Patient Benefits of Radical Prostatectomy in Certified Prostate Cancer Centers: Comparative Results from the Multicenter IMPROVE Study.

INTRODUCTION: We investigated differences in treatment outcomes following radical prostatectomy (RP) between certified centers (CCs) and noncertified centers (nCCs) within the IMPROVE study group. METHODS: A validated survey assessing various factors, including stress urinary incontinence (SUI) and decision regret (DR), was administered to 950 patients who underwent RP across 19 hospitals (12 CCs and 7 nCCs) at a median follow-up of 15 months after RP (interquartile range: 11-20). The response rate was 74%, with 703 patients participating, including 480 (68%) from CCs. Multivariate binary regression models were used to analyze differences between CCs and nCCs regarding the following binary endpoints: nerve-sparing (NS), positive surgical margins (PSM), SUI (defined as >1 safety pad), complications based on the Clavien-Dindo classification (grade ≥1, grade ≥3) and DR (>15 points indicating critical DR). RESULTS: Considering the multivariate analysis, the rate of NS surgery was lower in CCs than in nCCs (OR = 0.52; p = 0.004). No significant differences were observed in the PSM rate (OR = 1.67; p = 0.051), SUI (OR = 1.03; p = 0.919), and DR (OR = 1.00; p = 0.990). SUI (OR 0.39; p < 0.001) and DR (OR 0.62; p = 0.026) were reported significantly less frequently by patients treated with robotic-assisted RP, which was significantly more often performed in CCs than in nCCs (68.3% vs. 18%; p < 0.001). The total complication rate was 45% lower in CCs (OR = 0.55; p = 0.004), although the number of complications requiring intervention (Clavien-Dindo classification ≥3) did not differ significantly between CCs and nCCs (OR = 2.52; p = 0.051). CONCLUSION: Within the IMPROVE study group, similarly favorable outcomes after RP were found in both CCs and nCCs, which, however, cannot be transferred to the general treatment landscape of PCA in Germany. Of note, robotic-assisted RP was more often performed in CCs and associated with less SUI and DR, while open prostatectomy was the treatment of choice in low-volume nCCs. Future prospective and region wide studies should also investigate the surgeon caseload and experience as well as a spillover effect of the certification process on nCCs.

Patient's Desire and Real Availability Concerning Supportive Measures Accompanying Radical Prostatectomy: Differences between Certified Prostate Cancer Centers and Non-Certified Centers Based on Patient-Reported Outcomes within the Cross-Sectional Study Improve.

Certification as a prostate cancer center requires the offer of several supportive measures to patients undergoing radical prostatectomy (RP). However, it remains unclear how patients estimate the relevance of these measures and whether the availability of these measures differs between certified prostate cancer centers (CERTs) and non-certified centers (NCERTs). In 20 German urologic centers, a survey comprising questions on the relevance of 15 supportive measures was sent to 1000 patients at a median of 15 months after RP. Additionally, patients were asked to rate the availability of these measures using a four-item Likert scale. The aim of this study was to compare these ratings between CERTs and NCERTs. The response rate was 75.0%. In total, 480 patients underwent surgery in CERTs, and 270 in NCERTs. Patients rated 6/15 supportive measures as very relevant: preoperative medical counselling concerning treatment options, a preoperative briefing answering last questions, preoperative pelvic floor exercises (PFEs), postoperative PFEs, postoperative social support, and postoperative rehabilitation addressing physical fitness recovery. These ratings showed no significant difference between CERTs and NCERTs (p = 0.133-0.676). In addition, 4/9 of the remaining criteria were rated as more detailed by patients in CERTs. IMPROVE represents the first study worldwide to evaluate a patient-reported assessment of the supportive measures accompanying RP. Pertinent offers vary marginally between CERTs and NCERTs.

Patients Regret Their Choice of Therapy Significantly Less Frequently after Robot-Assisted Radical Prostatectomy as Opposed to Open Radical Prostatectomy: Patient-Reported Results of the Multicenter Cross-Sectional IMPROVE Study.

