Outpatient Photodynamic Diagnosis-guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis-guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low-grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial.

BACKGROUND: Transurethral resection of recurrent low-grade intermediate-risk Ta bladder tumor (BT) in general anesthesia (GA) is burdensome to patients and health care system. Laser technologies enable treatment in office-based settings, reducing morbidity and costs. OBJECTIVE: To compare 4-mo recurrence-free survival after outpatient department (OPD) diode laser coagulation of BT in local anesthesia and gold standard transurethral resection of BT (TUR-BT) in GA in intermediate-risk Ta low-grade BT, and to evaluate treatment-related morbidity. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized noninferiority trial with 4-mo follow-up, in the hospital setting, was conducted in Capital Region of Denmark from 2016 to 2020. Participants were patients with histologically verified Ta low-grade BT recurrence. A total of 206 patients were randomized; 176 finished treatment and follow-up as per protocol. INTERVENTION: Laser photocoagulation of bladder tumor (PC-BT) in OPD using a 980 nm diode laser compared with gold standard TUR-BT in GA, both performed with photodynamic diagnosis (PDD) guidance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Four-month recurrence-free survival was assessed; predefined inferiority criterion was set at 15%. The secondary outcomes were pain during PC-BT, postoperative morbidity, postoperative complications, and patient's preference. RESULTS AND LIMITATIONS: Four-month recurrence-free survival was 8% higher after PC-BT (95% confidence interval [CI]: -8% to 24%). The predefined noninferiority criterion was met. Pain score (1-10) during PC-BT was 2.4 (interquartile range 0.8-3.3). Postoperative lower urinary tract symptom score (0-100) was 13.9 points higher (95% CI: 6.9-21.0, p < 0.001) in the group with transurethral resection of the bladder. The frequency of minor complications was 8.1% higher after TUR-BT (95% CI: 1.0-14.6%, p = 0.026). Of the patients, 98% (95% CI: 92-100%) preferred PC-BT. CONCLUSIONS: PDD-guided PC-BT in OPD is as good as TUR-BT in GA to remove recurrent low-grade Ta BT. Postoperative quality of life is better after PC-BT and the frequency of minor complications was lower. PATIENT SUMMARY: This study evaluates the efficacy of outpatient laser removal of low-grade noninvasive bladder tumor. Outpatient tumor removal with laser was as good as transurethral resection in general anesthesia and less burdensome to patients.

Morpho-molecular signal correlation between optical coherence tomography and Raman spectroscopy for superior image interpretation and clinical diagnosis.

The combination of manifold optical imaging modalities resulting in multimodal optical systems allows to discover a larger number of biomarkers than using a single modality. The goal of multimodal imaging systems is to increase the diagnostic performance through the combination of complementary modalities, e.g. optical coherence tomography (OCT) and Raman spectroscopy (RS). The physical signal origins of OCT and RS are distinctly different, i.e. in OCT it is elastic back scattering of photons, due to a change in refractive index, while in RS it is the inelastic scattering between photons and molecules. Despite those diverse characteristics both modalities are also linked via scattering properties and molecular composition of tissue. Here, we investigate for the first time the relation of co-registered OCT and RS signals of human bladder tissue, to demonstrate that the signals of these complementary modalities are inherently intertwined, enabling a direct but more importantly improved interpretation and better understanding of the other modality. This work demonstrates that the benefit for using two complementary imaging approaches is, not only the increased diagnostic value, but the increased information and better understanding of the signal origins of both modalities. This evaluation confirms the advantages for using multimodal imaging systems and also paves the way for significant further improved understanding and clinically interpretation of both modalities in the future.

An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness. Both transcriptome-based subtyping and the level of chromosomal instability provide independent prognostic value beyond established prognostic clinicopathological parameters. High chromosomal instability, p53-pathway disruption and APOBEC-related mutations are significantly associated with transcriptomic class 2a and poor outcome. RNA-derived immune cell infiltration is associated with chromosomally unstable tumors and enriched in class 2b. Spatial proteomics analysis confirms the higher infiltration of class 2b tumors and demonstrates an association between higher immune cell infiltration and lower recurrence rates. Finally, the independent prognostic value of the transcriptomic classes is documented in 1228 validation samples using a single sample classification tool. The classifier provides a framework for biomarker discovery and for optimizing treatment and surveillance in next-generation clinical trials.

Do repeated transurethral procedures under general anesthesia influence mortality in patients with non-invasive urothelial bladder cancer? A Danish national cohort study.

