Faculty Bibliography

PURPOSE: The aim of this study was to conduct a prospective pilot study comparing the diagnostic performance of MRI alone and F-FDG simultaneous PET/MRI using a diuresis protocol in bladder cancer patients. METHODS: Twenty-two bladder cancer patients underwent F-FDG PET/MRI, using intravenous furosemide and oral hydration for bladder clearance. A radiologist scored probability of tumor in 3 locations (urinary bladder, pelvic lymph nodes, nonnodal pelvis) using 1- to 3-point scale (1 = negative, 2 = equivocal, 3 = definite tumor). A nuclear medicine physician reviewed fused PET/MRI images, after which scores were reassigned based on combined findings. Follow-up pathologic and imaging data served as reference. Performances of MRI alone and PET/MRI were compared. RESULTS: Of these patients, 82%, 38%, and 18% were positive for bladder, pelvic nodal, and nonnodal pelvic tumor, respectively. At a score of 3, PET/MRI exhibited greater accuracy for detection of bladder tumor (86% vs 77%), metastatic pelvic lymph nodes (95% vs 76%), and nonnodal pelvic malignancy (100% vs 91%). In the bladder, PET changed the level of suspicion in 36% of patients (50% increased suspicion, 50% decreased suspicion), with 75% of these changes deemed correct based on reference standard. For pelvic lymph nodes, PET changed suspicion in 52% (36% increase, 64% decrease), with 95% of changes deemed correct. For nonnodal pelvis, PET changed suspicion in 9% (100% increase), with 100% deemed correct. CONCLUSIONS: Additional PET information helped to appropriately determine level of suspicion in multiple anatomic sites for otherwise equivocal findings on MRI alone. Although requiring larger studies, findings suggest a possible role for simultaneous PET/MRI to assist bladder cancer management.

OBJECTIVES: To determine whether a combination of PCA3 and MRI suspicion score (mSS) could further optimize detection of prostate cancer on MRF-TB among men with no previous history of biopsy. MATERIALS AND METHODS: 187 men presenting to our institution between 6/12 and 8/14 who underwent multiparametric MRI and PCA3 prior to MRF-TB. Biopsy results, stratified by biopsy indication and PCA3 score, were recorded. Receiver operating characteristics (ROC) curves and multivariable logistic regressions were utilized to model the association of PCA3 and mSS with cancer detection on MRF-TB. RESULTS: PCA3 is associated with cancer detection on MRF-TB for men with no prior biopsies (AUC = 0.67, 95% CI 0.59-0.76). Using a cutoff of >/=35, PCA3 was associated with cancer risk among men with mSS 2-3 (p=0.004), but not among those with mSS 4-5 (p=0.340). The interaction of PCA3 and mSS demonstrated significantly higher discrimination for cancer than mSS alone (AUC: 0.83 vs. 0.79, p=0.0434). CONCLUSIONS: Urinary PCA3 is associated with mSS and the detection of cancer on MRF-TB for men with no prior biopsies. PCA3 notably demonstrates a high negative predictive value among mSS 2-3. However, in the case of high suspicion mpMRI, PCA3 is not associated with cancer detection on MRF-TB adding little to cancer diagnosis. Further studies are needed to evaluate the utility of PCA3 in predicting cancer among men with normal mpMRI.

PURPOSE: To provide a comprehensive overview and update of the joint consultation of the International Consultation on Urological Diseases (ICUD) and Societe Internationale d'Urologie for the treatment of localized high-risk upper tract urothelial carcinoma (UTUC). METHODS: A detailed analysis of the literature was conducted reporting on treatment modalities and outcomes in localized high-risk UTUC. An international, multidisciplinary expert committee evaluated and graded the data according to the Oxford System of Evidence-based Medicine modified by the ICUD. RESULTS: Radical nephroureterectomy (RNU) is the standard of treatment for high-grade or clinically infiltrating UTUC and includes the removal of the entire kidney, ureter and ipsilateral bladder cuff. The distal ureter can be managed either by extravesical or transvesical approach, whereas endoscopically assisted procedures are associated with decreased intravesical recurrence-free survival. Post-operative intravesical chemotherapy decreases the risk of subsequent bladder tumour recurrence. Regional lymph node dissection is of prognostic importance in infiltrative UTUC, but its extent has not been standardized. Renal-sparing surgery is an option for manageable, high-grade tumours of any part of the upper tract, especially of the distal ureter, as an alternative to RNU. Endoscopy-based renal-sparing procedures are associated with a higher risk of recurrence and progression. CONCLUSIONS: A multimodal approach should be considered in localized high-risk UTUC to improve outcomes. RNU is the standard of treatment in high-risk disease. Renal-sparing approaches may be oncologically equivalent alternatives to RNU in well-selected patients, especially in those with distal ureteric tumours.

