Bladder outlet obstruction (BOO) in men with castration-resistant prostate cancer.

OBJECTIVE: To evaluate the frequency of bladder outlet obstruction (BOO) and detrusor overactivity (DO) in patients with castration-resistant prostate cancer (CRPC) and lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Our prospective urodynamics database was queried. Inclusion criteria were CRPC and an International Prostate Symptom Score (IPSS) ≥ 20. Exclusion criteria were previous local therapy to the prostate gland, known urethral stricture disease, and a neurological component of LUTS. Twenty-one patients were identified. Urodynamic findings were analysed and compared with those of a matched cohort of 42 patients with benign prostatic enlargement (BPE). RESULTS: The median age of patients in the CRPC group was 74 years, and the median prostate-specific antigen (PSA) level at the time of the urodynamic study was 90 ng/mL. According to the BOO index, three patients (14%) were obstructed, three were equivocally obstructed (14%) and 15 were unobstructed. DO was seen in 12 patients (57%). Compared with the BPE group, patients with CRPC had lower cystometric bladder capacities (P = 0.003), were less likely to have BOO (14 vs 43%, P = 0.009) and more likely to have DO (57 vs 29%, P = 0.028). CONCLUSIONS: This study generates the hypothesis that only a minority of CRPC patients with LUTS have BOO, and that more than half of patients have DO. LUTS in CRPC may therefore be seldom attributable to BOO, but are, at least in part, related to DO and reduced cystometric capacity. A urodynamic investigation may be necessary before palliative transurethral resection of the prostate to select appropriate candidates. Larger prospective studies are needed to confirm our findings.

Evaluation of ABO blood group as a prognostic marker in renal cell carcinoma (RCC).

OBJECTIVE: To evaluate ABO blood group as a prognostic marker in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: This retrospective study included 556 consecutive patients who underwent surgery for RCC at a single institution. The associations of ABO blood group with clinical and pathological variables were assessed using Kruskal-Wallis and chi-squared tests. The impact on overall survival (OS) and RCC-specific survival (RCC-SS) was analysed using univariable and multivariable Cox proportional hazards regression models. RESULTS: Blood group O was associated with the absence of lymph node metastases (P = 0.034) and the presence of bilateral RCC (P = 0.017). No associations with age, gender, body mass index, Charlson comorbidity index, T stage, M stage, grade and histological subtype were observed. In univariable and multivariable survival analysis, ABO blood group was not associated with OS and RCC-SS. CONCLUSIONS: In the present study, ABO blood group was not linked with RCC prognosis. Blood group O may be associated with the absence of lymph node metastases and the presence of bilateral RCC. External validation in larger cohorts is necessary.

Nephrometry scoring systems for surgical decision-making in nephron-sparing surgery.

PURPOSE OF REVIEW: Herein, we review the various recently published nephrometry scoring systems and the available data on their ability to predict clinical outcomes and their usefulness for new operative techniques. RECENT FINDINGS: Several studies showed that the preoperative aspects and dimensions used for anatomical classification score, the RENAL system, and the centrality index are reproducible and able to predict certain clinical intraoperative and postoperative variables in patients undergoing nephron-sparing surgery. Addition of variables, such as the BMI, to the pre-existing scores might improve their predictive abilities. SUMMARY: Nephrometry scoring systems may allow better preoperative planning and counseling of patients. If they gain widespread use in clinical practice, they may also help to give reliable comparisons of morbidity rates among different partial nephrectomy techniques, individual surgeons, and institutions.

Prognostic impact of preoperative neutrophil-to-lymphocyte ratio in localized nonclear cell renal cell carcinoma.

