Location of Retroperitoneal Lymph Node Metastases in Upper Tract Urothelial Carcinoma: Results from a Prospective Lymph Node Mapping Study.

Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC). Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND). Design setting and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage >T1) and/or clinical lymph node-positive (cN+) disease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates. Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used. Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade ≥3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates. Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited. Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.

Bladder cancer grading using the four-tier combination of the World Health Organization (WHO) 1973 and WHO 2004 classifications.

OBJECTIVE: To investigate the impact of grading in urothelial bladder cancer (UBC) stages Ta and T1, comparing the World Health Organization (WHO) grading classifications of 1973 (WHO73) and 2004 (WHO04) and a combination of these (WHO73/04). PATIENTS AND METHODS: All patients with primary Ta and T1 UBC in the Östergötland region, Sweden, between 1992 and 2007 were included. From 1992, we introduced a new programme for management and follow-up of UBC, including prospectively performed registration of all patients, a systematic description of the location and size of all tumours, primary resection and intravesical treatment in the case of recurrence. All tumour specimens were retrospectively reviewed in 2008 and graded according to the WHO73 and WHO04. A combination of WHO73/04, Grade 1 (G1), Grade 2 low grade (G2LG), Grade 2 high grade (G2HG) and Grade 3 (G3) was analysed in relation to clinical variables and outcomes. RESULTS: There were 769 patients with a median age of 72 years and a median follow-up duration of 74 months. Recurrence was noted in 484 patients (63%) and progression in 80 patients (10%). Recurrence was more common in multiple tumours, larger tumours and in tumours of higher grade (G2LG, G2HG and G3). Progression was more common in tumours classified as larger, T1 and G2HG and G3. Notably, in tumours classified as G2HG, recurrence and progression were more common than in the G2LG group. Harrell's concordance index for the WHO73/04 was higher for recurrence and progression than in the WHO73 or WHO04. CONCLUSION: In the four-tier combined WHO73/04 for urothelial cancer, we observed two G2 sub-groups, G2HG and G2LG. There was a better outcome in the latter group, and the importance of G1 and G3 tumours could be fully evaluated. The WHO73/04 had greater accuracy for recurrence and progression than either the WHO73 or WHO04.

Stapled versus robot-sewn ileo-ileal anastomosis during robot-assisted radical cystectomy: a review of outcomes in urinary bladder cancer patients.

BACKGROUND: Whereas the literature has demonstrated an acceptable safety profile of stapled anastomoses when compared to the hand-sewn alternative in open surgery, the choice of intestinal anastomosis using sutures or staples remains inadequately investigated in robotic surgery. The purpose of this study was to compare the surgical outcomes of both anastomotic techniques in robotic-assisted radical cystectomy. METHODS: A retrospective analysis of patients with urinary bladder cancer undergoing cystectomy with urinary diversion and with ileo-ileal intestinal anastomosis at a single tertiary centre (2012-2018) was undertaken. The robotic operating time, hospital stay and GI complications were compared between the robotic-sewn (RS) and stapled anastomosis (SA) groups. The only difference between the groups was the anastomosis technique; the other technical steps during the operation were the same. Primary outcomes were GI complications; the secondary outcome was robotic operation time. RESULTS: There were 155 patients, of which 112 (73%) were male. The median age was 71 years old. A surgical stapling device was used to create 66 (43%) separate anastomoses, while a robot-sewn method was employed in 89 (57%) anastomoses. There were no statistically significant differences in primary and secondary outcomes between RS and SA. CONCLUSIONS: Compared to stapled anastomosis, a robot-sewn ileo-ileal anastomosis may serve as an alternative and cost-saving approach.

Period-specific mean annual hospital volume of radical cystectomy is associated with outcome and perioperative quality of care: a nationwide population-based study.

OBJECTIVE: To investigate the association between hospital volume and overall survival (OS), cancer-specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of <3 months. PATIENTS AND METHODS: We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1-T3 in Sweden between 1997 and 2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at ≥25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually. RESULTS: PSMAV in the highest tertile (≥25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75-1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of >3 months after diagnosis. CONCLUSIONS: The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral.

Second-look resection for primary stage T1 bladder cancer: a population-based study.

OBJECTIVE: This study aimed to evaluate the use of second-look resection (SLR) in stage T1 bladder cancer (BC) in a population-based Swedish cohort. MATERIALS AND METHODS: All patients diagnosed with stage T1 BC in 2008-2009 were identified in the Swedish National Registry for Urinary Bladder Cancer. Registry data on TNM stage, grade, primary treatment and pathological reports from the SLR performed within 8 weeks of the primary transurethral resection were validated against patient charts. The endpoint was cancer-specific survival (CSS). RESULTS: In total, 903 patients with a mean age of 74 years (range 28-99 years) were included. SLR was performed in 501 patients (55%), who had the following stages at SLR: 172 (35%) T0, 83 (17%) Ta/Tis, 210 (43%) T1 and 26 (5%) T2-4. The use of SLR varied from 18% to 77% in the six healthcare regions. Multiple adjuvant intravesical instillations were given to 420 patients (47%). SLR was associated with intravesical instillations, age younger than 74 years, discussion at multidisciplinary tumour conference, G3 tumour and treatment at high-volume hospitals. Patients undergoing SLR had a lower risk of dying from BC (hazard ratio 0.62, 95% confidence interval 0.45-0.84, p < .0022). Five-year CSS rates were as follows, in patients with the indicated tumours at SLR (p = .001): 82% in those with T1, 90% in T0, 90% in Ta/Tis and 56% in T2-4. CONCLUSIONS: There are large geographical differences in the use of SLR in stage T1 BC in Sweden, which are presumably related to local treatment traditions. Patients treated with SLR have a high rate of residual tumour but lower age, which suggests that a selection bias affects CSS.

