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Abstract: Objective: ABO blood type is an inherited characteristic that has been associated with the prognosis of several malignancies, but there is little evidence in urothelial carcinoma of the bladder (UCB). The purpose of this study was to evaluate the effect of ABO blood type on mortality in patients with UCB treated with radical cystectomy (RC). Methods: Multi-institutional data from 7,906 patients with UCB treated with RC between 1979 and 2012 were retrospectively analyzed. The effect of ABO blood type on UCB-related mortality was evaluated with univariable and multivariable competing-risks regression models. Results: ABO blood type was O in 3,728 (47%), A in 2,748 (35%), B in 888 (11%), and AB in 532 (7%) patients. Blood type B was associated with a greater likelihood of lymphovascular invasion (P = 0.010) and positive soft tissue margins (P = 0.008). The median follow-up was 41 months. The 5-year cumulative UCB-related mortality rates for blood type O, A, B, and AB were 29.5%, 30.5%, 33.2%, and 25.8%, respectively. In univariable competing-risks regression, patients with blood type B had worse UCB-related mortality than those with blood type O (P = 0.026) and AB (P = 0.020). In multivariable analysis, however, blood type lost its statistical significance. Conclusions: Among patients treated with RC, ABO blood type is associated with a statistically significant but clinically insignificant difference in UCB-related mortality. This association was not present in multivariable analysis. Our data therefore suggest no relevant association of ABO blood type with UCB-related prognosis. [Copyright &y& Elsevier]

Abstract: Objectives: To analyze pathobiology and prognosis of chromophobe renal cell carcinoma (CRCC). Patients and methods: We studied 124 patients with CRCC who underwent nephrectomy from 1989 to 2006 at two institutions. Clinicopathological characteristics and survival were compared with 1,693 consecutive patients with clear-cell RCC. Results: Compared with clear cell RCC, patients with CRCC presented with less advanced tumors, but had a higher prevalence of concomitant sarcomatoid features (15% vs. 6%, P < 0.001). Metastatic CRCC showed a high incidence of sarcomatoid features (50%) and a predilection for liver metastases. The 5-year DSS rate for all patients with CRCC was 78% compared with 60% for patients with clear-cell RCC (P = 0.008). When adjusted for metastatic status, this survival difference disappeared. Nonmetastatic RCCs had similar prognosis (P = 0.157), whereas survival of metastatic CRCC was inferior to that of patients with metastatic clear-cell tumors (median: 6 vs. 19 months, P = 0.0095). In multivariate analysis, ECOG PS, symptomatic presentation, T stage, N stage, M stage, nuclear grade, and presence of sarcomatoid features, but not histological sub-type, were independent prognostic factors of DSS. Ten patients received immunotherapy, none of whom were responders. Conclusions: Compared with clear-cell RCC, patients with CRCC present with less advanced tumors, which lead to better survival rates on the whole. However, adjustment for metastatic status negates this difference. Patients with metastatic CRCC show a high prevalence of sarcomatoid features, predilection for liver metastases, no response to immunotherapy, and exhibit poor prognosis. [Copyright &y& Elsevier]

Abstract: Patient''s history, physical examination, laboratory tests, and radiographic evaluation are the cornerstones of postoperative surveillance. It has been shown that localized renal cell carcinoma (RCC) can recur in nearly all organs of the body, but most commonly in the lung, bone, liver, brain, and renal fossa. Lung metastases can be sensitively detected through radiographic evaluation. Treatment of lung metastases might prolong survival, which supports surveillance x-ray or computed tomography scans. Surgical treatment of early detected liver metastases and local recurrences may also prolong survival, which supports a close abdominal surveillance program. Brain and bone metastases are usually symptomatic when they occur, and their treatment is generally palliative. Hence, surveillance protocols do not usually include their routine radiographic evaluation. Because partial nephrectomy does not increase the risk of local recurrence over radical nephrectomy, we recommend identical surveillance for completely resected tumors regardless of surgical approach. The risk of recurrence after nephrectomy is generally related to tumor stage, tumor grade, and patient performance status. The majority of recurrences occur within the first 5 years after surgery, supporting a more intense surveillance strategy within the first 5 years. The University of California Integrated Staging System (UISS) combines TNM stage, Fuhrman grade, and performance status, and categorizes patients into 3 different risk groups. The current surveillance protocol at our institution is based on the UISS. It is expected that molecular markers such as p53 will allow more individualized surveillance strategies in the future. [Copyright &y& Elsevier]

