PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer.

Objectives: This study aimed to investigate the anti-PD-1 inhibitor pembrolizumab as a potential agent for use in non-muscle-invasive bladder cancer (NMIBC) by conducting a Phase 1 safety run-in study to assess the safety and tolerability of intravesical pembrolizumab after transurethral resection of the bladder tumour (TURBT). Patients and methods: Eligible patients had recurrent NMIBC for which adjuvant treatment post TURBT was a reasonable treatment option, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 and adequate end-organ function. Pembrolizumab was administered by intravesical instillation once weekly for a total of six doses. Intra-patient dose escalation was performed in three paired patient cohorts with doses starting at 50 mg and increasing through 100 mg to a maximum of 200 mg. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with dose limiting toxicity (DLT) defined as a clinically significant, drug-related, Grade 4 haematological or Grade 3 or higher non-haematological toxicity occurring within 7 days of administration of the first treatment at a given dose for that patient. Results: Six patients were treated with no DLTs seen during dose escalation. Drug-related AEs were of low grade and included dysuria and fatigue. All patients completed six doses of treatment as planned. Pharmacokinetic and pharmacodynamic assays did not detect any pembrolizumab in the serum following repeated intravesical administration, and no changes in peripheral immune cell populations were observed. Conclusions: Administration of intravesical pembrolizumab was well tolerated and did not raise any safety concerns in patients with NMIBC following TURBT. There was no evidence of systemic absorption or systemic immune effects following intravesical administration. Further studies are required to assess whether intravesical administration has anti-tumour activity.

The STREAM Trial (Prostatic Artery Embolization for the Treatment of Benign Prostatic Hyperplasia) 24-Month Clinical and Radiological Outcomes.

PURPOSE: To establish factors predictive of success prior to Prostate Artery Embolization (PAE) with MRI imaging. MATERIALS AND METHODS: A prospective cohort study of 50 patients with Benign Prostatic Hyperplasia (BPH) were treated with PAE in a single institution. Patients had moderate to severe symptoms of BPH refractory to medical management for at least 6 months. Patients were imaged with multiparametric MRI imaging pre-PAE and at 3 months, 12 months and 24 months post-PAE. Clinical success was measured with IPSS, IIEF and EQ-5D-5L quality of life questionnaires. RESULTS: The technical success was 48/50 (96%).The mean age of the group was 67 (range 54-83). The mean IPSS score pre-PAE was 21 and at 24 months was 8 (p < 0.001). There was no deterioration in erectile function. The mean volume of the prostate post-PAE was reduced at 3 and 12 months post-PAE but not significantly different at 24 months. This did not correlate with the IPSS score. Patients with median lobe enlargement has similar symptomatic improvement as those without median lobe enlargement. Internally within the prostate patients with adenomatous-dominant BPH initially did better than patients with stromal enlargement; however, at 24 months patients with stromal enlargement of the prostate improved greatest. Initial volume of the prostate was not a good predictor of clinical success. CONCLUSION: PAE is a safe and effective treatment strategy for treating men with BPH. Patients with Adenomatous BPH clinically do better until 12 months but not at 24 months. Initial prostate volume does not affect outcome, and patients with median lobe enlargement do as well as those without.

Prostatic artery embolization (PAE) for prostatic origin bleeding in the context of prostate malignancy.

Prostate artery embolization (PAE) has been shown to be beneficial in treating men with benign prostatic hypertrophy (BPH). Here we describe treating four patients with prostate cancer (two with organ-confined and two with metastatic prostate cancer) with prostatic bleeding with PAE. Patients had other causes of hematuria excluded and were followed up at 3, 12, and 18 months after PAE. All four cases were technically successful and all cases of hematuria had resolved by the three-month follow-up (100%). There was one case of recurrence at 13 months after PAE which was successfully treated. PAE is useful for controlling significant prostatic bleeding in patients with prostate cancer and improves quality of life. Patients may, however, need repeated treatments to control the bleeding.

Urothelial cancer: a narrative review of the role of novel immunotherapeutic agents with particular reference to the management of non-muscle-invasive disease.

