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Objective: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice., Patients and Methods: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test., Results: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result., Conclusion: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To compare the incidence of postoperative flank bulges between patients with multiple-layer closure and single superficial-layer closure after retroperitoneal surgery via open flank incision in the SIngle versus MUltiple-LAyer wound Closure for flank incision (SIMULAC) trial., Patients and Methods: The study was a randomised controlled, patient- and assessor-blinded, multicentre trial. Between May 2015 and February 2017, 225 patients undergoing flank incisions were randomised 1:1 to a multiple-layer closure (SIMULAC-I) or a single superficial-layer closure (SIMULAC-II) group. The primary outcome was the occurrence of a flank bulge 6 months after surgery., Results: Overall, 177 patients (90 in SIMULAC-I, 87 in SIMULAC-II) were eligible for final assessment. The cumulative incidence of a flank bulge was significantly higher in the SIMULAC-II group (51.7%) compared to the SIMULAC-I group [34.4%; odds ratio (OR) 2.04, 95% confidence interval (CI) 1.11-3.73; P = 0.02]. Rate of severe postoperative complications (4.4% SIMULAC-I vs 10.3% SIMULAC-II; P = 0.21) or hernia (6.7% SIMULAC-I vs 10.3% SIMULAC-II; P = 0.59) was similar between the groups. There was no difference in pain (visual analogue scale) and the requirement for pain medication at 6 months postoperatively. Quality of life assessed with the European Quality of Life 5 Dimensions Questionnaire was higher in the SIMULAC-I group compared to the SIMULAC-II group at 6 months postoperatively, with a (median range) score of 80 (30-100) vs 75 (5-100) (P = 0.012)., Conclusion: The overall risk of a flank bulge after flank incision is high. Multiple-layer closure after flank incision should be performed as a standard procedure., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Objective: • To describe a multicentre experience with preoperative platinum-based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco-regional nodal metastases., Patients and Methods: • We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. • Group 1 comprised patients who received chemotherapy before RNU because of biopsy-proven loco-regional nodal metastases. • Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node-positive). • Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node-negative (N0) UTUC., Results: • Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5-year disease-free survival rates were 49%, 30% and 64%, whereas the 5-year cancer-specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. • In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan-Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). • Meanwhile, group 2 had significantly lower disease-free and cancer-specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively)., Conclusions: • Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco-regional nodal metastases. • These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: •To assess the impact of differences in ethnicity on clinico-pathological characteristics and outcomes of patients with upper urinary tract urothelial carcinoma (UTUC) in a large multi-center series of patients treated with radical nephroureterectomy (RNU)., Materials and Methods: •We retrospectively collected the data of 2163 patients treated with RNU at 20 academic centres in America, Asia, and Europe. •Univariable and multivariable Cox regression models addressed recurrence-free survival (RFS) and cancer-specific survival (CSS)., Results: •In all, 1794 (83%) patients were Caucasian and 369 (17%) were Japanese. All the main clinical and pathological features were significantly different between the two ethnicities. •The median follow-up of the whole cohort was 36 months. At last follow-up, 554 patients (26%) developed disease recurrence and 461 (21%) were dead from UTUC. •The 5-year RFS and CSS estimates were 71.5% and 74.2%, respectively, for Caucasian patients compared with 68.8% and 75.4%, respectively, for Japanese patients. •On univariable Cox regression analyses, ethnicity was not significantly associated with either RFS (P= 0.231) or CSS (P= 0.752). •On multivariable Cox regression analyses that adjusted for the effects of age, gender, surgical type, T stage, grade, tumour architecture, presence of concomitant carcinoma in situ, lymphovascular invasion, tumour necrosis, and lymph node status, ethnicity was not associated with either RFS (hazard ratio [HR] 1.1; P= 0.447) or CSS (HR 1.0; P= 0.908)., Conclusions: •There were major differences in the clinico-pathological characteristics of Caucasian and Japanese patients. •However, RFS and CSS probabilities were not affected by ethnicity and race was not an independent predictor of either recurrence or cancer-related death., (© 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: •To evaluate the characteristics and long-term outcome of patients with pT0 stage after radical cystectomy (RC) for urothelial carcinoma of the urinary bladder (UCB)., Patients and Methods: •Clinical and pathological records of 2403 patients treated with RC for UCB were collected in a multi-institutional database. •The patients met the following criteria: clinical tumour stage cTa-cT2, cN0, cM0, no neoadjuvant chemotherapy or radiotherapy. •Overall (OS) and cancer-specific survival rates (CSS) were calculated for the various clinical tumour stages in relation to their corresponding pathological tumour stage in the RC sample. •Further to this, a multivariable prediction model was developed based on the available clinical data to estimate the probability of tumour stage pT0., Results: •The mean follow-up was 53 months and 132 patients (5.5%) were stage pT0. •Patients with stage cT2-pT0 had a 5-year CSS of 87% vs 69% for cT2-pT2 (P= 0.012) and 57% for cT2-pT+ (P < 0.001). •In a multivariable Cox-model, stage pT0 led to a significant reduction of cancer-specific mortality (hazard ratio0.27; 95% confidence interval 0.12-0.61). •A logistical regression model identified clinical tumour stage (advantage for non-invasive stages) and transurethral resection of the urinary bladder (TURB) time frame (advantage for more recent surgery) as independent predictors for stage pT0., Conclusions: •In muscle-invasive clinical tumour stages, patients with pathological tumour stage pT0 form a subgroup showing a significantly better CSS. •A radical TURB is, assumedly, not causative of this improved survival rate, but rather it is that individual tumour characteristics allow for complete tumour eradication through the TURB procedure. •A TURB with R0 resection is, as such, only a sign of a better tumour prognosis., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: To study guideline recommendation (GR)-concordance rates of treatment in elderly patients with urothelial carcinoma of the bladder (UCB) and to identify predictors of survival., Patients and Methods: The records of 206 consecutive patients aged ≥ 75 years (median age 79 years; range 75-95) were reviewed. All patients underwent transurethral resection (TUR) or biopsy of UCB. The European Association of Urology and American Urological Association guidelines were used as reference when evaluating concordance with GRs and clinical outcome. Univariable and multivariable analyses were performed to identify predictors of survival., Results: The overall GR-concordance rate of treatment was 88.8% (183 of 206 patients). Patients who were older (P = 0.017), who underwent prior treatment for UCB (P = 0.010), and had greater comorbidities (P = 0.001) were less likely to undergo treatment following GRs. With a median (mean; range) follow-up of 14.7 (22.6; 0.3-111.5) months, 79 patients died (38.3%). More comorbidities (unadjusted Charlson comorbidity index; P = 0.007), a Karnofsky performance status (KPS) score of ≤ 80 (P = 0.001) and more advanced initial pathological tumour stage (P = 0.019) independently predicted reduced overall survival (OS). In the subgroup of patients with indication for cystectomy (n = 99), there was a trend for longer OS in patients treated with curative intent (cystectomy or radio-chemotherapy) compared with conservative treatment with TUR ± intravesical therapy only (P = 0.095)., Conclusions: The vast majority of elderly patients with UCB received adequate treatment at our tertiary institution. The KPS score, more comorbidities and more advanced pathological tumour stage are predictors for reduced OS and should be considered to optimize patient care., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: to test whether the expression of human epidermal growth factor receptor 2 (HER-2) is of prognostic value in a contemporary cohort of patients with urothelial carcinoma of the urinary bladder (UCB)., Patients and Methods: tissue microarrays of 198 patients were constructed and immunohistochemical stainings were performed on the primary tumours and on lymphatic nodal metastases. All patients were treated with radical cystectomy (RC) and regional lymphadenectomy for UCB. HER-2 expression was assessed using continuous HER-2 expression scores (ranging from 0.1 to 3.9) generated using an automated cellular imaging system. Scores of ≥ 1.0 in at least 10% of tumour cells were regarded as HER-2 positive. We correlated HER-2 scores with pathological and clinical variables, including disease recurrence and cancer-specific mortality., Results: of 198 patients undergoing RC with lymphadenectomy, there was HER-2 positivity in 55 primary tumours (27.8%) compared with 44.2% of the evaluable positive lymph nodes (P < 0.001). HER-2 positivity was significantly associated with the presence of lymphovascular invasion (LVI; P= 0.026). With a median (range) follow-up of 35.4 (1.3-176.1) months, 101 patients (51.0%) had UCB recurrence and 82 patients (41.4%) died from the disease. In multivariable analyses that adjusted for the effects of pathological tumour stage, grade, LVI, lymph node metastasis and adjuvant chemotherapy, HER-2 positive patients were at increased risk for both UCB recurrence (hazard ratio [HR] 1.955, P= 0.003) and UCB-specific mortality (HR 2.066, P= 0.004) compared with patients with negative HER-2 expression., Conclusion: a positive HER-2 status is associated with aggressive UCB and provides independent prognostic information for UCB recurrence and mortality. Assessment of HER-2 status can be used to identify patients at high risk of disease progression who may benefit from adjuvant HER-2-targeted mono- or combined therapy after RC.

