Long-Term Results after Suprapubic ARC Procedure for the Treatment of Stress Urinary Incontinence in Women: A Retrospective Data Analysis.

INTRODUCTION: The aim of this study was to evaluate long-term safety and efficacy of the suprapubic arc (SPARC) procedure for the surgical treatment of stress urinary incontinence (SUI). MATERIALS AND METHODS: 139 female patients treated by SPARC were included in this retrospective analysis, whereby 126 patients were available for follow-up after 1 year, 70 after 6 years, and 41 after 9 years. The cough test, pad test, uroflowmetry, and post-void residual volume measurements were performed. Severity of bother (visual analogous scale [VAS] 0-10), continence, and the satisfaction rate were assessed. Objective cure was defined as a negative cough test and pad weight ≤1 g, subjective cure as no urine loss during daily activities and no usage of pads. The VAS, pad weight, number of pads per day, and maximal flow rate were compared preoperatively and postoperatively. RESULTS: Objective cure rates at 1, 6, and 9 years were 78.6, 71.4, and 70.7% and subjective cure rates were 72.2, 55.7, and 65.8%, respectively. The VAS, pad weight, number of pads, and maximal flow rate decreased significantly. Study limitations include a relatively small sample size and the retrospective fashion of the analysis. CONCLUSIONS: In the long-term context, SPARC showed to represent an efficient and safe procedure for treatment of female SUI.

MiR-371a-3p Serum Levels Are Increased in Recurrence of Testicular Germ Cell Tumor Patients.

Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (ß-subunit of human chorionic gonadotropin (ß-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease (p = 0.014). In contrast, miR-367 levels were not different in these patient groups (p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.

Critical evaluation of the potential prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio under consideration of C-reactive protein levels in clear cell renal cell carcinoma.

BACKGROUND: We investigated the prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio (dNLR) and original NLR in relation to the commonly used inflammation marker C-reactive protein (CRP) in a large cohort of patients with clear cell renal cell carcinoma (RCC). METHODS: Clinicopathological data from 587 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single tertiary academic center, were evaluated retrospectively. Patients were categorised according to a cutoff value derived from receiver operating curve analysis. Overall (OS), cancer-specific (CSS) as well as metastasis-free survival (MFS) were assessed using the Kaplan-Meier method and multivariate Cox proportional models were applied. Spearman's rank correlation coefficient tested the association between dNLR and other markers of the systemic inflammatory response. RESULTS: The significant correlation between pretreatment NLR and dNLR was strong (ρ=0.84), whereas between dNLR and CRP it was weak (ρ=0.18). In multivariate analyses, dNLR achieved independent predictor status regarding CSS (P=0.037) and MFS (P=0.041), whereas CRP was confirmed as independent predictor of OS (P=0.010), CSS (P=0.039) and MFS (P=0.005), respectively. The NLR failed to reach independent predictor status regarding OS, CSS and MFS when CRP was included into the multivariate model. CONCLUSIONS: In the cohort studied, an elevated (⩾10.0) pretreatment CRP level and elevated dNLR (>2) were robust independent predictors of CSS and MFS. Our data suggest that CRP might be superior to both NLR and dNLR.

Blood Platelet Volume Represents a Novel Prognostic Factor in Patients with Nonmetastatic Renal Cell Carcinoma and Improves the Predictive Ability of Established Prognostic Scores.

