Diagnostic evaluation for adrenal tumors - What does the urologist need to know about endocrine metabolic work up?

PURPOSE OF REVIEW: Adrenal lesions are commonly discovered on abdominal imaging studies, whereas some patients with adrenal tumors present with symptoms of homonal excess. They are categorized as either hormone active or inactive and either as benign or malignant. This review is focused on the endocrine work up in patients with adrenal tumors. Knowledge of the use and limitations of hormonal assessment is essential for propper interpretation of the obtained test results. This article reviews which diagnostics are necessary to identify adrenal masses requiring treatment. RECENT FINDINGS: Delayed hormonal assessment is not uncommon and associated with delayed treatment. The endocrine work up is guided by data from prospective and retrospective observational studies. Adrenal tumors include a wide spectrum of diseases and as a principle, most patients require biochemical testing to select the appropriate treatment. SUMMARY: The most important factor for the outcome in the management of adrenal masses is, beside the exclusion of malignancy, a structured evaluation of the patients endocrine status.

Treatment of adrenocortical carcinoma: oncological and endocrine outcomes.

PURPOSE OF REVIEW: Adrenocortical carcinoma (ACC) is a rare, aggressive disease with a paucity of data and great variability between published studies regarding its treatment. This review provides information on current clinical management and oncological and endocrine outcomes. RECENT FINDINGS: Complete surgical resection is the only potentially curative treatment for adrenocortical carcinoma (ACC). Adjuvant mitotane treatment is recommended in patients with favourable/intermediate prognosis. As part of the endocrine follow-up, steroid hormones and thyroid hormones may be decreased or increased and may need to be substituted or suppressed. Recurrences are common. If the disease-free interval is more than 12 months, surgery is a treatment if complete resection is feasible. In advanced/metastatic ACC patients, the prognosis is poor. Mitotane monotherapy is only appropriate for patients with low tumour burden and indolent disease. Patients with unfavourable prognosis should be treated with aggressive cytotoxic therapy. Patients requiring third-line treatment should be considered for clinical trials. Immunotherapy and targeted therapy are currently being investigated, but have so far yielded only unsatisfactory results. SUMMARY: There is scarce evidence for the treatment of ACC, which often complicates clinical decision-making. Patients who progress on EDP-M should be treated in clinical trials.

Immunotherapy-based combinations in the first-line treatment of metastatic renal cell carcinoma with sarcomatoid features: a systematic review and network meta-analysis.

PURPOSE OF REVIEW: To perform indirect comparisons of efficacy and safety of first-line immune checkpoint inhibitor (ICI)-based combination therapies for renal cell carcinoma with sarcomatoid features (sRCC). RECENT FINDINGS: Five trials were included in our network meta-analyses comprising 568 patients. The combinations nivolumab plus ipilimumab and nivolumab plus cabozantinib achieved significant improvement of progression-free survival (PFS), overall survival (OS), and objective response rates (ORR). Nivolumab plus ipilimumab was associated with the highest likelihood of achieving a complete response. All the included combinations significantly improved PFS and ORR. The combinations of pembrolizumab plus axitinib did not show a statistically significant association with OS. Nivolumab plus cabozantinib had the highest likelihood of improving PFS and OS. SUMMARY: Our network meta-analysis demonstrates that sRCC are responsive to immune-based combinations. The dual ICI with nivolumab plus ipilimumab improved all efficacy outcomes and achieved the highest complete response rates (CRR). Although the association of nivolumab plus cabozantinib with CRR was not statistically significant, this combination demonstrated the highest likelihood of PFS and OS improvements.

Intraoperative aerosol viral transmission in minimally invasive surgery: a scoping review and impact on clinical guidelines and practice during the onset of the coronavirus disease 2019 (COVID-19) pandemic.

