Testicular Cancer Treatments and Sexuality: A Narrative Review.

The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

Comparing Robotic-Assisted to Open Radical Cystectomy in the Management of Non-Muscle-Invasive Bladder Cancer: A Propensity Score Matched-Pair Analysis.

BACKGROUND: For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques. METHODS: A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared. RESULTS: A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis. CONCLUSION: We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.

Presumed Takotsubo syndrome is associated with high in-hospital mortality in very elderly frail females: a case series.

Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach.

Ejection fraction at hospital admission stratifies mortality risk in HFmrEF patients aged ≥ 70 years: a retrospective analysis from a tertiary university institution.

BACKGROUND: During the last few years, increasing focus has been placed on heart failure with mildly reduced ejection fraction (HFmrEF), an intermediate phenotype from preserved to reduced ejection fraction (EF). However, clinical features and outcome of HFmrEF in elderly patients aged ≥ 70 yrs have been poorly investigated. METHODS: The present study retrospectively included all consecutive patients aged ≥ 70 yrs discharged from our Institution with a first diagnosis of HFmrEF, between January 2020 and November 2020. All patients underwent transthoracic echocardiography. The primary outcome was all-cause mortality, while the secondary one was the composite of all-cause mortality + rehospitalization for all causes over a mid-term follow-up. RESULTS: The study included 107 HFmrEF patients (84.3 ± 7.4 yrs, 61.7% females). Patients were classified as "old" (70-84 yrs, n = 55) and "oldest-old" (≥ 85 yrs, n = 52) and separately analyzed. As compared to the "oldest-old" patients, the "old" ones were more commonly males (58.2% vs 17.3%, p < 0.001), with history of coronary artery disease (CAD) (54.5% vs 15.4%, p < 0.001) and significantly lower EF (43.5 ± 2.7% vs 47.3 ± 3.6%, p < 0.001) at hospital admission. Mean follow-up was 1.8 ± 1.1 yrs. During follow-up, 29 patients died and 45 were re-hospitalized. Male sex (HR 6.71, 95% CI 1.59-28.4), history of CAD (HR 5.37, 95% CI 2.04-14.1) and EF (HR 0.48, 95% CI 0.34-0.68) were independently associated with all-cause mortality in the whole study population. EF also predicted the composite of all-cause mortality + rehospitalization for all causes. EF < 45% was the best cut-off value to predict both outcomes. CONCLUSIONS: EF at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFmrEF patients over a mid-term follow-up.

Age represents the main driver of surgical decision making in patients candidate to radical cystectomy.

BACKGROUND AND OBJECTIVES: Age might influence the choice of surgical approach, type of urinary diversion (UD) and lymph node dissection (LND) in patients candidate to radical cystectomy (RC) for urothelial bladder cancer (UBC). Similarly, age may enhance surgical morbidity and worsen perioperative outcomes. We tested the impact of age (octogenarian vs. younger patients) on surgical decision making and peri- and postoperative outcomes of RC. METHODS: Non-metastatic muscle-invasive UBC patients treated with RC at 18 high-volume European institutions between 2006 and 2021 were identified and stratified according to age (≥80 vs. <80 years). Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology guidelines recommendations were accomplished in collection and reporting of, respectively, intraoperative and postoperative complications. Multivariable logistic regression models (MVA) tested the impact of age on outcomes of interest. Sensitivity analyses after 1:3 propensity score matching were performed. RESULTS: Of 1955 overall patients, 251 (13%) were ≥80-year-old. Minimally invasive RC was performed in 18% and 40% of octogenarian and younger patients, respectively (p < 0.001). UD without bowel manipulation (ureterocutaneostomy, UCS) was performed in 31% and 7% of octogenarian and younger patients (p < 0.001). LND was delivered to 81% and 93% of octogenarian and younger patients (p < 0.001). At MVA, age ≥80 years independently predicted open approach (odds ratio [OR]: 1.55), UCS (OR: 3.70), and omission of LND (OR: 0.41; all p ≤ 0.02). Compared to their younger counterparts, octogenarian patients experienced higher rates of intraoperative (8% vs. 4%, p = 0.04) but not of postoperative complications (64% vs. 61%, p = 0.07). At MVA, age ≥80 years was not an independent predictor of length of stay, intraoperative or postoperative transfusions and complications, and readmissions (all p values >0.1). These results were replicated in sensitivity analyses. CONCLUSIONS: Age ≥80 years does not independently portend worse surgical outcomes for RC. However, octogenarians are unreasonably more likely to receive open approach and UCS diversion, and less likely to undergo LND.