Purpose: To investigate the effect of repeated transurethral procedures under general anesthesia on overall mortality in patients with non-invasive bladder cancer.Materials and methods: All Danish residents with non-invasive papillary urothelial carcinoma or primary urothelial carcinoma in situ diagnosed between 1 January 2000 and 1 January 2011 were included and followed until death or 31 March 2017. All transurethral procedures under general anesthesia, intravesical instillation therapy, recurrences and progression to invasive disease or cystectomy were recorded during follow-up. Associations between treatments and overall mortality were evaluated using multivariable regression analysis adjusted for age, gender, comorbidities and socioeconomic status. The effect of disease progression on mortality was removed by censoring patients at the time of progression or cystectomy.Results: Risk of death increased with the number of transurethral procedures under general anesthesia for Ta low- and high-grade tumors compared to patients who had only one procedure; after eight or more procedures the risk of death increased by 28% and 83%, respectively. There was no similar relationship for carcinomas in situ. In total, 36-52% of procedures under general anesthesia did not identify urothelial neoplasia.Conclusions: Repeated transurethral procedures under general anesthesia appear to be associated with increased risk of death in patients with primary non-invasive papillary urothelial carcinoma. Furthermore, a substantial number of procedures were without findings of neoplasia, indicating that too many patients are admitted for transurethral procedures under GA. Attempts should be taken to reduce unnecessary transurethral procedures under GA, e.g. by improved outpatient diagnosis of urothelial neoplasia.

Bladder tissue characterization using probe-based Raman spectroscopy: Evaluation of tissue heterogeneity and influence on the model prediction.

Existing approaches for early-stage bladder tumor diagnosis largely depend on invasive and time-consuming procedures, resulting in hospitalization, bleeding, bladder perforation, infection and other health risks for the patient. The reduction of current risk factors, while maintaining or even improving the diagnostic precision, is an underlying factor in clinical instrumentation research. For example, for clinic surveillance of patients with a history of noninvasive bladder tumors real-time tumor diagnosis can enable immediate laser-based removal of tumors using flexible cystoscopes in the outpatient clinic. Therefore, novel diagnostic modalities are required that can provide real-time in vivo tumor diagnosis. Raman spectroscopy provides biochemical information of tissue samples ex vivo and in vivo and without the need for complicated sample preparation and staining procedures. For the past decade there has been a rise in applications to diagnose and characterize early cancer in different organs, such as in head and neck, colon and stomach, but also different pathologies, for example, inflammation and atherosclerotic plaques. Bladder pathology has also been studied but only with little attention to aspects that can influence the diagnosis, such as tissue heterogeneity, data preprocessing and model development. The present study presents a clinical investigative study on bladder biopsies to characterize the tumor grading ex vivo, using a compact fiber probe-based imaging Raman system, as a crucial step towards in vivo Raman endoscopy. Furthermore, this study presents an evaluation of the tissue heterogeneity of highly fluorescent bladder tissues, and the multivariate statistical analysis for discrimination between nontumor tissue, and low- and high-grade tumor.

Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy.

Non-muscle-invasive bladder cancer affects millions of people worldwide, resulting in significant discomfort to the patient and potential death. Today, cystoscopy is the gold standard for bladder cancer assessment, using white light endoscopy to detect tumor suspected lesion areas, followed by resection of these areas and subsequent histopathological evaluation. Not only does the pathological examination take days, but due to the invasive nature, the performed biopsy can result in significant harm to the patient. Nowadays, optical modalities, such as optical coherence tomography (OCT) and Raman spectroscopy (RS), have proven to detect cancer in real time and can provide more detailed clinical information of a lesion, e.g. its penetration depth (stage) and the differentiation of the cells (grade). In this paper, we present an ex vivo study performed with a combined piezoelectric tube-based OCT-probe and fiber optic RS-probe imaging system that allows large field-of-view imaging of bladder biopsies, using both modalities and co-registered visualization, detection and grading of cancerous bladder lesions. In the present study, 119 examined biopsies were characterized, showing that fiber-optic based OCT provides a sensitivity of 78% and a specificity of 69% for the detection of non-muscle-invasive bladder cancer, while RS, on the other hand, provides a sensitivity of 81% and a specificity of 61% for the grading of low- and high-grade tissues. Moreover, the study shows that a piezoelectric tube-based OCT probe can have significant endurance, suitable for future long-lasting in vivo applications. These results also indicate that combined OCT and RS fiber probe-based characterization offers an exciting possibility for label-free and morpho-chemical optical biopsies for bladder cancer diagnostics.