Objective: to evaluate the impact of obesity on the costs of robotic-assisted (RALP), laparoscopic (LRP) and open retropubic radical prostatectomy (RRP)., Patients and Methods: the charts of 629 patients who underwent RP (262 RALP, 211 LRP and 156 RRP) between September 2003 and April 2008 at our institution were reviewed. Clinical and pathological data were collected, including age, American Society of Anesthesiologists score, body mass index (BMI), tumour stage, complications and length of stay. Direct and component costs (anaesthesia, laboratory, operating room service, radiology, room and board, pharmacy and surgical supplies) were obtained. Differences in costs were evaluated using three BMI categories (<25, normal weight; 25-<30, overweight; and ≥30 kg/m(2) , obese)., Results: of 629 patients, 136 (21.6%) had normal weight, 320 (50.9%) were overweight, and 173 (27.5%) were obese. Clinical and pathological characteristics were similar in the three BMI categories of the entire cohort. The median direct cost was higher for obese patients (P= 0.035). On further stratification by type of RP, costs were higher amongst obese than the other groups undergoing LRP (median US$5703 vs $5347; P= 0.002) and RRP (median $4885 vs $4377; P= 0.004). In patients who underwent RALP there were no significant differences in direct costs (median $6761 in obese vs $6745 in non-obese; P= 0.64)., Conclusion: obesity influenced the costs in patients who underwent LRP and RRP, mainly due to increased operating room service and anaesthesia costs in obese patients. RALP can be performed with no additional financial burden in obese patients.