Treatment Outcomes for Men with Clinical Stage II Nonseminomatous Germ Cell Tumours Treated with Primary Retroperitoneal Lymph Node Dissection: A Systematic Review.

CONTEXT: Guidelines recommend primary retroperitoneal lymph node dissection (RPLND) as a treatment option for tumour marker-negative stage II nonseminomatous germ cell tumour (NSGCT). OBJECTIVE: To review the literature on oncological outcomes for men with stage II NSGCT treated with RPLND. EVIDENCE ACQUISITION: A systematic review of studies describing clinicopathological outcomes following primary RPLND in stage II NSGCT was conducted in the MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. Baseline data, perioperative and postoperative parameters, and oncological outcomes were collected. EVIDENCE SYNTHESIS: In total, 12 of 4387 studies were included, from which we collected data for 835 men. Among men with clinical stage II NSGCT, pathological stage II was confirmed in 615 of 790 patients (78%). Most studies administered adjuvant chemotherapy in cases with large lymph nodes, multiple affected lymph nodes, or persistently elevated tumour markers. Recurrence was observed in 12-40% of patients without adjuvant chemotherapy and 0-4% of patients who received adjuvant chemotherapy. CONCLUSIONS: The literature describing RPLND in clinical stage II NSGCT is heterogeneous and no meta-analysis was possible, but RPLND can provide accurate staging and may be curative in selected patients. PATIENT SUMMARY: We reviewed the literature to summarise results after surgical removal of enlarged lymph nodes in the back of the abdomen in men with testis cancer. This procedure provides accurate information on how far the cancer has spread and may provide a cure in selected patients.

Genitourinary manifestations of Lynch syndrome in the urological practice.

Objective: Lynch syndrome (LS) is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in EPCAM gene. From a clinical perspective, LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general population. We aimed to provide a comprehensive overview of all the genitourinary manifestations of LS, focusing on incidence, diagnosis, clinical features, therapeutic strategies, and screening protocols. Methods: Previous literature was assessed through Medline, Scopus, and Google Scholar databases. A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was provided. Results: In the LS tumor spectrum, upper tract urothelial carcinoma (UTUC) represents the third most frequent malignancy, and the first most common cancer in the urological field, with an approximately 14-fold increased risk of developing UTUC compared to general population. LS diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process, including (i) clinical criteria, (ii) molecular testing, and (iii) genetic testing to confirm the hereditary disorder. The current European Association of Urology (EAU) guidelines recommend to perform molecular testing among UTUC patients under 65 years old, or UTUC patients with personal history of LS-related tumor, or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor, or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of onset. Newly diagnosed LS patients should be referred to a multidisciplinary management, including gastroenterologists and gynecologists. Finally, considering the increased risk of metachronous recurrence, treatments other than radical nephroureterectomy may be a valuable therapeutic alternative. Whether urological malignancies other than UTUC should be included in the LS tumor spectrum is still controversial. Conclusion: Considering the strict association between UTUC and LS, we believe that the urologist should recognize patients at increased risk for hereditary disease according to current EAU clinical criteria and address them to a comprehensive diagnostic algorithm, including molecular evaluation and genetic testing. To date, literature lacks clear evidence regarding the role of LS in developing bladder cancer, prostate cancer, or renal cell carcinoma, and current data are still inconclusive, highlighting the urgent need for further studies.

Micropapillary bladder cancer: an evolving biology.

