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Background: Photodynamic diagnosis (PDD) during transurethral resection of bladder tumor (TURBT) is guideline recommended, as it improves bladder cancer detection rates. However, the extent to which PDD is implemented in everyday clinical practice has not been thoroughly assessed. We aimed to evaluate the current trends and major perioperative outcomes of TURBT with PDD. Methods: The present study evaluated the GeRmAn Nationwide inpatient Data (GRAND) from 2010 (the year when PDD started to be coded separately in Germany) to 2021, which were made available from the Research Data Center of the German Bureau of Statistics. We undertook numerous patient-level and multivariable logistic regression analyses. Results: Overall, 972,208 TURBTs [228,207 (23%) with PDD and 744,001 (77%) with white light] were performed. Patients offered PDD during TURBT were younger (p < 0.001), presented fewer comorbidities (p < 0.001) and were discharged earlier from hospital (p < 0.001). PDD was associated with additional costs of about EUR 500 compared to white-light TURBT (p < 0.001). The yearly TURBT cases remained relatively stable from 2010 to 2021, whereas utilization of PDD underwent a 2-fold increase. After adjusting for major risk factors in the multivariate regression analysis, PDD was related to lower rates of transfusion (1.4% vs. 5.6%, OR: 0.29, 95% CI: 0.28 to 0.31, p < 0.001), intensive care unit admission (0.7% vs. 1.4%, OR: 0.56, 95% CI: 0.53 to 0.59, p < 0.001) and 30-day in-hospital mortality (0.1% vs. 0.7%, OR: 0.24, 95% CI: 0.22 to 0.27, p < 0.001) compared to white-light TURBT. On the contrary, PDD was related to clinically insignificant higher rates of bladder perforation (0.6% versus 0.5%, OR: 1.3, 95% CI: 1.2 to 1.4, p < 0.001), and reoperation (2.6% versus 2.3%, OR: 1.2, 95% CI: 1.1 to 1.2, p < 0.001). Conclusions: The utilization of PDD with TURBT is steadily increasing. Nevertheless, the road toward the establishment of PDD as the standard of care for TURBT is still long, despite of the advantages of PDD. [ABSTRACT FROM AUTHOR]

Objectives: To determine the oncological impact and adverse events of performing simultaneous transurethral resection of bladder tumour (TURB) and transurethral resection of the prostate (TURP), as evidence on the outcomes of simultaneous TURB for bladder cancer and TURP for obstructive benign prostatic hyperplasia is limited and contradictory. Patients and Methods: Patients from 12 European hospitals treated with either TURB alone or simultaneous TURB and TURP (TURB+TURP) were retrospectively analysed. A propensity score matching (PSM) 1:1 was performed with patients from the TURB+TURP group matched to TURB‐alone patients. Associations between surgery approach with recurrence‐free (RFS) and progression‐free (PFS) survivals were assessed in Cox regression models before and after PSM. We performed a subgroup analysis in patients with risk factors for recurrence (multifocality and/or tumour size >3 cm). Results: A total of 762 men were included, among whom, 76% (581) underwent a TURB alone and 24% (181) a TURB+TURP. There was no difference in terms of tumour characteristics between the groups. We observed comparable length of stay as well as complication rates including major complications (Clavien–Dindo Grade ≥III) for the TURB‐alone vs TURB+TURP groups, while the latest led to longer operative time (P < 0.001). During a median follow‐up of 44 months, there were more recurrences in the TURB‐alone (47%) compared to the TURB+TURP group (28%; P < 0.001). Interestingly, there were more recurrences at the bladder neck/prostatic fossa in the TURB‐alone group (55% vs 3%, P < 0.001). TURB+TURP procedures were associated with improved RFS (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.29–0.53; P < 0.001), but not PFS (HR 1.63, 95% CI 0.90–2.98; P = 0.11). Within the PSM cohort of 254 patients, the simultaneous TURB+TURP was still associated with improved RFS (HR 0.33, 95% CI 0.22–0.49; P < 0.001). This was also true in the subgroup of 380 patients with recurrence risk factors (HR 0.41, 95% CI 0.28–0.62; P < 0.001). Conclusion: In our contemporary cohort, simultaneous TURB and TURP seems to be an oncologically safe option that may, even, improve RFS by potentially preventing disease recurrence at the bladder neck and in the prostatic fossa. [ABSTRACT FROM AUTHOR]

Introduction: Metastatic urothelial cancer (mUC) is an aggressive disease with limited overall survival and treatment options. Antibody-drug conjugates (ADCs) were designed with the intent to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells by linking cytotoxins to monoclonal antibodies (mAbs) and have emerged as new treatment options in mUC, mainly in chemotherapy (CT) and immune-checkpoint inhibitors (ICI)-exposed patients. We aimed to perform a scoping review to assess activity, efficacy, treatment-related adverse events (TRAEs), and impact on quality of life of ADCs in mUC.Methods: A review of the literature was performed in January 2022 using Pubmed and Embase databases according to the recommendations of the Joanna Briggs Institute. The search method involved querying for the terms "bladder carcinoma" or "urothelial carcinoma" with any of the following: "enfortumab vedotin" (EV), "sacituzumab govitecan" (SG), antibody-drug conjugate. Only prospective clinical trials were included.Results: Ultimately, eleven clinical trials with 1417 patients were selected for inclusion, and five drugs were identified: enfortumab vedotin (EV), sacituzumab govitecan (SG), disitamab vedotin (RC48-ADC), ASG-15ME (anti-SLITRK6), and trastuzumab deruxtecan. The different ADCs have been tested mainly in phase 1 or phase 2 trials, as monotherapy or in combination with ICI. Response rate ranged from 27% with SG in previously treated patients to 73.3% with EV plus pembrolizumab in cisplatin-ineligible patients as first-line treatment. The phase 3 trial, EV-301, confirmed EV superiority over investigator-chosen CT after failure to platinum-based CT and ICI, improving overall survival (12.88 vs. 8.97 months; HR 0.70; 95% CI, 0.56-0.89; P=0.001). TRAEs of any grade occurred in more than 90% of patients in phase 2 or 3 trials, with high rates of grade 3 ≥ events ranging from 51.4 to 73.5% in different trials. TRAEs of particular interest related to EV were rash, neuropathy, and hyperglycemia. SG was associated with diarrhea and hematologic toxicity. Data from phase 2 and 3 trials of EV suggest no impact on quality of life but an improvement in pain symptoms compared to the control arm.Conclusions: ACDs represent a new therapeutic option for the treatment of mUC. Level-1 evidence has already been achieved by EV in the post-CT and post-ICI settings. A high incidence of potential adverse events was observed in phase 2 and 3 trials, including rash, neutropenia, hematologic toxicity, and neuropathy. Clinicians should be aware of possible adverse events and their optimal management. [ABSTRACT FROM AUTHOR]

Purpose: There is no consensus on which items of Enhanced Recovery After Surgery (ERAS) should and should not be implemented in radical cystectomy (RC). The aim of this study is to report current practices across European high-volume RC centers involved in ERAS. Methods: Based on the recommendations of the ERAS society, we developed a survey with 17 questions that were validated by the Young Academic Urologists–urothelial group. The survey was distributed to European expert centers that implement ERAS for RC. Only one answer per-center was allowed to keep a representative overview of the different centers. Results: 70 surgeons fulfilled the eligibility criteria. Of note, 28.6% of surgeons do not work with a referent anesthesiologist and 25% have not yet assessed the implementation of ERAS in their center. Avoiding bowel preparation, thromboprophylaxis, and removal of the nasogastric tube were widely implemented (> 90%application). On the other hand, preoperative carbohydrate loading, opioid-sparing anesthesia, and audits were less likely to be applied. Common barriers to ERAS implementation were difficulty in changing habits (55%), followed by a lack of communication across surgeons and anesthesiologist (33%). Responders found that performing a regular audit (14%), opioid-sparing anesthesia (14%) and early mobilization (13%) were the most difficult items to implement. Conclusion: In this survey, we identified the ERAS items most and less commonly applied. Collaboration with anesthesiologists as well as regular audits remain a challenge for ERAS implementation. These results support the need to uniform ERAS for RC patients and develop strategies to help departments implement ERAS. [ABSTRACT FROM AUTHOR]