Patient's regret (PatR) concerning the choice of therapy represents a crucial endpoint for treatment evaluation after radical prostatectomy (RP) for prostate cancer (PCA). This study aims to compare PatR following robot-assisted (RARP) and open surgical approach (ORP). A survey comprising perioperative-functional criteria was sent to 1000 patients in 20 German centers at a median of 15 months after RP. Surgery-related items were collected from participating centers. To calculate PatR differences between approaches, a multivariate regressive base model (MVBM) was established incorporating surgical approach and demographic, center-specific, and tumor-specific criteria not primarily affected by surgical approach. An extended model (MVEM) was further adjusted by variables potentially affected by surgical approach. PatR was based on five validated questions ranging 0−100 (cutoff >15 defined as critical PatR). The response rate was 75.0%. After exclusion of patients with laparoscopic RP or stage M1b/c, the study cohort comprised 277/365 ORP/RARP patients. ORP/RARP patients had a median PatR of 15/10 (p < 0.001) and 46.2%/28.1% had a PatR >15, respectively (p < 0.001). Based on the MVBM, RARP patients showed PatR >15 relative 46.8% less frequently (p < 0.001). Consensual decision making regarding surgical approach independently reduced PatR. With the MVEM, the independent impact of both surgical approach and of consensual decision making was confirmed. This study involving centers of different care levels showed significantly lower PatR following RARP.

Adherence to the EAU Guideline Recommendations for Local Tumor Treatment in Penile Cancer: Results of the European PROspective Penile Cancer Study Group Survey (E-PROPS).

INTRODUCTION: Penile cancer (PeCa) is an orphan disease in European countries. The current guidelines are predominantly based on retrospective studies with a low level of evidence. In our study, we aimed to identify predictors for guideline-conform treatment and hypothesize that reference centers for PeCa and physicians' experience promote guideline compliance and therefore correct local tumor therapy. METHODS: This study is part of the European PROspective Penile Cancer Study (E-PROPS), an international collaboration group evaluating therapeutic management for PeCa in Central Europe. For this module, a 14-item-survey was developed and sent to 681 urologists in 45 European centers. Three questions focused on therapeutic decisions for PeCa in clinical stage Tis, Ta-T1a, and T1b. Four questions addressed potential personal confounders. Survey results were analyzed by bootstrap-adjusted stepwise multivariate linear regression analysis to identify predictors for EAU guideline-conform local treatment of PeCa. RESULTS: For local therapy of cTis 80.4% recommended guideline-conform treatment, for cTa-cT1a 87.3% and for cT1b 59.1%. In total, 42.4% chose a correct approach in all tumor stages. The number of PeCa patients treated at the hospital, a higher level of training of the physicians, resource-based answering and the option of penile-sparing surgery offered at the hospital matched with giving guideline-conform recommendations and thus accurate local tumor treatment. CONCLUSION: Patients with PeCa are best treated by experienced physicians, in centers with a high number of cases, which also offer a wide range of local tumor therapy. This could be offered in reference centers.

[Differences between the inpatient complication rate after ureterorenoscopy and the 30-day outcome reported by the patient - results of the German prospective BUSTER study]. / Unterschiede zwischen der stationären Komplikationsdichte nach einer Ureterorenoskopie und dem durch Patienten berichteten 30 Tages-Outcome ­ Ergebnisse der deutschen prospektiven BUSTER-Studie.