PURPOSE: The average size of blood platelets determined by mean platelet volume might represent a biologically meaningful parameter in carcinogenesis and potentially serve as a novel prognostic biomarker in renal cell carcinoma. MATERIALS AND METHODS: In this retrospective analysis of the records of 652 patients we evaluated the potential prognostic value of mean platelet volume and its ability to improve existing risk assessment tools used in adjuvant clinical trials in nonmetastatic renal cell carcinoma cases. Associations of mean platelet volume with baseline covariates and clinical outcomes (recurrence, and death from renal cell carcinoma and other causes) were assessed with the competing risk estimators of Kaplan-Meier, and Marubini and Valsecchi, respectively. Univariable and multivariable Cox proportional hazard models were constructed. The Harrell c-index was applied to test improvements in the predictive accuracy of the established Leibovich prognosis score. RESULTS: Small platelet volume was associated with large tumors (p = 0.043), high Fuhrman grade (p = 0.001), sarcomatoid components (p <0.0001), histological tumor necrosis (p = 0.044) and vascular invasion (p = 0.022). On univariable and multivariable analyses small platelet volume accurately predicted recurrent renal cell carcinoma (continuously and binary coded) and cancer specific survival. Adding mean platelet volume to the Leibovich prognosis score improved its discriminative performance (c-index = 0.83, p = 0.004). CONCLUSIONS: Mean platelet volume represented a highly significant predictor of recurrence and cancer specific death in patients with renal cell carcinoma. This parameter improved the accuracy of the Leibovich prognosis score to better predict long-term outcomes in localized renal cell carcinoma cases after curative surgical resection.

Validation of the Preoperative Platelet-to-Lymphocyte Ratio as a Prognostic Factor in a European Cohort of Patients with Upper Tract Urothelial Carcinoma.

INTRODUCTION: This study is aimed at investigating the potential prognostic impact of the preoperatively assessed platelet-to-lymphocyte ratio (PLR) in a European cohort of patients with non-metastatic upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Clinicopathological data from 180 consecutive non-metastatic UTUC patients, operated between 1990 and 2012 at a single tertiary academic center, were evaluated retrospectively. The preoperative PLR was assessed one day before surgery. Patients were categorized using a PLR cut-off value according to receiver-operating curve analysis. Cancer-specific survival (CSS) and overall survival (OS) were assessed using the Kaplan-Meier method. Additionally, multivariate proportional Cox regression models were applied. RESULTS: In multivariate analyses, age at the date of surgery (<65 vs. ≥65 years, hazard ratio (HR) 1.827, 95% CI 1.051-3.175, p = 0.033), pathologic T-stage (pT1 vs. pT2-4, HR 1.873, 95% CI 1.066-3.292, p = 0.029), and pretreatment PLR (<150.0 vs. ≥150.0, HR 1.782, 95% CI 1.041-3.050, p = 0.035) were independent predictors of OS. Regarding CSS, pathologic T-stage (pT1 vs. pT2-4, HR 2.176, 95% CI 1.062-4.460, p = 0.034) and pretreatment PLR (<150.0 vs. ≥150.0, HR 2.026, 95% CI 1.045-3.930, p = 0.037) were considered independent predictors. CONCLUSIONS: In the cohort studied, patients with an elevated (≥150.0) preoperative PLR had a higher cancer-specific mortality and overall mortality after radical surgery for UTUC, compared with those with a low pretreatment PLR.

Current Insights into Long Non-Coding RNAs (LncRNAs) in Prostate Cancer.

The importance of long non-coding RNAs (lncRNAs) in the pathogenesis of various malignancies has been uncovered over the last few years. Their dysregulation often contributes to or is a result of tumour progression. In prostate cancer, the most common malignancy in men, lncRNAs can promote castration resistance, cell proliferation, invasion, and metastatic spread. Expression patterns of lncRNAs often change during tumour progression; their expression levels may constantly rise (e.g., HOX transcript antisense RNA, HOTAIR), or steadily decrease (e.g., downregulated RNA in cancer, DRAIC). In prostate cancer, lncRNAs likewise have diagnostic (e.g., prostate cancer antigen 3, PCA3), prognostic (e.g., second chromosome locus associated with prostate-1, SChLAP1), and predictive (e.g., metastasis-associated lung adenocarcinoma transcript-1, MALAT-1) functions. Considering their dynamic role in prostate cancer, lncRNAs may also serve as therapeutic targets, helping to prevent development of castration resistance, maintain stable disease, and prohibit metastatic spread.