Abstract: The treatment of renal tumors with the technique of partial nephrectomy continues to evolve. The relevant literature reviewed confirmed the excellent oncological outcomes associated with partial nephrectomy in properly selected patients. In addition, much data is being accumulated regarding the safety and efficacy of this technique via a laparoscopic approach. With either approach, the chance for renal preservation would appear to be a major benefit while “non-hilar” clamping techniques during the open approach may maximize the likelihood for maintenance of long-term renal function. [Copyright &y& Elsevier]

Objective: Several small single-center studies have reported conflicting results on the prognostic value of survivin expression in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy. We attempted to validate the prognostic utility of survivin using a large multi-institutional cohort.Material and Methods: Survivin expression was evaluated by immunohistochemistry in tumor tissue from 732 patients with unilateral, sporadic UTUC treated with radical nephroureterectomy between 1990 and 2008 at 7 centers. Survivin expression was considered altered when at least 10% of the tumor cells stained positive. Associations of altered survivin expression with recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Cox proportional hazards regression models.Results: Altered survivin expression was observed in 288 (39.3%) tumors and was associated with more advanced pathological tumor stages (P<0.001), lymph node metastases (P<0.001), lymphovascular invasion (P<0.001), tumor necrosis (P = 0.027), and tumor architecture (P<0.001). Median follow-up was 35 (16-64) months. There were 191 (25.4%) patients who experienced disease recurrence, and 165 patients (21.9%) died of the disease. In the univariable analysis, altered survivin expression was significantly associated with worse RFS and CSS (each P<0.001); however, altered survivin expression did not achieve independent predictive status on multivariable models (P = 0.24 and P = 0.53). Similarly, survivin was not independently associated with outcomes in subgroup analyses, including patients with high-grade tumors.Conclusions: In UTUC, altered survivin expression is associated with worse clinicopathological features and worse RFS and CSS. However, it does not appear to be independently associated with cancer outcomes when considering standard prognostic factors. [ABSTRACT FROM AUTHOR]