BACKGROUND: Following ureterorenoscopic stone removal (URS), patients are generally discharged after a short hospital stay, so that the estimation of complication rates is based on a narrow timeframe. Data derived from the so-called BUSTER-project (Evaluation of ureterorenoscopic stone management - results in terms of complications, quality of life and stone-free rates) were therefore analysed with respect to complication rates during hospital stay and patient-reported 30-day-complication rates and then correlated with quality of life (QoL) data. METHODS: Data of 307 patients undergoing URS were recorded in 14 German centres 01/2015 - 04/2015. Complications (classified according to the Clavien-Dindo classification, CDG) and data on QoL were additionally assessed 30 days after surgery, using questionnaires which were completed by 169/307 patients. The subgroups were analysed: no increase in CDG 30 days after surgery (n = 128), increase in CDG without any additional intervention (n = 39), and increase in CDG with an additional intervention (n = 2). The correlation between this categorisation and data on QoL were analysed by bivariate correlations according to Spearman's rank correlation coefficient (ρ). The impact of different clinic parameters on the endpoint "increase in CDG 30 days after surgery" was evaluated by a multivariate logistic regression model. RESULTS: During hospital stay, complications occurred in 13 patients (7.7 %, mostly CDG1). 30 days after surgery, 43 patients (25.4 %) reported complications (16 CDG2 and 2 CDG3). A statistically significant correlation was shown between an increase in CDG and all aspects of QoL, with the strongest correlation concerning pain (ρ = 0.425; p < 0.001). Stone size was the only factor associated with an independent impact on the endpoint "increase in CDG 30 days after surgery" (OR: 1.09; 95 % confidence interval [CI] 1.01 - 1.17; p = 0.040). Postoperative ureteral stenting had no significant impact on this endpoint, despite a remarkable odds ratio (OR: 4.19; 95 % CI 0.64 - 27.32; p = 0.134). This might be explained by a significantly imbalanced distribution of this covariate (86.4 % postoperative stenting). CONCLUSIONS: Assessment of complications should exceed the timeframe of hospital stay, as complications increased within 30 days of surgery and were associated with impairment of QoL. Further studies have to evaluate if lower complication rates and better QoL might be achieved by abstaining from postoperative ureteral stenting.

Matched-pair analysis of renal function in the immediate postoperative period: a comparison of living kidney donors versus patients nephrectomized for renal cell cancer.

PURPOSE: Living kidney donation (LKD) involves little risk for the donor and provides excellent functional outcome for transplant recipients. However, contradictory data exist on the incidence and degree of impaired renal function (IRF) in the donor. Only few studies compared the incidence of IRF in donors with that of patients having undergone radical nephrectomy (RN). METHODS: From 1992 to 2012, 94 healthy subjects underwent an open nephrectomy for living kidney donation at the University Medical Center of Würzburg. These patients were compared with matched subjects who had the same surgical procedure for renal cell carcinoma at the Carl-Thiem Hospital Cottbus (1:1 matching using propensity scores). RESULTS: In the LKD-group, no complication ≥ Grade 3 according to the Clavien-Dindo classification occurred. Donors had a preoperative median estimated glomerular filtration rate (eGFR) of 85.1 ml/min which changed to 54.4, 57.0 and 61.0 ml/min (all p < 0.001 in comparison with baseline) on postoperative days 7-10, 365 and 730, respectively. While median eGFR between LKD- and RN-groups was nearly equal (85.1 vs. 85.3 ml/min; p = 0.786), median immediate postoperative eGFR was significantly lower in the LKD-group (54.3 vs. 60 ml/min; p = 0.002). Furthermore, in LKD, the percentage decrease compared with baseline was significantly higher (34.4 vs. 32 %; p = 0.017). CONCLUSIONS: In living kidney donors, median eGFR decreased by 34.4 % immediately after surgery. Compared with matched RN-patients, immediate postoperative IRF is significantly more pronounced. One explanation may be that in kidney tumor patients, compensatory adaptive filtration activity of the contralateral kidney sets in already preoperatively.

Evaluating the use of prostate-specific antigen as an instrument for early detection of prostate cancer beyond urologists: results of a representative cross-sectional questionnaire study of general practitioners and internal specialists.

OBJECTIVES: The aim of this cross-sectional study was to evaluate the value of prostate-specific antigen (PSA) testing as a tool for early detection of prostate cancer (PCa) applied by general practitioners (GPs) and internal specialists (ISs) as well as to assess criteria leading to the application of PSA-based early PCa detection. METHODS: Between May and December 2012, a questionnaire containing 16 items was sent to 600 GPs and ISs in the federal state Brandenburg and in Berlin (Germany). The independent influence of several criteria on the decision of GPs and ISs to apply PSA-based early PCa detection was assessed by multivariate logistic regression analysis (MLRA). RESULTS: 392 evaluable questionnaires were collected (return rate 65%). 81% of the physicians declared that they apply PSA testing for early PCa detection; of these, 58 and 15% would screen patients until the age of 80 and 90 years, respectively. In case of a pathological PSA level, 77% would immediately refer the patient to a urologist, while 13% would re-assess elevated PSA levels after 3-12 months. Based on MLRA, the following criteria were independently associated with a positive attitude towards PSA-based early PCa detection: specialisation (application of early detection more frequent for GPs and hospital-based ISs) (OR 3.12; p < 0.001), physicians who use exclusively GP or IS education (OR 3.95; p = 0.002), and physicians who recommend yearly PSA assessment after the age of 50 (OR 6.85; p < 0.001). CONCLUSIONS: GPs and ISs frequently apply PSA-based early PCa detection. In doing so, 13% would initiate specific referral to a urologist in case of pathological PSA values too late. Improvement of this situation could possibly result from specific educational activities for non-urological physicians active in fields of urological core capabilities, which should be guided by joint boards of the national associations of urology and general medicine.

