Assessment of a clinical pathway for investigation of haematuria that reduces the need for cystoscopy.

AIM: To evaluate prospectively a clinical pathway for investigation of haematuria that involves an initial screening using a urinary biomarker of bladder cancer (Cxbladder Triage™ (CxbT)) in combination with either a renal ultrasound or a computed tomography imaging. Only test-positive patients are referred for specialist assessment and flexible cystoscopy. METHODS: The clinical outcomes of 884 patients with haematuria who presented to their general practitioner were reviewed. Outcome measurements included the findings of laboratory tests, imaging, cystoscopies, specialist assessment and histology. RESULTS: Forty-eight transitional cell carcinomas (TCC) and three small cell carcinomas were diagnosed in the study cohort. The clinical pathway missed a solitary, small, low-risk TCC. When combined, imaging and CxbT had a sensitivity of 98.1% and a negative predictive value of 99.9% to detect a bladder cancer. Follow-up for a median of 21 months showed no further new cases of bladder cancer had occurred in the patient cohort. Review of all new bladder cancers diagnosed in the 15 months following the study showed that none had been missed by haematuria assessment using the clinical pathway. CONCLUSIONS: The combination of CxbT and imaging reliably identifies patients with haematuria who can be managed safely in primary care without the need for a secondary care referral and a flexible cystoscopy.

Increasing use of positron emission tomography among medicare beneficiaries undergoing radical cystectomy.

OBJECTIVE: To examine factors associated with PET scan use in the pre-operative evaluation of patients diagnosed with bladder cancer. METHODS: Using SEER-Medicare data, we identified bladder cancer patients who underwent radical cystectomy from 2006 to 2011 (n = 4,138). The primary outcome was PET scan use within 6 months before surgery. To examine predictors of PET scan use, we fit a mixed logit model with health service area as a random effect to account for patients nested within health service areas. We also calculated the adjusted probability of use over time and examined variation among the highest volume surgeons. RESULTS: Among the 4,138 patients, 406 (10%) received a pre-operative PET scan. The adjusted probability of a patient undergoing a PET scan increased from 0.04 in 2004 to 0.10 in 2011 (p < .001). Among the 78 highest volume surgeons, there was significant variation in PET scan use (p < .001). Patients with non-urothelial histology, measurement of alkaline phosphatase levels, and receipt of neoadjuvant chemotherapy were more likely to receive PET scan (all p < .05). CONCLUSION: Use of PET prior to radical cystectomy doubled over a 5-year period, suggesting its increased use in patients with muscle-invasive bladder cancer, particularly those with high-risk disease. Whether its use is warranted and improves patient outcomes is not clear and requires further studies.

Eligibility and Radiologic Assessment in Adjuvant Clinical Trials in Bladder Cancer.

Objective: To harmonize eligibility criteria and radiographic disease assessments in clinical trials of adjuvant therapy for muscle-invasive bladder cancer (MIBC). Methods: National experts in bladder cancer clinical trial research, including medical and urologic oncologists, radiologists, biostatisticians, and patient advocates, convened at a public workshop on November 28, 2017, to discuss eligibility, radiographic entry criteria, and assessment of disease recurrence in adjuvant clinical trials in patients with MIBC. Results: The key workshop conclusions for adjuvant MIBC clinical trials included the following points: (1) patients with urothelial carcinoma with divergent histologic differentiation should be allowed to enroll; (2) neoadjuvant chemotherapy is defined as at least 3 cycles of neoadjuvant cisplatin-based combination chemotherapy; (3) patients with muscle-invasive, upper-tract urothelial carcinoma should be included in adjuvant trials of MIBC; (4) patients with severe renal insufficiency can enroll into trials using agents that are not renally excreted; (5) patients with microscopic surgical margins can be included; (6) patients should undergo a standard bilateral lymph node dissection prior to enrollment; (7) computed tomographic (CT) imaging should be performed within 4 weeks prior to enrollment. For patients with renal insufficiency who cannot undergo CT imaging with contrast, noncontrast chest CT and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be done; (8) biopsy of indeterminate lesions to evaluate for malignant disease should be done when feasible; (9) a uniform approach to evaluate indeterminate radiographic lesions when biopsy is not feasible should be included in any trial design; (10) a uniform approach to determining the date of recurrence is important in interpreting adjuvant trial results; and (11) new high-grade, upper-tract primary tumors and new MIBC tumors should be considered recurrence events. Conclusions and Relevance: A uniform approach to eligibility criteria, definitions of no evidence of disease, and definitions of disease recurrence may lead to more consistent interpretations of adjuvant trial results in MIBC.