National incidence and survival of patients with non-invasive papillary urothelial carcinoma: a Danish population study.

OBJECTIVE: To estimate national relative survival of low and high grade non-invasive papillary urothelial carcinoma (Ta LG and Ta HG) and urothelial carcinoma in situ (CIS). MATERIALS AND METHODS: All Danish citizens (17,941 patients) with a primary urothelial bladder tumour diagnosis in the period 2000- 2010 were followed until 1 January 2016 and recorded in the Danish Bladder Cancer Cohort database. Survival was compared to the background population matched on age and gender and adjusted by civil status, income, education, and comorbidity. RESULTS: Patients treated in daily practice with Ta LG have 46% (HR = 1.46 (1.42-1.51) p < 0.001) higher risk of death compared to a background population matched for age and gender. This risk of death ceases to 28% (HR = 1.28 (1.24-1.32) p < 0.001) after adjustment for civil status, income, education, and comorbidity. Relative survival of Ta LG patients is 0.94 (0.93-0.95). These estimates are constant throughout the observation period. Significantly higher mortality is found for patients with Ta HG and CIS, but, in contrast to Ta LG, the relative risk of death of Ta HG (HR = 1.79 (1.69-1.90) p < 0.001) and CIS (HR = 2.02 (1.79-2.26) p < 0.001) decreases considerably after 5 years survival (HR = 1.43 (1.30-1.57) p < 0.001 and HR = 1.64 (1.36-1.98) p < 0.001, respectively). CONCLUSION: Patients with Ta LG have a continuous lower survival and a 28% higher risk of death at any time compared to a matched background population when treated in daily practice.

Outpatient diode laser treatment of intermediate-risk non-invasive bladder tumors without sedation: efficacy, safety and economic analysis.

OBJECTIVE: This study aimed to validate a new method for outpatient diode laser ablation of bladder tumors without sedation or pain control. METHODS: Twenty-one patients with stage Ta low-grade intermediate-risk bladder tumors underwent photodynamic-guided laser ablation of their bladder tumors and 1 month later follow-up cystoscopy with photodynamic and IMAGE1 S™-guided biopsies. Pain was measured using a visual analog scale (range 0-10). Symptoms and worries about the future disease course were calculated using the Quality of Life Questionnaire for Non-Muscle-Invasive Bladder Cancer (range 0-100, high scores indicating worse symptoms or worry). Costs of outpatient laser treatment versus inpatient conventional bladder tumor resection in the operating theatre were compared. RESULTS: Patients had a median of three tumors (range 1-12). The median pain score was 1.0 (range 0-7) during laser ablation. Median quality of life scores were 24 (range 0-67) for symptoms and 42 (0-100) for worry. Two patients had minor hematuria and five had dysuria after laser therapy. Five patients (24%) had new Ta low-grade recurrence within 13 months that was biopsied and laser treated. No tumors progressed. Four patients had tumors identified using photodynamic diagnosis, and two had flat low-grade dysplasia identified using IMAGE1 S SPECTRA A and B and photodynamic diagnosis, none of which was seen using white-light cystoscopy. Outpatient laser treatment could save about €140,000 per million inhabitants versus inpatient bladder tumor surgery. CONCLUSION: Fluorescence-guided diode lasers provide efficient and almost pain-free treatment of low-grade urothelial cancer in conscious patients and could reduce healthcare costs.

Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups.

Purpose: The European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC.Experimental Design: We prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3, and ZIC4 methylation and FGFR3, TERT, PIK3CA, and RAS mutation status. Cox regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR = rate of progression per 100 patient-years) was calculated for subgroups.Results: In our cohort, 276 patients had a low, 273 an intermediate, and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared with older studies is likely due to improved treatment in the past two decades. Overall, wild-type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR = 0.34, 2.53, and 2.64, respectively). The PIR for EAU high-risk patients was 4.25. On the basis of FGFR3 mutation status and methylation of GATA2, this cohort could be reclassified into a good class (PIR = 0.86, 26.2% of patients), a moderate class (PIR = 4.32, 49.7%), and a poor class (PIR = 7.66, 24.0%).Conclusions: We conclude that the addition of selected biomarkers to the EAU risk stratification increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression. Clin Cancer Res; 24(7); 1586-93. ©2018 AACR.

Outpatient photodynamic-guided diagnosis of carcinoma in situ with flexible cystoscopy: an alternative to conventional inpatient photodynamic-guided bladder biopsies in the operating theatre?