Do young patients with renal cell carcinoma feature a distinct outcome after surgery? A comparative analysis of patient age based on the multinational CORONA database.

PURPOSE: We analyzed the distinct clinicopathological features and prognosis of patients with renal cell carcinoma age 40 years or less compared to a reference group of patients 60 to 70 years old. MATERIALS AND METHODS: Overall 2,572 patients retrieved from a multicenter international database comprised of 6,234 patients with surgically treated renal cell carcinoma were included in this retrospective study. Clinical and histopathological features of 297 patients 40 years old or younger (4.8%) were compared to those of 2,275 patients (36.5%) 60 to 70 years old, who served as the reference group. Median followup was 59 months. The impact of young age and further parameters on disease specific mortality and all cause mortality was evaluated by multivariate Cox proportional hazards regression analyses. RESULTS: Young patients more frequently underwent nephron sparing surgery (27% vs 20%, p = 0.008) and regional lymph node dissection compared to older patients (38% vs 32%, p = 0.025). Organ confined tumor stage (81% vs 70%, p <0.001), smaller tumor diameter (4.5 vs 4.7 cm, p = 0.014) and chromophobe subtype (10% vs 4%, p <0.001) were significantly more frequent in young patients. On multivariate analysis older patients had a higher disease specific (HR 2.21, p <0.001) and all cause mortality (HR 3.05, p <0.001). The c indices for the Cox models were 0.87 and 0.78, respectively. However, integration of the variable age group did not significantly increase the predictive accuracy of the disease specific and all cause mortality models. CONCLUSIONS: Young patients with renal cell carcinoma (40 years old or younger) have significantly different frequencies of clinical and histopathological features, and a significantly lower all cause and disease specific mortality compared to patients 60 to 70 years old.

Gender differences in clinicopathological features and survival in surgically treated patients with renal cell carcinoma: an analysis of the multicenter CORONA database.

PURPOSE: To investigate gender differences in clinicopathological features and to analyze the prognostic impact of gender in renal cell carcinoma (RCC) patients undergoing surgery. METHODS: A total of 6,234 patients (eleven centers; Europe and USA) treated by radical or partial nephrectomy were included in this retrospective study (median follow-up 59 months; IQR 30-106). Gender differences in clinicopathological parameters were assessed. Multivariable Cox regression models were applied to determine the influence of parameters on disease-specific survival (DSS) and overall survival (OS). RESULTS: A total of 3,751 patients of the study group were male patients (60.2 %), who were significantly younger at diagnosis and received more frequently NSS than women. Significantly, more often high-grade tumors and simultaneous metastasis were present in men. Whereas tumor size and pTN stages did not differ between genders, clear-cell and chromophobe RCC was diagnosed less frequently, but papillary RCC more often in men. Gender also independently influenced DSS (HR 0.75, p < 0.001) and OS (HR 0.80, p < 0.001) with a benefit for women. However, inclusion of gender in multivariable models did not significantly gain predictive accuracies (PA) for DSS (0.868-0.870, p = 0.628) and OS (0.775-0.777, p = 0.522). Furthermore, no significantly different DSS and OS rates were found in patients undergoing NSS. CONCLUSIONS: This study demonstrates important gender differences in clinicopathological features and outcome of RCC patients with improved DSS and OS for women compared to men, even if solely patients with clear-cell RCC or M0-stage are taken into evaluation. However, inclusion of gender in multivariable models does not significantly gain PA of multivariable models.