AIM: This narrative review describes current guidelines for treating NMIBC, provides an overview of the principle behind immune checkpoint inhibition, and summarizes current evidence for checkpoint inhibitors in urothelial malignancy. Further, we discuss potential strategies for immune checkpoint inhibition in the management of NMIBC. BACKGROUND: Adjuvant intravesical BCG immunotherapy has been the mainstay of treatment for high-risk non-muscle-invasive bladder cancer (NMIBC) for decades but is associated with both a significant side effect profile and failure rate. Recently, a substantial body of trial data has been published demonstrating the successful use of systemic immunotherapy in the treatment of advanced urothelial malignancy and, in particular, a class of drugs known as 'immune checkpoint inhibitors'. This has led to the approval of a number of these drugs by the UK National Institute of Health and Care Excellence and the US Food and Drug Administration, and ongoing trials are examining use in the management of NMIBC. METHODS: To identify relevant published data, using the PubMed/ Medline search engine, an online search of the Pubmed/ Medline archives was conducted using the terms bladder cancer' in combination with 'checkpoint inhibitors', and limited to articles in English published between 1966 and September 2017.To identify ongoing trials of interest but not yet published, a further search of the clinical trials.gov search engine was conducted using the term 'non-muscle-invasive bladder cancer'. CONCLUSION: There has been little advance in available adjuvant therapy for NMIBC treated with TURBT. Current intravesical therapies are associated with a high recurrence rate and significant side effect profile. The impending publication of the wealth of ongoing trials, both into the delivery and efficacy of checkpoint inhibition will direct the future treatment of NMIBC.

BCG therapy in NMIBC: How much and for how long?. / Terapia BCG en CVNMI: ?cuánto y por cuánto tiempo?.

Since its introduction in 1976 Bacille Calmette- Guerin (BCG) has become the standard of care in high risk non-muscle-invasive bladder cancer (NMIBC). Despite more than 40 years of experience, we do not know the most optimal BCG dose to maximize effectiveness whilst minimizing side effects. There is universal agreement that an initial induction course of BCG should consist of 6 weekly instillations if tolerated. However, with regards to the actual dose, data on the comparative effectiveness of one third dose versus full dose BCG is inconclusive. Similarly, whilst there is strong evidence supporting the use of BCG maintenance, this has not been universally adopted. The optimal maintenance regimen is unknown but the minimum length for effective maintenance BCG therapy seems to be 12 months whilst there is no evidence to support BCG maintenance beyond 36 months. Given the precarious state of worldwide BCG supplies in the last few years, it is imperative that high quality randomized trials are carried out to determine the minimum dose and length of BCG treatment in patients with NMIBC.

Terapia BCG en CVNMI: ¿cuánto y por cuánto tiempo? / BCG therapy in NMIBC: How much and for how long?

Desde su introducción en 1976, el Bacilo de Calmette-Guerin (BCG) se ha convertido en el estándar de tratamiento en cáncer de vejiga no músculo invasivo de alto riesgo (CVNMI). A pesar de más de 40 años de experiencia, no conocemos la dosis de BCG óptima para conseguir la máxima efectividad mientras se minimizan los efectos secundarios. Existe un acuerdo universal de que un ciclo de inducción inicial de BCG debe consistir en 6 instilaciones semanales si se tolera. Sin embargo, con respecto a la dosis real, los datos sobre la efectividad comparativa de un tercio de dosis frente a la dosis completa de BCG no son concluyentes. Del mismo modo, aunque existe una fuerte evidencia que respalda el uso de mantenimiento con BCG, no se ha adoptado universalmente. Se desconoce el régimen de mantenimiento óptimo, pero la duración mínima para el mantenimiento efectivo de la terapia con BCG parece ser de 12 meses, mientras que no hay evidencia para apoyar el mantenimiento de BCG más allá de los 36 meses.Dada la precariedad de los suministros mundiales de BCG en los últimos años, es imperativo que se lleven a cabo ensayos aleatorios de alta calidad para determinar la dosis mínima y la duración del tratamiento con BCG en pacientes con CVNMI

Since its introduction in 1976 Bacille Calmette-Guerin (BCG) has become the standard of care in high risk non-muscle-invasive bladder cancer (NMIBC). Despite more than 40 years of experience, we do not know the most optimal BCG dose to maximize effectiveness whilst minimizing side effects. There is universal agreement that an initial induction course of BCG should consist of 6 weekly instillations if tolerated. However, with regards to the actual dose, data on the comparative effectiveness of one third dose versus full dose BCG is inconclusive. Similarly, whilst there is strong evidence supporting the use of BCG maintenance, this has not been universally adopted. The optimal maintenance regimen is unknown but the minimum length for effective maintenance BCG therapy seems to be 12 months whilst there is no evidence to support BCG maintenance beyond 36 months

Prostatic Artery Embolization (PAE) for Benign Prostatic Hyperplasia (BPH) with Haematuria in the Absence of an Upper Urinary Tract Pathology.

