Acceptance and efficacy of recommended adjuvant radiotherapy in patients with positive lymph nodes at radical prostatectomy: a preference-based study.

PURPOSE: To investigate acceptance and efficacy of recommended adjuvant radiotherapy in patients with positive lymph nodes at radical prostatectomy. METHODS: Among 495 patients with positive lymph nodes who consecutively underwent radical prostatectomy between 2007 and 2017, we investigated 347 patients who were recommended to undergo adjuvant radiotherapy by a multidisciplinary post-therapeutic tumor board and in whom information whether such treatment was eventually given was available. The median follow-up for censored patients was 5.4 years. Univariate analyses were performed using Kaplan-Meier curves, Mantel-Haenszel hazard ratios and log rank tests. Proportional hazard models for competing risks were used for multivariable analyses. RESULTS: Adjuvant radiotherapy was independently associated with lower overall mortality and in high-risk patients (Gleason score 8-10 or three or more involved lymph nodes) also with lower prostate cancer-specific mortality. In patients with a Gleason score of 8-10 or three or more involved lymph nodes, the hazard ratio for adjuvant radiotherapy was 0.455 (95% confidence interval 0.257-0.806, p = 0.0069) for overall and 0.426 (95% confidence interval 0.201-0.902, p = 0.0259) for prostate cancer-specific mortality. Among patients receiving adjuvant radiotherapy, there was a trend to lower mortality when such treatment was combined with adjuvant androgen deprivation. CONCLUSION: Adjuvant radiotherapy decreased mortality in patients with positive lymph nodes at radical prostatectomy with further disease factors but not in patients with low-risk disease. Simultaneous androgen deprivation might increase efficacy. Multidisciplinary recommendations may possibly increase the use of adjuvant radiotherapy in this setting.

Neuropilin-2 is an independent prognostic factor for shorter cancer-specific survival in patients with acinar adenocarcinoma of the prostate.

Neuropilin-2 (NRP2) is a member of the neuropilin receptor family and known to regulate autophagy and mTORC2 signaling in prostate cancer (PCa). Our study investigated the association of immunohistochemical NRP2 expression with clinicopathological data in PCa patients. For this purpose, we generated a tissue microarray with prostate tissue specimens from 400 PCa patients treated by radical prostatectomy. We focused on patients with high-risk factors such as extraprostatic extension (pT ≥ 3), Gleason score ≥8 and/or the presence of regional lymph node metastases (pN1). Protein levels of NRP2, the vascular endothelial growth factor C (VEGFC) and oncogenic v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) gene as an indicator for TMPRSS2-ERG fusion was assessed in relation to the patients' outcome. NRP2 emerged as an independent prognostic factor for cancer-specific survival (CSS) (hazard ratio 2.360, 95% confidence interval = 1.2-4.8; p = 0.016). Moreover, the association between NRP2 expression and shorter CSS was also especially pronounced in patients at high risk for progression (log-rank test: p = 0.010). We evaluated the association between NRP2 and the TMPRSS2-ERG gene fusion status assessed by immunohistochemical nuclear ERG staining. However, ERG staining alone did not show any prognostic significance. NRP2 immunostaining is significantly associated with shorter CSS in ERG-negative tumors (log-rank test: p = 0.012). No prognostic impact of NRP2 expression on CSS was observed in ERG-positive tumors (log-rank test: p = 0.153). Our study identifies NRP2 as an important prognostic marker for a worse clinical outcome especially in patients with a high-risk PCa and in patients with ERG-negative PCa.

Which comorbidity classification is best suited to identify patients at risk for 90-day and long-term non-bladder cancer mortality after radical cystectomy?