Should we abstain from Gleason score 2-4 in the diagnosis of prostate cancer? Results of a German multicentre study.

PURPOSE: The present study analysed the loss of prognostic information related to the abandonment of Gleason score (GS) 2-4 by the International Society of Urological Pathology (ISUP-2005). METHODS: Within a 10-year period prior to the modification of GS, 856 patients (mean age 64.2 years) underwent radical prostatectomy (RP). The grade of agreement between GS in biopsy and definitive histology was calculated by Kappa statistics (κ). Univariable and multivariable influence of different preoperatively available parameters on disease-free survival (DFS) were assessed. The mean follow-up period was 39 months. RESULTS: Concordance between GS in biopsy versus RP samples was 58% (κ-value 0.354) and was improved by an increased number of biopsy cores. Undergrading in biopsy was present in 38% and not significantly enhanced by an extended time-period between biopsy and RP (threshold 90 d). PSA level, clinical tumour stage, fraction of positive cores (dichotomized at 34%), cases of RP per year and institution (dichotomized at 75), and GS independently influenced DFS. An upgrading to GS ≥ 7 was found in only 5.7% of patients presenting with GS 2-4 in the biopsy. Independent from definitive histology, patients with GS 2-4 had a significantly better prognosis compared to patients with a higher GS. CONCLUSIONS: The present study shows an independent prognostic impact of GS in biopsy samples classified according to the previous classification. The elimination of GS 2-4 by the ISUP 2005 results in a considerable loss of pretherapeutic prognostic information and therefore should be questioned in particular with regard to the increasing demand for active surveillance regimens.

Difference between clinical and pathologic renal tumor size, correlation with survival, and implications for patient counseling regarding nephron-sparing surgery.

OBJECTIVE: The aim of the current study was to evaluate the difference between clinical tumor size and pathologic tumor size and the influence of both parameters on cancer-specific survival in patients with renal cell carcinoma. MATERIALS AND METHODS: Clinical tumor size was measured by CT in 834 patients undergoing nephrectomy and was compared with pathologic tumor size. Clinical tumor size and clinical tumor stages were assessed in a central radiologic review. Several variables were analyzed regarding their impact on cancer-specific survival by use of the Kaplan-Meier method, multivariable Cox regression, and receiver operating characteristic analysis. RESULTS: The mean duration of follow-up for patients who were alive at the end of the study (n = 564) was 85 months. The mean clinical and pathologic tumor size was 5.93 and 5.53 cm, respectively (p = 0.005). Of 265 patients with cT1a tumors, only 3.0% (n = 8) had pathologic tumor stage pT3a or higher. In contrast, 15.2% of 317 patients with cT1b tumors had pathologic tumor stage pT2 or higher. Five-year cancer-specific survival according to clinical tumor size was 94% (≤ 4 cm), 83% (4.01-7 cm), and 68% (> 7 cm), respectively (p < 0.001). Multivariable regression analysis revealed that metastasis, sex, age, and clinical tumor size significantly influenced cancer-specific survival. Integration of pathologic tumor size instead of clinical tumor size into multivariable analysis resulted in a reduction of predictive accuracy of 2.3%. CONCLUSION: CT significantly overestimated tumor size in the overall study group, but this overestimation is unlikely to be of clinical importance regarding the decision about radical versus nephron-sparing surgery. However, clinical understaging in 15% of cT1b tumors should be considered in treatment decision making. Clinical tumor size had an independent impact on cancer-specific survival and revealed a higher prognostic value compared with pathologic tumor size.

Impact of body mass index and weight loss on cancer-specific and overall survival in patients with surgically resected renal cell carcinoma.