Introduction Partial nephrectomy (PN) is the standard therapy for small renal masses. Resection margin assessment continues to be a key issue during PN. Biopsy of the residual kidney and intraoperative gross pathological consultations are the most common methods today. Intraoperative imprint cytology (IC) examinations have been successfully used in other tumor entities to assess surgical margins. We aim to evaluate the diagnostic value of intraoperative IC for surgical margin assessment during PN. Materials and methods In addition to routinely performed frozen-section (FS) analysis, intraoperative IC examinations were performed on 114 tumors, which were resected with PN in our department between 2005 and 2010. These 2 were then matched with final histopathological examination findings. Before FS, roll-off IC slides were obtained, air dried, and stained by Hemacolor quick staining. Both the pathologist and the cytologist were blinded to the findings. Results Our study included 29 women and 76 men. Of 331 IC slides, 317 (96%) contained sufficient diagnostic cells. IC revealed 21 tumors with positive resection margins. Of the 21 positive resection margins, 2 were false positives. IC showed a specificity of 98%, sensitivity of 100%, a positive predictive value of 90%, and negative predictive value of 100%. FS examinations revealed positive resection margins in 20 tumors. One of these 20 margins was false positive. Furthermore FS examination failed to diagnose a positive resection margin in 1 tumor. FS examination showed a specificity of 99% and sensitivity of 98% in assessing surgical margins with a positive predictive value of 95% and negative predictive value 98%. Conclusion IC examinations exhibit equivalent diagnostic value compared with FS analysis. IC is an inexpensive method with an ability to give rapid and highly accurate information. Like any cytological examination, there is interobserver variability. IC could be considered as an alternative to FS especially when the nature of resection margins is suspected but further investigations are necessary. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Gender-specific differences in incidence of renal cell carcinoma (RCC) and its outcome have previously been reported. We used age as a surrogate to test whether this might be hormone-related in a large international RCC cohort. Methods and Materials: This study included patients treated by nephrectomy at 10 international academic centers. Clinicopathologic features were assessed using chi-square and the Student t-tests. Kaplan-Meier survival estimates and Cox proportional hazards models addressed the effect of gender and age on disease-specific survival. Results: Of the 5,654 patients, 3,777 (67%) were men and 1,877 (33%) were women. Generally, women presented at lower T stages (P<0.001), had fewer metastases (P<0.001), and had lower-grade tumors (P<0.001). Women more frequently had clear-cell (87% vs. 82%) and less frequently had papillary RCC (7% vs. 12%) than men (P<0.001). Women had a 19% reduced risk of death from RCC than men (hazard ratio 0.81, 95% confidence interval 0.73–0.90, P<0.001). The survival advantage for women was present to the greatest degree in the age group<42 years (P = 0.0136) and in women aged 42 to 58 years (P<0.001), but was not apparent in patients aged 59 years and older (P = 0.248). Age was an independent predictor of disease-specific survival in women (hazard ratio 1.011, 95% confidence interval 1.004–1.019, P = 0.004), but not in men. Conclusions: As a group, women present with less advanced tumors, leading to a 19% reduced risk of RCC-specific death compared with men. This survival difference is present only in patients aged<59 years. Because this gender-based survival difference is not related to pathologic features, the role of hormonal effects on the development and progression of RCC needs to be investigated. [Copyright &y& Elsevier]

• Evidence has shown controversial results between radical and partial nephrectomy. • Partial nephrectomy shows a decrease risk of early-stage chronic kidney disease. • Partial nephrectomy demonstrated a protective effect on cardiovascular events. • Benefit of partial nephrectomy is not maintained in advanced chronic kidney disease. This systematic review and meta-analysis aimed to evaluate the postoperative renal and cardiovascular outcomes of partial nephrectomy (PN) versus radical nephrectomy (RN) for the treatment of renal carcinoma. A systematic literature search was performed on scientific databases including Scopus, Web of Science, MEDLINE, and EMBASE from their inception to September 2021. Studies comparing renal and cardiovascular outcomes between PN and RN in patients with renal cancer were included. The generic inverse variance method with random-effects models was used to determine the pooled hazard ratios and odds ratio for each outcome. Quality Assessment for observational studies was guided by the New-Castle Ottawa Scale. Overall, a total of 31 studies (n=51,866) reported renal outcomes, while 11 studies (n= 101,678) reported cardiovascular outcomes. When compared to PN, RN had a higher rate of new-onset postoperative EGFR <60 mL/min/1.73 m2 (HR 3.39; CI 2.45 - 4.70; I2=93%; P=<0.00001) and EGFR <45 mL/min/1.73 m2 (HR 4.70; CI 2.26 - 9.79; I2=98%; P=<0.0001). No difference was observed in new-onset advanced kidney disease and end-stage renal disease. A 19% reduction in cardiovascular events was observed in the PN group (HR 0.81; CI 0.70 - 0.93, P=0.002). No protective effect of PN was observed in new-onset or worsening hypertension (HR 0.85; CI 0.64 - 1.14, P=0.28) nor myocardial infarction (HR 0.86; CI 0.71 - 1.04, P=0.13). PN was associated with a decreased risk of postoperative early-stage CKD and cardiovascular events compared with RN. However, no benefit of PN over RN was observed in advanced CKD, new-onset or worsening hypertension, myocardial infarction, and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