Objectives: To validate the association of lymphovascular invasion (LVI) with disease recurrence and cancer-specific survival (CSS) in a multicentre cohort of patients treated with radical cystectomy (RC) for urothelial bladder cancer (UBC)., Patients and Methods: We collected pathological and clinical data on 1099 lymph node-negative patients treated with RC at six German institutions. LVI was defined as the presence of tumour cells within an unequivocal endothelium-lined space in haematoxylin and eosin-stained sections., Results: LVI was present in 295 (26.8%) patients; the presence of LVI correlated significantly with increasing tumour stage, i.e. pT1, 65 (29.4%); pT2, 88 (31.5%); pT3 110 (31.8%); and pT4 32 (38.1%) (P= 0.002) and grade (P < 0.001). In univariable analysis the presence of LVI was significantly associated with reduced recurrence-free survival (P= 0.008) and reduced CSS (P= 0.039). On multivariable Cox regression analysis tumour stage (P < 0.001), age (>75 vs >or=75 years; P= 0.018) and LVI (P < 0.001) were identified as independent predictors of CSS., Conclusions: Our large multicentre study confirms the independent prognostic value of LVI in patients with node-negative UBC. LVI can be regarded as a surrogate variable for lymphatic micrometastasis in node-negative UBC. Assessment of LVI might improve the selection of patients who are likely to benefit from adjuvant therapy after RC. The identification of factors involved in the process of LVI could reveal new therapeutic targets for UBC.