OBJECTIVE: This study evaluated the impact of body mass index (BMI) and the influence of preoperative weight loss (WL) in each BMI category on survival in patients with surgically treated renal cell carcinoma (RCC). MATERIAL AND METHODS: In total, 834 patients undergoing nephrectomy for RCC were retrospectively reviewed. Overall survival (OS) and cancer-specific survival (CSS) were estimated by Kaplan-Meier analysis. Univariate and multivariate analyses were accomplished to assess the influence of preoperatively assessed clinical parameters, including BMI and WL, on survival. The mean postsurgical follow-up was 85 months (median 79 months, range 12-191 months). RESULTS: Of the patients studied, 251 (30%) presented with a BMI < 25 kg/m², while 362 patients (44%) were overweight (BMI ≥ 25 to < 30 kg/m²) and 221 patients (26%) were obese (BMI ≥ 30 kg/m²). Fifty-two patients (6.2%) experienced WL. While BMI did not significantly influence OS and CSS, WL had a significant impact on survival in patients with a BMI < 30 kg/m², in contrast to obese patients presenting with a BMI of ≥ 30 kg/m². Further analysis showed overweight to influence significantly disorders in wound healing, but neither other complications nor postoperative mortality. CONCLUSIONS: This is the first study providing information regarding the influence of BMI in relation to WL in patients with surgically treated RCC. While BMI did not significantly influence the survival of patients in the present series, WL had a significant impact on survival of patients presenting with a BMI < 30 kg/m². Hence, preoperative assessment of WL should be considered for the assessment of individual prognosis.

Ten-year survival analysis for renal carcinoma patients treated with an autologous tumour lysate vaccine in an adjuvant setting.

About 30% of renal cell carcinomas (RCC) will develop recurrence after surgery. Despite evidence for a significantly improved survival by autologous tumour cell vaccination therapy, the procedure has not become standard. Between August 1993 and December 1996, 1,267 RCC patients undergoing radical nephrectomy in 84 German hospitals were subsequently treated by autologous tumour cell vaccination therapy. The study group comprised 692 patients with complete follow-up (stages pT2-3, pNx-2, M0 based on the TNM classification, 4th edition). Subsequent propensity-score matching according to 7 defined criteria with 861 control patients undergoing nephrectomy alone without adjuvant treatment at the Carl-Thiem-Hospital Cottbus, resulted in 495 matched pairs. Overall and stage-specific survival rates were analysed after a median follow-up of 131 months. The 5- and 10-year overall survival (OS) rates were 80.6 and 68.9% in the vaccine group and 79.2 and 62.1% in the control group (p = 0.066). Patients with pT3 stage RCC revealed 5- and 10-year OS rates of 71.3 and 53.6% in the study group and 65.4 and 36.2% in the control group (p = 0.022). In multivariable analysis, patients in the vaccine group showed a significantly improved survival both in the whole study group (HR = 1.28, p = 0.030) and in the subgroup presenting with pT3 stage tumours (HR = 1.67, p = 0.011). Adjuvant treatment with autologous vaccination therapy resulted in a significantly improved overall survival in pT3 stage RCC patients, suggesting benefit especially in this subgroup. However, controlled clinical trials integrating the recent TNM classification and further risk constellations are required to define additional patient groups that may derive benefit from this treatment.

Prognostic accuracy of individual uropathologists in noninvasive urinary bladder carcinoma: a multicentre study comparing the 1973 and 2004 World Health Organisation classifications.

BACKGROUND: Grading of noninvasive papillary urinary bladder carcinoma (PUC) is routinely performed in clinical oncologic practice; however, reports regarding diagnostic and prognostic accuracy are contradictory. OBJECTIVE: To compare the 1973 and 2004 World Health Organisation (WHO) classifications in terms of interobserver variability and prognostic implications. DESIGN, SETTING, AND PARTICIPANTS: Two hundred PUC were retrospectively reviewed by four independent expert genitourinary pathologists blinded with respect to patient identity and clinical outcome. Tumour grading was assigned according to the 1973 and 2004 WHO classifications. Surveying a mean postsurgical follow-up of 71.8 mo (range: 18-163 mo), clinical outcome in terms of recurrence-free and progression-free survival was recorded for all patients. INTERVENTION: All of the patients underwent transurethral resection of the bladder. MEASUREMENTS: The generalised κ (kappa statistic) for interobserver variability was calculated, and Kaplan-Meier analysis as well as univariate regression analysis were performed to evaluate prognostic implications in terms of recurrence and progression rates. RESULTS AND LIMITATIONS: During the follow-up, a total of 84 (42%) patients experienced recurrence, whereas another 18 (9%) patients featured disease progression. Owing to the rare presence of papillary urothelial neoplasms of low malignant potential (PUNLMP) in our cohort (0-3.5%), the 2004 WHO classification approached a two-tier system (low and high grade), which showed less interobserver variability than the 1973 classification (κ: 0.30-0.52 vs 0-0.37, respectively). In comparing the power of both classifications to separate indolent from aggressive PUC, striking pathologist-dependent differences became apparent. CONCLUSIONS: Both WHO classifications for grading of PUC suffer from substantial interobserver variability, with the 2004 WHO classification showing less interobserver variability. Stark differences in the prognostic power of the individual grading approaches were also found. These significant differences in the individual interpretation of the WHO grading schemes for noninvasive PUC highlight the necessity of better-defined criteria for conventional tumour grading; otherwise, the subdivision into prognostically different groups by conventional histomorphology might remain of limited value.