PURPOSE: The preoperative neutrophil-to-lymphocyte ratio was proposed as a prognostic factor for localized clear cell renal cell carcinoma. We evaluated its role in nonclear cell renal cell carcinoma. MATERIALS AND METHODS: We queried 2 prospective kidney cancer databases. Patients who underwent full resection of localized (T1-3 N0/+ M0) nonclear cell renal cell carcinoma by radical or partial nephrectomy were included in analysis. Associations of the continuously coded neutrophil-to-lymphocyte ratio with disease-free survival were assessed with univariable and multivariable Cox regression models. Prognostic accuracy was evaluated with the Harrell concordance index. RESULTS: Our final cohort included 281 patients. The 5-year disease-free survival rate was 88.1%. The neutrophil-to-lymphocyte ratio was significantly associated with disease-free survival. With each 1.0 increase in the ratio the risk of recurrence increased by 15% (HR 1.15, p=0.028). On multivariable analysis TNM group (HR 2.84, p=0.025), Fuhrman grade (HR 3.40, p<0.001) and the neutrophil-to-lymphocyte ratio (HR 1.17, p=0.022) were independently associated with disease-free survival. Adding the neutrophil-to-lymphocyte ratio improved the accuracy of a base model to predict disease-free survival from 78.8% to 80.8%. CONCLUSIONS: The neutrophil-to-lymphocyte ratio is an independent prognostic factor for disease-free survival after surgery with curative intent for localized nonclear cell renal cell carcinoma. It significantly increases the accuracy of established prognostic factors. The neutrophil-to-lymphocyte ratio may provide a meaningful adjunct for patient counseling and clinical trial design.

Validation of serum C-reactive protein (CRP) as an independent prognostic factor for disease-free survival in patients with localised renal cell carcinoma (RCC).

OBJECTIVE: To validate high-sensitivity C-reactive protein (hs-CRP) serum levels as an independent marker for disease-free survival (DFS) in clinically localised clear cell renal cell carcinoma (ccRCC). PATIENTS AND METHODS: In all, 403 consecutive patients with clinically localised (T1-3N0M0) ccRCC treated by radical or partial nephrectomy were enrolled. Preoperative serum levels of hs-CRP were evaluated as both a continuous and categorical variables. Associations with clinical (age, gender) and pathological variables (T classification, grade, tumour necrosis) were assessed with the chi-square and Kruskal-Wallis tests. Univariable and multivariable Cox proportional hazards models were fitted. The prognostic accuracy (PA) was assessed with Harrell's C-index. RESULTS: The mean hs-CRP level was 1.32 mg/dL. The hs-CRP levels were associated with T classification (P = 0.05), high-grade disease (P < 0.001) and tumour necrosis (P = 0.003). After a median follow-up of 43 months, 41 patients (10.1%) had developed disease recurrence. With each unit increase in hs-CRP levels, the risk of recurrence increased by 10% (hazard ratio 1.10, P = 0.015). The thresholds of 0.5 and 0.75 mg/dL showed the best discrimination for stratification of patients according to the probability of recurrence. These categorically coded hs-CRP levels were identified as independent prognostic factors in multivariable analyses (P < 0.001) and led to a significant increase in the PA of a multivariable base model containing the variables of the 'Stage, Size, Grade and Necrosis' (SSIGN) score. CONCLUSIONS: This study validates preoperative serum hs-CRP levels as independent prognostic factor after surgery for localised ccRCC. Hs-CRP may be included in standard prognostic modelling after surgery and may guide surveillance and inclusion in adjuvant clinical trials.

Bladder outlet obstruction in men with acute urinary retention: an urodynamic study.

OBJECTIVE: To identify clinical predictors of bladder outlet obstruction (BOO) in men with the first episode of spontaneous acute urinary retention (AUR), in order to facilitate patient selection for early de-obstructive prostate surgery. METHODS: A multichannel urodynamic investigation was performed in 156 consecutive men ≥ 50 years five days following AUR. Clinical routine parameters were evaluated for their ability to predict BOO, which was defined as a BOO-index (BOOI) >40. Univariable and multivariable logistic regression models were fitted. A nomogram was constructed from significant variables of a reduced multivariable model. Discrimination and calibration of the nomogram were assessed. RESULTS: The mean age of the 156 men was 71.6 years, and the mean drained volume was 953 mL. Seventy-two men (46.2 %) had severe AUR-associated pain. On urodynamic evaluation, 79 (50.6 %) were obstructed (BOOI > 40). In multivariable regression analysis, age (p = 0.014) drained volume (p = 0.044) and pain intensity (p < 0.001) were independently associated with BOO. These variables formed the basis of the nomogram, which predicted BOO with a bootstrap-corrected accuracy of 78.2 %. The positive predictive value, sensitivity, and specificity of a 70 % nomogram cutoff was 83, 51, and 90 %, respectively. Decision-curve analysis demonstrated a net benefit with use of the nomogram. CONCLUSIONS: The routine clinical parameters age, drained volume, and pain intensity are independent predictors of BOO in men with AUR. According to our model, patients with a nomogram predicted BOO probability of >70 % might be candidates for early surgery. External validation of the nomogram is advocated.