PURPOSE: To assess the effectiveness of prostate artery embolization (PAE) in the control of haematuria and in patients with benign prostatic hyperplasia (BPH) and normal upper urinary tracts. SUBJECTS/PATIENTS: Twelve consecutive patients with haematuria were included in the prospective study. All patients had prior imaging and cystoscopy to exclude other causes of haematuria. Patients prostate arteries were embolized with particles (200-500 µm), and they were followed up at 3, 12 and 18 months following the procedure. QOL questionnaires, IPSS, IIEF and clinical review were all employed to assess the success of the treatment. To allow useful comparison, patients were age- and prostate volume-matched and compared to patients treated with PAE for BPH without haematuria. RESULTS: All 12/12 cases were technically successful with bilateral PAE being performed. All cases of haematuria resolved by the 3-month follow-up (100%). There was one case of recurrence during the 12-month follow-up (overall clinical success at 18 months 92%). This was due to over anticoagulation and ceased once corrected. There was a reduction in lower urinary tract symptoms noted by improvements in QOL indices, IPSS and IIEF. There was continued success even if the patient was subsequently anticoagulated. There was no associated sexual dysfunction. There was more prostatic arterial branching and volume of embolic required to achieve stasis in BPH and haematuria than in BPH alone (p < 0.05). CONCLUSION: PAE is a very useful technique for controlling the quite debilitating condition of haematuria in patients with visible haematuria of prostatic origin. Controlling haematuria and BPH allows a significant improvement in QOL.

Retrograde transileal conduit stent placement for obstructed uropathy--success of primary and exchange stent placement.

PURPOSE: To assess the safety, success, and complications associated with retrograde ureteric stent insertion via the ileal conduit. MATERIALS AND METHODS: The study population comprised 35 consecutive patients (17 men and 18 women; mean age, 55 y; age range, 40-75 y) requiring primary (20 stents) and exchange (70 stents) retrograde ureteric stent insertion via the ileal conduit over a 3-year period. Patient demographic data, procedural and technical data, and clinical follow-up data were collected. RESULTS: Technical success was 90% (18 of 20) for primary stent placement and 100% (70 of 70) for stent exchange. There were two immediate complications (< 24 h) of sepsis and ureteric injury and one early complication (> 25 h but < 30 d) of sepsis requiring observation and medical management. Difficult procedures (defined as a fluoroscopy screening time > 31 min) and technical failures were found to be associated with encrusted stents visualized on prior computed tomography (P = .012), increased length of ileal conduit (> 20 cm) (P = .023), and ileal conduit kink (< 90 degrees) (P = .032). Only the occurrence of encrusted stents visualized on prior computed tomography (P = .022) was associated with complications. CONCLUSIONS: Retrograde placement of ureteric stents via the ileal conduit is safe and effective. Retrograde stent placement should be considered the treatment option of choice for a first-time occurrence of obstructive uropathy at the ureteroileal anastomosis.

Recent advances in urinary bladder cancer detection.

Urinary bladder cancer (BCa) is the most common malignancy of the urinary tract. In recent decades, the overall incidence of BCa appears to be on the increase. Despite the increase in incidence, mortality rates in North America and Europe appear to have declined in the last decade, probably due to improved detection and treatment. The mainstay of diagnosis is by cystoscopy, aided with imaging and urine tests (e.g., cytology). This article reviews the recent advances made in detection of primary and recurrent bladder cancer.

Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder.

BACKGROUND: Meta-analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin-based combination regimens in the radical treatment of muscle-invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose-intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway. METHODS: Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro-oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m(2) , vinblastine 3 mg/m(2) , doxorubicin 30 mg/m(2) , and cisplatin 70 mg/m(2) ) were given at 2-week intervals, with granulocyte colony-stimulating factor support, prior to either radical surgery or radical radiotherapy. RESULTS: All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two-year disease-free and overall survival were 65% and 77%, respectively. CONCLUSIONS: AMVAC is safe and appears to be a well-tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials.

Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: results for 778 patients from a hospital haematuria clinic.

UNLABELLED: Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Haematuria clinics with same day imaging and flexible cystoscopy are an efficient way for investigating patients with haematuria. The principal role of haematuria clinics with reference to bladder cancer is to determine which patients are 'normal' and may be discharged, and which patients are abnormal and should undergo rigid cystoscopy. It is well recognised that CT urography offers a thorough evaluation of the upper urinary tract for stones, renal masses and urothelial neoplasms but the role of CT urography for diagnosing bladder cancer is less certain. The aim of the present study was to evaluate the diagnostic accuracy of CT urography in patients with visible haematuria aged >40 years and to determine if CT urography has a role for diagnosing bladder cancer. This study shows that the optimum diagnostic strategy for investigating patients with visible haematuria aged >40 years with infection excluded is a combined strategy using CT urography and flexible cystoscopy. Patients positive for bladder cancer on CT urography should be referred directly for rigid cystoscopy and so avoid flexible cystoscopy. The number of flexible cystoscopies required therefore may be reduced by 17%. The present study also shows that the diagnostic accuracy of voided urine cytology is too low to justify its continuing use in a haematuria clinic using CT urography and flexible cystoscopy. OBJECTIVES: To evaluate and compare the diagnostic accuracy of computed tomography (CT) urography with flexible cystoscopy and voided urine cytology for diagnosing bladder cancer. To evaluate diagnostic strategies using CT urography as: (i) an additional test or (ii) a replacement test or (iii) a triage test for diagnosing bladder cancer in patients referred to a hospital haematuria rapid diagnosis clinic. PATIENTS AND METHODS: The clinical cohort consisted of a consecutive series of 778 patients referred to a hospital haematuria rapid diagnosis clinic from 1 March 2004 to 17 December 2007. Criteria for referral were at least one episode of macroscopic haematuria, age >40 years and urinary tract infection excluded. Of the 778 patients, there were 747 with technically adequate CT urography and flexible cystoscopy examinations for analysis. On the same day, patients underwent examination by a clinical nurse specialist followed by voided urine cytology, CT urography and flexible cystoscopy. Voided urine cytology was scored using a 5-point system. CT urography was reported immediately by a uroradiologist and flexible cystoscopy performed by a urologist. Both examinations were scored using a 3-point system: 1, normal; 2, equivocal; and 3, positive for bladder cancer. The reference standard consisted of review of the hospital imaging and histopathology databases in December 2009 for all patients and reports from the medical notes for those referred for rigid cystoscopy. Follow-up was for 21-66 months. RESULTS: The prevalence of bladder cancer in the clinical cohort was 20% (156/778). For the diagnostic strategy using CT urography as an additional test for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 1.0 (95% confidence interval [CI] 0.98-1.00), specificity was 0.94 (95% CI 0.91-0.95), the positive predictive value (PPV) was 0.80 (95% CI 0.73-0.85) and the negative predictive value (NPV) was 1.0 (95% CI 0.99-1.00). For the diagnostic strategy using CT urography as a replacement test for flexible cystoscopy for diagnosing bladder cancer, when scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.83 (95% CI 0.80-0.86), the PPV was 0.58 (95% CI 0.52-0.64), and the NPV was 0.98 (95% CI 0.97-0.99). Similarly using flexible cystoscopy for diagnosing bladder cancer, if scores of 1 were classified as negative and scores of 2 and 3 as positive, sensitivity was 0.98 (95% CI 0.94- 0.99), specificity was 0.94 (95% CI 0.92-0.96), the PPV was 0.80 (95% CI 0.73-0.85) and the NPV was 0.99 (95% CI 0.99-1.0). For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), patients with a positive CT urography score are referred directly for rigid cystoscopy, and patients with an equivocal or normal score were referred for flexible cystoscopy. Sensitivity was 1.0 (95% CI 0.98-1.0), specificity was 0.94 (95% CI 0.91-0.95), the PPV was 0.80 (95% CI 0.73-0.85), and the NPV was 1.0 (95% CI 0.99-1.0). For the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 2), patients with a positive CT urography score are referred directly for rigid cystoscopy, patients with an equivocal score are referred for flexible cystoscopy and patients with a normal score undergo clinical follow-up. Sensitivity was 0.95 (95% CI 0.90-0.97), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.93 (95% CI 0.87-0.96), and the NPV was 0.99 (95% CI 0.97-0.99). For voided urine cytology, if scores of 0-3 were classified as negative and 4-5 as positive for bladder cancer, sensitivity was 0.38 (95% CI 0.31-0.45), specificity was 0.98 (95% CI 0.97-0.99), the PPV was 0.82 (95% CI 0.72-0.88) and the NPV was 0.84 (95% CI 0.81-0.87). CONCLUSIONS: There is a clear advantage for the diagnostic strategy using CT urography and flexible cystoscopy as a triage test for rigid cystoscopy and follow-up (option 1), in which patients with a positive CT urography score for bladder cancer are directly referred for rigid cystoscopy, but all other patients undergo flexible cystoscopy. Diagnostic accuracy is the same as for the additional test strategy with the advantage of a 17% reduction of the number of flexible cystoscopies performed. The sensitivity of voided urine cytology is too low to justify its continuing use in a hospital haematuria rapid diagnosis clinic using CT urography and flexible cystoscopy.