Sampling of the anterior apical region results in increased cancer detection and upgrading in transrectal repeat saturation biopsy of the prostate.

OBJECTIVE: To evaluate whether biopsy cores taken via a transrectal approach from the anterior apical region of the prostate in a repeat-biopsy population can result in an increased overall cancer detection rate and in more accurate assessment of the Gleason score. PATIENTS AND METHODS: The study was a prospective, randomised (end-fire vs side-fire ultrasound probe) evaluation of 288 men by repeat transrectal saturation biopsy with 28 cores taken from the transition zone, base, mid-lobar, anterior and the anterior apical region located ventro-laterally to the urethra of the peripheral zone. RESULTS: The overall prostate cancer detection rate was 44.4%. Improvement of the overall detection rate by 7.8% could be achieved with additional biopsies of the anterior apical region. Two tumours featuring a Gleason score 7 could only be detected in the anterior apical region. In three cases (2.34%) Gleason score upgrading was achieved by separate analysis of each positive core of the anterior apical region. A five-fold higher cancer detection rate in the anterior apical region compared with the transition zone could be shown. CONCLUSION: Sampling of the anterior apical region results in higher overall cancer detection rate in repeat transrectal saturation biopsies of the prostate. Specimens from this region can detect clinically significant cancer, improve accuracy of the Gleason Scoring and therefore may alter therapy.

Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) represents a deadly disease with rising mortality despite intensive therapeutic efforts. It comprises several subtypes in terms of distinct histopathological features and different clinical presentations. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the genome which vary in expression levels and length and perform diverse functions. They are involved in the inititation, evolution and progression of primary cancer, as well as in the development and spread of metastases. Recently, several lncRNAs were described in RCC. This review emphasises the rising importance of lncRNAs in RCC. Moreover, it provides an outlook on their therapeutic potential in the future.

The Preoperative AST/ALT (De Ritis) Ratio Represents a Poor Prognostic Factor in a Cohort of Patients with Nonmetastatic Renal Cell Carcinoma.

PURPOSE: Aminotransaminases, which are strongly involved in cellular metabolism and cancer cell turnover, represent easily measureable, potential blood based biomarkers. We evaluated the prognostic value of the preoperatively assessed AST/ALT (De Ritis) ratio on clinically meaningful end points in a large European cohort of patients with nonmetastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated clinicopathological data on 698 patients with nonmetastatic renal cell carcinoma operated on between 2005 and 2013 at a single tertiary academic center. The potential prognostic value of the AST/ALT ratio was analyzed using the Kaplan-Meier method, and univariate and multivariate Cox proportional regression models. The impact of the ratio on the predictive accuracy of the Leibovich prognosis score was determined by the Harrell c-index. RESULTS: An increased (1.26 or greater) preoperative AST/ALT ratio was statistically significantly associated with several well established prognostic factors, including pathological T stage, as well as with histological tumor necrosis (p <0.05). On multivariate analysis an increased preoperative AST/ALT ratio was an independent prognostic factor for metastasis-free survival (HR 1.61, 95% CI 1.25-2.07, p <0.001) and overall survival (HR 1.76, 95% CI 1.34-2.32, p <0.001). The Harrell c-index was 0.77 using the Leibovich prognosis score and 0.81 when AST/ALT was added. CONCLUSIONS: In our study cohort with nonmetastatic renal cell carcinoma the preoperatively assessed AST/ALT ratio represented an independent prognostic factor. This ratio might further improve the predictive accuracy of well established prognosis scores.

Is There a Role for Active Surveillance in Low-Risk Prostate Cancer?

