Viktor Soukup

Narrow Band Imaging Cystoscopy Improves the Detection of Non-muscle-invasive Bladder Cancer

OBJECTIVES To determine whether narrow band imaging (NBI) improves detection of non-muscle-invasive bladder cancer over white-light imaging (WLI) cystoscopy. METHODS We conducted a prospective, within-patient comparison on 103 consecutive procedures on 95 patients scheduled for (re-) transurethral resection of a bladder tumor (84) or bladder biopsies (19) in the Academic Medical Center, Amsterdam (September 2007-July 2009) and in the General Faculty Hospital, Prague (January 2009-July 2009). WLI and NBI cystoscopy were subsequently performed by different surgeons who independently indicated all tumors and suspect areas on a bladder diagram. The lesions identified were resected/biopsied and sent for histopathological examination. Number of patients with additional tumors detected by WLI and NBI were calculated; mean number of urothelial carcinomas (UCs) per patient, detection rates, and false-positive rates of both techniques were compared. RESULTS A total of 78 patients had a confirmed UC; there were 226 tumors in total. In 28 (35.9%) of these patients, a total of 39 additional tumors (17.3%) (26pTa, 6pT1, 1pT2, 6pTis) were detected by NBI, whereas 4 additional tumors (1.8%) (1pTa, 1pT1, 2pTis) within 3 patients (2.9%) were detected by WLI. The mean (SD, range) number of UCs per patient identified by NBI was 2.1 (2.6, 0-15), vs 1.7 (2.3, 0-15) by WLI (P <.001). The detection rate of NBI was 94.7% vs 79.2% for WLI (P <.001). The false-positive rate of NBI and WLI was 31.6% and 24.5%, respectively (P <.001). CONCLUSIONS NBI cystoscopy improves the detection of primary and recurrent nonmuscle invasive bladder cancer over WLI. However, further validation of the technique with comparative studies is required.

5‐aminolaevulinic acid‐induced fluorescence cystoscopy during transurethral resection reduces the risk of recurrence in stage Ta/T1 bladder cancer

To assess the influence of 5‐aminolaevulinic acid‐induced fluorescence cystoscopy (FC) during transurethral resection (TUR) on the recurrence rate and the length of tumour‐free interval in stage Ta/T1 transitional cell carcinoma (TCC) of the urinary bladder.

Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients

BACKGROUND The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

Follow-up After Surgical Treatment of Bladder Cancer: A Critical Analysis of the Literature

CONTEXT Follow-up of patients treated for bladder cancer (BCa) is of great importance for both non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa (MIBC) because of the high incidence of recurrence and progression. The schedule and methods of follow-up should reflect the individual clinical situation. OBJECTIVE To evaluate the existing evidence for intensity and duration of follow-up recommendations in patients after surgical treatment of BCa. EVIDENCE ACQUISITION We searched the Medline, Embase, and Cochrane databases for published data on the follow-up of patients with NMIBC and MIBC after radical cystectomy (RC). EVIDENCE SYNTHESIS Follow-up in patients with NMIBC is necessary because of the high probability of tumour recurrence and the risk of progression. Cystoscopy plus cytology are the standard methods for follow-up. Cystoscopy should be done 3 mo after the transurethral resection in every patient, and the frequency after that depends on the individual recurrence/progression risk. Cytology should be used as an adjunctive method to cystoscopy in intermediate- and high-risk patients. None of the currently available urinary markers or imaging methods can substitute for cystoscopy-based follow-up. High-risk NMIBC patients require regular lifelong upper urinary tract monitoring. Follow-up in MIBC is based on the fact that early detection of recurrence after RC allows for timely treatment with the aim of improving outcomes. Patients with extravesical and lymph node-positive disease should have the most intensive follow-up because of the highest recurrence risk. Routine upper urinary tract imaging is advisable for all patients and should continue in the long term. Follow-up also allows for early detection of urinary diversion-related complications, the rate of which increases with time. CONCLUSIONS Follow-up in BCa is necessary for diagnosing recurrence and progression, as well as for evaluating complications after radical treatment. Since randomised studies investigating the most appropriate follow-up schedule are lacking, most recommendations are based on only the retrospective experience. Nonetheless, reasonable recommendations can be made until further prospective randomised studies testing different follow-up schedules have been performed.