PURPOSE OF REVIEW: To summarize a comprehensive overview of more recent evidence on micropapillary bladder cancer (MPBC), focusing on actual incidence, clinical features, therapeutic strategies, and prognosis. RECENT FINDINGS: MPBC generally exhibits an aggressive behaviour compared with pure urothelial carcinoma (pUC) with advances in tumour stage and nodal and distant spread at diagnosis. Due to its rarity and presence of only small sample size and retrospective studies, no consensus currently exists regarding the most effective therapeutic strategy to be performed among nonmuscle-invasive (conservative treatment versus immediate radical cystectomy) and muscle-invasive MPBC (neoadjuvant therapy versus upfront radical cystectomy versus adjuvant chemotherapy). SUMMARY: The incidence of MPBC is recently increased according to latter literature, ranging from 2.9 to 7.6% of all bladder cancer. Despite its aggressive behaviour at time of presentation, more recent evidence fails to demonstrate a significant association between MPBC and worse outcomes compared with pUC when adjusted for clinical and pathological features. According to latter evidence, MPBC pathological response to NAC appears to be unsatisfactory compared with pUC patients while neoadjuvant immunotherapy with Pembrolizumab may represent an effective treatment among MPBC patients, based on PD-L1 and TMB expression.

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk-adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy. METHODS: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC). RESULTS: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recurrence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression. CONCLUSION: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis.

Selecting the Best Candidates for Cisplatin-based Adjuvant Chemotherapy After Radical Cystectomy Among Patients with pN+ Bladder Cancer.

A trend towards greater benefit from adjuvant chemotherapy (ACT) in pN+ bladder cancer (BCa) has been observed in multiple randomized controlled trials. However, it is still unclear which patients might benefit the most from this approach. We retrospectively analyzed a multicenter cohort of 1381 patients with pTany pN1-3 cM0 R0 urothelial BCa treated with radical cystectomy (RC) with or without cisplatin-based ACT. The main endpoint was overall survival (OS) after RC. We performed 1:1 propensity score matching to adjust for baseline characteristics and conducted a classification and regression tree (CART) analysis to assess postoperative risk groups and Cox regression analyses to predict OS. Overall, 391 patients (28%) received cisplatin-based ACT. After matching, two cohorts of 281 patients with pN+ BCa were obtained. CART analysis stratified patients into three risk groups: favorable prognosis (≤pT2 and positive lymph node [PLN] count ≤2; odds ratio [OR] 0.43), intermediate prognosis (≥pT3 and PLN count ≤2; OR 0.92), and poor prognosis (pTany and PLN count ≥3; OR 1.36). Only patients with poor prognosis benefitted from ACT in terms of OS (HR 0.51; p < 0.001). We created the first algorithm that stratifies patients with pN+ BCa into prognostic classes and identified patients with pTany BCa with PLN ≥3 as the most suitable candidates for cisplatin-based ACT. PATIENT SUMMARY: We found that overall survival among patients with bladder cancer and evidence of lymph node involvement depends on cancer stage and the number of positive lymph nodes. Patients with more than three nodes affected by metastases seem to experience the greatest overall survival benefit from cisplatin-based chemotherapy after bladder removal. Our study suggests that patients with the highest risk should be prioritized for cisplatin-based chemotherapy after bladder removal.

Retroperitoneal Robot-assisted Partial Nephrectomy: A Systematic Review and Pooled Analysis of Comparative Outcomes.