Evaluation of renicapsular involvement in Stages I and II renal cell carcinoma from the morphological and prognostic point of view.

BACKGROUND: Prognostic factors are essential for predicting postsurgical outcome in renal cell cancer (RCC). This study aimed to evaluate the prognostic impact of renicapsular involvement (RCI; invasion without penetration) in Stage I (pT1N0M0) and Stage II (pT2N0M0) RCC and to histomorphologically compare the structure of fibrous tumoral capsule with the pattern of RCI, the differentiation of which might by challenging in localized RCCs spreading near the renicapsule. MATERIALS AND METHODS: We retrospectively investigated a cohort of 635 study group patients (396 men and 239 women; mean age: 60.9 years; range: 18-84 years) in terms of histomorphology and clinical outcome after surgery (nephrectomy or elective nephron-sparing surgery) at Stages I and II RCC (pT1-2N0M0). In 489 patients who were still alive at the end of the study, median follow-up was 80 months (mean 86.1 months). Disease-free survival (DFS) was calculated using the Kaplan Meier method. Univariate and multivariate Cox proportional hazards regression models were fit to determine possible associations between various parameters and survival. Another 55 control group patients (38 men and 17 women) aged between 44 and 75 years (mean age 61.4 years) with pT3a RCC were analyzed for statistical comparison (mean and median follow-up of the survivors were 85.7 and 84 months). RESULTS: The 5-year DFS rate for patients with and without RCI was determined to be 76.9% and 86.3%, respectively (P < 0.01). Patients with histopathologically confirmed RCI appear to have the same adverse prognostic outcome as patients with RCC invading perinephric tissue (pT3aN0M0; P = 0.493). Histopathologically, fibrous tumoral capsule and RCI conventionally show a different morphology, making their separation straightforward. CONCLUSIONS: RCI reflects adverse prognostic outcome in surgically treated Stages I and II RCC. It can be determined by the pathologist without additional expense in time and cost. Hence, clinical pathologists should render a clear statement concerning RCI when reporting on small localized RCC specimens in order to provide additional prognostic information in individual cases and to facilitate selection of appropriate patients to be included in further standardized prospective studies, which are required to confirm the prognostic impact of RCI in Stages I and II RCC.

Validation of a postoperative prognostic model consisting of tumor microvascular invasion, size, and grade to predict disease-free and cancer-specific survival of patients with surgically resected renal cell carcinoma.

OBJECTIVES: To determine the value of microvascular invasion, tumor size, and Fuhrman grade to predict the survival of patients with surgically resected renal cell carcinoma (RCC). METHODS: A total of 771 consecutive patients (T1-4, Nx, M0) were retrospectively reviewed. For each patient with RCC, the prognostic Sao Paulo score (SPS) was calculated using the following variables: tumor size (>7 cm vs

Post-void residual urine as a predictor of urinary tract infection--is there a cutoff value in asymptomatic men?