Objective: To assess the impact of patient age on outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Patients and Methods: Data were collected on 1453 patients treated with RNU at 13 centres. Pathological slides were reviewed by dedicated genitourinary pathologists according to standardized criteria. Age at RNU was analysed both as a continuous and categorical variable (<50, n = 85; 50-59.9, n = 229; 60-69.9, n = 416; 70-79.9, n = 523; > or =80 years, n = 200). RESULTS Patients aged <50 years were less likely to have undergone previous ureteroscopy and to have a history of bladder cancer (P < or = 0.026). Advanced age was associated with infiltrative architecture and female gender (P < or = 0.003). Patients aged >70 years were less likely to undergo lymphadenectomy and to receive adjuvant chemotherapy (P < or = 0.026). In multivariable analyses, being older was associated with decreased all-cause (AC) survival (>60 years) and cancer-specific survival (CSS; >80 years) after controlling for the effects of standard pathological features (P < or = 0.006). However, addition of age did not improve the predictive accuracy of a base model that included standard pathological features for prediction of either disease recurrence, AC survival or CSS., Conclusions: Being older at the time of RNU was associated with decreased survival. This finding could be due to a change in the biological potential of the tumour cell, a decrease in the host's defence mechanisms, or differences in care patterns. Further work is needed to improve our understanding of UTUC outcomes in this growing segment of the population and to develop strategies to improve cancer control in the elderly.

Objective: To evaluate the profit margins for radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic prostatectomy (RALP), and the effect on the reimbursement to the urologist, as there has been a dramatic increase in use of RALP, with the cost of the robot borne by hospitals., Methods: Data on costs and payments to hospital and surgeon from 2003 to 2008 for RRP, LRP and RALP were obtained from the hospital and urology department. We determined the profit based on the difference between payments received and total cost., Results: Between 2000 and 2008, 1279 RPs were performed at our private hospital. The introduction of RALP increased total number of RPs and replaced most RRPs. RRP represents the only procedure where payments exceed total costs. For RRP there was a significantly higher profit for patients with comorbidities. The type of payer had a large effect on profit. Medicare provides a small profit for RRP but a significant loss of >US$4000 for RALP. While all insurance companies resulted in losses for LRP and RALP, there was variability of almost $600/case for LRP and >$1400/case for RALP. RALP provided the highest reimbursement for the surgeon due to additional reimbursement for the S2900 code (use of robot)., Conclusions: The introduction of RALP has increased the case volume at our hospital and improved profits for the surgeon. The hospital loses money on each LRP and RALP case compared with RRP, which provides a small profit.

Objective: To test whether assessing p53 expression could improve the ability to predict disease recurrence and disease-specific survival in a multi-institutional cohort of patients with advanced urothelial carcinoma of the urinary bladder (UCB)., Patients and Methods: The study comprised 692 patients with pT3-4 N0 or pTany N+ UCB treated with radical cystectomy and lymphadenectomy. The predictive accuracy (PA) was quantified using the 200 bootstrap-corrected concordance index. The base model comprised age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of lymph nodes positive, concomitant carcinoma in situ, and adjuvant chemotherapy., Results: p53 expression was altered in 341 (49.3%) patients. In multivariable analyses, p53 expression was independently associated with disease recurrence (hazard ratio, 1.66; P < 0.001) and cancer-specific mortality (hazard ratio 1.65, P < 0.001). Overall, adding p53 did not significantly improve the PA of the base model (recurrence +0.7%, P = 0.085, and cancer-specific mortality +1.2%, P = 0.050). In the subgroups of pT3N0 (280) and pT4N0 (83) patients, p53 slightly improved the PA of the base model by a statistically significant degree (recurrence +1.7% and +3.6%, respectively; cancer-specific mortality +1.9% and +3.5%, respectively; all P < 0.001). In 329 patients with pTany N+ disease p53 status did not improve the PA of the base model., Conclusion: While assessing p53 expression has limited utility in patients with lymph node-positive UCB, it marginally improves prognostication in patients with advanced non-metastatic UCB. Integration of p53 into a panel of biomarkers might be necessary to capture a more accurate picture of the biological potential of advanced UCB.