Context: Robot-assisted partial nephrectomy (RAPN) has gained increasing popularity as primary minimally invasive surgical treatment for localized renal tumors, and it has preferably been performed with a transperitoneal approach. However, the retroperitoneal approach represents an alternative approach given potential advantages. Objective: To provide an updated analysis of the comparative outcomes of retroperitoneal RAPN (R-RAPN) versus transperitoneal RAPN (T-RAPN). Evidence acquisition: A systematic review of the literature was performed up to September 2021 using MEDLINE, EMBASE, and Web of Science databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. A sensitivity analysis was performed considering only matched-pair studies. Evidence synthesis: Seventeen studies, which were published between 2013 and 2021, were retrieved. None of them was a randomized clinical trial. Among the 6,266 patients included in the meta-analysis, 2261 (36.1%) and 4,005 (63.9%) underwent R-RAPN and T-RAPN, respectively. No significant difference was found in terms of baseline features. The T-RAPN group presented a higher rate of male patients (odds ratio [OR]: 0.86, p = 0.03) and larger tumor size (weighted mean difference [WMD]: 0.2 cm; p = 0.003). The R-RAPN group reported more frequent posterior renal masses (OR: 0.23; p < 0.0001). The retroperitoneal approach presented lower estimated blood loss (WMD: 30.41 ml; p = 0.001), shorter operative time (OT; WMD: 20.36 min; p = 0.0001), and shorter length of stay (LOS; WMD: 0.35 d; p = 0.002). Overall complication rates were 13.7% and 16.05% in the R-RAPN and T-RAPN groups, respectively (OR: 1.32; p = 0.008). There were no statistically significant differences between the two groups regarding major (Clavien-Dindo classification ≥3 grade) complication rate, "pentafecta" achievement, as well as positive margin rates. When considering only matched-pair studies, no difference between groups was found in terms of baseline characteristics. Posterior renal masses were more frequent in the R-RAPN group (OR: 0.6; p = 0.03). Similar to the analysis of the entire cohort, R-RAPN reported lower EBL (WMD: 35.56 ml; p < 0.0001) and a shorter OT (WMD: 18.31 min; p = 0.03). Overall and major complication rates were similar between the two groups. The LOS was significantly lower for R-RAPN (WMD: 0.46 d; p = 0.02). No statistically significant difference was found between groups in terms of overall PSM rates. Conclusions: R-RAPN offers similar surgical outcomes to T-RAPN, and it carries potential advantages in terms of shorter OT and LOS. Available evidence remains limited by the lack of randomized clinical trials. Patient summary: In this review of the literature, we looked at comparative outcomes of two surgical approaches to robot-assisted partial nephrectomy. We found that the retroperitoneal technique offers similar surgical outcomes to the transperitoneal one, with potential advantages in terms of shorter operative time and length of hospital stay.

Oncologic Surveillance After Radical Nephroureterectomy for High-risk Upper Tract Urothelial Carcinoma.

BACKGROUND: The appropriate surveillance protocol after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is still poorly addressed. OBJECTIVE: To evaluate the appropriate intensity and duration of oncologic surveillance following RNU, according to a prior history of bladder cancer (BCa). DESIGN, SETTING, AND PARTICIPANTS: We identified 1378 high-risk UTUC patients, according to the European Association of Urology (EAU) guidelines, from a prospectively maintained database involving eight European referral centers. Surveillance protocol was based on cystoscopies and cross-sectional imaging, as per the EAU guidelines. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, we evaluated the noncumulative risk of bladder and other-site recurrences (including distant metastasis and locoregional relapse) against the follow-up time points, as suggested by the current EAU guidelines. Second, in an effort to identify the time points when the risk of other-cause mortality (OCM) exceeded that of recurrence and follow-up might be discontinued, we relied on adjusted Weibull regression. RESULTS AND LIMITATIONS: The median follow-up was 4 yr. A total of 427 and 951 patients with and without a prior BCa history, respectively, were considered. At 5-yr, the time point after which cystoscopies should be performed semiannually, the bladder recurrence risk was 10%; at 4 yr, the bladder recurrence risk was 13%. At 2 yr, the time point after which imaging should be obtained semiannually, the nonbladder recurrence risk was 42% in case of nonprior BCa and 47% in case of prior BCa; at 4 yr, the nonbladder recurrence risk was 23%. Among patients without a prior BCa history, individuals younger than 60 yr should continue both cystoscopies and imaging beyond 10 yr from RNU, 70-79-yr-old patients should continue only imaging beyond 10 yr, while patients older than 80 yr might discontinue oncologic surveillance because of an increased risk of OCM. Limitations include the fact that patients were treated and surveilled over a relatively long period of time. CONCLUSIONS: We suggest intensifying the frequency of imaging to semiannual till the 4th year after RNU, the time point after which the risk of recurrence was almost halved. Cystoscopies could be obtained annually from the 4th year given a similar risk of recurrence at 4 and 5 yr after RNU. Oncologic surveillance could be discontinued in some cases in the absence of a prior BCa history. PATIENT SUMMARY: In this study, we propose a revision of the current guidelines regarding surveillance protocols following radical nephroureterectomy. We also evaluated whether oncologic surveillance for high-risk upper tract urothelial carcinoma could be discontinued and, if so, in what circumstances.