BACKGROUND: Active surveillance (AS) represents an expectant treatment strategy for clinically localized prostate cancer (PCa) with low-risk features. OBJECTIVE: The actual management as well as the pros and cons of AS were evaluated. METHODS: A systematic review of the recent literature was performed using the Medline databases. CONCLUSIONS: Since a substantial number of men die with rather than from PCa, there is a considerable role for AS in carefully selected men. AS may also represent a strategy to reduce the burden of overtreatment rooted in intensified PSA testing. Facing the imprecision of risk stratification based on transrectal ultrasound-guided biopsy, accurate clinical staging represents a major medical challenge. Counseling and care require empathy as well as a profound understanding of the biology and the natural history of PCa.

Validation of the preoperative plasma fibrinogen level as a prognostic factor in a European cohort of patients with localized upper tract urothelial carcinoma.

PURPOSE: Fibrinogen is thought to have a potentially significant role in the progression and metastatic spread of different human cancers. A recent study from Asia indicated that elevated preoperative plasma fibrinogen might be associated with a worse outcome in patients with surgically treated localized upper tract urothelial carcinoma. We validated the prognostic impact of this potential biomarker in a European cohort of patients with localized upper tract urothelial carcinoma. MATERIALS AND METHODS: We evaluated data on 167 patients with nonmetastatic upper tract urothelial carcinoma who underwent surgery between 1990 and 2012 at a single tertiary academic center. Patients were categorized using an optimal cutoff value of preoperative plasma fibrinogen. Patient cancer specific and overall survival was assessed using the Kaplan-Meier method. Univariate and multivariate Cox regression models were performed for each end point. The influence of fibrinogen on the predictive accuracy of the multivariate model was further determined by the Harrell c-index. RESULTS: Multivariate analysis identified increased preoperative plasma fibrinogen as an independent prognostic factor for cancer specific survival (HR 3.00, 95% CI 1.32-6.80, p = 0.008) and overall survival (HR 2.48, 95% CI 1.31-4.68, p = 0.005). The estimated c-index of the multivariate model for cancer specific survival was 0.72 without fibrinogen and 0.74 when fibrinogen was added. The risk model that we developed significantly differentiated between low, intermediate and high risk groups for cancer related death (p <0.001). CONCLUSIONS: Elevated fibrinogen seems to represent a negative prognostic factor for cancer specific and overall survival in patients with upper tract urothelial carcinoma. This parameter should be considered an additional prognostic factor for upper tract urothelial carcinoma in the future.

Validation of pretreatment neutrophil-lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma.

OBJECTIVE: To investigate the potential prognostic significance of the neutrophil-lymphocyte ratio (NLR) in a large European cohort of patients with upper urinary tract urothelial cell carcinoma (UUT-UCC). PATIENTS AND METHODS: We retrospectively evaluated data from 202 consecutive patients with non-metastatic upper urinary tract urothelial cell carcinoma (UUT-UCC), who underwent surgery between 1990 and 2012 at a single tertiary academic centre. Patients' cancer-specific survival (CSS) and overall survival (OS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the NLR, multivariate proportional Cox regression models were applied for both endpoints. RESULTS: A higher NLR was significantly associated with shorter CSS (P = 0.002, log-rank test), as well as with shorter OS (P < 0.001, log-rank test). Multivariate analysis identified a high NLR as an independent prognostic factor for patients' CSS (hazard ratio 2.72, 95% CI 1.25-5.93, P = 0.012), and OS (hazard ratio 2.48, 95% CI 1.31-4.70, P = 0.005). CONCLUSIONS: In the present cohort, patients with a high preoperative NLR had higher cancer-specific and overall mortality after radical surgery for UUT-UCC, compared with those with a low preoperative NLR. This easily identifiable laboratory measure should be considered as an additional prognostic factor in UUT-UCC in future.

Innovations in diagnostic imaging of localized prostate cancer.