Gender differences in benign renal masses.

PURPOSE: To examine gender-specific differences in benign renal tumors. METHODS: This retrospective study included 135 adult Caucasian patients with 143 benign renal tumors, which were treated surgically at a single institution. Demographics, comorbidity, histology, renal function, and management were compared by gender. A systematic review and meta-analysis of the literature were performed. RESULTS: A total of 73 women were compared with 62 men. The female-to-male ratio was significantly higher in patients with benign renal tumors than in those with renal cell carcinoma (1.18:1 vs. 0.57:1, p < 0.001). Only 17 % of benign renal tumors were correctly classified by preoperative computed tomography. The most frequently observed histological types were oncocytoma (44 %) and angiomyolipoma (37 %). Angiomyolipoma occurred more than twice as often in women than in men (72 vs. 28 %), while oncocytoma was more frequently found in men (59 vs. 41 %, p = 0.001). Men with benign renal tumors were older (p = 0.002) and had higher body mass indices (p = 0.019), higher comorbidity indices (p < 0.001), lower ECOG performance status (p < 0.001), and smaller tumors (p = 0.045). No differences were seen in pack years, mode of diagnosis, bilaterality, renal function, use of laparoscopic surgery, and the rate of radical nephrectomy. In the meta-analysis of 9,665 renal tumors, women had a 2.55-fold increased chance of benign pathology and a greater chance of angiomyolipoma (OR 4.66) than men. CONCLUSIONS: This study demonstrated several gender-specific differences in benign renal tumors, especially in the histological types. Despite this, clinical-pathological features and management of benign renal tumors in men and women appear more alike than different.

Sex hormone-binding globulin is an independent predictor of biochemical recurrence after radical prostatectomy.

PURPOSE: We studied the association of serum sex hormone levels with clinicopathological variables and biochemical recurrence in men with prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: We prospectively studied preoperative serum sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and free and total testosterone in 372 patients undergoing radical prostatectomy. Biochemical recurrence was analyzed in 285 patients and defined as prostate specific antigen 0.2 ng/ml or higher at least 30 days after radical prostatectomy. Median followup was 43.6 months. RESULTS: Median sex hormone-binding globulin was 37.4 nmol/l, luteinizing hormone 4.1 mU/ml, follicle-stimulating hormone 5.9 mU/ml, and free and total testosterone 0.069 and 3.7 ng/ml, respectively. There was no significant association of sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone or total testosterone with T and N stage, and margin status. Luteinizing hormone, follicle-stimulating hormone, and free and total testosterone were not associated with biochemical recurrence. In contrast, for each 10 U increase in sex hormone-binding globulin the risk of biochemical recurrence increased by 12% (p = 0.045). On multivariable analysis sex hormone-binding globulin achieved independent predictor status after adjusting for standard clinicopathological variables. After stepwise regression a model containing T and N stage, Gleason score, margin status, prostate weight and sex hormone-binding globulin improved the accuracy of a base model by 1.3% (79.0% vs 77.7%). CONCLUSIONS: Preoperative serum sex hormone-binding globulin is independently associated with biochemical recurrence after radical prostatectomy and increases the predictive accuracy of a standard multivariable model. Routine assessment of sex hormone-binding globulin sex hormone-binding globulin may be a helpful adjunct to identify patients who need early adjuvant therapy.

The value of transurethral bladder biopsy after intravesical bacillus Calmette-Guérin instillation therapy for nonmuscle invasive bladder cancer: a retrospective, single center study and cumulative analysis of the literature.