Evaluation of upper tract urothelial carcinomas by contrast-enhanced ultrasound. / Valoración del carcinoma urotelial de vías superiores mediante ecografía con contraste.

AIM: To describe the findings and behaviour of contrast-enhanced ultrasound in the study of upper tract urothelial tumours and to assess its usefulness for diagnosis. MATERIAL AND METHODS: We reviewed our hospital's database over a period of 45 months to identify patients diagnosed with upper tract urothelial carcinomas. We reviewed the findings on mode B-ultrasound, contrast-enhanced ultrasound (location and qualitative assessment of intensity and washout of enhancement), and made a comparison with other techniques (computed tomography or magnetic resonance), and with the surgical specimen. RESULTS: We found 42 patients with a diagnosis of upper tract urothelial carcinoma confirmed with surgery over the period reviewed. Twenty-eight (67%) patients underwent contrast-enhanced ultrasound. Baseline ultrasound showed hydronephrosis with or without ureteral dilatation with echogenic content occupying the renal calyx (6), pelvis (10) or ureter (12). After injection of contrast, enhancement was noticed in 100% of the lesions, with similar intensity to the cortex in 23, and less in 5. Twenty-four lesions showed early washout, before the cortex, between 40 and 55seconds after the injection. The diagnosis was correct in 27 cases. Localisation coincided with the histological specimen in 28 cases, and 3 patients had additional distal carcinoma foci. CONCLUSION: Contrast-enhanced ultrasound is a useful technique for diagnosing upper tract urothelial tumours that increases confidence in the diagnosis.

Imaging response assessment of immunotherapy in patients with renal cell and urothelial carcinoma.

PURPOSE OF REVIEW: Recent advances in anticancer immunotherapy have revolutionized the treatment of metastatic renal cell (RCC) and urothelial carcinoma. In this review, we discuss the mechanisms of action of these new therapeutic approaches, explicate the common adverse events, and highlight different imaging-based response criteria. RECENT FINDINGS: The recent introduction of immune-checkpoint inhibitors led to substantial advances in therapy of metastatic RCC and urothelial carcinoma. Because of the distinct effector mechanisms of these new substances, atypical response patterns such as transient enlargements of tumor lesions, appearance of new lesions after therapy, no measurable decrease in tumor size, or delayed responses are observed in medical imaging studies. This indicates that the established imaging-based response assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines has shortcomings to comprehensively evaluate treatment effects. SUMMARY: While monitoring response to immunotherapy still relies on RECIST criteria, immune-related response criteria have been established to better address the imaging changes occurring under immunotherapy. Further studies with long-term follow-up are needed to properly identify and predict response after treatment beyond progression. Because of the expanding clinical use of immune checkpoint inhibitors, radiologists, urologist, and oncologists should be familiar with common imaging findings under this respective therapy.

NBI-assisted digital flexible ureteroscopy in transitional renal cell carcinoma - an evidence-based assessment "through the looking glass" of the pathological analysis.

INTRODUCTION: Digital flexible ureteroscopy (FURS) increasingly became a routine diagnostic procedure in upper urinary tract transitional cell carcinoma (UUT-TCC). Identifying elements that may suggest the malignant nature of a lesion and obtaining biopsy specimens sufficient for a reliable pathological analysis remain difficult challenges. Narrow-band imaging (NBI) technology appears to provide a more accurate observation of the upper tract urothelium. PATIENTS, MATERIALS AND METHODS: During this prospective analysis, white light (WL) and NBI-assisted digital FURS were performed in 87 consecutive patients admitted for primary suspicion of UUT-TCC. The endoscopic technique comprised digital WL FURS, followed by the NBI assessment of the renal collecting system' mucosa. All suspicious areas of the pyelocaliceal urothelium were biopsied using the grasping forceps, separately for WL and NBI findings. RESULTS: A total of 113 UUT-TCC tumors (104 pTa and nine carcinoma in situ - CIS) were confirmed by pathology in 62 patients. The patients' detection rate was significantly improved in NBI mode when compared to standard FURS (98.4% versus 91.9%, respectively), due to cases either exclusively diagnosed with UUT-TCC (8.1%) or presenting additional urothelial tumors (12.9%). Overall, 13 pTa and two CIS lesions were solely observed in NBI, which was on the other hand characterized by a significantly increased proportion of unnecessary biopsies (NBI versus WL rate of false-positive results - 17.5% versus 10.1%, respectively). CONCLUSIONS: As additional tool for the standard WL evaluation of the pyelocaliceal system' urothelium, NBI-guided biopsies were emphasized as providing a significant diagnostic improvement during digital FURS.