Metastasis Within Three Years from Radical Nephroureterectomy as a Potential Surrogate for Overall Survival.

INTRODUCTION: The only phase III trial that evaluated the role of adjuvant chemotherapy following radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) was terminated early. Thus, eventual overall survival (OS) surrogacy, as per Prentice, cannot be assessed in this setting. We aimed to identify an intermediate clinical endpoint (ICE) that could serve as an OS surrogate after RNU for UTUC. PATIENTS AND METHODS: We retrospectively analyzed 823 high-grade UTUC patients treated with RNU at 8 tertiary referral centers. We explored the role of any recurrence (aR), defined as recurrence in the urinary tract or in the resection bed as well the presence of distant metastasis (DM), defined as metastatic disease outside the urinary tract and regional lymph nodes, on OS through a time-varying Cox regression analyses fitted at the landmark points of 1, 2, 3, and 4 years from RNU. Models' discrimination was assessed using Harrell's c index, after internal validation. RESULTS: Median follow-up for survivors was 5.6 years (interquartile range: 2.0-8.8). Overall, 391 and 212 patients experienced aR and DM, respectively. In a time-varying model, aR and DM were predictors of OS: hazard ratio [HR]:1.20, 95% confidence interval [CI]: 1.13-1.28 (P < .001) and HR:1.26, 95% CI: 1.18-1.34 (P < .001), respectively. Progression to DM within 3 years from RNU was the most informative ICE for predicting OS (c index: 0.81; HR: 4.40; 95%CI: 2.45-7.92; P < .001), compared to DM within 1, 2, and 4 years (c indexes: 0.74, 0.76, and 0.78, respectively). Progression to DM within 3 years from RNU was further found superior for predicting OS compared to aR at any landmark points. CONCLUSIONS: Progression to DM within 3 years represents a potential OS surrogate for surgically-treated UTUC. This information could help in patient counseling, future study design and expedite results release of ongoing randomized controlled trials.

CHA2DS2-VASc score stratifies mortality risk in heart failure patients aged 75 years and older with and without atrial fibrillation.

BACKGROUND: During the last decade, the CHA2DS2-VASc score has been associated with adverse clinical outcomes in several cardiovascular (CV) and non-cardiovascular diseases beyond atrial fibrillation (AF). Whether the CHA2DS2-VASc score stratifies mortality risk in elderly patients with AF and without AF is not well established. METHODS: All consecutive patients aged ≥ 75 yrs hospitalized due to heart failure (HF), between January 2020 and November 2020, were retrospectively enrolled. All patients underwent physical examination, blood tests, electrocardiography and conventional transthoracic echocardiography. Primary endpoint was all-cause mortality, while secondary endpoint was the composite of all-cause mortality + rehospitalizations for all causes over mid-term follow-up. RESULTS: The study included 261 HF patients (86.3 ± 6.4 years, 60.5% females). 85 AF and 176 non-AF patients were separately analyzed. Compared to non-AF patients, those with AF had significantly higher CHA2DS2-VASc score (5.6 ± 1.4 vs 5.1 ± 1.4, p = 0.007) and lower ejection fraction (47.4 ± 16.5 vs 56.7 ± 15.1%, p < 0.001). Mean follow-up was 1.7 ± 0.5 yrs. During follow-up, 96 patients died (58.3% due to CV causes) and 79 were rehospitalized (58.2% due to CV causes). CHA2DS2-VASc score was independently associated with all-cause mortality in whole study population (HR 1.61, 95% CI 1.36-1.92) and in both AF (HR 1.41, 95% CI 1.09-1.82) and non-AF patients (HR 1.84, 95% CI 1.40-2.40). CHA2DS2-VASc score also predicted the secondary endpoint in the same study groups. CHA2DS2-VASc score ≥ 5 was the best cut-off value for predicting both outcomes. CONCLUSION: At mid-term follow-up, a CHA2DS2-VASc score ≥ 5 predicts increased risk of all-cause mortality and re-hospitalizations for all causes in elderly HF patients, regardless of AF.