PURPOSE: There is no consensus on the best comorbidity measure in candidates for radical cystectomy. The aim of this study was to identify tool best suited to identify patients at risk for 90-day or premature long-term non-bladder cancer mortality. METHODS: We studied 1268 patients who underwent radical cystectomy to identify patients at risk for 90-day and later-than-90-day mortality, respectively. Six classifications were investigated as possible predictors of both types of mortality. Multivariable models including age as continuous variable and each classification separately were calculated. A heuristic ranking was based on the evaluation of the hazard ratios, p values, Akaike's information criteria, and concerning the logit models also the areas under the curve. RESULTS: The median follow-up was 5.7 years. Within 90 days after surgery, the mortality rate was 4.2%. The greatest independent contribution concerning the prediction of 90-day mortality was seen with the American Society of Anesthesiologists (ASA) physical status classification (classes 3-4 versus 1-2: hazard ratio 7.98, 95% confidence interval 3.54-18.01, p < 0.0001). In the longer term, countable diseases (Canadian Cardiovascular Society classification of angina pectoris, conditions contributing the Charlson score) were of greater importance. The results of heuristic ranking were confirmed by multivariate analyses including age and all classifications together. CONCLUSIONS: Besides to chronological age, clinicians should pay particular attention to the ASA classification to identify patients at risk for 90-day mortality after radical cystectomy, whereas long-term mortality is more determined by countable comorbid diseases.

Validation of a Questionnaire-Suitable Comorbidity Index in Patients Undergoing Radical Cystectomy.

OBJECTIVE: To investigate the capability of a modified self-administrable comorbidity index recommended in the standard sets for neoplastic diseases published by the International Consortium for Health Outcomes Measurement (ICHOM) to predict 90-day and long-term mortality after radical cystectomy. METHODS: A single-center series of 1,337 consecutive patients who underwent radical cystectomy for muscle-invasive or high-risk non-muscle-invasive urothelial or undifferentiated bladder cancer were stratified by the modified self-administrable comorbidity index and Charlson score, respectively. Multivariate logit models (for 90-day mortality) and proportional-hazards models (for overall and non-bladder cancer mortality) were used for statistical workup. RESULTS: Considering 90-day mortality, both comorbidity indexes contributed independent information when analyzed together with age (p < 0.0001). The Charlson score performed slightly better (area under the curve [AUC] 0.74 vs. 0.72 for the ICHOM-recommended comorbidity index). Considering 5-year overall mortality in 727 patients with complete observation, the performance of both measures was similar (AUC 0.63 vs. 0.62, including age AUC 0.66 for both indexes). With 6-sided stratifications, the modified self-administrable comorbidity index separated the risk groups slightly better (p values for directly neighboring curves: 0.0068-0.1043 vs. 0.0001-0.8100). CONCLUSION: The ICHOM-recommended modified self-administrable comorbidity index is capable of predicting 90-day mortality and long-term non-bladder cancer mortality after radical cystectomy similarly to the commonly used Charlson score.

Socioeconomic Status-Related Parameters as Predictors of Competing (Non-Bladder Cancer) Mortality after Radical Cystectomy.

OBJECTIVE: To investigate the impact of socioeconomic status-related parameters on competing (non-bladder cancer) mortality after radical cystectomy. PATIENTS AND METHODS: A total of 1,268 consecutive patients who underwent radical cystectomy for urothelial or undifferentiated bladder cancer at our institution between 1993 and 2016 with a mean age of 69 years (median 70 years) were studied. The mean -follow-up of the censored patients was 7.2 years (median 5.7 years). Proportional hazard models for competing risk were used to identify predictors of non-bladder cancer (competing) mortality. The following parameters were included into multivariate analyses: age, American Society of Anesthesiologists physical status classification, Charlson score, gender, level of education, smoking status, marital status, local tumour stage, lymph node status, adjuvant and neoadjuvant chemotherapy. RESULTS: Besides age and both comorbidity classifications, the socioeconomic status-related parameters gender (female versus male, hazard ratio [HR] 0.58, 95% CI 0.40-0.84, p = 0.0042), level of education (university degree or master craftsman versus others, HR 0.76, 95% CI 0.56-0.1.03, p = 0.0801), smoking status (current smoking versus others, HR 1.47, 95% CI 1.10-1.96, p = 0.0085) and marital status (married versus others, HR 0.68, 95% CI 0.50-0.92, p = 0.0133) were independent predictors of competing mortality after radical cystectomy. If considered in combination (multiplication of HRs), the prognostic impact of socioeconomic parameters superseded that of the investigated comorbidity classifications. CONCLUSION: Socioeconomic status-related parameters may provide important information on the long-term competing mortality risk after radical cystectomy supplementary to chronological age and comorbidity.