PURPOSE: We evaluated the need of routine transurethral biopsies after an induction course of intravesical bacillus Calmette-Guérin for high grade nonmuscle invasive bladder cancer. MATERIALS AND METHODS: This retrospective study included 180 patients with high grade nonmuscle invasive bladder cancer who underwent a 6-week induction course of bacillus Calmette-Guérin. Cystoscopic findings, urinary cytology and pathological results of transurethral biopsy were evaluated. For cumulative meta-analysis we systematically reviewed studies indexed in MEDLINE®, EMBASE® and Web of Science®. The records of 740 patients from a total of 7 studies were finally analyzed. RESULTS: Biopsy was positive in 58 patients (32%). Cystoscopy appeared normal in 75 patients (42%) and showed only erythema in 51 (28%) and tumor in 54 (30%), of whom 6 (8%), 11 (22%) and 41 (76%), respectively, showed positive findings at biopsy. The positive predictive value of erythema was 15% with negative cytology and 56% with positive cytology. The positive predictive value of a tumor with negative and positive cytology was 63% and 89%, respectively. A combination of negative cytology and normal cystoscopy was associated with a negative biopsy in 94% of cases. A total of 970 bladder biopsies were taken, of which 137 (14%) were positive, including 20 of 125 erythematous lesions (16%), 73 of 107 tumors (68%) and 44 of 738 normal-appearing areas (6%). Cumulative analysis findings were comparable. CONCLUSIONS: Routine transurethral bladder biopsies after a bacillus Calmette-Guérin induction course are not necessary. An individually approach is recommended, tailored from cystoscopic findings and cytology.

Is ¹5³Samarium-ethylene-diamine-tetramethyl-phosphonate (EDTMP) bone uptake influenced by bisphosphonates in patients with castration-resistant prostate cancer?

OBJECTIVE: To evaluate the impact of biphosphonate administration on subsequent (153)Samarium-ethylene-diamine-tetramethyl-phosphonate (EDTMP) uptake in bone metastases of patients with castration-resistant prostate cancer. PATIENTS AND METHODS: The bone uptake of (153)Sm-EDTMP was assessed in 40 consecutive patients with castration-resistant prostate cancer and multiple painful bone metastases and no prior bisphosphonate therapy. (153)Sm-EDTMP was repeated after 3 months in the presence of bisphosphonates (zoledronic acid every 4 weeks, first administration 1 week after (153)Sm-EDTMP administration). The retained activity in bone was evaluated 20 h after application using whole-body scintigraphy (acquisition 15 cm/min). RESULTS: Mean patient age was 69 ± 4.8 years (range 57-77 years). Mean PSA level at study entry was 18.2 ± 21.0 ng/ml. (153)Sm-EDTMP uptake ranged from 36.3 to 75.3% (mean 55.1 ± 10.9%) before bisphosphonate administration and 35.6 to 73.3% (mean 55.2 ± 10.4%) after bisphosphonate administration. No significant intra-individual difference with or without bisphosphonate treatment was observed (P = 0.647). CONCLUSIONS: Bisphosphonate treatment does not affect (153)Sm-EDTMP bone uptake in patients with castration-resistant metastatic prostate cancer. Thus, bisphosphonate treatment can be continued safely during samarium therapy.

Age-specific PCA3 score reference values for diagnosis of prostate cancer.

PURPOSE: We evaluated the impact of age on PCA3 score and the utility of age-specific reference values in predicting initial prostate biopsy (pBx) outcomes. PATIENTS AND METHODS: This single-center, retrospective study included 205 men who underwent an initial 14-core TRUS-guided pBx due to PSA > 3.0 ng/ml or suspicious digital-rectal examination (DRE). PCA3 scores were measured with the Progensa assay. Linear regression models were fit to identify factors that impact PCA3 score and to determine age-specific reference values. Predictive accuracies of logistic regression models predicting presence of prostate cancer (PCa) were analyzed. RESULTS: The positive biopsy rate was 37%. In multivariable linear regression, age (P < 0.001), presence of PCa (P < 0.001), and multifocal HG-PIN (P = 0.012) were independent predictors of PCA3 score. Age showed the strongest impact on PCA3 score (T = 4.77). The upper 95% confidence interval of PCA3 score in each age category was defined as the age-specific limit. A PCA3-score over the age-specific limit (PCA3-age) was associated with an 4.17-fold increased odds of being diagnosed with PCa (P < 0.001). In multivariable logistic regression models predicting the presence of PCa, predictive accuracy of a base model (age, DRE, PSA, volume) increased from 69.6 to 75.4% (P = 0.037) by adding the continuous PCA3 score, to 73.9% (P = 0.098) with the 35 cutoff (PCA3-35) and to 77.1% (P = 0.008) with PCA3-age. CONCLUSIONS: PCA3 score increases with age, independent of PCa presence. Age-specific PCA3 score reference values are superior to PSA, continuous PCA3 score, and PCA3-35 in predicting initial pBx outcome. Therefore, an age-adjusted PCA3 score should be used for interpretation of the results.