Urinary Cytology and Quantitative BTA and UBC Tests in Surveillance of Patients with pTapT1 Bladder Urothelial Carcinoma

OBJECTIVES To compare results of urinary cytology, quantitative detection of human complement factor H-related protein (BTA TRAK), and urinary fragments of cytokeratins 8 and 18 (UBC IRMA) with the recurrence status in patients with pTapT1 bladder cancer and to define the possible role of these methods in a surveillance protocol. METHODS We collected urine from 88 consecutive patients with primary pTapT1 tumors before the first transurethral resection (TURB) and before each follow-up cystoscopy. In all samples urinary cytology and quantitative BTA and UBC tests were performed. We compared results with recurrence status and with tumor characteristics in the case of recurrence. We constructed receiver operator characteristic (ROC) curves for quantitative methods. In addition, we evaluated individual cutoffs based on pretreatment levels. RESULTS During the mean follow-up of 16.96 months, we performed 313 cystoscopies, 93 of which were positive in 51 patients. The sensitivity and specificity of cytology, BTA, and UBC were 19.8% and 99%, 53.8% and 83.9%, and 12.1% and 97.2%, respectively. The sensitivity of pTis detection was 66.6%, 0%, and 100%, respectively. With cutoffs set to a sensitivity of 90%, the specificity of BTA and UBC dropped to 24.8% and 20.4%, respectively. Individually calculated cutoffs did not provide a significant benefit. CONCLUSIONS Because of high specificity and sensitivity in pTis detection, urinary cytology fulfills requirements for an adjunctive method to cystoscopy. Quantitative BTA and UBC tests have a low sensitivity in the detection of bladder cancer recurrence and cannot be used routinely to reduce the number of cystoscopies during follow-up.

The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guerin

To determine if a re‐transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1‐high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).

Does the Expression of Fascin-1 and Tumor Subclassification Help to Assess the Risk of Recurrence and Progression in T1 Urothelial Urinary Bladder Carcinoma?

Introduction: To evaluate the prognostic value of T1 subclassification and fascin-1 expression in T1 human urothelial cell carcinoma of the bladder. Materials and Methods: In a prospective study with 105 consecutive patients, T1 tumors were subclassified into 2 groups according to the depth of tumor invasion. The tunica muscularis mucosae was used as a landmark. The expression of fascin-1 was examined by using an anti-fascin-1 mouse monoclonal antibody and was evaluated semiquantitatively for both intensity and distribution. The patients were followed up for 27.3 ± 13.7 months. Results: The T1 tumor subclassification was feasible in 99 patients (94%). T1a tumor was detected in 77 patients (73%), T1b tumor in 22 patients (21%). An invasive tumor was found in 5 patients (4.8%) during the restaging transurethral resection of the bladder. The risk of understaging in patients with T1b tumor was 18%. There was not a significant difference in time to the recurrence in the T1a and the T1b group. The progression-free survival rates were significantly different between both groups (p = 0.0034). No correlation was found between fascin-1 positivity and the depth of tumor invasion. Fascin-1 positivity did not correlate with recurrence or the progression-free intervals. In the multivariate analysis, only the extent of lamina propria invasion was an independent predictor of the tumor progression. The fascin positivity was not an independent prognostic factor relating to the risk of recurrence or progression. Conclusion: The finding of T1b tumor was connected with a significantly higher risk of progression and understaging. The fascin-1 expression did not correlate with the depth of tumor invasion or with the tumor recurrence or progression.

The expression of PAX5, p53 immunohistochemistry and p53 mutation analysis in superficial bladder carcinoma tissue. Correlation with pathological findings and clinical outcome.