OBJECTIVE: The aim of this prospective open comparative study was to establish whether conventional photodynamic-guided bladder biopsies using general anaesthesia and rigid resectoscopes (inpatient) can be replaced with less traumatic flexible cystoscopy in non-sedated patients (outpatient), without compromising the diagnosis of carcinoma in situ (CIS). MATERIALS AND METHODS: Thirty-one patients were included. After BCG instillation for CIS, bladder biopsies were obtained using photodynamic-guided flexible cystoscopy. Two weeks later, patients underwent the conventional inpatient procedure. An external pathologist reviewed the biopsy samples. Pain and quality of life (QoL) symptom score were recorded. RESULTS: Post-BCG biopsies showed only CIS in 10 patients; high-grade Ta or T1 tumour in three patients, who were referred for cystectomy; and normal or low-grade tumour tissue in 18 patients. There was a high agreement of identification of high-grade disease in biopsies and cytology using the two methods (κ = 0.93, 95% confidence interval 0.8-1.0). The outpatient procedure identified four high-grade patients diagnosed as 'normal/low-grade' in the inpatient procedure. The opposite was observed in two patients. Quality of biopsies did not differ between the two procedures. Pain scores for outpatients were low, and median QoL symptom score was significantly lower than for inpatients (24 vs 33, p = 0.02). Hospital length of stay was significantly longer for inpatients. CONCLUSIONS: Outpatient photodynamic-guided flexible cystoscopy is less traumatic than the conventional inpatient procedure in the diagnosis of CIS. It is safe and cost-effective, and may be an alternative to conventional inpatient biopsy procedures in patients with malignant urine cytology and normal white-light cystoscopy.

Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study.

BACKGROUND: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. OBJECTIVE: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. DESIGN, SETTING, AND PARTICIPANTS: We enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0-76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. RESULTS AND LIMITATIONS: The progression score was significantly (p<0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guérin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2-11.6; p<0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p<0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R2=0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/750 patients). CONCLUSIONS: The 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. PATIENT SUMMARY: Clinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non-muscle-invasive bladder cancer to optimal treatment regimens.

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.

Hospitalization for transurethral bladder resection reduces quality of life in Danish patients with non-muscle-invasive bladder tumour.

Objective The aim of the study was to evaluate the impact of transurethral resection of bladder tumour (TURBT) on patients' quality of life (QoL) and to validate a tool to quantify problems associated with TURBT in a Danish population. Materials and methods A prospective study was carried out using a combination of questionnaires and interviews. The study included 165 consecutive patients undergoing a TURBT owing to non-muscle-invasive bladder cancer (NMIBC) from 1 May 2011 to 30 April 2012. Seven patients were selected for interviews. The Danish translation of the QLQ-NMIBC24 Quality of Life Questionnaire for NMIBC, from the European Organisation for Research and Treatment of Cancer (EORTC), was used. The interviews were semi-structured. The reliability of the subscales quantifying QoL as defined by the EORTC was tested by computing Cronbach's coefficient alpha and confirmatory factor analysis. The interviews were analysed using the phenomenological method. Results The questionnaire was returned by 121 (77%) patients at a mean of 12 days after hospital discharge. Over half had substantial voiding problems and one-third had emotional concerns. These results were confirmed by the interviews. The mean ± SD score for urinary symptoms was 45.21 ± 23.9 and the mean score for the future worries subscale was 39.9 ± 29.9. Cronbach's coefficient alpha was 0.84 for the urinary symptom subscale and 0.93 for the future worries subscale, which satisfied the reliability criterion for clinical use. Conclusions This first prospective study on QoL following TURBT in patients with NMIBC shows that TURBT has a significant impact on QoL. The Danish version of the EORTC questionnaire QLQ-NMIBC24 has been validated and confirmed in a Danish population.

Office-based transurethral devascularisation of low grade non-invasive urothelial cancer using diode laser. A feasibility study.