Interpersonal variability and present diagnostic dilemmas in Bosniak classification system.

OBJECTIVE: The purpose of the study was to evaluate the management and interpersonal variability of Bosniak classification and demonstrate the present diagnostic dilemmas. MATERIAL AND METHODS: One-hundred and four patients with 113 complex renal cystic masses (26 Bosniak II,15 IIF,28 III and 44 IV) were included and analysed between April 1996 and May 2009.In total, 71 cystic masses were characterized by two radiologists in consensus initially as the first diagnosis (group 1), and then by a radiologist (group 2) and a urologist (group 3) independently in a blinded fashion. RESULTS: Only 11 patients (10.6%) were symptomatic (one Bosniak IIF, six III and four IV). Only one had renal cell carcinoma (RCC) on final histology, whereas the others (n = 10) had benign lesions. An overall pathological result was obtained in 71 masses (62.8%) (two Bosniak II, three IIF, 27 III and 39 IV). The overall incidence of RCC in surgically treated patients was 0%, 20%, 55.6% and 76.9% for each category, respectively. The interpersonal variability was significant among the three groups (especially in Bosniak II, IIF), and the overall category was changed in 54%, 20% and 41%, respectively (p < 0.001). After correlation with final histology and presumed benign character of Bosniak II/IIF lesions (all patients having reached 5-year follow-up) the differences were not significant. CONCLUSION: It is challenging to minimize unnecessary surgical procedures in Bosniak category III. According to these results, it may make practical sense to group Bosniak II and IIF masses in one category.

Renal cell carcinoma Fuhrman grade and histological subtype correlate with complete polymorphic deletion of glutathione S-transferase M1 gene.

PURPOSE: We outlined the putative significance of GST in renal cell carcinoma biology by investigating the influence of its deletion polymorphisms on renal cell carcinoma progression. MATERIALS AND METHODS: Genomic DNA was purified from peripheral blood leukocytes. GSTM1 and GSTT1 genes were polymerase chain reaction amplified and gene fragments were separated by agarose gel electrophoresis. Intact GSTM1 and GSTT1 alleles were identified by the presence of 230 and 480 bp fragments, respectively. Genotypes were associated with clinicopathological variables and survival. RESULTS: Of 147 patients with renal cell carcinoma 80 (54%) had the GSTM1 null and 27 (18%) had the GSTT1 null genotype. The GST genotype distribution did not differ significantly from that in 112 controls without renal cell carcinoma. However, the GSTM1 null genotype was associated with 60% lower odds of the papillary subtype (OR 0.40, 95% CI 0.18 to 0.92, p = 0.032), lower Fuhrman grade (chi-square 9.77, p = 0.008) and a lower risk of metastatic disease in patients with the clear cell subtype (chi-square 4.48, p = 0.034). Of patients with the clear cell subtype those with the GSTM1 null genotype had improved cancer specific survival (p = 0.0412). GSTT1 did not correlate with any pathological variable except age at renal cell carcinoma onset since patients with renal cell carcinoma and the GSTT1 null genotype were significantly younger than their counterparts (mean +/- SD age 58.5 +/- 14.2 vs 65.4 +/- 12.8 years, p = 0.016). CONCLUSIONS: GSTM1 deletion polymorphism impacts renal cell carcinoma histological subtype, Fuhrman grade and metastatic behavior while GSTT1 deletion leads to renal cell carcinoma onset at a younger age. In patients with clear cell renal cell carcinoma the GSTM1 null genotype may be associated with better prognosis.