Purpose: This study was carried out to assess whether a prolonged time between primary transurethral resection of non-muscle-invasive bladder cancer (TURB) and implementation of bacillus Calmette–Guerin (BCG) immunotherapy (time to BCG; TTBCG) is associated with adverse oncological survival in patients with T1 high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). Materials and methods: Data on 429 patients from 13 tertiary care centers with primary T1HG NMIBC treated with reTURB and maintenance BCG between 2001 and 2019 were retrospectively reviewed. Change-point regression was applied following Muggeo's approach. The population was divided into subgroups according to TTBCG, whereas the recurrence-free survival (RFS) and progression-free survival (PFS) were estimated with log-rank tests. Additionally, Cox regression analyses were performed. Due to differences in baseline patient characteristics, propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. Results: The median TTBCG was 95 days (interquartile range (IQR): 71–127). The change-point regression analysis revealed a gradually increasing risk of recurrence with growing TTBCG. The risk of tumor progression gradually increased until a TTBCG of approximately 18 weeks. When the study population was divided into two subgroups (time intervals: ≤ 101 and > 101 days), statistically significant differences were found for both RFS (p = 0.029) and PFS (p = 0.005). Furthermore, in patients with a viable tumor at reTURB, there were no differences in RFS and PFS. After both PSM and IPW, statistically significant differences were found for both RFS and PFS, with worse results for longer TTBCG. Conclusion: This study shows that delaying BCG immunotherapy after TURB of T1HG NMIBC is associated with an increased risk of tumor recurrence and progression. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the trends in risk-group distribution and Pentafecta outcomes in patients treated with nerve-sparing (NS), robot-assisted radical prostatectomy (RARP) in a single low-intermediate volume prostate cancer (PCa) center over a 10-year period. Materials and methods: We queried a prospectively maintained database for patients who underwent NS RARP between 2009 and 2018 in a low-intermediate volume PCa center. Risk-groups were defined according to the D'Amico classification. Pentafecta outcomes referred to the postsurgical presence of potency and continence, and the absence of biochemical recurrence (BCR), positive surgical margins (PSM), and perioperative complications. The Kruskall–Wallis test, the t test and the Mann–Whitney tests were used when appropriate. Results: 603 patients underwent NS RARP and 484 patients were evaluated for Pentafecta outcomes. Median postsurgical follow-up was 28 months. Overall, 137 (22.7%), 376 (62.3%), and 90 (15%) patients were diagnosed in the low-, intermediate-, and high-risk groups, respectively. Patients undergoing NS RARP shifted from 33 to 20% in the low-risk group, from 52 to 62% in the intermediate-risk group, and from 10 to 13% in the high-risk group. Patients reaching Pentafecta increased from 38 to 44%. No postoperative potency was the main reason for non-achieving Pentafecta (71%). BCR strongly limited Pentafecta achievement in the high-risk group (61%), but not in intermediate (24%) and low-risk (30%) groups. Conclusions: Low-intermediate volume PCa centers show similar trends to high-volume centers regarding risk group distributions over time in PCa patients undergoing NS RARP. We reported an increase in Pentafecta outcomes achievement over time even for experienced surgeons. Pentafecta outcomes achievement is risk-group dependent. [ABSTRACT FROM AUTHOR]

Purpose: To improve patient selection for neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in bladder cancer patients (BCa). Methods: Retrospective evaluation of 1057 patients with cT2–4N0M0 BCa treated with RC and pelvic lymph node dissection between 1990 and 2018 at 3 referral centers. Adverse pathologic features (APF) were defined as pT3–pT4/pN + disease at RC. A regression tree model (CART) was used to assess preoperative risk group classes. A multivariable logistic regression (MVA) was performed to identify predictors of APF at RC. Results: Median age was 70 years and most of the patients were men (83%). Of the 1057 patients included in our study, 688 (65%) had APF. CART analysis was able to stratify patients into 3 risk groups: low (cT2 and single disease, odds ratio [OR] 0.62), intermediate (cT2 and multiple disease, OR 1.08), and high (cT3–cT4, OR 1.28). On MVA APF were associated with variant histology (odds ratio [OR] 3.97, 95% confidence interval [CI] 1.46–10.83, p = 0.007), multifocality at TUR (OR 2.56, CI 1.27–5.17, p = 0.09), completeness of resection (OR 0.47, CI 0.23–0.96, p = 0.04) and clinical extravesical disease (OR 3.42, CI 1.63–7.14, p = 0.001). Conclusion: We defined three pre-operative risk classes. Our results indicate that patients with a cT3–T4 disease are those who might benefit more from NAC whereas those with T2 single disease should be those to whom NAC probably shouldn't be proposed. Given the high rate of understaging in BCa patients, NAC can be proposed in selected cases of cT2/multifocal disease. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the technical feasibility, oncological and functional outcomes of nerve sparing cystoprostatectomy (NSCP) and prostate capsule‐sparing cystectomy (PCSC) for the treatment of organ‐confined bladder cancer at a single referral centre. Patients and Methods: From April 2001 to June 2012, 60 patients underwent PCSC and 47 were treated with NSCP. Inclusion criteria for PCSC were: fully informed consent for the well‐motivated patient; negative transurethral resection of the bladder neck; normal prostatic specific antigen (PSA) level (defined as <4 ng/dL during the first year of the study, which was later lowered to 2.5 ng/dL); and normal transrectal ultrasonography, with biopsy for any suspicious nodule. Patients received a complete oncological and functional follow‐up. The Kaplan–Meier method was used to depict survival outcomes after surgery. Results: After a median follow‐up of 73 and 62 months for PCSC and NSCP, respectively, the 5‐year cancer‐specific survival was 90% for the PCSC group and 78% for the NSCP group (P = 0.055). Considering complications within 30 days after surgery, 13% and 21% patients had Clavien ≥III complications in the PCSC and NSCP groups, respectively (P = 0.2). For functional outcomes, at 3 months after surgery, 54 (90%) and 24 (51%) patients reported full recovery of daytime urinary continence in the PCSC and NSCP groups, respectively (P < 0.001); and for erectile function recovery, 32 (53%) and four (9%) patients in the PCSC group and in the NSCP group were respectively potent without any treatment (P < 0.001). Conclusions: NSCP and PCSC are appropriate for a subset of patients with bladder cancer, with excellent oncological and functional results. These surgical procedures should be proposed to well‐motivated patients. [ABSTRACT FROM AUTHOR]

The purpose of this article is to retrace the useful elements for delineating the proprium of Hegelian thought as thinking of the true, also through Augusto Vera's interpretation - the idea as content and therefore as the inevitable "premise" emerging from Hegel's thought. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of a complete transurethral resection of bladder tumors (c-TURBT) on oncological outcomes after radical cystectomy (RC) and its relationship with adverse pathological features. Methods: We retrospectively analyzed data of 727 patients treated with RC and bilateral pelvic lymph node dissection at three tertiary referral centers. Possible c-TURBT was reported by the treating surgeon. Multivariable Cox regression analyses were used to assess the relationship of c-TURBT and survival outcomes after surgery in 1:1 propensity score-matched cohort adjusted for age and gender. Moreover, multivariable logistic regression (MVA) was built to predict the relationship between c-TURBT and pT3–T4 stages at RC, lymph node invasion (LNI) and positive soft tissue surgical margin (STSM). Results: A total of 433 (60%) patients received a c-TURBT. 3.0% of patients with a c-TURBT achieved a pT0–pTa–pTis status vs. 2.0% of patients with incomplete TURBT. At multivariable Cox regression analyses, c-TURBT was not associated with survival outcomes. At MVA, incompleteness of TURBT was significantly associated with a pT3–T4 stage [odds ratio (OR) 8.04, 95% confidence interval (CI) 2.33–27.67, p = 0.001]. No significant association was found between c-TURBT, LNI and STSM. Conclusion: We found a low rate of achievement of pT0 stage at RC. An incomplete TURBT before RC represented a predictor of pT3–T4 stages, but no effect of a c-TURBT was shown on survival outcomes. Given the current inadequacy of clinical staging strategies with more than 50% of extravesical disease being under-staged, our results could improve patients selection for NAC, driving the decision-making in doubtful cases. [ABSTRACT FROM AUTHOR]