Urinary MicroRNAs as Potential Markers for Non-Invasive Diagnosis of Bladder Cancer.

Currently, voided urine cytology (VUC) serves as the gold standard for the detection of bladder cancer (BCa) in urine. Despite its high specificity, VUC has shortcomings in terms of sensitivity. Therefore, alternative biomarkers are being searched, which might overcome these disadvantages as a useful adjunct to VUC. The aim of this study was to evaluate the diagnostic potential of the urinary levels of selected microRNAs (miRs), which might represent such alternative biomarkers due to their BCa-specific expression. Expression levels of nine BCa-associated microRNAs (miR-21, -96, -125b, -126, -145, -183, -205, -210, -221) were assessed by quantitative PCR in urine sediments from 104 patients with primary BCa and 46 control subjects. Receiver operating characteristic (ROC) curve analyses revealed a diagnostic potential for miR-96, -125b, -126, -145, -183, and -221 with area under the curve (AUC) values between 0.605 and 0.772. The combination of the four best candidates resulted in sensitivity, specificity, positive and negative predictive values (NPV), and accuracy of 73.1%, 95.7%, 97.4%, 61.1%, and 80.0%, respectively. Combined with VUC, sensitivity and NPV could be increased by nearly 8%, each surpassing the performance of VUC alone. The present findings suggested a diagnostic potential of miR-125b, -145, -183, and -221 in combination with VUC for non-invasive detection of BCa in urine.

Leiomyosarcoma of the Urinary Bladder in Adult Patients: A Systematic Review of the Literature and Meta-Analysis.

PURPOSE: Leiomyosarcoma of the urinary bladder is exceedingly rare. Most clinicians come across only a few cases during their career, and information regarding treatment and outcome is scattered in the scientific literature. Interested clinicians and patients have to undertake troublesome search for treatment and outcome information. MATERIAL AND METHODS: We performed a systematic review of the literature using the PubMed and Web of Science databases and included all identified cases published in English language between 1970 and June 2018 into a meta-analysis. Prior to the literature search, key questions were formulated and with the data obtained, answers to these questions should be derived. RESULTS: We analyzed clinical data of 210 cases of urinary bladder leiomyosarcoma revealed by this review and seen in our institution. The mean age of patients was 52 years. The majority (75%) of the tumors was classified as high-grade sarcomas. We found no report of a prior radiation therapy to the pelvic organs, but some authors suggested an association between cyclophosphamide treatment and the development of bladder leiomyosarcoma, especially in patients with retinoblastoma. For the whole sample, we determined 5- and 10-year cancer-specific cumulative mortality rates of 38 and 50%. Patients with high-grade sarcomas had a trend toward a higher mortality compared with low-grade tumors (p = 0.0280). The most promising treatment option seems to be surgery (radical or partial cystectomy) with negative resection margins, possibly supplemented by chemotherapy or radiation. CONCLUSION: About half of patients with bladder leiomyosarcoma survived on the long run. Low-grade tumors may have a better outcome with, nevertheless, countable long-term mortality. For better assessment of that rare bladder tumor, its best treatment options, and the influence of neoadjuvant or adjuvant therapies on the outcome of patients, a larger series with long-term survival data is required.

Long-Term Mortality in Patients with Positive Lymph Nodes at the Time of Radical Prostatectomy.