Objectives: The expression pattern of PAX5 in thetissue of superficial bladder transitional cell carcinoma (TCC), itsprognostic value and its correlation with p53immunohistochemistry and p53 mutation analysis were evaluated.Methods: Study comprised 61 patients with histologicallyconfirmed superficial bladder TCC. Expression level of PAX5mRNA was investigated using reverse transcriptase-polymerase chainreaction (RT-PCR) and determined semiquantitatively. The presence ofp53 mutations was determined by SSCP and confirmed by directsequencing. The p53 immunohistochemistry was performed with DO1antibody and semiquantitatively evaluated using HSCORE (HS) method. Asthe control group for the evaluation of the PAX5 expressionserved 8 men with benign prostatic hyperplasia. Results:PAX5 expression was found in 50 patients with bladder TCC butin no patient from the control group. Its quantity however correlatedneither with the stage nor with the grade of the tumor. P53mutation was confirmed only in 1 patient with pTaG2 tumor in exon 5(deletion of proline 128). On the contrary, positive immunohistochemicalstaining of p53 was detected in most patients. Using the cutoffvalue of HS 200, 56.9% of patients showed p53overexpression. Quantity of p53 immunochistochemical positivitydid not correlate with the quantity of PAX5 expression. Usingthe cutoff values of HS 200 for p53 and of 0.2 forPAX5, 7 of 8 patients with future progression had p53and 4 had PAX5 overexpression respectively.Conclusion: The expression of gene PAX5 is a frequentevent in superficial TCC of the bladder.

Prognostic Performance and Reproducibility of the 1973 and 2004/2016 World Health Organization Grading Classification Systems in Non–muscle-invasive Bladder Cancer: A European Association of Urology Non-muscle Invasive Bladder Cancer Guidelines Panel Systematic Review

CONTEXT Tumour grade is an important prognostic indicator in non-muscle-invasive bladder cancer (NMIBC). Histopathological classifications are limited by interobserver variability (reproducibility), which may have prognostic implications. European Association of Urology NMIBC guidelines suggest concurrent use of both 1973 and 2004/2016 World Health Organization (WHO) classifications. OBJECTIVE To compare the prognostic performance and reproducibility of the 1973 and 2004/2016 WHO grading systems for NMIBC. EVIDENCE ACQUISITION A systematic literature search was undertaken incorporating Medline, Embase, and the Cochrane Library. Studies were critically appraised for risk of bias (QUIPS). For prognosis, the primary outcome was progression to muscle-invasive or metastatic disease. Secondary outcomes were disease recurrence, and overall and cancer-specific survival. For reproducibility, the primary outcome was interobserver variability between pathologists. Secondary outcome was intraobserver variability (repeatability) by the same pathologist. EVIDENCE SYNTHESIS Of 3593 articles identified, 20 were included in the prognostic review; three were eligible for the reproducibility review. Increasing tumour grade in both classifications was associated with higher disease progression and recurrence rates. Progression rates in grade 1 patients were similar to those in low-grade patients; progression rates in grade 3 patients were higher than those in high-grade patients. Survival data were limited. Reproducibility of the 2004/2016 system was marginally better than that of the 1973 system. Two studies on repeatability showed conflicting results. Most studies had a moderate to high risk of bias. CONCLUSIONS Current grading classifications in NMIBC are suboptimal. The 1973 system identifies more aggressive tumours. Intra- and interobserver variability was slightly less in the 2004/2016 classification. We could not confirm that the 2004/2016 classification outperforms the 1973 classification in prediction of recurrence and progression. PATIENT SUMMARY This article summarises the utility of two different grading systems for non-muscle-invasive bladder cancer. Both systems predict progression and recurrence, although pathologists vary in their reporting; suggestions for further improvements are made.

The Prognostic Value of T1 Bladder Cancer Substaging: A Single Institution Retrospective Study

Objective: To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer. Subjects and Methods: 200 patients were treated between the years 2002 and 2009. Tumours with depth of invasion above the muscularis mucosae level were categorised as pT1a and those with depth of invasion up to or beyond the muscularis mucosae as pT1b. Results: Categorisation for pT1a and pT1b was performed in 176 of 200 patients (88%). In 10 patients a muscle-invasive tumour was found in re-transurethral resection samples. 131 (79%) of 166 analysed patients had pT1a tumour and 35 (21%) had pT1b tumour. During the follow-up, in 101 (61%) patients the tumour had recurred and in 27 (16.3%) the tumour had progressed. Of all the investigated parameters, T1 substaging (p < 0.0001), grade (p = 0.0003) and the number of bacillus Calmette-Guérin instillations (p = 0.0490) were significant in predicting progression. The only significant factor for disease-specific survival was T1 substaging in univariable (p = 0.0008) and multivariable (hazard ratio 4.407) analysis. T1 substaging (p = 0.0149) and tumour multiplicity (p = 0.0448) have a statistically significant prognostic value with respect to overall survival. Conclusions: Deep invasion of the lamina propria is a significant adverse prognostic factor for tumour progression, disease-specific survival and overall survival.