Diagnostic accuracy of computed tomography urography and visual assessment during ureterorenoscopy in upper tract urothelial carcinoma.

OBJECTIVE: To investigate diagnostic accuracy of multiphase computed tomography urography (MCTU) and visual assessment at ureterorenoscopy (URS) for detection of upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Consecutive patients referred to our tertiary care centre were included in a prospective study covering the period 2005 to 2012. The patients underwent initial imaging and URS with focal samples taken. Cytopathological results served as reference standard. RESULTS: We investigated 174 renal units (RUs; renal pelvis and adjacent ureter) in 148 patients. UTUC was found in 104 RUs. MCTU had an accuracy of 0.74, sensitivity of 0.89, specificity of 0.51, positive predictive value of 0.73, and negative predictive value of 0.75; corresponding values for URS were 0.84, 0.84, 0.85, 0.89, and 0.78, respectively. MCTU had significantly higher sensitivity and accuracy compared with other imaging techniques (P<0.05). Compared with MCTU, URS had similar sensitivity but significantly greater specificity and accuracy. CONCLUSION: Both MCTU and URS are important tools in the diagnostic evaluation of UTUC although neither of those techniques achieves 100% accuracy. MCTU should be chosen as the radiographical method if there are no contraindications and URS should always be combined with focal cytology and biopsies of suspicious lesions. To enhance diagnostic precision both MCTU and URS with focal samples should be included in the diagnostic procedure. The present results add impact to current diagnostic guidelines.

Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC).

PURPOSE: Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment. METHODS: Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance. RESULTS: UTUC accounts for 5-10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed. CONCLUSIONS: Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.

Trends in the utilization of imaging for upper tract urothelial carcinoma.

OBJECTIVES: To evaluate the changes in use of the different imaging modalities for diagnosing upper tract urothelial carcinoma (UTUC) and assess how these changes have affected tumor stage at the time of surgery. MATERIALS AND METHODS: We assessed the Surveillance, Epidemiology, and End Results (SEER) cancer registry and linked Medicare claims data (1992-2009) for 5377 patients who underwent surgery for UTUC. We utilized International Classification of Disease-Oncology 3 codes to identify UTUC. International Classification of Disease, ninth Revision, Clinical Modification and Current Procedure Terminology codes identified surgical treatment and imaging modalities. We assessed for use of intravenous pyelography, retrograde pyelography (RGP), computed tomography urography (CTU), magnetic resonance urography (MRU), and endoscopy. For each modality, patients were categorized as having received the modality at least once or not at all. Patient characteristics were compared using chi-squared tests. Usage of imaging modalities and tumor stage was trended using Cochran-Armitage tests. We stratified our data into 2 multivariate logistic regression models to determine the effect of imaging modalities on tumor stage: 1992 to 1999 with all modalities except MRU, and 2000 to 2009 with all modalities. RESULTS: Our patient population was predominantly White males of more than 70 years old. Intravenous pyelography and RGP declined in use (62% and 72% in 1992 vs. 6% and 58% in 2009, respectively) while computed tomography urography, MRU, and endoscopy increased in use (2%, 0%, and 37% in 1992 vs. 44%, 6%, and 66% in 2009, respectively). In both regression analyses, endoscopy was associated with lower-stage tumors. In the 2000 to 2009 model, RGP was associated with lower-stage tumors, and MRU was associated with higher-stage tumors. Finally, our data showed an increasing number of modalities utilized for each patient (1% receiving 4 modalities in 1992 vs. 20% in 2009). CONCLUSIONS: We found trends toward the utilization of newer imaging modalities to diagnose UTUC and more modalities per patient. Endoscopy and RGP were associated with smaller tumors, whereas MRU was associated with larger tumors. Further studies are needed to evaluate the utility of the different modalities in diagnosing UTUC.

Interim fluorine-18 fluorodeoxyglucose positron emission tomography for early metabolic assessment of therapeutic response to chemotherapy for metastatic transitional cell carcinoma.