• The prognostic role of histomorphological subtyping in papillary renal cell carcinoma (papRCC) is an issue of debate due to previously reported controversial outcomes. • Type 2 is found to be associated with advanced nuclear grade, pT and pN stages in this study. • Type 2 is found to predict worse recurrence free- and cancer specific survival. • Histomorphological subtyping is relevant from the point of prognostic view. • It may guide follow-up after curative surgery and selection of adjuvant treatment candidates. The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33–2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20–3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92–1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16–2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91–2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68–1.48]; P = 0.981) This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view. [ABSTRACT FROM AUTHOR]

Purpose: Overexpression of Caveolin-1 has been associated with cancer growth, migration, and metastases in several malignancies, but only few data are available on its role in bladder cancer (BCa). The aim of this study is to validate Caveolin-1 as a prognosticator of recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) in a large cohort of patients treated with radical cystectomy (RC) for BCa.Methods: Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray from 424 patients treated with RC for UCB at a single institution. Caveolin-1 was considered overexpressed when at least 50% of the tumor cells stained positively. Univariable and multivariable Cox proportional hazards regression models were used to assess the association of Caveolin-1 expression with RFS, OS, and CSS.Results: Overexpression of Caveolin-1 was observed in 116 (27.4%) patients and was associated with lymph node metastasis (P = 0.003). Median follow-up for patients alive at last follow-up was 129 months (interquartile range [IQR]: 82-178). Patients with overexpression of Caveolin-1 had significant worse RFS, OS, and CSS compared to those with normal expression (log-rank test, P = 0.008, P = 0.001, and P = 0.005, respectively). At multivariable analyses that adjusted for the effects of standard clinicopathologic features, Caveolin-1 remained associated with OS (hazard ratio = 1.47, P = 0.002) and CSS (hazard ratio = 1.42, P = 0.03). Conversely, no association with RFS was found (P = 0.1). Addition of Caveolin-1 in a model for prediction of survival did not improve the accuracy of the prognostic model. Actually, C-index did not differ among models with or without Caveolin-1 (0.72 for a model predicting RFS, 0.65 for OS, and 0.71 for CSS).Conclusions: Caveolin-1 is overexpressed in one-third of patients with BCa treated with RC. Overexpression of Caveolin-1 is significantly associated with OS and CSS, but not with RFS, in patients with BCa treated with RC. However, it is not clinically useful as it does not improve upon the predictive accuracy of survival achieved by pathologic variables alone. [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]

Introduction: The impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern.Material and Methods: This is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed.Results: After matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18-3.58, P-value = 0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01-1.16; P-value = .04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64-1.06; P-value = .14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study.Conclusions: The risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS. [ABSTRACT FROM AUTHOR]

Objective: Recently, VENUSS (VEnous extension, NUclear Grade, Size, Stage), as a prognostic model, was defined to predict disease recurrence (DR) after curative surgery of non-metastatic papillary renal cell carcinoma (papRCC). This study aimed to validate the VENUSS prognostic model in a large multi-institutional European cohort of patients with histopathologically proven papRCC after curative surgery for non-metastatic disease.Patients and Methods: Overall, 980 patients undergoing partial or radical nephrectomy for sporadic, unilateral and non-metastatic papRCC between 1987 and 2020 were included from 7 European tertiary institutions. The primary outcome was the prediction of DR by VENUSS score and VENUSS risk groups. Chi-square, Kruskal-Wallis, Cox-regression and Kaplan-Meier survival analyses were used in statistical methods. The Concordance (C) Index was calculated to assess model's discriminatory power.Results: The median age was 64 (IQR:55-70) years and 82.6 % (n = 809) of patients were male. Median VENUSS score was 2 (IQR: 0-4), and 62.9 % (n = 617), 23.9 % (n = 234) and 13.2 % (n = 129) of patients was classified into low, intermediate and high risk according to the VENUSS model, respectively. At a median follow-up of 48 (IQR:23-88) months, the disease recurred in 6.6%, 18.8% and 63.8%, and the 5-year recurrence-free survival was 93.8%, 80.7% and 26.7% in low, intermediate and high-risk groups, respectively. (P < 0.001) Each increase in VENUSS score had 1.52-fold (95%CI:1.45-1.60, P < 0.001) DR risk. Compared with the VENUSS low risk, the intermediate risk had a 2.91-fold increased DR risk (95%CI:1.90-4.46, P < 0.001) and 17.9-fold (95%CI:12.25-26.25, P < 0.001) in high risk, while it was 6.07-fold greater in high risk vs. intermediate risk (95%CI:4.17-8.83, P < 0.001). The discrimination was 81.2% (95%CI:77.5%-84.8%) for the VENUSS score, and 78.6% (95%CI:74.8%-82.4%) for VENUSS risk groups, respectively. Both the VENUSS score and groups were well calibrated.Conclusions: This contemporary multi-institutional European large dataset validated the use of VENUSS score and VENUSS risk groups on the prediction of DR after curative surgery in patients with non-metastatic papRCC. The VENUSS prognostic model can provide valuable information for patient counselling, follow-up and patient selection for adjuvant trials. [ABSTRACT FROM AUTHOR]