Objectives Patients and Methods Results Conclusion To evaluate the impact of incorporating neoadjuvant chemotherapy (NAC) into the ‘quadrifecta’ outcomes composite for reporting outcomes of radical cystectomy (RC) creating a pentafecta score.This is a retrospective multicentre analysis of patients treated with RC, with or without NAC, for bladder cancer between 2002 and 2023. The primary outcome was the effect of adding NAC to a quadrifecta outcomes composite on cancer‐specific (CSS) and overall survival (OS). The quadrifecta outcomes composite included a yield of ≥16 lymph nodes, negative soft tissue surgical margin, absence of major complication within 30 days from surgery, and no delay in RC.A total of 590 patients were included in the analyses. A total of 233 (39.5%) patients achieved all quadrifecta outcomes and 82 (13.9%) patients were additionally treated with NAC, achieving the pentafecta. Achieving the quadrifecta outcomes composite was significantly associated with better CSS (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.32–0.75; P = 0.001) and OS (HR 0.48, 95% CI 0.34–0.69; P < 0.01). The addition of NAC to the quadrifecta composite outcomes significantly improved the discrimination of patients more likely to have better CSS (HR 0.21, 95% CI 0.08–0.57; P = 0.002) and OS (HR 0.26, 95% CI 0.12–0.55; P < 0.01).We propose a new pentafecta that may serve as a tool for standardising outcomes reporting and measuring the quality of RC. [ABSTRACT FROM AUTHOR]

Introduction: Bladder cancer (BCa) is three-to-four times more common in men than in women. To explain this gender gap, several theories have been proposed, including the impact of androgen hormones. The aim of this study was to investigate the differential impact of androgen deprivation therapy (ADT) on subsequent risk of developing BCa in men with prostate cancer (PCa). Methods: A total of 196,914 patients diagnosed with histologically confirmed localized PCa between 2000 and 2009 were identified in the SEER-Medicare insurance program-linked database. Competing-risk regression analyses were performed to assess the risk of developing BCa adjusting for the risk of all-cause mortality. Univariable and multivariable competing-risk regression analyses were performed to test the effect of ADT on BCa incidence for each PCa treatment modality. Results: Of the 196,914 individuals included in the study, 68,421 (34.7%) received ADT. Median (IQR) follow-up was 59 (29–95) months. Overall, a total of 2495 (1.3%) individuals developed BCa during follow-up. After stratification according to ADT, the 10-year cumulative incidence rate was 1.75% (95% CI 1.65–1.85). In the untreated group, the 10-year cumulative incidence rate was 1.99% (95% CI 1.83–2.15). In multivariable competing-risk regression, the use of ADT was not associated with BCa, after accounting for the risk of dying from any cause (p = 0.1). Conclusion: We failed to identify any impact of ADT on the risk of developing a subsequent BCa even after stratifying according to the type of treatment. Further studies are required to explain the gender gap in BCa incidence and outcomes. [ABSTRACT FROM AUTHOR]

Introduction: According to TNM staging, pathological T4ab are comprehensive of the invasion of prostate, seminal vesicles, uterus or vagina and pelvic or abdominal wall. However, few data are available on the perioperative and oncological outcomes of specific organ invasion. Materials and Methods: A total of 917 consecutive bladder cancer (BCa) patients treated with radical cystectomy (RC) at a single institution between 1990 and 2015 were studies. Cox regression analyses were used to stratify pT4ab according to the site of invasion and survival. Results: Overall, 176 (19.2%) and 40 (4.4%) patients harbored pT4a or pT4b disease. Specifically, 84 (9.2%) patients reported prostate and/or SVI invasion, 62 (6.8%) prostate only, 16 (1.7%) uterus, 14 (1.5%) vaginal, 24 (2.6%) pelvic wall, and 16 (1.7%) abdominal wall invasion. The median follow-up in pT4 patients was 48 months. The 1-year cancer-specific mortality (CSM) rates were 71, 65, 24, 50, 50, and 72%, for vaginal, uterus, prostate only, prostate and/or seminal vesicles, pelvic wall, and abdominal wall invasions, respectively. At multivariable Cox regression, the invasion of prostate only (hazard ratio [HR] 3.53), prostate and/or SVI (HR 4.98), uterus (HR 7.16), vagina (HR 6.12), pelvic (HR 11.81), abdominal (8.36) were associated with adverse CSM. Conclusions: Our study described the differences in survival related to invasion site in pT4 patients, confirming poor survival expectancies in this subgroup. Patients with prostate invasion only seem to be associated with better survival than those affected by concomitant invasion of seminal vesicles. Uterus and vaginal invasions were associated with poor survival outcomes. Patients Summary: In this study, we looked at the outcome of locally advanced invasive BCa (stage pT4) in patients treated with RC at a tertiary referral hospital. We analyzed the differences in survival related to the specific organ invasion. We confirmed poor survival in this subgroup of patients. Only patients who had prostate invasion only seem to have a better survival. [ABSTRACT FROM AUTHOR]

Abstract Background Long-term survival can be achieved in patients affected by localized prostate cancer (PCa) treated with either radical prostatectomy (RP) or external beam radiotherapy (EBRT). However, development of a second primary tumor is still poorly investigated. Objective To investigate the impact of RP and EBRT on subsequent risk of developing bladder (BCa) and/or rectal cancer (RCa) among PCa survivors. Design, setting, and participants A total of 84 397 patients diagnosed with localized PCa, treated with RP or EBRT between 1988 and 2009, and older than 65 yr of age were identified in the Surveillance, Epidemiology, and End Results Medicare insurance program-linked database. Our primary objective was to investigate the effect of EBRT and RP on the second primary BCa and RCa incidence. Outcome measurements and statistical analysis Multivariable competing-risk regression analyses were performed to assess the risk of developing a second primary BCa or RCa. Results and limitations Of the 84 397 individuals included in the study, 33 252 (39%) were treated with RP and 51 145 (61%) with EBRT. Median follow-up was 69 months, and follow-up periods for patients who did not develop BCa, RCa, or pelvic cancer were 68, 69, and 68 mo, respectively. A total of 1660 individuals developed pelvic tumors (1236 BCa and 432 RCa). The 5- and 10-yr cumulative BCa incidence rates were 0.75% (95% confidence interval [CI]: 0.64–0.85%) and 1.63% (95% CI: 1.45–1.80%) versus 1.26% (95% CI: 1.15–1.37%) and 2.34% (95% CI: 2.16–2.53%) for patients treated with RP versus EBRT, respectively. The 5- and 10-yr cumulative RCa incidence rates were 0.32% (95% CI: 0.25–0.39%) and 0.73% (95% CI: 0.61–0.85%) versus 0.36% (95% CI: 0.30–0.41%) and 0.69% (95% CI: 0.60–0.79%) for patients treated with RP versus EBRT, respectively. On multivariable competing risk regression analyses, treatment with EBRT was independently associated with the risk of developing a second primary BCa (hazard ratio: 1.35, CI: 1.18–1.55; p < 0.001), but not RCa (p = 0.4). Limitations include lack of information regarding the dose of radiotherapy and the retrospective nature with the implicit risk of selection bias. Conclusions Patients treated with EBRT are at increased risk of developing a second primary BCa compared with those treated with RP. However, no differences were found considering RCa incidence in patients treated with RP or EBRT within the first 5 yr after primary therapy. These results need to be validated in a well-designed randomized prospective trial. Patient summary We retrospectively analyzed the risk of developing a second primary bladder or rectal cancer during follow-up for patients treated with radical prostatectomy or external beam radiotherapy for a localized prostate cancer. We found that those treated with external beam radiotherapy are at an increased risk of developing a second primary bladder cancer tumor. Take Home Message Patients treated with external beam radiotherapy for a localized prostate cancer are at an increased risk of developing a second bladder cancer tumor compared with those treated with radical prostatectomy. Conversely, no differences regarding rectal cancer incidence were reported between the two techniques. [ABSTRACT FROM AUTHOR]