BACKGROUND: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. METHODS: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. RESULTS: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. CONCLUSIONS: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. (c) 2016 Wiley Periodicals, Inc.

Purpose Pre-operative three-dimensional (3D) printed renal malignancy models are tools with potential benefits in surgical training and patient education [1,2]. Most importantly, 3D models may facilitate surgical planning by allowing surgeons to assess tumor complexity as well as the relationship of the tumor to major anatomic structures [3]. The objective of this study was to evaluate this impact. Methods Imaging was obtained from an IRB approved, prospectively collected database of multiparametric magnetic resonance imaging (MRI) of renal masses. Ten cases eligible for elective partial nephrectomy were retrospectively selected. High-fidelity models were 3D printed in multiple colors based on T1 images (Fig. 1). Cases were reviewed by three attending surgeons and six senior residents with imaging alone and in addition to the 3D model. A standardized questionnaire was developed to capture the planned surgical approach and intraoperative technique in both sessions. Results Surgical approach was changed in 20 % of decisions, intraoperative considerations were changed in 40 % (Fig. 2). Thirty percent and 23 % of decisions in the attending and resident groups, respectively, were altered by the 3D model. Overall, every case was modified with this additional information. All participants reported that the models helped plan the surgical approach for partial nephrectomy. Most reported improved comprehension of anatomy and confidence in surgical plan. Half reported that the 3D printed model altered their surgical plan significantly. Due to use of T1 images, reconstruction of calyces and tertiary blood vessels were limited: 8 of the 9 participants desired more information regarding these structures. (Figure presented) Conclusion Utilization of 3D modeling may aid in pre-operative and intra-operative planning for both attending and resident surgeons. While 3D models with MR imaging is feasible, computed tomography (CT) imaging may provide additional anatomical information. Future study is required to prospectively assess the utility of models and pre-operative planning and intra-operative guidance

OBJECTIVE: The purpose of this article is to compare the effectiveness of a treatment algorithm for small renal tumors incorporating the nephrometry score, a renal tumor anatomy scoring system developed by urologists, with the current standard of uniformly recommended partial nephrectomy in patients with mild-to-moderate chronic kidney disease (CKD). MATERIALS AND METHODS: We developed a state-transition microsimulation model to project life expectancy (LE) in hypothetic patients with baseline mild or moderate CKD undergoing treatment of small renal masses. Our model incorporated the nephrometry score, which is predictive of postsurgical renal function loss. The two tested strategies were uniform treatment with partial nephrectomy and selective treatment based on nephrometry score and CKD stage, including percutaneous ablation for CKD stages 2 or 3a and intermediate-to-high nephrometry score or stage 3b CKD and any nephrometry score; otherwise, partial nephrectomy was assumed for other CKD stages and nephrometry scores. The model accounted for benign and malignant lesions, renal function decline, recurrence, and metastatic disease rates specific to each treatment, mortality by CKD stage, and comorbidities. Sensitivity analysis tested the stability of results when varying key parameters. RESULTS: Selective treatment with partial nephrectomy resulted in an average LE benefit of 0.48 year (95% interpercentile range, 0.42-0.54 year) in 65-year-old men and 0.37 year (95% interpercentile range, 0.30-0.43 year) in 65-year-old women relative to nondiscriminatory surgery, due to worsening CKD and cardiovascular mortality associated with partial nephrectomy. Model results were most sensitive to the rate of renal function decline and CKD-related mortality. CONCLUSION: Nephron-sparing treatment selection for small renal masses based on nephrometry score may improve LE in patients with mild or moderate CKD.