Metastases to regional lymph nodes are a common early event in many malignant diseases and have a poor prognosis, including in urological cancers. Molecular pathways contributing to lymphatic tumour dissemination and lymph node metastasis remain poorly understood. Besides the process of lymphovascular invasion (LVI), recent studies suggested de novo lymphatic vessel formation (i.e. lymphangiogenesis) as a potential mechanism of lymphatic tumour spread. Specific markers for lymphatic endothelium have recently been discovered, enabling basic morphological studies on lymphatic vessel density. There is a gap in the knowledge of the functional relationship between tumoral lymphatic vessels, LVI, lymphangiogenesis and the formation of lymph node metastases. The identification of lymph-specific growth factors (e.g. vascular endothelial growth factor-C and -D) as promoters of lymphatic metastasis has resulted in the interesting idea of targeting the pathways involved in lymphatic tumour progression. We summarize preliminary evidence on the role of lymphangiogenesis during the formation of lymphatic metastasis in the most common urological cancers.

Objective: To evaluate the effect of body mass index (BMI, kg/m(2)) on the cost and clinical variables after radical cystectomy (RC), as studies show that obesity might adversely affect the outcomes after RC., Patients and Methods: The charts of patients who had RC from January 2004 to March 2007 were reviewed retrospectively. Complete cost and clinical information was available for 99 patients; the patient and tumour characteristics and peri-operative outcomes were recorded. Detailed cost information (room and board, laboratory, pharmacy, radiology, operating room, surgical supply, anaesthesia, and recovery room) was obtained from hospital billing. Patients were stratified and compared in three groups of BMI, i.e. normal weight (<25), overweight (25-<30) and obese (> or =30)., Results: The mean age of the patients was 66 years; 27% were normal weight, 38% were overweight and 34% were obese. Of obese patients, 24% had an Eastern Cooperative Oncology Group performance score of 0, vs none and 2.6% in the normal and overweight groups, respectively (P = 0.001). Those of normal weight had the highest overall and major complication rates (P = 0.57 and 0.28, respectively). Obese patients had insignificantly higher transfusion rates (P = 0.28). The direct cost was higher in normal weight ($14,314) than overweight ($13,808) and obese ($13,666) patients (P = 0.47). Higher room and board cost in normal-weight patients was the only significant cost difference (P = 0.008)., Conclusion: BMI was not associated with increased costs of cystectomy. The absence of differences in cost-related and clinical outcomes might be attributable to variable comorbidity among groups and the experience of a high-volume surgeon and staff at a tertiary-care referral centre that routinely cares for obese patients.

Objective: To examine interobserver variations in assessing grade and stage of penile squamous cell carcinoma (SCC)., Patients and Methods: We retrospectively reviewed the pathological features and clinical outcome in 75 patients with SCC of the penis, who were treated in participating urological centres between 1996 and 2005; the assessments of the local pathologists and the review pathologists were compared., Results: There was conformity in tumour grade in 67% and the assessment of tumour stage conformed in 84%; the combination assessment of both grade and stage conformed in 56%., Conclusion: Accurate histological subtyping by the surgical pathologist demands standardized guidelines, in particular for histological grading, which is crucial for clinical treatment, but shows significant interobserver variation.

Objective: To examine the potential effect of tumour-induced lymphangiogenesis in squamous cell carcinoma of the penis as a possible mechanism responsible for lymphatic spread., Patients and Methods: Specimens from 65 patients with invasive tumours (31 with and 34 without metastases) were evaluated for lymphatic vessel density (LVD) by the 'hot-spot' method as the density of lymphatic endothelium hyaluronan receptor (LYVE-1)-positive lymphatic vessels per unit area of tissue. LVD was examined in peritumoral, intratumoral and normal tissue areas. The LVD of each tumour in these locations was calculated as the mean of the three highest lymph vessel counts in three to five hot-spots. The nodal status was based on histopathological examination or an uneventful follow-up of >or=2 years., Results: In all patients the mean (SD) peritumoral LVD of 8.05 (3.14)/0.75 mm(2) was significantly higher than for intratumoral and normal tissue, of 4.67 (2.58) and 5.20 (1.87), respectively (P < 0.001). The slightly lower intratumoral LVD than in normal tissue was not significant. The peritumoral LVD was 8.07 (3.29) in metastatic and 8.03 (3.03) in non-metastatic carcinomas. The intratumoral LVD was 5.13 (3.01) in node-positive carcinomas and 4.28 (2.15) in tumours with no lymphatic node metastasis (LNM). Comparing tumours with and without LNM, there was no statistically significant difference between intra- and peritumoral LVD., Conclusion: Increased LVD does not significantly affect the lymphatic spread in penile carcinomas, indicating that there must be alternative mechanisms that selectively enable tumour cells to invade lymph vessels and to metastasize into the lymph nodes.