Objects: This study hypothesized that biopsy Gleason score 8 (b.G.S. 8) disease may dilute the substantial poor risk associated with b.G.S. 9 disease, specifically associated with primary Gleason 5 disease. Materials and methods: The study reviewed 18,299 patients treated with radical prostatectomy (R.P.) between 1990 and 2011, and identified 1,080 men with b.G.S. 4 + 4 (n = 614, 56.9%), 4 + 5 (n = 347, 32.1%), and 5 + 4 (n = 119, 11%) P.Ca. Variation trends of high risk prostate cancer (H.R.P.Ca.) characteristics were recorded over time: The association of b.G.S. with survival outcomes was assessed using Kaplan Meier and multivariable Cox regression analyses. Median follow-up was 6.1 years (I.Q.R. = 3-10.8). Results: The number of patients included in H.R.P.Ca. due to their b.G.S. increased consistently over time. On multivariable regression, b.G.S. 4 + 5 and b.G.S. 5 + 4 vs b.G.S. 4 + 4 were found to be independently associated with seminal vesical involvement (Odds ratio [O.R.] = 1.58 and 2.22; p < 0.005), extracapsular extension (O.R. = 1.51 and 1.7; p < 0.02) and surgical margins (O.R. = 1.50 and 2.03; p < 0.01), respectively. Ten-year cancer-specific survival was 83%, 73% and 70% in patients with b.G.S. 4 + 4, 4 + 5 and 5 + 4, respectively (p < 0.01). b.G.S. 4 + 5 and b.G.S. 5 + 4 compared to b.G.S. 4 + 4 were associated with an increased risk of cancer-specific mortality (C.S.M.) (Hazard ratio = 1.76, p = 0.02 and 2.38, p = 0.003, respectively). Conclusions: B.G.S. 9 and specifically pattern 5 + 4 P.Ca. is associated with substantial disease burden, adverse pathological features and the presence of locally advanced disease, in addition to inferior survival outcomes in comparison to b.G.S. 4 + 4 disease. Distinction of b.G.S. 9 patients from b.G.S. 8 patients at diagnosis may permit more precise pre-treatment risk stratification. [ABSTRACT FROM AUTHOR]

Objective: Growing literature supports good survival expectancies in bladder cancer (BCa) patients affected by clinical node metastases (cN+) treated with multimodal therapy. We evaluated the role of adjuvant chemotherapy in cN+BCa patients treated with radical cystectomy (RC) and pelvic lymph node dissection (PLND) without neoadjuvant chemotherapy (NAC).Methods: We evaluated a total of 192 patients with BCa and cN+. All patients were treated with RC and PLND without NAC between 2001 and 2013. Kaplan-Meier analyses and Cox regression analyses were used to assess the impact of adjuvant chemotherapy (ACT) on recurrence, cancer-specific mortality (CSM) and overall mortality (OM) after surgery.Results: Overall, 99 patients (51.6%) were found without node metastases at RC, while 18 (9.4%), 58 (30.2%) and 17 (8.9%) patients were found pN1, pN2 and pN3, respectively. With a median follow-up of 48 months, in cN+ patients we recorded 5-year recurrence, CSM and OM of 55, 53 and 51%, respectively. Overall, 36 (18.8%) patients were treated with adjuvant chemotherapy. At univariable analyses, ACT was associated with improved overall survival [Hazard ratio (HR): 0.42, confidence interval (CI) 0.20-0.86, p = 0.02) in pN+ subgroup only. These results were confirmed at multivariable analyses, where ACT was associated with improved CSS (HR: 0.45, CI 0.21-0.89, p = 0.03) and OS (HR: 0.37, CI 0.17-0.81, p = 0.01).Conclusions: We report good survival outcomes in cN+ patients treated with RC. The use of ACT after surgery increases survival expectancies, especially in those patients with pathological node disease. Our data need to be further evaluated in prospective setting. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate temporal trends in the delivery and extent of lymphadenectomy (LND) in radical nephroureterectomy (RNU) performed in upper tract urothelial carcinoma (UTUC) patients. Methods: We evaluated a multi institutional collaborative database composed by 1512 consecutive patients diagnosed with UTUC treated with RNU between 1990 and 2016. Year of surgery were grouped in five periods: 1990-1996, 1997-2002, 2003-2007, 2008-2012 and 2013-2016. Data about LND were available for all patients and numbers of nodes removed and positive were reported by dedicate uropathologists. The Mann-Whitney and Chi square tests were used to compare the statistical significance of differences in medians and proportions, respectively. Results: Five hundred forty-five patients (36.0%) received a concomitant LND while 967 (64.0%) did not; 41.9% of open RNU patients received a concomitant LND compared to 24.4% of laparoscopic RNU patients. The rate of concomitant LND increased with time in the overall, laparoscopic and open RNU patients (all p < 0.03). Patients treated with open RNU also had an increasing likelihood to receive an adequate concomitant LND ( p < 0.001) while those undergoing a laparoscopic approach did not ( p = 0.1). Patients treated with concomitant LND had a median longer operative time of 20 min ( p = 0.01). There were no differences in perioperative outcomes and complications between patients who received a concomitant LND and those who did not ( p > 0.1). Conclusion: Although an increased trend was observed, most patients treated with RNU did not receive LND. Surgeons using a laparoscopic RNU were less likely to perform a concomitant LND, and when done, they remove less nodes. [ABSTRACT FROM AUTHOR]

Objective: To investigate the characteristics and outcomes of late recurrence (LR) in patients with bladder cancer (BCa) treated with radical cystectomy (RC) and to identify clinicopathologic predictors of LR and postrecurrence survival.Materials and Methods: This multicenter study included 1652 BCa patients. LR was defined as occurring more than 5 years after RC. Differences in postrecurrence overall survival according to the timing of disease recurrence and the location of recurrence were calculated using the log-rank test. A logistic regression model was used to identify predictors of LR, and Cox regression models were used to evaluate variables associated with postrecurrence overall survival (OS).Results: Overall, 548 patients experienced disease recurrence. Of these, 67 patients (12.2%) experienced LR, with a median time to recurrence of 86 months (interquartile range 70.5-107.2). LR was more likely to be located in the urothelium (P = .005). On multivariable analysis, younger age (P = .008) and non-organ confined disease (P = .03) were found to be predictors of LR. Postrecurrence 5-year OS was worse in patients who experienced early recurrence compared with those with LR (12% vs 25%, P = .02) and in those with nonurothelial recurrence compared to those with disease recurrence in the remaining urothelium (12% vs 51%, P < .001). Older age (P < .001), non-organ confined disease at RC (P = .02), and nonurothelial recurrence site (P = .002) were independently associated with postrecurrence OS.Conclusion: LR after RC is an uncommon but non-negligible event that harbors unique characteristics. LR is associated with better OS compared to early recurrence. Our findings reinforce the need for lifelong follow-up of BCa patients after RC. [ABSTRACT FROM AUTHOR]

Context The incidence of low-risk prostate cancer (PCa) has increased as a consequence of prostate-specific antigen testing. Objective In this collaborative review article, we examine recent literature regarding low-risk PCa and the available prognostic and therapeutic options. Evidence acquisition We performed a literature review of the Medline, Embase, and Web of Science databases. The search strategy included the terms: prostate cancer, low risk, active surveillance, focal therapy, radical prostatectomy, watchful waiting, biomarker, magnetic resonance imaging, alone or in combination. Evidence synthesis Prospective randomized trials have failed to show an impact of radical treatments on cancer-specific survival in low-risk PCa patients. Several series have reported the risk of adverse pathologic outcomes at radical prostatectomy. However, it is not clear if these patients are at higher risk of death from PCa. Long-term follow-up indicates the feasibility of active surveillance in low-risk PCa patients, although approximately 30% of men starting active surveillance undergo treatment within 5 yr. Considering focal therapies, robust data investigating its impact on long-term survival outcomes are still required and therefore should be considered experimental. Magnetic resonance imaging and tissue biomarkers may help to predict clinically significant PCa in men initially diagnosed with low-risk disease. Conclusions The incidence of low-risk PCa has increased in recent years. Only a small proportion of men with low-risk PCa progress to clinical symptoms, metastases, or death and prospective trials have not shown a benefit for immediate radical treatments. Tissue biomarkers, magnetic resonance imaging, and ongoing surveillance may help to identify those men with low-risk PCa who harbor more clinically significant disease. Patient summary Low-risk prostate cancer is very common. Active surveillance has excellent long-term results, while randomized trials have failed to show a beneficial impact of immediate radical treatments on survival. Biomarkers and magnetic resonance imaging may help to identify which men may benefit from early treatment. [ABSTRACT FROM AUTHOR]