OBJECTIVE: To identify the available evidence on aerosol viral transmission risk during minimally invasive surgery (MIS) and evaluate its impact on guidelines development and clinical activity worldwide during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We performed a scoping review on PubMed, Cochrane, the Excerpta Medica dataBASE (EMBASE), Clinical Trial Register, and the Grey Literature Repository databases, to identify reports on viral transmission via surgical smoke or aerosolisation. A systematic review of all available national and international guidelines was also performed to report their recommendations. Additionally, a worldwide transdisciplinary survey was performed to capture the actual compliance to dedicated guidelines and their impact on MIS activity. RESULTS: Based on a selection of 17 studies, there was no evidence to support the concerns of an intraoperative viral transmission via pneumoperitoneum aerosolisation. Most national surgical and urological societies either did address this topic or referred to international guidelines. The guidelines of the American College of Surgery, the Royal College of Surgeons, and the European Association of Urology Robotic Urology Section, recommended an avoidance of MIS due to an increased risk of intraoperative aerosol-enhanced transmission. The results of the survey completed by 334 respondents, from different surgical abdominal specialties, suggested a lack of compliance with the guidelines. CONCLUSION: There seems to be a dissonance between contemporary guidelines and ongoing surgical activity, possibly due to the perceived lack of evidence. Recommendations regarding changes in clinical practice should be based on the best available research evidence and experience. A scoping review of the evidence and an assessment of the benefits and harms together with a survey showed that laparoscopic procedures do not seem to increase the risk of viral transmission. Nevertheless, the few publications and low quality of existing evidence limits the validity of the review.

COVID-19 crisis and minimally invasive surgery: a narrative review on intraoperative aerosol viral transmission and their impact on guidelines and clinical practice in Austria.

PURPOSE OF REVIEW: The purpose of this review is to evaluate the risk of intraoperative aerosol viral transmission and the impact of updated COVID-19 guidelines on minimally invasive surgery (MIS) in Austria. RECENT FINDINGS: The current literature does not support the risk of intraoperative viral transmission nor does it suggest a harm of minimally invasive procedures in the context of the COVID-19 pandemic. However, medical societies mostly adopted a precautionary approach with a focus on protective measures. Austrian surgeons considered MIS safe during the pandemic and Austria managed to keep the initial outbreak in control. Yet, MIS programs were still affected due to the postponements of elective procedures and switches to other methods by some surgeons. SUMMARY: The postponement and cancellation of MIS caused complexities in health-care delivery in Austria, whilst the evidence to substantiate this precautionary approach is missing. It must be noted, both the guidelines and our review are limited by the scarcity of evidence. In further consequence, regional factors should be considered while taking precautions. Specific studies on the severe acute respiratory syndrome coronavirus type 2 transmission risk during MIS are urgently needed.

Adverse events of systemic immune-based combination therapies in the first-line treatment of patients with metastatic renal cell carcinoma: systematic review and network meta-analysis.

PURPOSE OF REVIEW: To compare the safety profiles of systemic immune checkpoint inhibitor-based combination therapies that were evaluated in the first-line setting of the management of patients with advanced or metastatic renal cell carcinoma (mRCC). RECENT FINDINGS: Six phase III randomized control trials comparing first-line immune-based combination therapies to sunitinib in previously untreated patients with mRCC. Network meta-analyses were conducted to compare treatment-related adverse events (TRAEs), treatment discontinuation, and treatment-related mortality. SUMMARY: Lenvatinib plus pembrolizumab was associated with the highest likelihood of grade ≥3 TRAEs, and treatment discontinuation rates. Nivolumab plus ipilimumab was associated with the lowest rates of grade ≥3 TRAEs. However, it was associated with a higher likelihood of endocrine-related adverse events (AEs). A higher likelihood of high-grade diarrhea was associated with pembrolizumab plus axitinib and avelumab plus axitinib. All combinations showed low rates of hematological AEs.

Dual immune check point blockade or immune check point-tyrosine kinase inhibitor combination: as a first-line treatment in metastatic renal cell carcinoma?

PURPOSE OF REVIEW: To discuss treatment decisions in the first-line setting of metastatic renal cell carcinoma (mRCC). RECENT FINDINGS: Immune check point inhibitor (ICI) combinations have replaced sunitinib as the standard of care in the first-line treatment of mRCC. Dual ICI treatment with nivolumab and ipilimumab was shown to significantly improve overall survival and objective response rates. Similarly, the ICI-tyrosine kinase inhibitor combinations pembrolizumab and axitinib and nivolumab and cabozantinib have demonstrated superiority in terms of overall survival, objective response rates and progression-free survival versus sunitinib. The lack of both comparative trials and predictive markers impedes individualized treatment decisions. Clinicians are left to make treatment choices based on clinical and biological factors. These factors may include differences in toxicity profiles, the rate of complete remission, a clinical situation that requires urgent tumor shrinkage, the presence of inflammation, histological or immune-histochemical features and others. SUMMARY: In the absence of comparative trials, clinical and biological factors may facilitate the choice between various treatment options in the first-line setting of mRCC. In addition, both the experience of the physician with a specific treatment together with patient's preferences and expectations of systemic therapy may be part of the decision-making process.