Intravesical instillations and cancer-specific survival in patients with primary carcinoma in situ of the urinary bladder.

OBJECTIVE: The aim of this study was to evaluate the use of intravesical treatment and cancer-specific survival of patients with primary carcinoma in situ (CIS). MATERIALS AND METHODS: Data acquisition was based on the Swedish National Registry of Urinary Bladder Cancer by selecting all patients with primary CIS. The analysis covered gender, age, hospital type and hospital volume. Intravesical treatment and death due to bladder cancer were evaluated by multivariate logistic regression and multivariate Cox analysis, respectively. RESULTS: The study included 1041 patients (median age at diagnosis 72 years) with a median follow-up of 65 months. Intravesical instillation therapy was given to 745 patients (72%), and 138 (13%) died from bladder cancer during the observation period. Male gender [odds ratio (OR) = 1.56, 95% confidence interval (CI) 1.13-2.17] and treatment at county (OR = 1.65, 95% CI 1.17-2.33), university (OR =2.12, 95% CI 1.48-3.03) or high-volume (OR = 1.92, 95% CI 1.34-2.75) hospitals were significantly associated with higher odds of intravesical instillations. The age category ≥80 years had a significantly lower chance of receiving intravesical therapy (OR = 0.44, 95% CI 0.26-0.74) and a significantly higher risk of dying from bladder cancer (hazard ratio = 3.03, 95% CI 1.71-5.35). CONCLUSION: Significantly more frequent use of intravesical treatment of primary CIS was found for males and for patients treated at county, university and high-volume hospitals. Age ≥80 years was significantly related to less intravesical treatment and poorer cancer-specific survival.

Should we Refrain from Performing Oophorectomy in Conjunction with Radical Cystectomy for Bladder Cancer?

Radical cystectomy with neoadjuvant chemotherapy is the gold standard for treating muscle-invasive bladder cancer. Women subjected to radical cystectomy are frequently postmenopausal, and the median age for bladder cancer diagnosis in women in Sweden is currently 73 yr (Swedish National Bladder Cancer Register). Traditionally, most women treated with radical cystectomy have undergone simultaneous bilateral oophorectomy and hysterosalpingectomy to diminish the risk of later ovarian disease and ovarian bladder cancer recurrence, but also the belief that there is no impact on health or health-related quality of life associated with oophorectomy and the fact that it might be easier surgery to take the ovarian pedicles, rather than sparing the ovaries. However, pelvic organ preservation is considered in some younger women to diminish postoperative functional impairment. Based on recent literature in several areas related to oophorectomy, we question the rationale and arguments for performing oophorectomy in women in conjunction with radical cystectomy for bladder cancer.

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

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.

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

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.

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

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.

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

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.

Impact of surgical experience on recurrence and progression after transurethral resection of bladder tumour in non-muscle-invasive bladder cancer.

OBJECTIVE: This study aimed to evaluate the impact of experience in transurethral resection of bladder tumour (TURBT) on recurrence and progression in primary Ta/T1 urinary bladder cancer. MATERIAL AND METHODS: Clinical and pathological characteristics of patients with primary Ta/T1 urinary bladder cancer were recorded prospectively from 1992 to 2007 inclusive. Data on surgeons' experience were categorized as follows: experience by training status (residents or specialists); number of TURBTs performed by each surgeon during the registration period, with cut-off levels at more than 100, more than 150, more than 200, greater than the median and above the third quartile of surgical volume; and lifetime high-volume surgeons (>100 TURBTs). Hazard ratios (HRs) were estimated using Cox regression with 95% confidence intervals (CIs) in multivariate analyses. RESULTS: The analysis included 768 evaluable patients with a median follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). Surgery was performed by residents in 100 cases and specialists in 668, with recurrence in 75 (75%) and 403 (60%) patients, and progression in nine (9%) and 62 (9%), respectively. Surgery performed by specialists was significantly associated with a lower recurrence rate (HR = 0.68, 95% CI 0.53-0.87) but not progression (HR = 0.76, 95% CI 0.37-1.56). Surgical volume had no significant impact on recurrence or progression in any of the analyses at the chosen cut-offs. CONCLUSIONS: Surgical experience (specialist/resident) was predictive for recurrence after TURBT for Ta/T1 bladder cancer. Training programmes, checklists and specialist-assisted surgery may shorten the learning curve and improve results.

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.

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

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.

Impact of tumour size on recurrence and progression in Ta/T1 carcinoma of the urinary bladder.

OBJECTIVE: This study aimed to evaluate the impact of tumour size on recurrence and progression in a population-based series of non-muscle-invasive bladder cancers. MATERIAL AND METHODS: Clinical and pathological characteristics of patients with primary Ta/T1 bladder cancer were registered. The patients' tumours were categorized by size into five size groups (1-10, 11-20, 21-30, 31-40 and >40 mm) or three size groups (1-15, 16-30 and >30 mm). 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%). Tumour size was associated with recurrence for tumours sized 21?30, 31?40 and >40 mm (p = 0.03, p < 0.001, p < 0.001, respectively) in the five size group and for tumours sized 16?30 and >30 mm (p = 0.003 and p < 0.001) in the three size group. Other factors affecting recurrence were T1 tumour category, multiplicity and surgery performed by residents (p < 0.001, p < 0.001, p = 0.002, respectively). Considering progression, there was no significant association with tumour size, and T1 category and local recurrence were the only significant risk factors (both p < 0.001). CONCLUSION: Tumour size ?15 mm is associated with a lower risk of recurrence but not progression. Dividing tumour size into three size groups gives additional information compared with two size groups with cut-off at 30 mm.