BACKGROUND AND OBJECTIVE: Frequent recurrence of non-muscle invasive bladder tumours (NMIBC) requiring transurethral resection of bladder tumour (TUR-BT) and lifelong monitoring makes the lifetime cost per patient the highest of all cancers. A new method is proposed for the removal of low grade NMIBCs in an office-based setting, without the need for sedation and pain control and where the patient can leave immediately after treatment. STUDY DESIGN/PATIENTS AND METHODS: An in vitro model was developed to examine the dose/response relationship between laser power, treatment time, and distance between laser fibre and target, using a 980 nm diode laser and chicken meat. The relationship between depth and extent of tissue destruction and the laser settings was measured using microscopy and non-parametric statistical analysis. A patient with low grade stage Ta tumour and multiple comorbidity, and therefore not fit for general anaesthesia, had a tumour devascularised using the laser at the tumour base, in the outpatient department. The tumour was left in the bladder. RESULTS: In the in vitro model, depth of tissue destruction increased with laser illumination up to 30 seconds, where median depth was 4.1 mm. With longer illumination the tissue destruction levelled off. The width of tissue destruction was 2-3 mm independent of laser illumination time. The in vivo laser treatments devascularised the tumour, which was later shed from the mucosa and passed out with the urine in the days following treatment. Pain score was 0 on a visual log scale (0-10). The tumour had completely disappeared two weeks after treatment. CONCLUSION: This diode laser technique may provide almost pain-free office-based treatment of low grade urothelial cancer using flexible cystoscopes in conscious patients. A prospective randomised study will be scheduled to compare the technique with standard TUR-BT in the operating theatre.

Delayed healing at transurethral resection of bladder tumour sites after immediate postoperative mitomycin C instillation.

The most common reactions to mitomycin C are dysuria and drug-related palmar and genital desquamation. This report describes two cases of delayed healing of the mucosa at resection sites after transurethral resection of bladder tumours, most likely due to immediate postoperative mitomycin C instillation of the bladder.

Role of hexaminolevulinate-guided fluorescence cystoscopy in bladder cancer: critical analysis of the latest data and European guidance.

OBJECTIVE: Hexaminolevulinate (HAL) is an optical imaging agent used with fluorescence cystoscopy (FC) for the detection of non-muscle-invasive bladder cancer (NMIBC). Guidelines from the European Association of Urology (EAU) and a recent, more detailed European expert consensus statement agree that HAL-FC has a role in improving detection of NMIBC and provide recommendations on situations for its use. Since the publication of the EAU guidelines and the European consensus statement, new evidence on the efficacy of HAL-FC in reducing recurrence of NMIBC, compared with white light cystoscopy (WLC), have been published. MATERIAL AND METHODS: To consider whether these new trials have an impact on the expert guidelines and on clinical practice (e.g. supporting existing recommendations or providing evidence for a change or expansion of practice), a group of bladder cancer experts from Denmark, Finland, Norway and Sweden met to address the following questions: What is the relevance of the new data on HAL-FC for clinical practice in managing NMIBC? What impact do the new data have on European guidelines? How could HAL-FC be used in clinical practice? and What further information on HAL-FC is required to optimize the management of NMIBC? RESULTS AND CONCLUSIONS: This article reports the outcomes of the discussion at the Nordic expert panel meeting, concluding that, in line with European guidance, HAL-FC has an important role in the initial detection of NMIBC and for follow-up of patients to assess tumour recurrence after WLC. It provides practical advice, with an algorithm on the use of this diagnostic procedure for urologists managing NMIBC.

Outpatient diagnostic of bladder tumours in flexible cystoscopes: evaluation of fluorescence-guided flexible cystoscopy and bladder biopsies.

OBJECTIVE: The aim of this study was to evaluate photodynamic diagnosis (PDD) in flexible cystoscopes and the diagnostic quality of biopsies for diagnosis of non-muscle-invasive bladder cancer in the outpatients department (OPD). MATERIAL AND METHODS: Seventy-three patients (aged 36-91 years) with recurrent non-muscle-invasive bladder cancer and a medium to high risk of recurrence had a flexible PDD cystoscopy performed in the OPD. The bladder was first examined in standard white light followed by PDD. RESULTS: PDD was superior to white light diagnosis; PDD was positive in 16 patients (22%) where white light showed a normal bladder mucosa. Four of these patients had bladder tumour [4/73, 6%; two carcinoma in situ (CIS), two Ta]. The diagnosis was verified by transurethral resection of the bladder tumour in the operating room. In 20 patients (20/73, 27%) PDD identified additional tumour lesions that were not identified in white light (five CIS, 15 Ta). The false-positive detection rate of PDD was 0.41. False positivity was significantly reduced by simultaneous flex biopsies disproving malignancy. Biopsies were obtained from 57 patients and diagnosis of stage and grade were possible in 55 of these (97%). In two patients (4%) the tissue material was too small for diagnostic evaluation. Biopsies from 47 patients (83%) included muscularis mucosa and from 20 patients (35%) muscularis propria. In 30 patients all but one diagnosis from the OPD was confirmed by biopsy in rigid scopes in the operating room. CONCLUSIONS: PDD-guided cystoscopy and bladder biopsy in flexible cystoscopes can be performed in an OPD setting and with reliable results for diagnosis of tumour stage Ta, CIS and T1a bladder cancer.