Oncologic outcomes and survival in pT0 tumors after radical cystectomy in patients without neoadjuvant chemotherapy: results from a large multicentre collaborative study.

PURPOSE: To assess the postsurgical survival of patients with urothelial carcinoma of the bladder with pT0 tumor at pathologic examination of cystectomy specimens. METHODS: A multi-institutional, retrospective database was analyzed with data from 4758 radical cystectomy (RC) patients who underwent RC without neoadjuvant chemotherapy and who were diagnosed with pT0 on the basis of the pathologic specimen. Survival curves were estimated. A multivariate Cox model was used to evaluate the association between prognosis factors and disease recurrence or survival. RESULTS: Overall, 258 patients (5.4%) were included in the study. The median age was 64 years. At last resection, 171 tumors were invasive (at least pT2), and 87 were not. Median follow-up was 51 months. At multivariate analysis, initial location of the tumor and absence of lymphadenectomy were associated with tumor recurrence (P = 0.03 and P = 0.005, respectively) and specific mortality (P = 0.005 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of this situation. Cancer-specific and recurrence-free survival rates were 89 and 85%, respectively, at 5 years and 82 and 80%, respectively, at 10 years. CONCLUSIONS: Despite acceptable oncological outcomes, patients with a pT0 tumor at the time of RC are still at risk of recurrence and progression and should not be considered to be entirely cured. In this population, stringent follow-up according to current recommendations should be effective.

Imaging bladder cancer.

PURPOSE OF REVIEW: To review recent developments in imaging for bladder cancer (BCa) diagnosis and staging. RECENT FINDINGS: Recent technical advances in multidetector computed tomography (CT) and, especially, CT urography make CT the preferred imaging modality for diagnosis and staging of BCa. CT urography combined with cystoscopy is emerging as the diagnostic imaging pathway of choice for investigating haematuria. CT provides information about local, lymph node and distant spread in a single examination. SUMMARY: Imaging for BCa should only be performed when it makes a difference to patient management. CT is the preferred imaging modality for diagnosing and staging urothelial cancer. Magnetic resonance (MR) imaging is superior for evaluation of the depth of tumour invasion into the bladder wall, but this knowledge may not ultimately affect treatment as feasibility for radical cystectomy depends on staging by a combination of clinical, histopathological and imaging findings. Radical cystectomy may include resection of adjacent organs and regional lymph nodes. The current purpose of CT or MR imaging is to detect T3b disease or higher and, especially, locoregional lymph node metastases. In the future, MR imaging with ultrasmall superparamagnetic iron oxide contrast agents may detect lymph nodes containing metastatic tumour, which may change treatment from surgery to chemotherapy with or without radiotherapy.

Automated uro-oncology data collection: the Cancer Research Uro-Oncology Database.