PURPOSE: In recent years, various imaging modalities have been developed to improve diagnosis, staging, and localization of early-stage prostate cancer (PCa). METHODS: A MEDLINE literature search of the time frame between 01/2007 and 06/2013 was performed on imaging of localized PCa. RESULTS: Conventional transrectal ultrasound (TRUS) is mainly used to guide prostate biopsy. Contrast-enhanced ultrasound is based on the assumption that PCa tissue is hypervascularized and might be better identified after intravenous injection of a microbubble contrast agent. However, results on its additional value for cancer detection are controversial. Computer-based analysis of the transrectal ultrasound signal (C-TRUS) appears to detect cancer in a high rate of patients with previous biopsies. Real-time elastography seems to have higher sensitivity, specificity, and positive predictive value than conventional TRUS. However, the method still awaits prospective validation. The same is true for prostate histoscanning, an ultrasound-based method for tissue characterization. Currently, multiparametric MRI provides improved tissue visualization of the prostate, which may be helpful in the diagnosis and targeting of prostate lesions. However, most published series are small and suffer from variations in indication, methodology, quality, interpretation, and reporting. CONCLUSIONS: Among ultrasound-based techniques, real-time elastography and C-TRUS seem the most promising techniques. Multiparametric MRI appears to have advantages over conventional T2-weighted MRI in the detection of PCa. Despite these promising results, currently, no recommendation for the routine use of these novel imaging techniques can be made. Prospective studies defining the value of various imaging modalities are urgently needed.

The hypothalamic-pituitary-gonadal axis and prostate cancer: implications for androgen deprivation therapy.

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) may play important roles in prostate cancer (PCa) progression. Specifically, LH expression in PCa tissues has been associated with metastatic disease with a poor prognosis, while FSH has been shown to stimulate prostate cell growth in hormone-refractory PCa cell lines. Gonadotropin-realizing hormone (GnRH) analogues are common agents used for achieving androgen deprivation in the treatment for PCa. GnRH analogues include LH-releasing hormone (LHRH) agonists and GnRH antagonists, both of which exhibit distinct mechanisms of action that may be crucial in terms of their overall clinical efficacy. LHRH agonists are typically used as the primary therapy for most patients and function via a negative-feedback mechanism. This mechanism involves an initial surge in testosterone levels, which may worsen clinical symptoms of PCa. GnRH antagonists provide rapid and consistent hormonal suppression without the initial surge in testosterone levels associated with LHRH agonists, thus representing an important therapeutic alternative for patients with PCa. The concentrations of testosterone and dihydrotestosterone are significantly reduced after treatment with both LHRH agonists and GnRH antagonists. This reduction in testosterone concentrations to castrate levels results in significant, rapid, and consistent reductions in prostatic-specific antigen, a key biomarker for PCa. Evidence suggests that careful maintenance of testosterone levels during androgen deprivation therapy provides a clinical benefit to patients with PCa, emphasizing the need for constant monitoring of testosterone concentrations throughout the course of therapy.

Prostate cancer at the peripheral end of prostate biopsy specimen predicts increased risk of positive resection margin after radical prostatectomy: results of a prospective multi-institutional study.

PURPOSE: To test a novel technique of processing prostate biopsy specimen by marking the peripheral end (PE) as a predictive tool for positive resection margin after radical prostatectomy (RP) or for locally advanced carcinoma of the prostate (PC). METHODS: Prospective, multi-institutional study of a consecutive cohort of men who underwent prostate biopsy with marking the peripheral biopsy end and subsequent RP at the same institution. RESULTS: The study cohort comprised 445 men with a mean age of 63 years (40-77 years). Overall, PE-positive cores were found in 174 men (39.1 %) and R1 status was diagnosed in 132 men after RP (29.7 %). In the multivariate analysis, the presence of at least one PE-positive core was correlated with an increased risk of R1 status (OR 2.29, 95 % CI 1.31-4.00, p = 0.003) and was the strongest predictor followed by Gleason score, PSA and percentage of positive cores. Including all predictive parameters, a nomogram with a concordance index of 72.1 % was calculated. In the pT3/pT4 subgroup, PE positivity was the only predictive factor for R1 status (OR 3.03, 95 % CI 1.36-6.75, p = 0.006). In pT2 stage, no single factor was predictive for R1 status. PE-positive biopsies were not predictive for pT3/pT4 stages. CONCLUSIONS: PC at the peripheral end of prostate biopsy specimen predicts an increased risk of R1 status in subsequent RP. This simple and cheap technique may contribute to an increased accuracy of risk stratification for curative treatment for PC.