PURPOSE: Post-void residual urine can lead to various complications, including urinary tract infection. Recently investigators calculated that a cutoff value of 180 ml has considerably high sensitivity and specificity for significant bacteriuria in asymptomatic men. We determined the association between post-void residual urine volume and urinary tract infection, and validated the suggested 180 ml cutoff in asymptomatic men. MATERIALS AND METHODS: In a prospective study we analyzed certain criteria in 225 asymptomatic male patients, including prostate specific antigen, prostate volume, International Prostate Symptom Score, peak urine flow rate, urine culture results and post-void residual urine volume using transabdominal ultrasound. Using ROC analysis a cutoff predicting bacteriuria was calculated. Different cutoff values were validated. RESULTS: Of the study group 60% were able to completely empty the bladder and had a post-void residual urine volume of 10 ml or less. However, in 31% of the study group urine culture was positive. Patients presenting with urinary tract infection had significantly higher mean post-void residual urine volume than patients without urinary tract infection (113 vs 41 ml, p <0.001). In 29 men (13%) post-void residual volume was 180 ml or greater. Confirming urinary tract infection, this cutoff showed only 28% sensitivity and 94% specificity (AUC 0.606, p = 0.01). CONCLUSIONS: No cutoff value could be determined to predict positive urine culture with sufficient sensitivity and specificity. Based on the results of the current study it seems premature to recommend a cutoff value leading to therapeutic consequences.

Impact of macroscopic tumour necrosis to predict survival of patients with surgically resected renal cell carcinoma.

OBJECTIVE: The determination of further prognostic factors is essential for the establishment of risk groups for patients with surgically treated renal cell carcinoma (RCC). The objective of this study was to validate the prognostic value of macroscopic tumour necrosis, concerning postoperative survival. MATERIAL AND METHODS: A total of 607 patients (387 men, 220 women), who had undergone surgical treatment for RCC, was retrospectively reviewed. Necrotic areas in the tumour were identified macroscopically followed by microscopic confirmation. Cancer-specific survival (CSS) and overall survival (OS) were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were fitted to determine associations between tumour necrosis, clinical and pathological features, and survival. In 447 patients who were still alive at the end of the study, median follow-up was 66 months (mean 71.2 months). RESULTS: Tumour necrosis was identified in 25.5% of patients (n=155). After 5 years, CSS and OS in the group of patients with tumour necrosis amounted to 77.0% and 64.4%, respectively, compared with 89.8%and 81.9% in the group of patients without tumour necrosis (in each case p<0.001). Patients with tumour necrosis significantly more often showed a metastatic stage, lymph-node involvement, a higher pathological tumour stage, a higher grading and a larger tumour size. In addition, a more frequent appearance of microvascular invasion and thrombocytosis could be proven in patients with tumour necrosis in comparison to patients without these histopathological findings. On multivariate regression analysis, only metastatic stage, lymph-node involvement, platelet count >400/nl and tumour necrosis remained significant for survival (CSS, OS). CONCLUSIONS: According to the results, tumour necrosis may be a useful factor in the prognostic assessment of patients with RCC. The integration of this parameter in prognostic models for postoperative survival is recommended.

Expression of alpha-methylacyl-CoA racemase correlates with histopathologic grading in noninvasive bladder cancer.

Alpha-methylacyl-CoA racemase (AMACR, p504S), an enzyme involved in cellular energy metabolism by the oxidation of branched-chain fatty acids, is a biomarker that is known to be overexpressed in prostatic and colorectal carcinoma as well as in papillary renal cell carcinoma. We aimed to correlate its immunohistochemically detected expression with histopathological grading in noninvasive bladder cancer in order to hint at a so far unknown role of AMACR in the pathobiology of this tumor entity. Therefore, a cohort of 163 patients (mean age 65.3 years) diagnosed with noninvasive bladder cancer was immunohistochemically investigated in terms of AMACR expression. There was variable positive AMACR staining in 52 (31.9%) of the cases investigated. All tumors were graded by three independent clinical histopathologists according to the 1973 World Health Organization (WHO) and the 1998 WHO/International Society of Urological Pathology (ISUP) system. We found a significant positive correlation between AMACR expression and higher tumor grades using both histopathologic grading schemes. These novel findings clearly allow including high-grade noninvasive bladder carcinomas in the group of AMACR-positive neoplasms and might reflect a so far unknown role of AMACR racemase in the pathobiology and tumor cell energy metabolism of the latter tumor entity.