Diagnostic accuracy of preoperative lymph node staging of bladder cancer according to different lymph node locations: A multicenter cohort from the European Association of Urology - Young Academic Urologists.

BACKGROUND: The preoperative lymph node (LN) staging of bladder cancer (BCa) addresses the subsequent therapeutic strategy and influences patient's prognosis. However, sparce evidence exists regarding the accuracy of conventional cross-sectional imaging, such as computed tomography or magnetic resonance imaging, in correctly detect LN status. We aimed to assess the diagnostic accuracy of conventional cross-sectional imaging in detecting preoperative LN involvement among BCa patients treated with radical cystectomy and pelvic lymph node dissection. METHODS: We retrospectively analyzed data of 1,104 patients who underwent preoperative LN staging with computed tomography or magnetic resonance imaging and subsequent radical cystectomy with pelvic lymph node dissection for BCa between 1997 and 2017 at three tertiary referral centers. Patients receiving neoadjuvant chemotherapy were excluded. We assessed the concordance between clinical (cN) and pathological LN (pN) status, defined as the accuracy of imaging in detecting LN involvement using pathological specimen as reference; concordance was expressed according to Cohen's kappa coefficient. Location-based sub-analyses were performed, distinguishing among external iliac, intern iliac, obturator, common iliac, presacral and paraaortic LNs. RESULTS: Among 870 cN0 patients, 68.9% were confirmed pN0 at pathological report; while among 234 cN+ patients, 50.5% were found with LN metastases at pathological specimen. Overall, conventional imaging showed slight concordance (64.9%) between cN and pN stages (sensitivity: 30%; specificity: 84%). At sub-analysis, no agreement between cN and pN status was found in each LN location, with the only exception of common iliac LNs with slight concordance (37.5%). Common iliac LNs achieved the highest sensitivity and positive likelihood ratio (15% and 2.4, respectively) compared to other LN locations. CONCLUSIONS: Overall, preoperative cross-sectional imaging exhibited a slight concordance between cN and pN status. Our location-based sub-analyses showed unsatisfactory results in each LN location- Thus, nomograms combining morphological patterns with serological and clinicopathological features are urgently required.

The Role of Prior Bladder Cancer on Recurrence in Patients Treated with Radical Nephroureterectomy.

INTRODUCTION: The prognostic role of prior history of bladder cancer (BCa) among patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) is poorly addressed. We aimed to investigate the role of prior BCa on any recurrence, distant metastases, and bladder recurrence following RNU among low-grade (LG) and high-grade (HG) UTUC patients. PATIENTS AND METHODS: We retrospectively analyzed 1,580 UTUC patients treated with RNU at 8 tertiary referral centers between 1992 and 2016. Any recurrence was defined as recurrence in the urinary tract, in the resection bed, or distant metastases (defined as disease outside the urinary tract and regional lymph nodes). Time to recurrence was computed from RNU. Multivariable Cox models were generated to predict risk of any recurrence, distant metastases, and bladder recurrence according to prior BCa history, coded as no prior BCa, non-muscle-invasive (NMIBC), and muscle-invasive BCa (MIBC). RESULTS: Median follow-up for survivors was 4 years. Overall, 71%, 25%, and 4% of patients had no prior BCa, NMIBC and MIBC. 5-year any recurrence-free survival was 61%, 41%, and 19% in LG (P < .001) and 42%, 34%, and 30% in HG patients (P = .1) with no prior BCa, NMIBC, and MIBC. On multivariable models, LG patients with NMIBC and MIBC showed a significantly higher risk of any recurrence compared to no prior BCa (both p≤0.005); previous NMIBC was associated with any recurrence among HG patients (P = 0.04). 5-year distant metastases-free survival was 92%, 90%, and 87% in LG (P > .05) and 68%, 75%, and 45% in HG patients (P = .01) with no prior BCa, NMIBC, and MIBC. Previous NMIBC increased the risk of bladder recurrence among LG (P < .001) and HG (P = .003) patients. CONCLUSIONS: UTUC patients with prior history of BCa exhibit a higher risk of any recurrence after RNU. Our study provides important information which could address patient's counseling and decision-making process.

Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration.

PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.