Association of diabetes mellitus and metformin use with biochemical recurrence in patients treated with radical prostatectomy for prostate cancer.

PURPOSE: The impact of diabetes mellitus (DM) and metformin use on biochemical recurrence (BCR) in patients treated with radical prostatectomy (RP) remains controversial. METHODS: We retrospectively evaluated 6,863 patients who underwent RP for clinically localized PC between 2000 and 2011. Univariable and multivariable Cox regression models addressed the association of DM and metformin use with BCR. RESULTS: Overall, 664 patients had a diagnosis of DM from which 287 (43 %) were on metformin and 377 (57 %) were on anti-diabetics other than metformin. DM and metformin were not associated with any clinicopathologic features (p values >0.05). Within a median follow-up of 25 months (interquartile range 35 months), 774 (11.3 %) patients experienced BCR. Actuarial 5-year biochemical-free survival was 83 % for non-diabetic, 79 % for diabetic patients without metformin use, and 85 % for diabetic patients with metformin use (log rank p = 0.17). In uni- and multivariable Cox regression analyses with the non-diabetic group as referent, DM without metformin use (HR = 0.99; 95 % CI 0.75-1.30, p = 0.65) and DM with metformin use (HR = 0.84, 95 % CI 0.58-1.22, p = 0.36) were not associated with BCR after RP. A subgroup analysis stratified by nodal status, surgical margins, tumor stage, and Gleason sum did not reveal any significant association between DM, use of metformin and risk of BCR. CONCLUSIONS: We found no association between DM or metformin use and cancer-specific features or BCR in patients treated with RP. The effect of DM and metformin on complications, wound healing and overall survival needs to be assessed in similar cohorts.

Relationship between prostate cancer gene 3 (PCA3) and characteristics of tumor aggressiveness.

BACKGROUND: Data supporting prostate cancer gene 3 (PCA3) as prognostic marker are still inconsistent. With special emphasis to Gleason pattern specific tumor volumes (TVs) the relationships between PCA3 score and different characteristics of tumor aggressiveness were meticulously analyzed. METHODS: In 127 patients treated with radical prostatectomy for clinically localized prostate cancer, urinary PCA3 score was quantified using Progensa™ PCA3 assay. Total TV and Gleason patterns' specific tumor volumes (GPTV) were assessed by computer-assisted planimetry. Spearman's rank correlations coefficients (r) were calculated to assess relationships between PCA3 and TV as well as GPTV. Regression analyses were performed to estimate the relationship between PCA3 and TV as well as non-organ confined disease. RESULTS: Mean patients' age was 60.8 years. Patients showed a mean PSA level of 8.1 ng/ml and a mean PCA3 score of 68.5. PCA3 was not significantly correlated with TV (r = 0.131, P = 0.142). Stratified by Gleason score groups ≤ 6, 7, and ≥ 8, PCA3 showed no significant correlations with TV. In a subgroup analysis of 50 patients with different primary and secondary Gleason patterns there was neither a correlation with the primary GPTV (r = 0.071, P = 0.626) nor with the secondary GPTV (r = 0.052, P = 0.722). The PCA3 score was neither an independent predictor for TV nor for non-organ confined disease. CONCLUSIONS: The PCA3 score did not show any significant correlation with TV, primary or secondary GPTV. Moreover, the PCA3 score was not an independent predictor for TV or for non-organ confined disease. Thus, the PCA3 score had no impact for the prediction of aggressive prostate cancers.

Presence and extent of histological tumour necrosis is an adverse prognostic factor in papillary type 1 but not in papillary type 2 renal cell carcinoma.