Objective To investigate the long-term utility of adjuvant therapy after radical prostatectomy ( RP) for prostate cancer with seminal vesicle invasion ( SVI; pT3b), as the published data are conflicting. Patients and Methods Patients with SVI during RP and pelvic lymph node dissection at two major referral centres from 1986 to 2014 were included. Kaplan-Meier analyses and multivariable Cox regressions were used to determine if adjuvant radiotherapy ( aRT) and adjuvant hormonal therapy ( aHT) were predictors of biochemical recurrence ( BCR), cancer-specific mortality ( CSM) and overall mortality ( OM). Subset analyses were performed for pN0 patients and pN+ patients. Results Overall, 3 279 patients with prostate cancer and SVI were included with a median follow-up of 148 months. Considering the whole SVI population, 1 387 (42%) received no adjuvant therapy, 1 179 (36%) received aHT, 461 (14.1%) received aRT, while 252 (7.7%) received both aHT and aRT. The 10-year BCR, CSM, and OM rates were 64%, 14%, and 27%, respectively. In the overall population, aRT and aHT were predictors of BCR, CSM and OM (all P < 0.04). When only pT3bN0 patients were considered, aHT was a significant multivariate predictor of BCR [hazard ratio ( HR) 0.50, P < 0.001), CSM ( HR 0.62, P = 0.01) and OM ( HR 0.75, P = 0.004). Conversely, aRT was not associated with survival outcomes (all P > 0.05). When only the subgroup pT3bN+ was considered, the use of aRT was related to an improvement in CSM ( HR 0.65, P = 0.03) and OM (HR 0.78, P = 0.03). Conclusions aHT + aRT seems to be effective in pT3b patients. However, when stratified according to the presence of nodal metastases, aHT remains effective only in the node-negative subgroup, while aRT remains effective only in the node-positive subgroup. Further data including prospective trials are warranted to study the utility of adjuvant therapies in this setting. [ABSTRACT FROM AUTHOR]

Purpose: To assess the role of N-cadherin as prognostic biomarker in patients with upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. Patients and methods: Immunohistochemistry was used to evaluate the status of N-cadherin expression in 678 patients with unilateral sporadic UTUC treated with radical nephroureterectomy. N-cadherin was considered positive if any immunoreactivity with membranous staining was detected. The Kaplan-Meier method was used to estimate recurrence-free survival, overall survival and cancer-specific survival. Disease recurrence, overall mortality and cancer-specific mortality probabilities were tested in Cox regression models. Results: Expression of N-cadherin was observed in 292 (43.1%) of patients, and it was associated with advanced tumour stage ( p < 0.04), lymph node metastases ( p = 0.04) and sessile architecture ( p < 0.02). Within a median follow-up of 37.5 months (IQR 20-66), 171 patients (25.2%) experienced disease recurrence and 150 (22.1%) died from UTUC. In univariable analyses, N-cadherin expression was significantly associated with higher probability of recurrence ( p = 0.01), but not overall ( p = 0.9) or cancer-specific mortality ( p = 0.06). When adjusted for the effects of all available confounders, N-cadherin was not associated with any of the survival outcomes. Conclusion: N-cadherin is expressed in approximately 2/5 of UTUs. It is associated with adverse pathologic factors but not with survival outcomes. Its clinical value remains limited. [ABSTRACT FROM AUTHOR]

Introduction: We sought to describe incidence of histological variants after radical cystectomy (RC) due to bladder cancer (BCa). Moreover, we investigated survival outcomes accounting for this parameter.Methods: We retrospectively evaluated data from 1,067 patients with BCa treated with RC between 1990 and 2013 at a single tertiary care referral center. All specimen were evaluated by dedicated uropathologists. Univariable and multivariable Cox regression analyses tested the effect of different histopathological variant on recurrence, cancer-specific mortality (CSM), and overall mortality (OM) after accounting for all available confounders.Results: Of 1,067 patients, 729 (68.3%) harbored pure urothelial BCa while 338 (31.7%) were found to have a variant. Considering uncommon variants, 21 (2.0%) were sarcomatoid, 10 (0.9%) lymphoepitelial, 19 (1.8%) small cell, 109 (10.2%) squamous, 89 (8.3%) micropapillary, 23 (2.2%) glandular, 34 (3.2%) mixed variants, and 33 (3.1%) were found with other types of variants. With a median follow-up of 6.2 years, 343 recurrence, 365 CSM, and 451 OM were recorded, respectively. At multivariable Cox regression analyses, the presence of small cell variant was associated with higher recurrence (hazard ratio [HR] = 3.47, P<0.001), CSM (HR = 3.30, P<0.04), and OM (HR = 2.97, P<0.003) as compared with pure urothelial cancer. Conversely, no survival differences were recorded considering other histological variants (all P> 0.1).Conclusion: Our study confirms that histological variant is not an infrequent event at RC specimen. However, in our single-center series, only patients found with small cell variant were associated with a negative effect on survival after RC. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to evaluate the impact of the different types of prostate involvement at the time of radical cystoprostatectomy (RCP). Methods: Data from 893 male patients treated with RCP at a referral center for bladder cancer (BCa) were assessed. Prostatic urothelial carcinoma (PUC) was stratified as stromal vs. urethral/duct involvements. Multivariable Cox regression analyses were built to test the impact of the presence of incidental prostate cancer (PCa) and PUC on survival outcomes. Results: PCa was present in 319 (35.7%) RCP patients, of which 45 (14.1%) had significant PCa disease. PUC was identified in 181 patients (20%): 75 (41.1%) with urethral/duct involvement and 106 (58.6%) with stromal. Within a median follow-up of 72 months, stromal PUC, but not the other forms of PUC or PCa, was associated with worse survival outcomes. In multivariable analyses adjusted for the effects of standard features, stromal PUC remained associated with recurrence (hazards ratio [HR] 2.01, p = 0.03), cancer-specific mortality (HR 1.65, p = 0.01), and overall mortality (HR 1.45, p = 0.03). Conclusion: Prostatic stromal invasion with urothelial carcinoma confers a poor survival expectation to BCa patients after surgical treatment. Conversely, other type of urothelial prostatic invasions or the presence of concomitant PCa does not seem to be associated with differences in survival outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study was to evaluate the expression pattern of HER2 overexpression in patients with upper tract urothelial carcinoma (UTUC) and to evaluate its association with clinical outcomes. Methods: This multicenter retrospective study included 732 patients treated with radical nephroureterectomy for UTUC. HER2 expression was assessed using immunohistochemistry and scored according to the HercepTest: Scores of 0 or 1 were considered negative and 2 or 3 as positive. To qualify for 2 scoring, complete membrane staining of more than 10 % of tumor cells at a moderate intensity had to be observed. Results: HER2 was overexpressed in 262 (35.8 %) patients. It was associated with pathologic characteristics such as more advanced T stage ( p < 0.001), presence of lymph node metastasis ( p = 0.006), high-grade tumor ( p < 0.001), tumor necrosis ( p = 0.01) and lymphovascular invasion ( p = 0.02). Patients with HER2 overexpression had a 1.66-fold increased risk of experiencing disease recurrence (95 % CI 1.24-2.24, p = 0.001), 1.55-fold increased risk of death (95 % CI 1.21-1.99, p = 0.001) and 1.81-fold increased risk of cancer-specific death (95 % CI 1.33-2.48, p < 0.001). On multivariable analysis that adjusted for the effects of standard clinicopathologic variables, HER2 overexpression remained associated with disease recurrence ( p = 0.04), overall ( p = 0.02) and cancer-specific mortality ( p = 0.02). Conclusions: Approximately, one-third of UTUC patients overexpressed HER2. HER2 overexpression was associated with features of clinically and biologically aggressive disease as well as prognosis. HER2 may represent a good marker for therapeutic risk stratification and potentially a target for therapy in some UTUC tumors. [ABSTRACT FROM AUTHOR]

Stage and cancer-specific mortality differ within specific Asian ethnic groups in upper tract urothelial carcinoma: North American population-based study. Despite Asian Americans being approximately 6% of the USA population, with a constantly growing rate in the past two decades, they still represent the most underreported and underinvestigated ethnic minority group.1 Furthermore, recent evidence showed a significant heterogeneity among different Asian American subgroups,2 suggesting that subgroup disparities might lead to heterogenous disease patterns, as well as different prognosis.3 To address this unmet need, Collà Ruvolo I et al i . analyzed the effect of different Asian American subgroups on pathological features and survival outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.4 The authors, relying on the Surveillance, Epidemiology and End Results database, analyzed 584 Asian American patients, including Chinese, Japanese, Korean, Filipino and Vietnamese subgroups, treated with radical nephroureterectomy for upper tract urothelial carcinoma between 2004 and 2016. Editorial Comment from Dr Lonati and Dr Moschini to Stage and cancer-specific mortality differ within specific Asian ethnic groups in upper tract urothelial carcinoma: North American population-based study. [Extracted from the article]

Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®. Decipher™ is a tool based on 22 genes and evaluates the risk of adverse outcomes (metastasis) after radical prostatectomy (RP). Oncotype DX® is based on 17 genes and focuses on the ability to predict outcomes (adverse pathology) in very low-low and low-intermediate PCa patients, while Prolaris® is built on a panel of 46 genes and is validated to evaluate outcomes for patients at low risk as well as patients who are affected by high risk PCa and post-RP. Finally, ProMark® is based on a multiplexed proteomics assay and predicts PCa aggressiveness in patients found with similar features to Oncotype DX®. These biomarkers can be helpful for post-biopsy decision-making in low risk patients and post-radical prostatectomy in selected risk groups. Further studies are needed to investigate the clinical benefit of these new technologies, the financial ramifications and how they should be utilized in clinics. [ABSTRACT FROM AUTHOR]

The authentic concreteness of thought made possible by the first principle of every being is the basic speculative argument of Italian critical ontology. In the undividable relation between thought and being a direction of thinking in philosophy has been formed in Italy in the first half of the 20th century. This direction is based on Kant's premises and, in extremely turbulent context of speculative thinking and often in polemics with dominant currents of though, it has pointed out the fundamental importance of the »God issue« as a true philosophical argument. The concept of consciousness, as consciousness of God and from God, within that that exists in (ἐν) Him, made possible by Him, is the proof of the phenomenal unconfined-ness of what is thought, through implementation of the Augustinian-Bonaventurian principles of the Franciscan tradition. The intention of this article is, therefore, to present speculative consistency of this extremely vital school of Italian ontology, but also the most prominent argument of its philosophical reflection, i.e. the concreteness of consciousness in existential being as a manifestation of uniqueness of being [ABSTRACT FROM AUTHOR]

Objective To assess the impact of primary or progressive status on recurrence-free survival ( RFS), cancer-specific mortality ( CSM) and overall mortality ( OM) after radical cystectomy ( RC) for muscle- invasive bladder cancer ( MIBC). Patients and Methods A total of 768 consecutive patients underwent RC as treatment for MIBC at our institution between 2000 and 2012. Primary MIBC was defined as no previous history of bladder cancer and progressive was defined as recorded previous treated non- MIBC ( NMIBC) that had progressed to MIBC. The median follow-up was 85 (60-109) months. Univariate and multivariate Cox regression models were used to compare RFS, CSM and OM between these two cohorts. Results In all, 475 (61.8%) patients had primary and 293 (38.2%) patients had progressive MIBC. There were no differences between the two groups in terms of demographics, pathological and peri-operative complications (all P > 0.1). The 10-year RFS, CSM and OM rates for primary vs progressive status were 43 vs 36% ( P = 0.01), 43 vs 37% ( P = 0.01), and 35 vs 28% ( P = 0.03), respectively. On multivariable Cox regression analyses, progressive status remained significantly associated with a higher rate of recurrence (hazard ratio [ HR] 1.47, 95% confidence interval [ CI] 1.12-1.79; P = 0.03), CSM ( HR 1.42, 95% CI 1.07-1.89; P = 0.01) and OM ( HR1.42, 95% CI 1.13-1.65; P = 0.02). Conclusions Among patients treated with RC for MIBC, progressive status was associated with a higher CSM, OM and recurrence rate after RC. The present study thus provides an impetus to improve risk sub-stratification when bladder cancer is still at the NMIBC stage, be it through new biomarkers or improved imaging, as a subset of patients with NMIBC are likely to benefit from early RC. [ABSTRACT FROM AUTHOR]

Introduction Several definitions of erectile function (EF) recovery after bilateral nerve-sparing radical prostatectomy (BNSRP) have been proposed based on the results of the International Index of EF (IIEF). Aim We aimed at evaluating overall satisfaction (OS) after BNSRP according to the ability to achieve the pretreatment EF. Methods We evaluated data of 652 patients treated with BNSRP for clinically localized prostate cancer (PCa). Erectile dysfunction (ED) was classified according to the IIEF-EF domain score. Return to baseline EF was defined as patients who reached the same preoperative ED category during the 3-year follow-up. Cox regression analyses were fitted to predict return to baseline IIEF-EF and to predict OS defined according to the IIEF-OS in the overall population. Logistic regression analyses were performed to analyze OS in men who reached the back to baseline status. Main Outcome Measures The outcome of the study was to evaluate back to baseline EF status and to correlate it with postoperative OS. Results Preoperative satisfaction was reported by 218 (33.4%) patients. Postoperative satisfaction was achieved by 103 patients. Overall, 383 patients were able to achieve the preoperative IIEF-EF score. However, only 26.9% reported being satisfied. Age and preoperative IIEF-EF score were significantly associated with baseline IIEF-EF recovery (all P ≤ .02). Patients who were able to return to baseline IIEF-EF were more likely to be satisfied ( P < .001). Time elapsed between surgery and achievement of baseline IIEF-EF was significantly associated with OS ( P < .001). Among patients who were able to achieve the baseline IIEF-EF score, a preoperative IIEF-EF of 22–25 and 26–30 was significantly associated with postoperative satisfaction (all P < .001). Conclusion After BNSRP, reaching the baseline IIEF-EF score is not always sufficient to obtain patient satisfaction. Only patients with a preoperative IIEF-EF ≥22 who reached the baseline score after surgery considered themselves satisfied. This should be taken into account in preoperative patient counseling. [ABSTRACT FROM AUTHOR]

Objective: To investigate the staging of lymphadenectomy during radical cystectomy (RC) due to bladder cancer. No data exist about the possibility to limit the extension of pelvic lymph node dissection (PLND) on the basis of preoperative or intraoperative parameters without losing accuracy in the staging procedure.Materials and Methods: Between 1995 and 2012, 1016 RC due to bladder cancer were performed at a single tertiary care institution. The relationship between the number of nodes removed and the probability to find node metastases at final pathology examination was assessed using receiver operating characteristic analyses.Results: Among the patients who underwent RC plus PLND, the lymph node metastases prevalence was 35.7% (363 of 1016). Receiver operating characteristic curve analyses were used to explore graphically the relationship between the numbers of removed and examined nodes and the probability of finding one or more metastatic nodes in the overall population. The curve indicated that 25, 35, and 45 nodes need to be removed to achieve 75%, 90%, and 95% probability, respectively, of detecting one or more lymph node metastases. When the analyses were stratified according to preoperative characteristics, only slight differences were recorded among the sensitivity analyses stratified for pathological stage, primary or progressive status, or radiological N status.Conclusion: Our results show that it is necessary to extend PLND to improve the ability to stage node metastases accurately. Preoperative parameters can minimally change this indication and an extended PLND should be always performed. [ABSTRACT FROM AUTHOR]

Objective: The impact of positive surgical margin (SM) on cancer control outcomes in prostate cancer patients is a subject of continuous debate. We test the hypothesis that the impact of SM on clinical recurrence (CR) rate may vary based on the other clinical/pathologic characteristics of the tumor. Materials and Methods: We focused on 5290 patients treated with robot-assisted radical prostatectomy and pelvic node dissection, between 2002 and 2013, at three tertiary care centers. Regression tree analysis stratified patients into risk groups based on their tumor characteristics and the corresponding CR rate. Kaplan-Meier log-rank and multivariable Cox regression models tested the relationship between SM status and CR rate in each tree-generated risk group. Results: Mean (median) follow-up time was 47.7 (39.0) months. Regression tree analysis that considered all available covariates, except SM status, divided patients based on their CR risk into the following risk groups: (1) high risk (any pT3b/pT4 disease); (2) intermediate risk (≤pT3a disease and pGS 8-10); (3) low risk (≤pT3a, pGS ≤7, and prostate-specific antigen [PSA] >9 ng/mL); and (4) very low risk (≤pT3a, pGS ≤7, and PSA ≤9 ng/mL). Positive SM had a significant detrimental impact on CR risk only in two groups: intermediate risk ( p < 0.001) and high risk ( p = 0.01). These observations were confirmed by multivariable analyses. Conclusions: Our findings show that positive SM had a detrimental impact on CR only in a minority of patients (15%), specifically in those with advanced pathologic stage and/or pathologically poorly differentiated tumor. For all the remaining patients (85%), positive SM by itself did not increase the risk of CR. [ABSTRACT FROM AUTHOR]