Objective: To describe the localization and to assess the clinical implications of areas of undetected prostate cancer in radical prostatectomy (RP) specimens, focusing on patients with unilaterally negative preoperative biopsy cores., Patients and Methods: The study included 149 of 559 consecutive patients (26.7%) who had RP for prostate cancer. Unilateral prostate cancer was diagnosed from prostate biopsies, taken by several physicians, but > or = pT2c disease was present in the RP specimen. The prostate was dissected by standardized transversal cuts and tumour areas were mapped by one genitourinary pathologist. To estimate the tumour size and location, areas of prostate cancer were transferred to a digital grid database representing the prostate by 794 units., Results: The most frequent location of undetected prostate cancer was in the dorsalateral region and in the apex of the prostate. The mean tumour volume of the false-negative lobe was significantly lower than contralaterally (18.9 vs 47.5 units, P < 0.001). In 36 of 149 patients (24.2%), the tumour volume on the negative biopsy side was equal or higher than on the positive biopsy side; in the final RP specimen, 60 patients (40.3%) had capsular involvement on the negative biopsy side., Conclusion: Significantly many patients with newly diagnosed prostate cancer remain clinically understaged. The apical and dorsolateral region of the prostate are not adequately represented in current biopsy strategies. Undetected tumour areas are often clinically significant by size and capsular involvement, indicating a direct clinical implication when planning nerve-sparing RP or focal therapy. Our results show a continuing need for optimized and standardized biopsy protocols.

Objective: To describe the lymphatic vessel density and to determine the functional and prognostic significance of tumoral lymphatic vessels in upper tract urothelial carcinoma (UTUC)., Patients and Methods: The study included 65 patients who had a radical nephroureterectomy (RNU) for UTUC between 1997 and 2004. All pathological slides were re-evaluated by one reference pathologist and clinical data were reviewed. Lymphatic endothelial cells (LECs) were stained immunohistochemically using D2-40. The lymphatic vessel density (LVD) was described in representative intratumoral (ITLVD), peritumoral (PTLVD) and non-tumoral (NTLVD) areas. Random samples were selected for double-immunostaining with D2-40 and CD-34 (to distinguish blood and lymphatic vessels) and the proliferation marker Ki-67 to detect lymphangiogenesis. The primary outcome measures were disease-specific survival (DSS) and disease recurrence (urothelial and/or distant)., Results: The median (interquartile range) PTLVD was 4.0 (3.0-6.3), and significantly higher than that for ITLVD, of 0.3 (0-1.7) (P < 0.001), and NTLVD, of 3 (2.0-3.7) (P < 0.001). Both a higher ITLVD and PTLVD, the presence of lymphovascular invasion (LVI) (each P < 0.001) and a high tumour grade (P = 0.004) were associated with reduced DSS on univariate analysis. A higher PTLVD (P = 0.028) and the presence of LVI (P = 0.020) independently predicted reduced DSS on multivariate analysis. IT and PT lymphatic vessels showed proliferating LECs in all analysed samples., Conclusion: Lymphangiogenesis is present in UTUC, as shown by a significantly increased PTLVD and proliferating LECs. Our findings suggest functional relevance of PT lymphatic vessels during lymphatic tumour spread. PTLVD is a potential novel prognostic factor for DSS in UTUC, and further prospective studies will be needed to determine the effect of its routine evaluation on clinical outcomes of this malignancy.