Introduction: Bladder cancer (BC) is diagnosed by cystoscopy, which is invasive, costly and causes considerable patient discomfort. MicroRNAs (miR) are dysregulated in BC and may serve as non-invasive urine markers for primary diagnostics and monitoring. The purpose of this study was to identify a urinary miR signature that predicts the presence of BC.Methods: For the detection of potential urinary miR markers, expression of 384 different miRs was analyzed in 16 urine samples from BC patients and controls using a Taqman™ Human MicroRNA Array (training set). The identified candidate gene signature was subsequently validated in an independent cohort of 202 urine samples of patients with BC and controls with microscopic hematuria. The final miR signature was developed from a multivariable logistic regression model.Results: Analysis of the training set identified 14 candidate miRs for further analysis within the validation set. Using backward stepwise elimination, we identified a subset of 6 miRs (let-7c, miR-135a, miR-135b, miR-148a, miR-204, miR-345) that distinguished BC from controls with an area under the curve of 88.3%. The signature was most accurate in diagnosing high-grade non-muscle invasive BC (area under the curve = 92.9%), but was capable to identify both low-grade and high-grade disease as well as non-muscle and muscle-invasive BC with high accuracies.Conclusions: We identified a 6-gene miR signature that can accurately predict the presence of BC from urine samples, independent of stage and grade. This signature represents a simple urine assay that may help reducing costs and morbidity associated with invasive diagnostics. [ABSTRACT FROM AUTHOR]