Clinical lymphadenopathy (cN+) from prostate cancer (PCa) identified on imaging remains a contraindication to radical prostatectomy (RP) according to guidelines. We tested the hypothesis that there would be no difference in survival between patients with and without cN+ on preoperative imaging who underwent RP and pelvic lymph node dissection with detection of pelvic lymph node metastasis (LNM). A total of 302 patients with LNM were retrospectively reviewed (1988–2003) and stratified according to cN status on the basis of preoperative imaging. Univariable and multivariable Cox regression analyses were performed to evaluate cN+ as a predictor of survival. Of the 302 patients, 50 (17%) had cN+; the 252 (83%) patients with negative preoperative imaging comprised the cN0 group. During median follow-up of 17.4 yr, 161 deaths were recorded, 70 of which were from PCa. Among the entire LNM cohort, the number of positive lymph nodes (hazard ratio [HR] 1.10; p = 0.02) and pathologic Gleason score 8–10 versus ≤6 (HR 2.37; p = 0.04) were significant predictors of cancer-specific mortality (CSM). cN+ was not a significant predictor of CSM ( p = 0.6). Selected patients with cN+ have similar clinical outcomes to those with normal preoperative imaging in the setting of LNM. Patient summary Clinical lymph node metastases are not a factor in determining survival after radical prostatectomy and pelvic lymph node dissection in patients with prostate cancer. Thus, the presence of clinical lymph node metastases should not be considered as an absolute contraindication to treatment with curative intent. [ABSTRACT FROM AUTHOR]

The purpose of this article is to present speculative presuppositions of Italian critical ontology, a philosophical movement started by the work of Pantaleo Carabellese in the fi rst half of the 20th century, which is still active primarily at the Italian University in Perugia. Carabellese´s life itself was a proof that authentic philosophical refl ection leads to the affi rmative position on God as the fundamental condition and the basis of human existence that, as such, represents, in his words, »the only true object of philosophical refl ection«. In the fi rst thirty years of the author´s work, starting with the defence of his diploma thesis on Rosmini at the University of Naples in 1907 until the publication of The Theological Problem as Philosophy in 1931, theoretical relevancy of the concept of being as the unique basis of consciousness has been affi rmed. At the same time it has become obvious that a refl ection that, on the basis of its own presuppositions, does not necessarily aims for theological outcomes of its own speculation, cannot not refl ect on God, if it approaches the argument of contemplative nature in an authentic way. The true »object« of philosophical refl ection is, therefore, the theological argument, while philosophy is a true journey towards the metaphysical awareness of God. [ABSTRACT FROM AUTHOR]

Background Patients with lymph node (LN)-positive prostate cancer (PCa) at radical prostatectomy (RP) face a high risk of cancer recurrence. Nevertheless, recurrence patterns of LN-positive PCa and their prognostic significance remain understudied in the literature. Objective To analyze a large single-institution series with long-term follow-up to elucidate the various clinical recurrence patterns of LN-positive PCa and their association with oncologic outcomes. Design, setting, and participants Years 1987–2012 of a prospectively maintained institutional RP registry were queried for men with LN-positive PCa at RP. Clinical recurrences were categorized as local, nodal, skeletal, or visceral. Outcome measurements and statistical analysis In addition to descriptive statistics and Kaplan-Meier analysis, univariable and multivariable Cox proportional hazards models were constructed to predict recurrence and to quantify the impact of recurrence patterns on cancer-specific mortality (CSM). Results and limitations Data from 1011 men with LN-positive PCa at RP were analyzed with 17.6 yr of median follow-up. The 15-yr clinical recurrence rate was 33% (95% confidence interval [CI], 31–35%) for all patients and 52.2% (95% CI, 47.3–57.1%) for patients with biochemical recurrence. The solitary locations were skeletal ( n = 94, 55%), nodal ( n = 59, 34%), local soft tissue ( n = 29, 17%), and visceral ( n = 8, 5%). Significant multivariable predictors of recurrence were Gleason score 8–10, number of positive nodes, pathologic Gleason score, and more recent year of surgery. The 15-yr CSM after clinical recurrence was 80%, with a mean overall survival of 30 mo after recurrence. On multivariable analysis, recurrences after 5 yr from RP (hazard ratio [HR]: 0.05), multiple recurrences (HR: 1.97), skeletal (HR: 3.13), and visceral metastases (HR: 7.43) were independently associated with CSM (all p < 0.05). Conclusions Recurrences after RP for LN-positive PCa are heterogeneous in terms of time from RP, location, and number of concomitant lesions. Patient summary We found that impact of recurrence patterns on cancer-specific mortality varies significantly and allows these patients to be stratified for purposes of prognostication, follow-up, and therapy. [ABSTRACT FROM AUTHOR]

Radical cystectomy completed with an extended pelvic lymph node dissection represents the most adequate curative treatment for muscle-invasive bladder cancer . After surgery, the tumor should be considered as completely removed only if the pathologist finds negative surgical margins. However, although the presence of positive surgical margins (PSM) intuitively appears as a factor conditioning a poor prognosis, the studies published at data could not definitively confirm this relationship. This fact may be mainly attributed to the lack of statistical independence between the presence of PSM and other pathologic factors such as tumor stage and lymph node status, that are themselves well known predictors of poor prognosis. The incidence of PSM has been estimated to be 3-9%. Although the persistence of tumor at both urethral and ureteral margins has been correlated with an increased risk of local recurrence, only perivesical soft tissue PSM have been associated with a significantly reduced risk of cancer-specific survival. Female gender, locally advanced cancer, presence of vascular invasion and rare/mixed histology have been recognized as consistent risk factors for soft tissue PSM. Although, to date, the predictive role of both number and location of PSM remains totally to be investigated, there is general agreement that patients found with soft tissue PSM at the time of radical cystectomy should be proposed for adjuvant strategies, including radiation and chemotherapy. In this direction, many recent studies suggest to include the status of surgical margins in the pathologic report of any radical cystectomy. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Urinary incontinence and erectile dysfunction are the most bothersome sequelae affecting health-related quality of life in patients treated with radical prostatectomy for prostate cancer. While it has been widely reported that a nerve-sparing approach significantly improves postoperative erectile function, the impact of neurovascular bundle preservation on urinary continence recovery is still a matter of controversy., Our study clearly demonstrates that patients treated with nerve-sparing radical prostatectomy have higher chances of recovering full continence after surgery. The results indicate that, when technically and oncologically feasible, an attempt at a nerve-sparing approach should be planned in order to increase the probability of achieving full continence after radical prostatectomy., Objective To demonstrate that nerve-sparing radical prostatectomy ( NSRP) is associated with higher rates of urinary continence ( UC) recovery compared with non-nerve-sparing procedures in patients with surgically treated organ-confined prostate cancer., Patients and Methods The study included 1249 patients treated with radical prostatectomy between 2003 and 2010. Patients were divided into three preoperative risk groups: low ( PSA < 10 ng/mL, cT1, biopsy Gleason sum ≤6), high ( cT3 or biopsy Gleason 8-10 or PSA > 20 ng/mL) and intermediate (all the remaining)., Postoperative UC recovery was defined as the absence of any protection device., The association between nerve-sparing status and UC recovery was assessed in univariable and multivariable Cox regression analyses after accounting for age at surgery, Charlson Comorbidity Index and preoperative risk group., Results At a mean follow-up of 42.2 months (range 1-78), 993 patients (79.5%) recovered UC. Overall, UC recovery rate at 1 and 2 years was 76% and 79%, respectively., On univariable Cox regression analysis, age at surgery, preoperative risk group, medical comorbidities and nerve-sparing status were significantly associated with UC recovery (all P ≤ 0.001)., On multivariable analysis, age, risk group and nerve-sparing status were also independently associated with UC recovery (all P < 0.003). Patients treated with bilateral NSRP had a 1.8-fold higher chance of full UC recovery., Conclusions Patients treated with bilateral NSRP have significantly higher chances of recovering full continence., Therefore, when oncologically and technically feasible, a nerve-sparing procedure should be attempted. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To give an updated review concerning the role of combined regimen (CT) based on microwave- induced hyperthermia (MwHT, CT-MwHT) with intravesical chemotherapy (ICT) as a treatment for non-muscle invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION: The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. An electronic search of the Medline, Embase, Cochrane Library, CancerLit, and ClinicalTrials.gov databases was undertaken. Relevant conference abstracts and urology journals were also included. The primary end-point was the time to recurrence. Secondary end-points included time to progression, bladder preservation rate, and adverse event (AE) rate. EVIDENCE SYNTHESIS: A total of 24 studies met inclusion criteria and underwent data extraction. When feasible, data were combined using random-effects meta-analytic techniques. Recurrence was seen 59% less after CT-MwHT than after MMC alone, however, due to the short follow-up, no definitive conclusions can be drawn about the impact on the time to recurrence and progression. The overall bladder preservation rate after CT-MwHT was 87.6%. This rate appeared higher than after MMC alone, but valid comparison studies could not be drawn due to the absence of randomized trials in neo-adjuvant settings. AEs were higher with CT-MwHT than with MMC alone, but this difference was not statistically significant. cOnclusiOns: Published data suggest that recurrence rates for chemo-hyperthermia are substantially reduced compared with chemotherapy alone in adjuvant settings. Patients with refractory disease fare worse than those being treated with chemo-hyperthermia for their first tumor. Progression rates to muscle-invasive disease are markedly lower after combination treatment than after chemotherapy alone, with very high rates of bladder preservation. Tolerability is good, with few dropouts in the clinical trials. The results support CT-MwHT in the future as a standard procedure for high-risk recurrent patients, for subjects in whom the treatment with Bacillus Calmette-Guérin is contraindicated, and those unsuitable for radical cystectomy. [ABSTRACT FROM AUTHOR]

