Georg Jancke

Gender-related differences in urothelial carcinoma of the bladder: a population-based study from the Swedish National Registry of Urinary Bladder Cancer

Abstract Objective: The aim of this investigation was to describe tumour characteristics, treatments and survival in patients with urinary bladder cancer (UBC) in a national population-based cohort, with special reference to gender-related differences. Material and methods: All primary UBC patients with urothelial pathology reported to the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) from 1997 to 2011 were included in the study. Groups were compared regarding tumour, node, metastasis classification, primary treatment and survival. Results: In total, 30,310 patients (74.9% male, 25.1% female) with UBC were analysed. A larger proportion of women than men had stage T2–T4 (p < 0.001), and women also had more G1 tumours (p < 0.001). However, compared to women, a larger proportion of men with carcinoma in situ or T1G3 received intravesical treatment with bacillus Calmette–Guérin or intravesical chemotherapy, and a larger proportion of men with stage T2–T4 underwent radical cystectomy (38% men vs 33% women, p < 0.0001). The cancer-specific survival at 5 years was 77% for men and 72% for women (p < 0.001), and the relative survival at 5 years was 72% for men and 69% for women (p < 0.001). Conclusions: In this population-based cohort comprising virtually all patients diagnosed with UBC in Sweden between 1997 and 2011, female gender was associated with inferior cancer-specific and relative survival. Although women had a higher rate of aggressive tumours, a smaller proportion of women than men received optimal treatment.

Local recurrence and progression of non-muscle-invasive bladder cancer in Sweden: a population-based follow-up study

Abstract Objective. The aim of this study was to investigate recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) in a large population-based setting. Materials and methods. Patients with bladder cancer (stage Ta, T1 or carcinoma in situ) diagnosed in 2004-2007 (n = 5839) in Sweden were investigated 5 years after diagnosis using a questionnaire. Differences in time to recurrence and progression were analysed in relation to age, gender, tumour stage and grade, intravesical treatment, healthcare region, and hospital volume of NMIBC patients (stratified in three equally large groups). Results. Local bladder recurrence and progression occurred in 50 and 9% of the patients, respectively. The rate of local recurrence was 56% in the southern healthcare region compared to 37% in the northern region. A multivariate Cox proportional hazards model, adjusting for age, gender, tumour stage and grade, intravesical treatment, healthcare region and hospital volume, showed that recurrence was associated with TaG2 and T1 disease, no intravesical treatment and treatment in the southern healthcare region, but indicated a lower risk of recurrence in the northern healthcare region. Adjusting for the same factors in a multivariate analysis suggested that increased relative risk of progression correlated with older age, higher tumour stage and grade, and diagnosis in the Uppsala/Örebro healthcare region, whereas such risk was decreased by intravesical treatment (relative risk 0.72, 95% confidence interval 0.55–0.93, p = 0.012). Conclusions. The incidence of NMIBC recurrence and progression was found to be high in Sweden, and important disparities in outcome related to care patterns appear to exist between different healthcare regions.

Residual tumour in the marginal resection after a complete transurethral resection is associated with local recurrence in Ta/T1 urinary bladder cancer

Abstract Objective. This study investigated the presence of residual tumour in the marginal resection (MR) after a complete transurethral resection (TURB) of Ta/T1 transitional urinary bladder cancer. The association between positive MR and recurrence was analysed. Material and methods. After macroscopically complete TURB, a marginal resection of 7 mm (corresponding to the diameter of the resection loop) was removed around the entire resection area. Univariate and multivariate Cox regression analyses were performed to assess the influence of residual disease on recurrence. Results. In all, 94 patients with a median follow-up time of 36 months were included, and residual tumour in the MR was present in 24 (26%). The recurrence rates for all cases, for those with a tumour-positive and a tumour-free MR were 60 (64%), 20 (83%) and 40 (57%), respectively. Local recurrence was found in 14 (58%) of the patients with tumour presence in the MR compared to 13 (19%) of those with a tumour-free margin. A positive MR was significantly associated with overall recurrence (p < 0.001) and local recurrence (p = 0.001). Conclusion. Incomplete transurethral resection of bladder cancer is common, as demonstrated in 26% patients with positive MR. The presence of tumour in the MR may be a risk factor for recurrence, and particularly local recurrence.

Risk factors for local recurrence in patients with pTa/pT1 urinary bladder cancer.

Objective. This study evaluated risk factors for local tumour recurrence, defined as recurrence at the same location in the bladder within 18 months after primary resection in patients with newly diagnosed pTa or pT1 bladder cancer. Patients and methods. The study included 472 patients with newly diagnosed pTa/T1 bladder cancer between 1992 and 2001. The patients were followed prospectively in accordance with a control programme and possible risk factors for tumour recurrence were registered. Results. Local tumour recurrence was observed in 164 (35%) patients, another 117 (25%) patients had recurrence at other locations in the bladder (non-local recurrence) and 191 (40%) had no recurrence at all. Tumour size and multiple tumours were significantly associated with a higher risk for developing local recurrence as opposed to non-local recurrence. Tumour category was of borderline statistical significance. Gender and tumour grade were not found to be risk factors for developing local recurrence. Conclusion. Tumour size and multiplicity are risk factors for development of recurrence at the same location in the bladder as the primary tumour. Local tumour recurrence may be a result of non-radical primary transurethral resection. One may consider recommending standard re-resection within 6–8 weeks in patients with tumours >3 cm or those with multiple primary tumours.

Swedish National Registry of Urinary Bladder Cancer: No difference in relative survival over time despite more aggressive treatment.