Fluorescence-guided transurethral resection of bladder tumours reduces bladder tumour recurrence due to less residual tumour tissue in Ta/T1 patients: a randomized two-centre study.

OBJECTIVES: •To compare the bladder tumour recurrence rate in stage Ta and T1 tumours after conventional transurethral resection of the bladder in white light (WL TURB) and after fluorescence-guided TURB (HAL TURB) using hexaminolaevulinate (HAL: Hexvix®, Photocure, Norway) for photodynamic diagnosis during 12 months of follow-up. •As secondary objectives, to relate the tumour recurrence rate to fluorescence-detected residual tumour after WL TURB and to assess the false positive rate. PATIENTS AND METHODS: •This was a prospective, comparative, randomized, open-label study carried out in hospital outpatient urology clinics and the operating theatre. A total of 233 patients presenting with suspected superficial bladder tumour were recruited. Both patients with new tumours and patients with recurrent tumours were included. •The study duration was 2.5 years with follow-up cystoscopic investigations at 4, 8 and 12 months. •Patients were randomized to cystoscopy and WL TURB (118 patients) or WL TURB followed immediately by HAL TURB (115 patients). Cystoscopy/TURB and bladder biopsies were performed under general anaesthesia. No patients had intravesical chemotherapy immediately after TURB. •Recurrences were verified histologically. RESULTS: •The two groups were similar regarding age and previous bladder cancer history. •In all, 90 patients from the HAL TURB group had bladder tumour. Fluorescence-guided cystoscopy after complete WL TURB identified residual tumour tissue in 44 of 90 patients (49%). In 37 of 83 (45%) residual Ta tumour was found; in three of seven residual T1 was found and in four cases carcinoma in situ. •True (and false) positive detection rate of photodynamic diagnosis was 64% (25%) and of white light 83% (16%). •In all, 145 patients were eligible for analysis of tumour recurrence. Twelve patients had their last follow-up after 4 months. The recurrence rate in patients followed for 12 months was 47.3% (35/74) after WL TURB and 30.5% (18/59) after HAL TURB (P= 0.05). •Kaplan-Meier analyses comprising data from all 145 patients showed that the recurrence-free period was significantly longer in the HAL TURB group than in the WL TURB group (P= 0.02). CONCLUSION: •WL TURB often leaves residual tumour in the bladder. HAL TURB improves the detection of Ta/T1 tumours of the bladder resulting in more complete TURB procedures and thus a reduced recurrence rate.

The load on family and primary healthcare in the first six weeks after transurethral resection of the prostate.

OBJECTIVE: The extent of load on spouses and primary healthcare after transurethral resection of the prostate (TURP) and the number of treatment-related symptoms in the first 6 weeks after TURP were studied. MATERIAL AND METHOD: A combined interview (qualitative) and questionnaire (quantitative) study was carried out. In the first part of the study 10 spouses underwent semi-structured interviews concerning their husbands' treatment-related symptoms 6 weeks after TURP. Based on these interviews a questionnaire was framed. In the second part questionnaires were sent to 78 spouses whose husbands had undergone TURP 6 weeks before. RESULTS: 69 questionnaires were returned (88.5%). The median age of spouses and their husbands was 65 years (range 43-90) and 70 years (range 46-85), respectively. Length of hospitalization, including day of operation, was 3 days (range 2-9). There were 43 (62%) unscheduled contacts with the health system after discharge. In relation to discharge, 55 (79.7%) were incontinent to some degree and 29 (42%) were incontinent for more than 4 weeks, 26 (37.7%) had urinary tract infection, 30 (40%) had long-lasting bleeding, 10 (14%) urinary retention, and 41 (59.4%) urgency. Of the spouses, 20 (34.8%) had sleep disorders, 27 (39%) an affected social life and 22 (31.9%) extra work at home; 19 (27.5%) of the spouses felt that their husbands had been discharged too early, 55 (80%) were satisfied with the information given before the operation and 46 (68%) were satisfied with the information given in relation to discharge. The treatment results after 6 months are comparable to other studies. CONCLUSIONS: Among patients discharged after TURP there is a considerable number of treatment-related symptoms in the first few weeks affecting the family as well as health services. The study has resulted in better oral and written information in relation to discharge. More pads are delivered and patients have a urine culture and telephone consultation with a nurse 1 week after discharge.