OBJECTIVE: To develop a relational database (Cancer Research Uro-Oncology Database, CRUD) to enable automatic data collection on all urological malignancies within our region, as there is increasing emphasis on good data collection for surgical patients with cancer, and numerous overlapping systems that are amassing data on the same patients. METHODS: Links have been established between pathological databases, multidisciplinary team data-collection systems and patient-survival monitoring facilities, providing accurate pathology, treatment and survival data on all of uro-oncology patients. We are also developing individual modules for the oncological surgeons within our unit that are compatible with the British Association of Urological Surgeons (Section of Oncology), and have plans to connect to the Medical and Clinical Oncology data systems in the future. RESULTS: Pre-existing protocols for fresh tissue, plasma and urine collection have been incorporated within CRUD via a tissue-tracking system, to comply with the Human Tissue Act 2004, and link these samples to accurate clinical, pathological and survival data. Many research and audit projects have already used these data, including the construction of a 274-case tissue microarray for renal cell carcinoma, microRNA hybridization arrays and analysis of 900 nephrectomy cases from the past three decades. CONCLUSIONS: Our work over the past 3 years in Oxford has established numerous links with organizations collecting data on our uro-oncological patients, and we are now able to collect this excellent combined data on all of these patients, in an automated manner.

The type 1 insulin-like growth factor receptor is over-expressed in bladder cancer.

OBJECTIVE: To analyse bladder cancer biopsies and investigate the pattern of expression of the type 1 insulin-like growth factor receptor (IGF1R), a receptor tyrosine kinase that mediates tumour cell proliferation, motility and protection from apoptosis. MATERIALS AND METHODS: Formalin-fixed specimens of bladder cancer (40 whole-mount, 80 cores on a tumour microarray) and normal bladder (15 samples) were stained immunohistochemically for the IGF1R. The IGF1R expression was also measured by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) on RNA extracted from fresh frozen bladder cancers (61) and benign bladder (12). RESULTS: Of the 15 samples of normal bladder, 14 showed negligible (1+) or light (2+) IGF1R immunostaining. By contrast moderate (3+) or heavy (4+) staining for IGF1R was detected in 89 (74%) of the 120 samples of malignant urothelium. Q-RT-PCR showed significantly higher levels of steady-state IGF1R mRNA in tumours (all cases, Ta-T4) than in normal bladder (P < 0.05), indicating up-regulation at the transcriptional level. This difference was particularly evident when comparing normal urothelium with superficial (Ta-T1) or invasive (T2-4) tumours; only the latter showed significant IGF1R over-expression at the RNA level (P < 0.05 vs normal bladder). CONCLUSION: The IGF1R is up-regulated in bladder cancer compared with non-malignant bladder, and might contribute to a propensity for invasion.

Multidetector computed tomography urography for diagnosing upper urinary tract urothelial tumour.

OBJECTIVE: To evaluate multidetector computed tomography urography (MDCTU) for diagnosing upper urinary tract (UUT) urothelial tumour by comparison with retrograde ureteropyelography (RUP). PATIENTS AND METHODS: MDCTU and RUP were used in a selected series of adult patients presenting with haematuria. Entry criteria were based on findings on intravenous urography and were chosen to ensure a high prevalence of UUT urothelial tumour to allow a valid retrospective comparison of the diagnostic techniques. MDCTU and RUP studies were scored for the presence and absence of UUT urothelial tumour by two radiologists, retrospectively and independently, and while unaware of the demographic and clinical information. The reference standards were the histopathology and clinical follow-up. RESULTS: MDCTU and RUP were used in 106 patients over a 24-month period. RUP was attempted in 151 of 212 UUTs; the corresponding MDCTU for each UUT was reviewed. MDCTU was a true-positive (TP) for urothelial tumour in 31, true-negative (TN) in 111, false-positive (FP) in eight and false-negative (FN) in one UUT, giving a sensitivity of 0.97, a specificity of 0.93, a positive predictive value (PPV) of 0.79 and a negative PV (NPV) of 0.99. RUP was technically successful and diagnostic in 96% of the UUTs (143/151). For diagnosing urothelial tumour, RUP was TP in 26, TN in 112, FP in four and FN in one UUT, giving a sensitivity of 0.97, specificity of 0.93, a PPV of 0.79 and NPV of 0.99. CONCLUSION: This study validates quantitatively the use of MDCTU for diagnosing UUT urothelial tumour.