Abstract Objective. The aim of this study was to use the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) to investigate changes in patient and tumour characteristics, management and survival in bladder cancer cases over a period of 15 years. Materials and methods. All patients with newly detected bladder cancer reported to the SNRUBC during 1997–2011 were included in the study. The cohort was divided into three groups, each representing 5 years of the 15 year study period. Results. The study included 31,266 patients (74% men, 26% women) with a mean age of 72 years. Mean age was 71.7 years in the first subperiod (1997–2001) and 72.5 years in the last subperiod (2007–2011). Clinical T categorization changed from the first to the last subperiod: Ta from 45% to 48%, T1 from 21.6% to 22.4%, and T2–T4 from 27% to 25%. Also from the first to the last subperiod, intravesical treatment after transurethral resection for T1G2 and T1G3 tumours increased from 15% to 40% and from 30% to 50%, respectively, and cystectomy for T2–T4 tumours increased from 30% to 40%. No differences between the analysed subperiods were found regarding relative survival in patients with T1 or T2–T4 tumours, or in the whole cohort. Conclusions. This investigation based on a national bladder cancer registry showed that the age of the patients at diagnosis increased, and the proportion of muscle-invasive tumours decreased. The treatment of all tumour stages became more aggressive but relative survival showed no statistically significant change over time.

Bladder wash cytology at diagnosis of Ta-T1 bladder cancer is predictive for recurrence and progression.

OBJECTIVE To evaluate the effect of the bladder wash cytology finding at the primary diagnosis of Stage Ta-T1 urinary bladder cancer on recurrence and progression. METHODS The clinical and pathologic characteristics of all patients with primary Stage Ta-T1 urinary bladder cancer were prospectively registered. The data were divided according to the bladder wash cytology results at diagnosis. Multivariate analyses were performed to determine the influence of bladder wash cytology on recurrence and progression. RESULTS The analysis included 768 evaluable patients with a mean follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). High-grade malignant bladder wash cytology was predictive for recurrence and progression (P < .001 and P = .036, respectively). Other factors affecting recurrence were missing bladder wash cytology data, tumors size 16-30 mm and >30 mm, Stage T1 tumor category, and multiplicity (P = .008, P = .006, P < .001, P = .002, and P < .001, respectively). Progression was also associated with T1 tumor category, local recurrence, and primary concomitant carcinoma in situ (P < .001, P < .001, and P = .024, respectively). CONCLUSION High-grade malignant bladder wash cytology at the primary diagnosis was predictive for recurrence and progression. This could be taken into account in designing future follow-up schedules.

Tumour location adjacent to the ureteric orifice in primary Ta/T1 bladder cancer is predictive of recurrence

Abstract Objective: The aim of this study was to evaluate tumour growth located around the ureteric orifice (LUO) at primary diagnosis of Ta/T1 urinary bladder cancer in relation to effects on recurrence and progression. Materials and methods: Clinical and pathological characteristics of patients diagnosed with primary Ta/T1 urinary bladder cancer from 1992 to 2007 were recorded prospectively. Location of the primary tumour and growth around the ureteric orifice (within 1 cm) were recorded and correlated with recurrence and progression during further follow-up. Hazard ratios (HRs) were estimated using Cox regression with 95% confidence intervals (CIs) in both univariate and multivariate analysis. Results: The study included 768 evaluable patients with a median follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). Growth of a primary tumour adjacent to the ureteric orifice was associated with recurrence (HR = 1.28, 95% CI = 1.07–1.54) but not progression (HR = 1.04, 95% CI = 0.65–1.67). The most common location of the first recurrence was the posterior bladder wall (29%). Other locations in the bladder did not predict recurrence or progression. Additional factors affecting recurrence were tumour size greater than 15 mm, T1 tumour category, multiplicity, malignant or missing/not representative bladder wash cytology and surgery performed by residents. Conclusions: A primary tumour located around the ureteric orifice was predictive of recurrence, which could be taken into account in future follow-up schedules.

Reply to Francesco Montorsi and Giorgio Gandaglia's Letter to the Editor re: Georg Jancke, Firas Aljabery, Sigurdur Gudjonsson, et al. Port-site Metastases After Robot-assisted Radical Cystectomy: Is There a Publication Bias? Eur Urol 2018;73:641–2

We thank Professor Montorsi and Doctor Gandaglia for their comments based on their vast experience with robotassisted radical cystectomy (RARC). We agree that the adoption of minimally invasive surgery in patients with muscle-invasive bladder cancer should not be discouraged. However, to further extend the debate, we would like to explain the setting in which our case series data were collected [1] and add a few thought-provoking facts. The 0.3% incidence of port-site metastases observed at nine centres of excellence [2] might not be at the same low level in a population-based setting. Five of the eight cases with port-site metastases after RARC occurred during the first 100 procedures, and the other three during the first 200 cystectomies performed with robot assistance in the respective institutions. This suggests an incidence that is at least twice as high (0.7%) during the learning curve, not taking into account clinical underreporting. Regarding oncological outcomes after RARC, positive bladder margins in 4–15% of cases in randomised studies have been reported [3–5]. Thus, it seems that this endpoint must also be carefully monitored when adopting RARC. This is further supported by the recent update with long-term oncological follow-up from another randomised investigation [6], which revealed a higher risk of abdominopelvic recurrences after RARC. In the current series, 50% of the patients received neoadjuvant chemotherapy, and four patients (aged 70, 71, 75, and 79 yr) underwent surgery without such pretreatment. We agree with Montorsi and Gandaglia that one or two of these elderly patients might have been treatable with cisplatin-based combination chemotherapy before cystectomy, which as of 2016 was administered to 59% of all patients with muscle-invasive disease aged 75 yr undergoing surgery in Sweden [7]. Although neoadjuvant