Overactive bladder symptoms in patients undergoing rigid and flexible cystoscopy.

PURPOSE: To evaluate overactive bladder (OAB) symptoms in patients undergoing diagnostic cystoscopy. Overall changes in the entire study population were assessed, as well as broken down by various subgroups. METHODS: A prospective multi-center study among consecutive 450 adults undergoing diagnostic cystoscopy was conducted. OAB-symptoms were evaluated with the validated eight-item OAB Screening Awareness Tool (OAB-V8) immediately before and on days 1, 4, and 7 after cystoscopy. Patients were distinguished between being OAB-negative and OAB-positive (< 8 and ≥ 8 sum-score, respectively). Average sum-scores and subdomains were evaluated. RESULTS: Before cystoscopy, 44.7% of patients were screened OAB-positive and 55.3% OAB-negative. Out of those being screened negative, development of de-novo OAB was noticed in 16.8%, declining to 8.1% on day 7 (p < 0.001). In patients being OAB-positive before cystoscopy, a decline of OAB-positivity was noted during follow-up (p < 0.001). No statistically significant differences were noted when broken down by gender (p = 0.92), age (p = 0.82) and type cystoscope (rigid vs. flexible, p = 0.38). Average sum-scores declined from 8.68 before cystoscopy to 6.9 during follow-up. Flexible cystoscopy was superior over rigid in four subdomains: uncomfortable urge to urinate (p = 0.04), sudden urge to urinate with little or no warning (p = 0.02), uncontrollable urge to urinate (p = 0.03), and urine loss associated with a strong desire to void (p = 0.009). CONCLUSION: OAB-symptoms are common in patients undergoing cystoscopy. Cystoscopy itself can cause de-novo OAB-symptoms. Controversially, a decline of OAB-symptoms was noted after cystoscopy when patients were screened OAB-positive before cystoscopy. Flexible scopes were superior in some subdomains.

Metastasectomy in patients with renal cell carcinoma: when and how?

PURPOSE OF REVIEW: The role of metastasectomy in the management of metastatic renal cell carcinoma (mRCC) remains controversial. The aim of this review is to summarize and evaluate the recent findings about the surgical treatment of patients with mRCC focusing on the literature published in the last 2 years. RECENT FINDINGS: Despite the lack of randomized controlled trials, the benefit of metastasectomy in term of cancer-specific and overall survival have been demonstrated in large observational studies. Results of ongoing clinical trials evaluating the impact of combination of surgical and systemic therapies are eagerly awaited and may shed the light on a new treatment armamentarium in this subset of patients. SUMMARY: Several novel systemic agents have emerged and is continuously changing the treatment paradigm in patients with advanced RCC. However, surgical resection of the primary tumor and metastatic deposits represents a definitive cure option in well selected patients.

Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study.

PURPOSE: To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0-3, with BAP1 loss defined as an average intensity of < 1. Clinicopathologic characteristics and oncologic outcomes [recurrencefree (RFS), cancer-specific (CSS), and overall survival (OS)] were stratified by BAP1 status. The prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p < 0.05. RESULTS: 348 patients were included for analysis and 173 (49.7%) showed BAP1 loss. Median follow-up was 36.0 months. BAP1 loss was associated with papillary architecture and absence of tumor necrosis or CIS. On univariable analysis, BAP1 loss was associated with improved RFS (HR 0.60, p = 0.013) and CSS (HR 0.55, p = 0.007), although significance was lost on multivariable analysis (HR 0.71, p = 0.115 and HR 0.65, p = 0.071; respectively) after adjusting for other significant parameters. BAP1 expression was not significantly associated with OS. CONCLUSIONS: BAP1 loss was associated with favorable pathologic features and better oncologic outcomes in univariate but not multivariate analysis in patients with high-grade UTUC. In contrast to renal cell carcinoma, loss of BAP1 expression appears to confer a better prognosis in high-grade UTUC. The role of the BAP1 pathway in UTUC pathogenesis remains to be further elucidated.

Postmicturition Dribble: A Physiological Phenomenon?