Objective: Due to lacking external validation, molecular biomarkers are currently not applied for risk-stratification of patients with localized renal cell carcinoma. The objective of this study was to externally validate a molecular multi-marker panel included in a previously proposed prognostic nomogram for the prediction of postoperative disease-free survival.Methods and Materials: Besides pathologic tumor stage (pT) and ECOG-Performance Status, the nomogram includes 5 molecular markers (Ki-67, p53, VEGFR-1 endothelial or epithelial, and VEGF-D epithelial). The validation cohort comprised 343 renal cell carcinoma patients treated by radical nephrectomy or nephron-sparing surgery from 1999 to 2004 at a single academic center (median follow-up: 100 months). By multivariable Cox proportional-hazards regression models, the impact of clinical and molecular markers included in the nomogram on disease progression (DP) and cancer-specific mortality (CSM) was assessed; in addition, it was evaluated to what extent molecular markers added to the models' predictive accuracy (PA).Results: Of all parameters included in the nomogram, ECOG-PS and pT-stage only revealed a significant impact on both endpoints. p53 (per 10% measures) showed a significant impact on DP (HR = 1.31; P = 0.008), albeit not on CSM, while all other molecular markers did not impact study endpoints. Using Martingale residuals, a cut-off value for p53-expression<20% (negative) vs. ≥20% (positive) yielded the highest impact on DP and CSM. In outcome-models including further well-established histo-pathological factors, p53-expression dichotomized at 20% independently impacted DP (HR = 4.13; P = 0.004) and CSM (HR = 3.74; P = 0.033), while no significant PA gain was achieved.Conclusions: p53 showed a statistically significant impact on DP, albeit not on CSM, when applying the 10% expression cut-off as used in the original nomogram, while the prognostic value of all other examined markers included in the nomogram could not be confirmed. When an alternative cut-off of 20% was applied in multivariable models, p53 independently impacted DP and CSM, while the PA was not significantly enhanced. Hence, the clinical significance of p53 is still to be determined. Based on the results of this study it is not recommendable to use p53-expression and the Klatte nomogram in routine clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: There are no clear data regarding the association between body mass index (BMI) and outcomes after radical prostatectomy (RP). This study aimed to investigate the association between BMI and biochemical recurrence (BCR) after RP in a large international contemporary cohort of patients with prostate cancer.Methods: We retrospectively analyzed data from 6,519 patients who underwent RP at 5 institutions. BMI was analyzed as both a continuous and categorical variable (<25kg/m2, 25-29.9kg/m2 [overweight], and≥30kg/m2 [obese]). The associations of continuous and categorical BMI with BCR were evaluated using univariable and multivariable Cox models, and prognostic accuracy was assessed using Harrell׳s C-index.Results: The median BMI was 28kg/m2 (interquartile range: 24-32kg/m2); 2,155 patients (33.1%) had a BMI = 25 to 29.9kg/m2 and 2,462 patients (37.7%) had a BMI≥30kg/m². Overweight and obese status were associated with extracapsular extension (P = 0.001) and seminal vesicle invasion (P = 0.005). The median follow-up was 28 months, and the estimated 5-year BCR-free survival rates for patients with a BMI<25kg/m2, 25 to 29.9kg/m2, and≥30kg/m² were 92%, 86%, and 79%, respectively (P<0.001). Multivariable analyses (adjusted for preoperative prostate-specific antigen levels, biopsy Gleason score, and clinical stage) revealed that obesity was associated with the risk of extracapsular extension (P<0.001), seminal vesicle invasion (P<0.001), and BCR (hazard ratio: 1.37, P<0.001). BMI and obesity remained associated with BCR after adjusting for postoperative characteristics. Addition of BMI slightly increased the discrimination of the multivariable clinical prognostic model (from 79.9%-80.9%).Conclusions: Overweight and obese status was associated with adverse pathological features and BCR after RP. However, the addition of BMI did not significantly improve the prognostic accuracy of a model that was based on established predictors. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the incidence of carcinoma in situ (CIS) in patients treated with radical cystectomy (RC) due to bladder cancer and to assess its effect on recurrence and survival rates.Methods: The study focused on 1,128 consecutive nonmetastatic patients with bladder cancer treated with RC at a single tertiary care referral center from 1994 to 2014. The Kaplan-Meier method was used to compare recurrence, cancer-specific mortality (CSM), and overall mortality-free rates in the overall population and in pT0-pT2 and pT3-pT4 patients after stratifying according to the presence of CIS. Multivariable (MVA) Cox regression analyses tested the effect of the presence of CIS on survival outcomes. MVA competing risk analyses were performed to assess the effect of CIS on urothelial recurrence.Results: The presence of CIS was reported in 277 (24.6%) patients. During a median follow-up of 6 years, 355 recurrences, 377 CSM, and 468 overall mortality were reported. At MVA Cox regression analyses, the presence of concomitant CIS was not associated with any survival effect when the overall population was considered (all P≥0.3). At MVA Cox regression analyses, there was no effect of CIS on survival outcomes in pT3-pT4 patients (all P>0.2); on the contrary, the presence of CIS was associated with worse CSM in pT0-pT2 patients only (hazard ratio [HR] = 1.82; CI: 1.01-3.29; P = 0.04). At MVA competing risk analyses predicting urothelial recurrence only, the presence of CIS was associated to an increased risk of urothelial recurrence in pT0-pT2 patients (HR = 2.99; CI: 1.05-8.53; P = 0.04), pT3-pT4 patients (HR = 10.29; CI: 1.40-75.75; P = 0.02), and in the overall population (HR = 4.47; CI: 1.81-11.07; P = 0.001).Conclusion: An increased risk of developing urothelial recurrence only was recorded in patients diagnosed with CIS at RC. Physicians should consider this aspect ensuring a more severe follow-up schemes in patients who harbored this pathological feature. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the overexpression of human epidermal growth factor receptor 2 (HER2) in patients with bladder cancer (BCa) and to assess its association with oncological outcomes.Methods: This retrospective single-center study included 354 patients with BCa treated with radical cystectomy (RC). HER2 status was assessed with immunohistochemistry and scored according to HercepTest. Conditional survival and competing risk regression were performed to assess the association between HER2 expression and survival outcomes.Results: HER2 was overexpressed in 36% of patients. HER2 overexpression was associated with features of tumor aggressiveness such as lymph-node metastases (P = 0.002). At a median follow-up of 123 months (interquartile range: 79-180), 160 patients (45%) experienced disease recurrence, 263 patients (74%) died and 157 (44%) died of cancer. On multivariable analyses, HER2 overexpression was not significantly associated with any oncological outcomes. Adding HER2 status to a model for the prediction of survival outcomes did not change the accuracy of the model for any of the outcomes. Interestingly, HER2 status significantly affected late disease recurrence (P = 0.05 for conditional survival at 24 months).Conclusions: More than one third of RC patients overexpress HER2 in their tumors. HER2 overexpression was associated with features of biological and clinical aggressiveness. HER2 did not add prognostic significance to the standard established predictors of survival outcomes after RC. However, due to the high overexpression rate, it could represent a target for therapy in select advanced BCa tumors. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-to-lymphocyte ratio (NLR) and the C-reactive protein (CRP) are markers of systemic inflammatory response, which have been associated with the prognosis of multiple malignancies, but their relationships with oncologic outcomes of non-muscle-invasive bladder cancer (NMIBC) have not been well studied yet.Patients and Methods: We retrospectively reviewed the medical records of 1,117 patients with NMIBC who underwent a transurethral resection of the bladder. Univariable and multivariable competing risk regression models were used to assess the association of preoperative NLR and CRP with disease recurrence and progression to muscle-invasive disease. The median follow-up was 64 months.Results: In total, 360 patients (32.2%) had a high NLR (≥2.5) and 145 (13.0%) had a high CRP (≥5mg/l). On multivariable analyses, a high NLR was associated with both disease recurrence (subhazard ratio [SHR] = 1.27, P = 0.013) and progression (SHR = 1.72, P = 0.007), and high CRP was associated with disease progression (SHR = 1.72, P = 0.031). Adding NLR and CRP to the multivariable model predicting disease progression lead to a relevant change in discrimination (+2.0%). In a subgroup analysis of 300 patients treated with bacillus Calmette-Guerin, both high NLR and high CRP were associated with disease progression (SHR = 2.80, P = 0.026 and SHR = 3.51, P = 0.021, respectively), and NLR was associated with disease recurrence (SHR = 1.46, P = 0.046). There was also an increase in the discrimination of the model predicting progression after bacillus Calmette-Guerin following the inclusion of both markers (+2.4%).Conclusion: In patients with NMIBC, markers of systemic inflammation response are associated with disease recurrence and progression. The inclusion of such markers in prognostic models does enhance their accuracy. [ABSTRACT FROM AUTHOR]