The evidence available suggests that open and robot-assisted radical cystectomy lead to similar outcomes in bladder cancer. True advances will come from a better understanding of the biology of the disease, and a comprehensive, multimodal approach that aims to improve patient survival and quality of life is more critical than the surgical technique. [ABSTRACT FROM AUTHOR]

Objective: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node‐positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. Patients and Methods: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose‐dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1–3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni‐ and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer‐specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. Results: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2‐year OS estimates were 63% (95% confidence interval [CI] 0.53–0.74) and 63% (95% CI 0.58–0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni‐ or multivariable Cox regression analyses. Conclusion: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation. [ABSTRACT FROM AUTHOR]

Background: Ureteral cancer is a rare cancer. This study aimed to provide an up-to-date and comprehensive analysis on the global trends of ureteral cancer incidence and its association with lifestyle and metabolic risk factors. Methods: The incidence of ureteral cancer was estimated from the Cancer Incidence in Five Continents Plus and Global Cancer Observatory databases. We analyzed the (1) global incidence of ureteral cancer by region, country, sex, and age group by age-standardized rates (ASR); (2) associated risk factors on a population level by univariable linear regression with logarithm transformation; and (3) incidence trend of ureteral cancer by sex and age group in different countries by Average Annual Percentage Change (AAPC). Results: The global age-standardized rate of ureteral cancer incidence in 2022 was 22.3 per 10,000,000 people. Regions with higher human development index (HDI), such as Europe, Northern America, and East Asia, were found to have a higher incidence of ureteral cancer. Higher HDI and gross domestic product (GDP) and a higher prevalence of smoking, alcohol drinking, physical inactivity, unhealthy dietary, obesity, hypertension, diabetes, and lipid disorder were associated with higher incidence of ureteral cancer. An overall increasing trend of ureteral cancer incidence was observed for the past decade, especially among the female population. Conclusions: Although ureteral cancer was relatively rare, the number of cases reported was rising over the world. The rising trends among females were more evident compared with the other subgroups, especially in European countries. Further studies could be conducted to examine the reasons behind these epidemiological changes and confirm the relationship with the risk factors identified. [ABSTRACT FROM AUTHOR]

A study published in BJU International examined the complications associated with robot-assisted radical cystectomy (RARC) with intracorporeal neobladder reconstruction. The study analyzed data from 858 patients who underwent the procedure at 16 European centers between 2003 and 2022. The results showed a high overall rate of complications, with urinary tract infection (UTI) being the most common complication. The study highlighted the need for improvements in surgical technique and peri-operative management to reduce complications. The findings also suggested the importance of careful management of the urinary device and consideration of neoadjuvant therapy in patient care. [Extracted from the article]

Background: Follow-up after radical cystectomy (RC) for bladder cancer can be divided into oncological and functional surveillance. It remains unclear how follow-up after RC should ideally be scheduled. The aim of this report was to gain insight into the organization of follow-up after RC in Europe, for which we conducted a roundtable inventory within the EAU Young Academic Urologists Urothelial Cancer working group. Methods: An inventory semi-structured survey was performed among urologists of the EAU Young Academic Urologists Urothelial Cancer working group to describe the organization of follow-up. The surveys were analyzed using a deductive approach. Similarities and differences in follow-up after RC for bladder cancer were described. Results: The survey included 11 urologists from six different European countries. An institutional follow-up scheme was used by six (55%); three (27%) used a national or international guideline, and two (18%) indicated that there was no defined follow-up scheme. Major divergent aspects included the time points of follow-up, the frequency, and the end of follow-up. Six centers (55%) adopted a risk-adapted follow-up approach tailored to (varying) patient and tumor characteristics. Laboratory tests and CT scans were used in all cases; however, the intensity and frequency varied. Functional follow-up overlapped with oncological follow-up in terms of frequency and duration. Patient-reported outcome measures were only used by two (18%) urologists. Conclusions: Substantial variability exists across European centers regarding the follow-up after RC for bladder cancer. This highlights the need for an international analysis focusing on its organization and content as well as on opportunities to improve patients' needs during follow-up after RC. [ABSTRACT FROM AUTHOR]

Using preimmunotherapy stool samples collected from patients enrolled in the PURE-01 clinical trial, testing neoadjuvant pembrolizumab in patients with muscle-invasive bladder cancer, we identified some bacterial taxa that were enriched differentially in responders and nonresponders to immunotherapy. Among those, the genus Sutterella was enriched in responders, while the species Ruminococcus bromii was enriched in nonresponders. We further used an animal model of bladder cancer to provide further evidence suggesting a negative role of R. bromii in anti–PD-1 efficacy. However, further studies are needed to confirm our findings. Neoadjuvant pembrolizumab has been shown to be a valid treatment for patients affected by muscle-invasive bladder cancer (MIBC), as demonstrated in the PURE-01 clinical trial (NCT02736266). Among the tumor-extrinsic factors influencing immunotherapy efficacy, extensive data highlighted that the microbiome is a central player in immune-mediated anticancer activity. This report aimed to investigate the composition and role of stool microbiome in patients enrolled in the PURE-01 clinical trial. An orthotopic animal model of bladder cancer (MB49-Luc) was used to support some of the findings from human data. An analysis of stool microbiome before pembrolizumab was conducted for 42 patients, of whom 23 showed a pathologic response. The information in the preclinical model of orthotopic bladder cancer treated with anti–PD-1 antibody or control isotype was validated. Linear discriminant analysis effect size and linear models were used to identify the bacterial taxa enriched in either responders or nonresponders. The identified taxa were also tested for their association with event-free survival (EFS). Survival at 31 d after tumor instillation was used as the study endpoint in the preclinical model. Responders and nonresponders emerged to differ in terms of enrichment for 16 bacterial taxa. Of these, the genus Sutterella was enriched in responders, while the species Ruminococcus bromii was enriched in nonresponders. The negative impact of R. bromii on anti–PD-1 antibody activity was also observed in the preclinical model. EFS and survival of the preclinical model showed a negative role of R. bromii. We found different stool bacterial taxa associated with the response or lack of response to neoadjuvant pembrolizumab. Moreover, we provided experimental data about the negative role of R. bromii on immunotherapy response. Further studies are needed to externally validate our findings and provide mechanistic insights about the host-pathogen interactions in MIBC. Using prepembrolizumab stool samples collected from patients enrolled in the PURE-01 clinical trials, we identified some bacterial taxa that were enriched in patients who either responded or did not respond to immunotherapy. Using an animal model of bladder cancer, we gathered further evidence of the negative impact of the Ruminococcus bromii on immunotherapy efficacy. Further studies are needed to confirm the current findings and test the utility of these bacteria as predictive markers of immunotherapy response. [ABSTRACT FROM AUTHOR]