Purpose: Percutaneous thermal ablation (PTA) is a minimally-invasive, nephron-sparing alternative to surgery for patients with small renal cancers. We examined short- and long-term complications and disease-specific survival in older adults with small renal cancers who received partial (PN) nephrectomy, radical nephrectomy (RN) or PTA. Materials: In the linked Surveillance, Epidemiology and End Results-Medicare dataset we identified patients age 66 or older who received PN, RN or PTA within 6 months of diagnosis of a clinically-staged T1a renal cancer in 2006-2011. Follow-up for survival and cause of death was available through 2012. Complications assessed at 30 days and 31-365 days post procedure based on Medicare claims included renal insufficiency and periprocedural and cardiovascular complications. Associations between procedure type and complications were estimated in propensity score-matched logistic regression models. Associations with cancer-specific survival (CSS) were estimated in propensity score-adjusted, competing-risk models. Results: There were 4,508 patients with cT1a renal cancer, of whom 469 (10%) had PTA, 1,673 (37%) PN and 2,366 (53%) RN. Patients who had PTA were older and had greater comorbidity than those treated surgically (p<0.0001). At 30 days, rates of acute renal failure, structural kidney injury, cardiovascular complications and other periprocedural complications were significantly lower with PTA than PN or RN (adjusted odds ratios [AOR] 0.10-0.52, p<0.05). Rates of cardiovascular and renal structural complications at 1 year were similar across procedure types. PTA was associated with a lower risk of renal insufficiency in days 31-365 compared with RN (AOR 0.56, 95% CI 0.34-0.93, p< 0.05), but not with PN. At 46 months median follow-up, there were 112 deaths due to kidney cancer. Cancer-specific survival did not vary by procedure type. Conclusions: In a population-based cohort of older adults, PTA was associated with a lower risk of early complications than RN or PN, and a lower rate of long-term renal insufficiency than RN. PTA may be safer than surgery for well-selected patients, with no detriment to oncologic outcomes at nearly 4 years median follow-up

Background: Cisplatin-based chemotherapy before radical cystectomy (RC) improves survival in pts with MIBC. DD-GC therapy is active in the metastatic setting [6 cycles (cy), 18 months median survival; Bamias et al, 2012)] and as neo therapy (3 cy, 44% < pT1 rate; Plimack et al, 2014), but the optimal dose and number of cy of neo therapy has not been defined. We prospectively evaluated the activity and safety of 6 cy of neo DD-GC over 12 weeks in MIBC. Methods: Pts with T2-4aN0 disease received six 14-day cy of DD-GC as follows: G 2500 mg/m2 day 1, C 35 mg/m2 days 1 and 2, pegfilgrastim day 3. RC with bilateral pelvic lymph node dissection was planned within 8 weeks of DD-GC completion, regardless of clinical response. The primary endpoint was pathologic response ( < pT1) rate > 55% (exact Binomial one-sided test). Pts not undergoing RC were deemed non-responders regardless of clinical stage after DD-GC. Pts receiving < 3 cy were inevaluable and replaced. All pts were evaluable for toxicity. Results: 49 pts (40 male) were enrolled. Median age was 64 (range: 37-78). Clinical stage was T2N0 (32 pts), T3N0 (12 pts), and T4aN0 (5 pts). Toxicities resulting in cy delay and/or dose modifications included thrombocytopenia (9 pts), renal insufficiency (5 pts), vascular access complication (2 pts), ototoxicity (1 pt), significant urinary symptoms (1 pt), and transient ischemic attack (1 pt). Three pts are inevaluable for the primary endpoint ( < 3 cy). As of 9/7/15, 2 pts are pending RC. Of the 44 pts evaluable for response to date, 31 completed 6 cy of DD-GC, 6 pts completed 5, 3 pts completed 4, and 4 pts completed 3 (median: 6 cy). The median time to RC was 46 days. Four of 44 pts did not undergo RC (consent withdrawal, pt refusal, disease progression prior to RC, death from other causes). Trial accrual has closed with completion of clinical and pathologic data expected by 11/1/15. Of 40 pts with RC pathology available to date, 24 (60%) were < pT1 and 7 (18%) were pT0. Conclusions: Six cy of DD-GC is an active well-tolerated neo chemotherapy regimen in pts with MIBC. The pathologic response rate is encouraging. Thrombocytopenia was the most common toxicity resulting in cy delays/dose modifications