Objective: To validate the impact of lymphovascular invasion (LVI) on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) in a large multiinstitutional cohort.Material and Methods: Retrospective data from 6,678 patients treated with a RP and bilateral lymphadenectomy for prostate cancer (PC) from 8 centers were collected. The primary endpoint was BCR.Results: Overall, 767 patients (11.5%) had LVI. Patients with LVI had significantly higher Gleason scores (P = 0.01). After a median follow-up of 28 months (interquartile range: 21-44), patients with LVI had a 1.66 fold increased risk of BCR (P<0.001). The 1-, 2- and 5-year biochemical recurrence-free survival probabilities for LVI vs. no LVI were 94% vs. 97%, 91% vs. 94%, and 76% vs. 84%, respectively. On multivariable analysis that adjusted for the effects of established prognostic factors, LVI was an independent predictor of BCR (hazard ratio = 1.42, P<0.001). Adding LVI to a multivariable base model increased the discrimination by a small but significant margin (+0.2%, P = 0.0005). In subgroup analyses, LVI remained an independent predictor for BCR in patients with worse pathological features.Conclusions: About 10% of patients with localized PC have LVI on their RP specimen. We confirm that LVI is associated with features of biologic aggressive PC such as high Gleason grade and BCR after RP. Adverse further studies with strict definitions of LVI and longer follow-up periods are needed to determine the prognostic and predictive utility of LVI in the management of PC. [ABSTRACT FROM AUTHOR]