BACKGROUND: Postmicturition dribble (PMD) is a common condition in the male population. OBJECTIVES: Despite its common occurrence, there are only a few studies on this topic so far. The aim of this study was to investigate possible physiological aspects of PMD. METHOD: Seventeen men complaining of PMD and 10 healthy subjects were assessed via uroflometry, IPSS questionnaire, IIEF-5 questionnaire, and an adapted visual analogue scale (VAS) for ejaculation force -(0-10) and the amount of bother concerning PMD (0-10) were completed. In addition to that, a retrograde urethrography at 40 and 60 cm water column as pressure unit to measure the width of the bulbar urethra was performed, and the amount of PMD was measured with an adjusted pad test. RESULTS: The PMD group showed a significantly worse IPSS score, a lower Qmax rate in uroflowmetry, a worse IIEF-5 score, and a worse VAS score concerning ejaculation force. In both groups, worse IPSS levels correlated with a low bulbar urethral diameter at 40 and 60 cm water column. -Another correlation was found between a high maximum urine flow rate and a larger bulbar urethral diameter at 40 and 60 cm. Both groups showed urine loss after micturition, with no bother (VAS 0) in the control group, whereas the PMD group showed a VAS of 6. CONCLUSIONS: PMD should be regarded as a physiological occurrence in men rather than a disease by itself. Suffering is only to be expected in combination with other lower urinary tract symptoms.

Focal therapy of prostate cancer.

PURPOSE OF REVIEW: The aim of this study was to summarize the latest evidence, as well as the rationale behind using focal therapy for the treatment of prostate cancer. With patients becoming more educated, knowledge of the available evidence is key when discussing treatment. RECENT FINDINGS: In older works, the natural history of prostate cancer has been described as being multifocal, driven by one index lesion. This represents the key argument for most experts, why focal therapy is feasible in prostate cancer. Most modalities have similar results. For high-intensity focussed ultrasound (HIFU), a pooled data analysis with a median follow-up of 2.2 years showed a negative biopsy rate of 77% with a salvage therapy free rate of 92%. A matched pair analysis comparing irreversible electroporation with robot-assisted radical prostatectomy showed a better side effect profile for focal therapy in evenly matched groups, yet with worse disease-free survival. Interestingly, the better outcomes concerning continence and erectile function did not translate into better patient-reported outcomes. SUMMARY: Focal therapy modalities are generally well tolerated and show good results in terms of continence and potency. Long-term follow-up is not available, and inclusion criteria for trials are not yet uniform. Newer technologies, such as photodynamic therapy, are being developed, as well as improvements to older techniques, such as HIFU.

Prostate biopsy: guidelines and evidence.

PURPOSE OF REVIEW: To summarize the highest level evidence that was acquired within the last years, with regard to diagnosis of prostate cancer. With many secondary diagnostic tools becoming available, and not being mentioned in the guidelines, this review is meant to assist clinical decision-making in initial biopsy and rebiopsy settings. RECENT FINDINGS: The PROMIS Trial delivered level 1b evidence about the diagnostic accuracy of prostate multiparametric MRI (mpMRI) as a triage tool for prostate biopsy. MRI-ultrasound-fusions-targeted biopsy has been evaluated and compared with the standard of care, and has been found to have a higher cancer detection rate. The different approaches to MRI-guided biopsies do not show significant differences. Urine biomarkers analysing RNA as well as genetic assays of biopsy specimen have also shown to be helpful in the decision to (re-)biopsy a patient, especially in combination with MRI. SUMMARY: Patients and doctors alike have been trying to avoid prostate biopsies, the risks, and the side effects of potential overtreatment. Imaging and other biomarkers are used to increase diagnostic accuracy, yielding more precise information to act on. None of these secondary diagnostic tools are perfect, yet they can, and should be used if one stays aware of their limitations.

The evolving role of percutaneous biopsy in renal masses.

PURPOSE OF REVIEW: To review the current literature concerning the role of biopsy for renal masses. RECENT FINDINGS: Improvements in biopsy techniques lead to a redefinition of the role of renal mass biopsy (RMB).Additionally, several studies highlighted the safety, high diagnostic accuracy, and very low rate of clinically relevant complications of RMB. As the knowledge about the nature of renal masses has expanded, and management options for small renal masses are increasing, the current indications for RMB and its role for the management of small renal masses are also expanding. SUMMARY: The future role of RMB will be influenced by the combination of pathological, molecular, and genetic information that will, heighten and improve our knowledge about these lesions and set the stage for risk-adapted personalized medicine.