Development and external validation of a nomogram predicting disease specific survival after nephrectomy for papillary renal cell carcinoma.

PURPOSE: We developed and externally validated a prognostic nomogram specifically for papillary renal cell carcinoma. MATERIALS AND METHODS: We retrospectively studied 435 patients who underwent radical or partial nephrectomy for papillary renal cell carcinoma at 3 institutions. Slides were reviewed by 1 uropathologist per institution. We constructed a nomogram predicting 5-year disease specific survival as a graphic representation of significant variables on multivariate Cox proportional hazards regression analysis using data on 258 patients from 2 of the 3 institutions. Nomogram discrimination and calibration were assessed by bootstrapping to obtain relatively unbiased estimates. External validation was done in 177 patients from a third institution. RESULTS: At a median 50.8-month followup 77 papillary renal cell carcinoma related deaths had occurred. In the multivariate Cox proportional hazards model incidental detection, T classification, M classification, vascular invasion and tumor necrosis extent were retained as independent prognostic factors of disease specific survival and formed the basis of the nomogram. The nomogram predicted well with a 93.6% bootstrapped corrected concordance index and showed good calibration. External independent validation revealed 94.2% predictive accuracy. CONCLUSIONS: We developed a highly accurate tool specifically for papillary renal cell carcinoma using basic clinical and pathological information to predict disease specific survival. This tool should be helpful to identify papillary renal cell carcinoma with aggressive clinical behavior and may contribute to the ability to individualize postoperative surveillance and therapy.

Features and outcomes of renal cell carcinoma of native kidneys in renal transplant recipients.

OBJECTIVE: To outline the features and outcomes of renal cell carcinoma (RCC) in native kidneys of renal transplant recipients, who are at increased risk of developing this disease. PATIENTS AND METHODS: We retrospectively studied the clinicopathological features and survival of 28 surgically treated RCCs, which developed in 24 renal transplant recipients. Features and outcomes were compared with 671 patients with RCC who had no renal transplant. RESULTS: The median interval between renal transplantation and the occurrence of RCC was 5.6 years. Acquired cystic kidney disease was present in 83% of the transplanted patients. Compared with the patients with RCC and no renal transplant, RCCs of native kidneys in transplant recipients were more frequently incidental findings (92% vs 77%, P = 0.092), multifocal (39% vs 15%, P < 0.001), bilateral (17% vs 4%, P = 0.006), had lower T stages (P = 0.040), were smaller (P = 0.027), of lower grades (P = 0.010), were more frequently papillary (43% vs 19%, P = 0.019) and occurred at a significantly younger age (P = 0.022). After a median follow-up of 6.7 years, eight renal transplant recipients had died (33%), but only two deaths were due to RCC. Survival with metastatic RCC was only 4 months, if a full resection of all metastatic sites was not achieved. In multivariate analysis the presence of a renal transplant had no effect on survival. CONCLUSIONS: Most RCCs in renal transplant recipients are incidental low-stage, low-grade tumours with a favourable prognosis. The outstanding pathological findings are bilateral occurrence, papillary subtype and multifocality. Prognosis of metastatic RCC is poor but might be favourable if all metastases are resected. Screening for early detection of asymptomatic RCC is advocated.

A delay in radical nephroureterectomy can lead to upstaging.

STUDY TYPE: Prognosis (case series). LEVEL OF EVIDENCE: 4. OBJECTIVE: To examine the association between the delay from diagnosis of upper-tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU), and the pathological features and outcomes, as the decision to proceed to RNU for an individual patient is complex. PATIENTS AND METHODS: The records of 187 patients who had RNU were reviewed; the interval from diagnosis to RNU was analysed as both a continuous (months) and categorical variable (<3 vs > or =3 months). Logistic regression and survival analyses were used to evaluate the association between time from diagnosis to RNU with pathological characteristics and clinical outcomes. RESULTS: The median time from diagnosis to RNU was 45 days (interquartile range 68). A delay from diagnosis to RNU analysed as a continuous variable was associated with advanced stage, higher grade, previous endoscopic procedure, tumour necrosis, infiltrative tumour architecture, and lymphovascular invasion (P = 0.034), but not disease recurrence or cancer-specific mortality. In the subgroup of patients (90, 48.1%) who had muscle-invasive disease (> or =pT2) a longer delay from diagnosis to RNU as a continuous variable was associated with advanced stage (P = 0.030), higher grade (P = 0.014), infiltrative tumour architecture (P = 0.044), lymphovascular invasion (P = 0.034), disease recurrence (P = 0.02), and cancer-specific mortality (P = 0.03). CONCLUSIONS: Our data suggest that a delay in the interval from diagnosis to RNU is associated with more advanced disease stage. These findings might have important implications for trial design in the ongoing evaluation of neoadjuvant regimens. Timely consideration of definitive treatment for patients with high-risk UTUC is of high importance. Further studies are necessary to validate these hypothesis-generating findings.