Objective Accurate postoperative stratification of patients with renal cell carcinoma (RCC) in distinct prognostic groups is essential for tailoring follow-up, medical therapy, and inclusion in clinical trials. Increasing evidence suggests that Onodera׳s prognostic nutritional index (PNI) is a stage- and grade-independent predictor of poor outcomes in patients with cancer, but there are no data in RCC. Materials and methods We reviewed medical records of 1,344 patients with RCC who underwent radical or partial nephrectomy at the Medical University of Vienna and the University of California—Los Angeles between 1991 and 2012. Associations with cancer-specific survival were assessed with univariable and multivariable Cox proportional hazards models. Discrimination was measured with the C -index. Results The median postoperative follow-up was 40 months. An increase of PNI by 1 unit was associated with a decrease in the risk of death from RCC by 7% (hazard ratio = 0.93, P <0.001). In multivariable analyses, the PNI was an independent prognostic factor ( P <0.001). Adding the PNI improved the discrimination of a base model by 0.4%. Conclusions The PNI is an independent prognostic factor in patients with RCC. Its use increases the accuracy of established prognostic factors. PNI may be a meaningful adjunct for tailoring surveillance, medical therapy, and clinical trial design. [ABSTRACT FROM AUTHOR]

Objective To validate the biological and prognostic value of tertiary Gleason pattern 5 (TGP5) in patients with Gleason score 7 (GS 7) prostate cancer (PCa) and to develop a prognostic model to identify the high-risk group of patients with TGP5. Material and methods We retrospectively reviewed the data from 4,146 patients with localized (pT2–3 N0 M0) GS 7 PCa treated by radical prostatectomy (RP) without adjuvant therapy. The primary end point was biochemical recurrence (BCR), and the secondary one was to build a bootstrap-corrected multivariable Cox model. Results Of the 4,146 patients, 416 (10%) had a TPG5 in the RP specimen. TGP5 was associated with BCR in both univariable and multivariable analyses that adjusted for the effects of standard pathological features ( P <0.001). A prognostic model based on preoperative prostate-specific antigen levels (<10 vs.≥10 ng/ml), primary and secondary Gleason pattern (3+4 vs. 4+3), pathological tumor category (pT2/pT3a vs. pT3b), and surgical margin status (R0 vs. R+) stratified patients with a discrimination of 72.2%. Patients in the low-risk group had a 5-year BCR-free survival rate of 76.3% compared with only 18.5% for those in the high-risk group ( P <0.001). Conclusions Knowledge of TGP5 improves our prognostication of patients with GS 7 PCa treated with RP. We developed a statistical tool to help identify the patients with TGP5 who are at the highest risk of BCR after RP, thereby helping with the clinical decision making regarding adjuvant trials and follow-up scheduling. [ABSTRACT FROM AUTHOR]