Objective: To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive., Patients and Methods: The study included 1363 patients with UTUC and treated with radical NU at 12 centres worldwide. All slides were re-reviewed according to strict criteria by genitourinary pathologists who were unaware of the findings of the original pathology slides and clinical outcomes. Gross tumour architecture was categorized as sessile vs papillary., Results: Papillary growth was identified in 983 patients (72.2%) and sessile growth in 380 (27.8%). The sessile growth pattern was associated with higher tumour grade, more advanced stage, lymphovascular invasion, and metastasis to lymph nodes (all P < 0.001). In multivariable Cox regression analyses that adjusted for the effects of pathological stage, grade and lymph node status, tumour architecture (sessile or papillary) was an independent predictor of cancer recurrence (hazard ratio 1.5, P = 0.002) and cancer-specific mortality (1.6, P = 0.001). Adding tumour architecture increased the predictive accuracy of a model that comprised pathological stage, grade and lymph node status for predicting cancer recurrence and cancer-specific death by a minimal but statistically significant margin (gain in predictive accuracy 1% and 0.5%, both P < 0.001)., Conclusion: The tumour architecture of UTUC is associated with established features of biologically aggressive disease, and more importantly, with prognosis after radical NU. Including tumour architecture in predictive models for disease progression should be considered, aiming to identify patients who might benefit from early systemic therapeutic intervention.

Objective: To determine the risk factors associated with clinical outcome in patients with lymph node (LN)-positive urothelial carcinoma of the upper urinary tract (UTUC) treated with radical nephroureterectomy (RNU) and lymphadenectomy, focusing on the concept of LN density (LND)., Patients and Methods: Patients undergoing RNU with regional lymphadenectomy were identified through multi-institutional databases. All pathology slides were re-evaluated by genitourinary pathologists unaware of the clinical data. The exposure variable used was LND (continuously coded and that of all possible thresholds) with recurrence-free and disease-specific survival (DSS) serving as the outcome measures., Results: Of 432 patients undergoing RNU with lymphadenectomy, 135 (31%) had LN metastases. Within a median follow-up of 4.1 years, 90 of the 135 patients with LN metastases (68%) had disease recurrence and 76 (58%) died from UTUC. The mean (sem) 5-year recurrence-free and DSS probabilities were 27 (4)% and 33 (5)%, respectively. The median (range) LND was 50 (3-100)%. The most informative threshold for LND in relation to outcome was 30%. In multivariable analyses that adjusted for the effects of tumour stage and grade, patients with a LND of > or =30% were at greater risk of both cancer recurrence, with 5-year rates of 25 (5)% vs 38 (8)% (hazard ratio 1.8, P = 0.021) and mortality, with 5-year rates of 30 (6)% vs 48 (9)% (1.7, P = 0.032) compared to those with a LND of <30%. Our results are primarily limited by a lack of standardization in the lymphadenectomy template., Conclusion: We evaluated the concept of LND for the first time in UTUC. LND provides additional prognostic information in patients with node-positive disease after RNU. The use of LND in clinical trials might provide an additional insight into the value of LN dissection in patients undergoing RNU.

Objective: To evaluate the metastatic risk of pT1 G2 squamous cell carcinoma (SCC) of the penis., Patients and Methods: We retrospectively reviewed 20 patients with pT1 G2 penile SCC and determined their groin status at first presentation, their nodal status after inguinal lymph node dissection and their follow-up for at least 18 months., Results: Four of the 20 patients had a clinically positive groin; three of these were found to have lymph node metastases. Among the 16 patients with a clinically negative groin, one of five who had surgical lymph node staging had lymph node metastases. During surveillance six of 11 patients developed lymph node metastases. There was lymphovascular invasion in three of 10 patients with lymph node metastases., Conclusions: As the metastatic risk of pT1 G2 penile SCC was 50% in this series of patients, and 44% in those with an initially negative groin, surgical staging of inguinal lymph nodes is recommended in patients with pT1 G2 penile SCC.