significantly greater stretched penile length compared to those who did not use penile traction therapy (4.4 mm [SD 0.5] vs 1.3 mm [SD 0.8], p=0.04). CONCLUSIONS Routine penile traction therapy during intralesional injection with interferon α-2b for Peyronies disease may result in a small but subjectively meaningful improvement in stretched penile length, without affecting curvature, if used for at least 3 hours a day.

Outcome of Surgical Treatment of Patients with Upper versus Lower Urinary Tract Urothelial Carcinoma: Stage-by-Stage Comparison

Objectives: It remains controversial whether we can apply similar principles in the management of upper urinary tract urothelial carcinoma (UUT-UC) based on the behavior of bladder urothelial carcinoma (B-UC). We sought to assess whether UUT-UC and B-UC have similar biology and performed a stage-by-stage comparative analysis of outcome between the 2 groups. Methods: A retrospective review was performed on patients who underwent nephroureterectomy for UUT-UC and radical cystectomy for B-UC from 1991 to 2006. Standard variables were collected and recurrence-free and overall survival (OS) rates were calculated. Results: 280 patients with a median age of 69 years were included (99 UUT-UC treated via nephroureterectomy and 181 B-UC treated via radical cystectomy). Median follow-up was 29 months. None received neoadjuvant chemotherapy. Patients with UUT-UC presented less commonly with invasive disease compared to those with B-UC (44 vs. 77% were >pT2). Overall, 5-year OS for the B-UC group was significantly lower than for the UUT-UC group (60.8 vs. 74.5%, p = 0.02). However, when patients were stratified by stage (>pT2), patients with B-UC had similar OS compared to those with UUT-UC (54.6 vs. 60.8%, p = 0.74). Conclusion: Invasive UUT-UC appears to have similar tumor biology compared to B-UC. Whether we can safely extrapolate on the benefit of neoadjuvant and adjuvant strategies to patients with UUT-UC requires further investigation.

Contemporary management of muscle-invasive bladder cancer

Over the past decade, there have been a number of substantial changes in the treatment of invasive bladder cancer. Muscle-invasive bladder cancer is an aggressive disease that often presents at an advanced stage with or without distant metastases. The potential for cure is highest when the disease is confined to the bladder. Optimal management depends on our understanding of disease biology, refinements to our clinical staging, and improvements in the quality of treatment. This review will focus on the contemporary management of muscle-invasive urothelial carcinoma of the bladder and will discuss the role of radical cystectomy, extended lymphadenectomy, neoadjuvant/ adjuvant chemotherapy, and various forms of bladderpreservation strategies.