BACKGROUND: The prognostic impact of early metabolic response by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) after 2 cycles of first-line chemotherapy is still unrecognized in metastatic transitional cell carcinoma (TCC). PATIENTS AND METHODS: Patients with metastatic TCC receiving the modified combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), according to institutional protocol, underwent computed tomography (CT) and FDG-PET imaging at baseline, a restaging with PET imaging after 2 cycles only (PET2), and a CT (± FDG-PET) scan at the end of treatment and during follow-up. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method; univariate (UVA) and multivariate (MVA) Cox models were fitted. Prespecified variables were the presence of visceral metastases, nodal or soft tissue disease, and early PET response. RESULTS: In the period from May 2010 to October 2012, 31 patients with Eastern Cooperative Oncology Group performance status 0 received the modified MVAC regimen every 3 weeks. In all, 6 patients (19.3%) had a complete response (CR) and 17 (54.8%) a partial metabolic response (PR), 4 had stable disease (SD), and 4 progressed. PET2 responders had a median PFS of 8 months (95 % CI, 7-11 mo) compared with 3 months (95 % CI, 2-5 mo) of patients without response (P = .024). They also had a significant benefit in 8-month PFS (P < .001 via Klein test) and 15-month OS (P = .016). PET2 response was significant for PFS in both UVA and MVA Cox models (P = .027 and P = .023, respectively). CONCLUSION: PET response after 2 cycles of first-line chemotherapy, compared with detection by early CT, was associated with longer PFS and OS in advanced TCC and warrants further investigation in the field.

[Modern diagnostic assessment of the upper urinary tract using multislice CT urography]. / Moderne Diagnostik des oberen Harntraktes mittels Mehrschicht-CT-Urographie.

The advent of Multislice Computed Tomography (MSCT) has made evaluation of the entire urinary tract with high-resolution sections during a single breath-hold a reality. Acquisition of multiple thin overlapping slices provides excellent two-dimensional (2D) and three-dimensional (3D) reformations of the urinary tract. The concept of "Multislice CT Urography (MSCTU)" has emerged from this technical improvement. As a result, a wide range of pathologies inside and outside the urinary tract can be identified. During the last several years, MSCTU has challenged intravenous urography (IVU) in the evaluation of urinary tract abnormalities. Compared with IVU, MSCT(U) is more sensitive and specific in the detection and characterization of a variety of urinary tract disorders, including renal masses and urolithiasis. The main advantage of IVU has been its ability to offer excellent delineation of pelvicalyceal and ureteral anatomy and to depict subtle uroepithelial abnormalities. MSCTU has already shown promising results for overcoming this challenge. Optimal opacification and distension appear to be an essential requirement for a thorough evaluation of the collecting system. Dedicated preparation strategies have been developed to meet these technical difficulties. The biggest disadvantage of MSCTU is the significant radiation exposure. For broad routine clinical application, there is still a need for dose reduction protocols despite the ongoing technical developments in MSCTU. In this article, we outline the different concepts of technical processing for MSCTU and summarize the current role of MSCTU in the evaluation of the upper urinary tract.

Transitional cell carcinoma involving the distal ureter: assessment with transrectal and color Doppler ultrasonography.

OBJECTIVE: The purpose of this study was to compare the feasibility of transrectal ultrasonography (TRUS) and color Doppler ultrasonography (CDUS) with transabdominal ultrasonography (TAUS) for the diagnosis of transitional cell carcinoma (TCC) involving the distal ureter. METHODS: Our study group consisted of 12 patients having TCC involving the distal ureter who had undergone TAUS and TRUS. Verification of the TCC involving the distal ureter was made by surgery (n = 9) or urine cytologic examination combined with the imaging findings (n = 3). The gray scale images of TAUS and TRUS were retrospectively evaluated to determine whether the ureteral mass was visualized. The CDUS findings were compared with the T stage, the histopathologic grade, and the mean microvessel density of histopathologically proved distal ureteral TCCs (n = 8). RESULTS: Transabdominal ultrasonography showed hypoechoic ureteral dilatation in 6 patients, a ureteral mass in 5, and anechoic ureteral dilatation in 1. Transrectal ultrasonography showed a ureteral mass in all 12 patients. Color Doppler ultrasonography could show blood flow in the ureteral mass in all patients. The tumor vascularity on CDUS showed no statistically significant relationship with the T stage, the histopathologic grade, and the mean microvessel density. CONCLUSIONS: Compared with TAUS, TRUS seems to improve the ability to detect TCC involving the distal ureter. In conjunction with TRUS, CDUS shows blood flow in the ureteral mass, and this may be helpful for the diagnosis of TCC involving the distal ureter.

Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with bladder cancer.