Postoperative Nomogram for Relapse-Free Survival in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: We developed a prognostic nomogram for patients with high grade urothelial carcinoma of the upper urinary tract after extirpative surgery. MATERIALS AND METHODS: Clinical data were available for 2,926 patients diagnosed with high grade urothelial carcinoma of the upper urinary tract who underwent extirpative surgery. Cox proportional hazard regression models identified independent prognosticators of relapse in the development cohort (838). A backward step-down selection process was applied to achieve the most informative nomogram with the least number of variables. The L2-regularized logistic regression was applied to generate the novel nomogram. Harrell's concordance indices were calculated to estimate the discriminative accuracy of the model. Internal validation processes were performed using bootstrapping, random sampling, tenfold cross-validation, LOOCV, Brier score, information score and F1 score. External validation was performed on an external cohort (2,088). Decision tree analysis was used to develop a risk classification model. Kaplan-Meier curves were applied to estimate the relapse rate for each category. RESULTS: Overall 35.3% and 30.7% of patients experienced relapse in the development and external validation cohort. The final nomogram included age, pT stage, pN stage and architecture. It achieved a discriminative accuracy of 0.71 and 0.76, and the AUC was 0.78 and 0.77 in the development and external validation cohort, respectively. Rigorous testing showed constant results. The 5-year relapse-free survival rates were 88.6%, 68.1%, 40.2% and 12.5% for the patients with low risk, intermediate risk, high risk and very high risk disease, respectively. CONCLUSIONS: The current nomogram, consisting of only 4 variables, shows high prognostic accuracy and risk stratification for patients with high grade urothelial carcinoma of the upper urinary tract following extirpative surgery, thereby adding meaningful information for clinical decision making.

Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. RESULTS: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). CONCLUSIONS: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.

Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of low-risk upper tract urothelial carcinoma.

INTRODUCTION: The conservative management of upper tract urothelial carcinoma (UTUC) has historically been offered to patients with imperative indications. The recent International Consultation on Urologic Diseases (ICUD) publication on UTUC stratified treatment allocations based on high- and low-risk groups. This report updates the conservative management of the low-risk group. METHODS: The ICUD for low-risk UTUC working group performed a thorough review of the literature with an assessment of the level of evidence and grade of recommendation for a variety of published studies in this disease space. We update these publications and provide a summary of that original report. RESULTS: There are no prospective randomized controlled studies to support surgical management guidelines. A risk-stratified approach based on clinical, endoscopic, and biopsy assessment allows selection of patients who could benefit from kidney-preserving procedures with oncological outcomes potentially similar to radical nephroureterectomy with bladder cuff excision, with the added benefit of renal function preservation. These treatments are aided by the development of high-definition flexible digital URS, multi-biopsies with the aid of access sheaths and other tools, and promising developments in the use of adjuvant topical therapy. CONCLUSIONS: Recent developments in imaging, minimally invasive techniques, multimodality approaches, and adjuvant topical regimens and bladder cancer prevention raise the hope for improved risk stratification and may greatly improve the endoscopic treatment for low-risk UTUC.

HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC).

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.

Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study.

PURPOSE: To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients. METHODS: Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %). RESULTS: Decreased E-cadherin expression was observed in 353 patients (52.1 %) and was associated with advanced pathological stage (P < 0.001), higher grade (P < 0.001), lymph node metastasis (P = 0.006), lymphovascular invasion (P < 0.001), concomitant carcinoma in situ (P < 0.001), multifocality (P = 0.004), tumor necrosis (P = 0.020) and sessile architecture (P < 0.001). Within a median follow-up of 30 months (interquartile range 15-57), 171 patients (25.4 %) experienced disease recurrence and 150 (21.9 %) died from UTUC. In univariable analyses, decreased E-cadherin expression was significantly associated with worse recurrence-free survival (P < 0.001) and cancer-specific survival CSS (P = 0.006); however, in multivariable analyses, it was not (P = 0.74 and 0.84, respectively). The lack of independent prognostic value of E-cadherin remained true in all subgroup analyses. CONCLUSION: In UTUC patients treated with RNU, decreased E-cadherin expression is associated with features of biologically and clinically aggressive disease and worse outcome in univariable, but not multivariable, analyses. If E-cadherin's association with factors of advanced disease is confirmed on UTUC biopsy specimens, it could be used to help in the clinical decision-making regarding kidney-sparing approaches and/or neo-adjuvant chemotherapy.

Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

OBJECTIVE: To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT). METHODS: A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis. RESULTS: One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7-24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16-1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16-1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS. CONCLUSIONS: Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.