AIMS: To date, only limited information is available on the prognostic significance of the presence and extent of histological tumour necrosis with regard to papillary renal cell carcinoma (RCC) types 1 and 2 subclassification. Thus, the aim of this study was to evaluate the prognostic impact of these pathological features on the clinical outcome in papillary subtypes. METHODS AND RESULTS: The influence of histological tumour necrosis on the clinical outcome in 177 patients with papillary RCC was evaluated. For papillary subtype 1, the presence of histological tumour necrosis was an independent negative prognostic factor for disease-free survival (P = 0.039), and a greater extent of necrosis (>20%) was significantly associated with both poor disease-free and overall survival (P = 0.033 and P = 0.041, respectively). Regarding papillary subtype 2, neither the presence nor extent of histological tumour necrosis was a statistically significant negative prognostic factor. CONCLUSION: Our findings suggest that the presence and extent of histological tumour necrosis are independent prognosticators in papillary RCC subtype 1, but not in papillary subtype 2. Thus, previously reported conflicting data regarding the prognostic impact of tumour necrosis in papillary RCC might be explained, in part, by heterogeneous subtypes.

Comparison of the 2002 and 2010 TNM classification systems regarding outcome prediction in clear cell and papillary renal cell carcinoma.

AIMS: A novel version of the tumour-node-metastasis (TNM) classification system for renal cell carcinoma (RCC) was introduced in 2010, although the prognostic significance with regard to different histological subtypes has not been explored. Therefore, the aim of our study was to compare the predictive ability of the 2002 and 2010 versions of the TNM classification system for clear cell and papillary RCC. METHODS AND RESULTS: Data from 2263 consecutive clear cell and 309 papillary RCC patients, operated at a single tertiary academic centre, were evaluated. According to TNM 2010, statistically significant differences for cancer-specific survival (CSS) were observed for pT1a versus pT1b (P < 0.001) and pT3a versus pT3b (P < 0.004) in clear cell RCC; and pT1b versus pT2a (P = 0.002) and pT3b versus pT3c (P = 0.046) in papillary RCC. The c-index for CSS in clear cell RCC was 0.74 and 0.73, and in papillary RCC 0.79 and 0.78, for the 2002 and 2010 versions of the TNM classification system, respectively. CONCLUSIONS: According to our data, the predictive ability of the 2010 version of the TNM classification system regarding CSS is not superior to the 2002 version, either in clear cell or in papillary RCC.

Tumour-associated macrophages might represent a favourable prognostic indicator in patients with papillary renal cell carcinoma.

AIMS: Tumour-associated macrophages (TAM) have been reported to be regulators of progression in various human cancers. We evaluated the prognostic relevance of TAM in a large series of patients with papillary renal cell carcinoma (PRCC). METHODS AND RESULTS: The impact of TAM on cancer-specific survival (CSS) in 177 patients with PRCC was assessed using the Kaplan-Meier method and log-rank test. A multivariate Cox regression analysis was performed with respect to CSS. The presence of TAM was noted in 112 of 177 (63%) tumours and was associated statistically significantly with favourable pathological parameters, including low pathological T stage, node-negative tumours, low tumour grade, absence of vascular invasion and papillary subtype (all P < 0.05), respectively. Five-year CSS probabilities for patients with TAM-positive tumours were 93.5%, compared with 72.5% in patients with TAM-negative tumours, respectively (P < 0.001). Multivariate analysis revealed node-positive tumours, distant metastases and UICC stage (I versus II-IV) as independent predictors of death from PRCC, whereas the presence of TAM was associated independently with favourable outcome (hazard ratio = 0.45, 95% confidence interval 0.24-0.84, P = 0.012). CONCLUSIONS: The presence of TAM was shown independently to reduce the risk of death from cancer by 55%. The presence of TAM should therefore become part of routine pathology reporting in PRCC.