The purpose of this study was to assess the feasibility of imaging of bladder cancer with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scanning. We studied 12 patients with histologically proven bladder cancer who had undergone surgical procedures and/or radiotherapy. Retrograde irrigation of the urinary bladder with 1000-3710 ml saline was performed during nine of the studies. Dynamic and static PET images were obtained, and standardized uptake value images were reconstructed. FDG-PET scanning was true-positive in eight patients (66.7%), but false-negative in four (33.3%). Of 20 organs with tumor mass lesions confirmed pathologically or clinically, 16 (80%) were detected by FDG-PET scanning. FDG-PET scanning detected all of 17 distant metastatic lesions and two of three proven regional lymph node metastases. FDG-PET was also capable of differentiating viable recurrent bladder cancer from radiation-induced alterations in two patients. In conclusion, these preliminary data indicate the feasibility of FDG-PET imaging in patients with bladder cancer, although a major remaining pitfall is intense FDG accumulation in the urine.

Transurethral ultrasonographic assessment of bladder carcinoma: its value and limitation.

PURPOSE: We assess the value and limitation of transurethral ultrasonography in the diagnostic evaluation of bladder carcinoma. MATERIALS AND METHODS: A total of 115 patients underwent the procedure, either at the same setting as transurethral resection (76) or 2 weeks before radical cystectomy (39). The results were compared with the pathological findings of transurethral and cystectomy specimens. RESULTS: The correlation between transurethral ultrasonography and pathological staging was 100% in tumors without muscle invasion (stages Ta and T1), 95.7% and 96.8% in muscle invasive tumors (stages T2 and T3a, respectively), and 70% in tumors with extravesical spread. CONCLUSIONS: Transurethral ultrasonography is most valuable in determining the stage of tumor confined to the bladder wall. Also, it is of value in detecting tumors in a diverticulum, and monitoring the distensibility of the bladder wall and transurethral resection of disease. The main limitations are the inabilities to discriminate between stages Ta and T1 tumors, and to detect involvement of the pelvic lymph nodes.

Routine excretory urography in follow-up of superficial transitional cell carcinoma of bladder.

To determine cost-effective guidelines for the follow-up of patients with superficial transitional cell carcinoma of the bladder (STCCAB), we reviewed clinical histories, pathology reports, and intravenous pyelography results in 84 patients with Stage Ta or T1 disease. In 4 patients (4.8%) subsequent upper tract tumors developed with an average interval from initial presentation to the development of upper tract disease of 5.4 years. Three of these patients were treated successfully. We recommend upper tract surveillance in this group of patients with intravenous pyelography at diagnosis and every twenty-four months thereafter, or selection of those patients who are at high risk for development of upper tract disease (i.e., ureteral-vesical reflux) with voiding cystourethrography one month following each resection of tumors near a ureteral orifice. Refluxing patients should then either undergo surgical repair of their reflux or yearly pyelography.

Cost-effectiveness of investigations for invasive bladder cancer.

The results of diagnostic and staging investigations in consecutive cases of invasive transitional cell carcinoma of the bladder are reviewed. Urine culture, urine cytology and intravenous urography had positive results in a high percentage of cases. As diagnostic investigations they are cost-effective but certainly do not remove the obligation to perform cystoscopy and examination under anaesthetic. Isotopic bone scan and liver scan showed metastases in 4 and one cases respectively and only when there were clinical signs of disseminated disease. Chest X-ray showed metastases in one case. These investigations are not cost-effective. Lymphangiography was positive in 12 of the 94 cases and, although expensive (pounds 70), is still a staging investigation of value in planning treatment.

Ultrasonic assessment of renal transitional cell carcinoma: preliminary report.

The value of ultrasound in determining the etiology of nonopaque filling defects seen in the renal pelvis at intravenous urography is under study. The ultrasound findings in three patients with proven transitional cell carcinoma of the kidney were similar and consisted of separation of the central renal echo complex by a region of low-intensity echoes. This pattern is distinct from characteristically echogenic nonopaque renal calculi and anechoic hydronephrosis. Renal collecting system blood clots may have an echo pattern similar to collecting system tumors, but can usually be distinguished by their mobility and transitory nature. Further investigation into the specificity and sensitivity of the ultrasonic diagnosis of renal collecting system masses is underway.

Direct radiographic magnification for skeletal radiology. An assessment of image quality and clinical application.

Recent advances in technology have made radiographic magnification of the skeleton clinically feasible. A new electron gun micro-focal tube combined with new high-resolution recording systems were used to perform magnification radiography which was then compared with conventional contact radiography. Quantitative evaluation included measurements of speed, contrast, resolution, and noise. Qualitative evaluation included an analysis of 215 clinical cases in which both techniques were used. The superior image quality of direct radiographic magnification is confirmed and the clinical areas in which it proved most helpful are defined.