External validation of the preoperative anatomical classification for prediction of complications related to nephron-sparing surgery.

PURPOSE: Ficarra et al. (Eur Urol 56:786-793, 2009) published a preoperative anatomical classification (PADUA) to assess the impact of anatomical parameters of renal tumors on complication rate of nephron-sparing surgery (NSS). The objective of this study is to provide a bi-center external validation of this classification using the technique of hilar arterial clamping during open and laparoscopic NSS and to correlate the PADUA score to the ischemia time. METHODS: 240 consecutive tumors treated with open and laparoscopic NSS were reclassified according to the PADUA classification. Complications were graded according to the modified Clavien system (Dindo et al. in Ann Surg 240:205-213, 2004). Chi-square tests and multivariate logistic regression models addressed the predictive value of PADUA classification on overall complication rate and grade. RESULTS: Mean patient age was 62.2 +/- 13.3 years. Eastern Cooperative Oncology Group performance was 0 in 76%, 1 in 22% and 2 in 2%. 61 (25%) were treated laparoscopically. The median PADUA score was 7.5 (range 6-13). Mean surgery and ischemia time was 189 +/- 95 and 24 +/- 22 min, respectively. Overall complication rate was 23% (n = 54). On univariate analysis, the PADUA score correlated with complication rate (p < 0.001) of open and laparoscopic NSS. On multivariate, only the PADUA score correlated with complication rate (p = 0.0056). Ischemic time correlated with the PADUA score and was significantly higher in PADUA score > or = 10 (p = 0.034). CONCLUSIONS: The PADUA score is a reliable tool to preoperatively predict the risk of complications. In addition, it might be beneficial for a more objective patient selection for laparoscopic surgery and teaching NSS.

The oncological results of laparoscopic nephroureterectomy for upper urinary tract transitional cell cancer are equal to those of open nephroureterectomy.

OBJECTIVE: To compare the overall, tumour-specific, recurrence-free, and progression- free survival of patients with upper urinary tract transitional cell carcinoma (UUT-TCC) treated with laparoscopic nephroureterectomy (LNU) or standard open NU (ONU). PATIENTS AND METHODS: Clinical, pathological and follow-up data were analysed for 43 LNUs and 59 ONUs performed at our institution from 1999 to 2006. In LNU the kidney was removed laparoscopically as in radical nephrectomy, but without transecting the ureter. The specimen was then removed intact with the entire ureter and a bladder cuff through a nonmuscle-splitting supra-inguinal incision. ONU was performed through separate intercostal and supra-inguinal incisions with the entire specimen being removed intact with a bladder cuff through the latter. RESULTS: The mean (SD) follow-up was 41 (20) months for LNU and 41 (29) for ONU. Pathological staging was: pTa 26% vs 20%, pT1 21% vs 27%, pT2 12% vs 17%, pT3 42% vs 34% for LNU and ONU, respectively. In all, seven vs six patients had positive nodes on final histology. Recurrent tumours in the bladder were detected in 26% of patients after LNU and in 27% after ONU after the mean follow-up. There were no local recurrences after LNU but there was local recurrence in six patients after ONU. There were no port-site metastases during the follow-up. Five LNU patients and seven ONU patients developed distant or lymph node metastasis. The actuarial 5-year tumour free-survival rate was 79% in the LNU group vs 76% in the ONU group (P = 0.82). The actuarial disease-specific survival at 5-years was 85% for LNU and 80% for ONU patients (P = 0.62). The surgical approach did not influence recurrence or survival. CONCLUSION: Oncological results of LNU and ONU are comparable. The lower morbidity of LNU offers advantages for the patient.

Tumour architecture is an independent predictor of outcomes after nephroureterectomy: a multi-institutional analysis of 1363 patients.

OBJECTIVE: To assess whether tumour architecture can help to refine the prognosis of patients treated with nephroureterectomy (NU) for urothelial carcinoma (UC) of the upper urinary tract (UT), as the prognostic value of tumour architecture (papillary vs sessile) in UTUC remains elusive. PATIENTS AND METHODS: The study included 1363 patients with UTUC and treated with radical NU at 12 centres worldwide. All slides were re-reviewed according to strict criteria by genitourinary pathologists who were unaware of the findings of the original pathology slides and clinical outcomes. Gross tumour architecture was categorized as sessile vs papillary. RESULTS: Papillary growth was identified in 983 patients (72.2%) and sessile growth in 380 (27.8%). The sessile growth pattern was associated with higher tumour grade, more advanced stage, lymphovascular invasion, and metastasis to lymph nodes (all P < 0.001). In multivariable Cox regression analyses that adjusted for the effects of pathological stage, grade and lymph node status, tumour architecture (sessile or papillary) was an independent predictor of cancer recurrence (hazard ratio 1.5, P = 0.002) and cancer-specific mortality (1.6, P = 0.001). Adding tumour architecture increased the predictive accuracy of a model that comprised pathological stage, grade and lymph node status for predicting cancer recurrence and cancer-specific death by a minimal but statistically significant margin (gain in predictive accuracy 1% and 0.5%, both P < 0.001). CONCLUSION: The tumour architecture of UTUC is associated with established features of biologically aggressive disease, and more importantly, with prognosis after radical NU. Including tumour architecture in predictive models for disease progression should be considered, aiming to identify patients who might benefit from early systemic therapeutic intervention.

Comparison of type I and II papillary renal cell carcinoma (RCC) and clear cell RCC.

OBJECTIVE: To compare the pathological features of clear cell renal cell carcinoma (ccRCC) with papillary RCC (pRCC) and further differentiate type I and II pRCC as independent prognosticators for survival. PATIENTS AND METHODS: From September 1994 to February 2007 557 RCCs were treated and reviewed. All patients underwent radical nephrectomy or nephron-sparing surgery. We reviewed patient data and correlated RCC subtypes to tumour size, pathological stage, nuclear grade, and 5-year cancer-specific survival (CSS). pRCC was re-evaluated in to type I and II. The 2002 Tumour-Node-Metastasis and Fuhrman classifications were used. RESULTS: In all, 391 (70%) patients had ccRCC, 96 (17%) had pRCC, 34 (6%) had chromophobe RCC, seven (1%) had ductus Bellini RCC and 29 (5%) had unclassified RCC. Upon re-evaluation 34 patients had type I pRCC and 62 had type II. The pRCCs were significantly smaller than the ccRCCs, at a mean (sd) of 4.5 (2.5) cm vs 5 (2.9) cm (P = 0.013), and multifocal (25% vs 12%, P = 0.001). Whereas patients with ccRCC had significantly more primary metastases (12% vs 3%, P = 0.014). The mean (sd) follow-up was 42.3 (41.4) months. The 5-year CSS for M0 patients was 84% for ccRCC and 90% for pRCC (P = 0.573). At multivariate analyses predictors for 5-year CSS were only tumour size (hazard ratio, HR 2.6, P < 0.001), pathological stage (HR 3.9, P < 0.001) and nuclear grade (HR 2.7, P < 0.001). The type I and II pRCCs had significantly different lymphovascular invasion (LVI) and 5-year CSS rates (94% vs 74%, P = 0.03). CONCLUSIONS: The ccRCCs were significantly larger at diagnosis than the pRCCs. The histological subtype (pRCC vs ccRCC) had no impact on the 5-year CSS in multivariate analyses. The type I and II pRCCs had similar histopathological features except for a significant difference in LVI. However, the 5-year CSS was significantly different in type I and II pRCC.