BACKGROUND: The aim of this study was to determine prognostic factors and to provide long-term mortality data in patients with positive lymph nodes at the time of radical prostatectomy in a sample with long-term follow-up. METHODS: A total of 527 patients with complete data sets treated in the years 1992-2014 were studied. The median follow-up was 7.2 years. The median number of removed lymph nodes was 15. Age, year of surgery, Gleason score, local tumor stage, prostate-specific antigen level, lymph node density, lymph node count and the number of positive lymph nodes were included in multivariable competing risk analyses with prostate cancer mortality as endpoint. RESULTS: After 20 years, 28% of patients (95% CI 20-36%) died from non-prostate cancer (competing) causes, whereas 29% (95% CI 23-36%) died from prostate cancer. Only lymph node density (stratified by the median of 11.1%; hazard ratio [HR] 1.66, 95% CI 1.04-2.64, p = 0.0340) and Gleason score (8-10 vs. <8: HR 5.97, 95% CI 3.18-11.23, p < 0.0001) were independent predictors of prostate cancer mortality. Patients with a Gleason score <8 and a lymph node density < median had a 20-year prostate cancer mortality of only 5% (95% CI 0-10%), whereas this rate in patients with Gleason score 8-10 and a lymph node density ≥ median was 44% (95% CI 32-56%), p < 0.0001. CONCLUSIONS: Mortality in patients with positive lymph nodes was determined by tumor aggressiveness and the relative extent of spread; neither the year of surgery nor the number of removed lymph nodes was associated with outcome. Patients with a lymph node density of <11.1% and a Gleason score <8 had an excellent long-term outcome.

Evaluation of Transperineal Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Compared to Transrectal Systematic Biopsy in the Prediction of Tumour Aggressiveness in Patients with Previously Negative Biopsy.

OBJECTIVES: We compared the transperineal MRI/ultrasound-fusion biopsy (fusPbx) to transrectal systematic biopsy (sysPbx) in patients with previously negative biopsy and investigated the prediction of tumour aggressiveness with regard to radical prostatectomy (RP) specimen. MATERIAL AND METHODS: A total of 710 patients underwent multiparametric magnetic resonance imaging (mpMRI), which was evaluated in accordance with Prostate Imaging Reporting and Data System (PI-RADS). The maximum PI-RADS (maxPI-RADS) was defined as the highest PI-RADS of all lesions detected in mpMRI. In case of proven prostate cancer (PCa) and performed RP, tumour grading of the biopsy specimen was compared to that of the RP. Significant PCa (csPCa) was defined according to Epstein criteria. RESULTS: Overall, scPCa was detected in 40% of patients. The detection rate of scPCa was 33% for fusPbx and 25% for sysPbx alone (p < 0.005). Patients with a maxPI-RADS ≥3 and a prostate specific antigen (PSA)-density ≥0.2 ng/mL2 harboured more csPCa than those with a PSA-density < 0.2 ng/mL2 (41% [33/81] vs. 20% [48/248]; p < 0.001). Compared to the RP specimen (n = 140), the concordance of tumour grading was 48% (γ = 0.57), 36% (γ = 0.31) and 54% (γ = 0.6) in fusPbx, sysPbx and comPbx, respectively. CONCLUSIONS: The combination of fusPbx and sysPbx outperforms both biopsy modalities in patients with re-biopsy. Additionally, the PSA-density may represent a predictor for csPCa in patients with maxPI-RADS ≥3.

Prospective comparison of transperineal magnetic resonance imaging/ultrasonography fusion biopsy and transrectal systematic biopsy in biopsy-naïve patients.

OBJECTIVES: To evaluate the value of multiparametric magnetic resonance imaging (mpMRI) in the detection of significant prostate cancer (PCa) and to compare transperineal MRI/ultrasonography fusion biopsy (fusPbx) with conventional transrectal systematic biopsy (sysPbx) in biopsy-naïve patients. PATIENTS AND METHODS: This multicentre, prospective trial investigated biopsy-naïve patients with suspicion of PCa undergoing transperineal fusPbx in combination with transrectal sysPbx (comPbx). The primary outcome was the detection of significant PCa, defined as Gleason pattern 4 or 5. We analysed the results after a study period of 2 years. RESULTS: The study included 214 patients. The median (range) number of targeted and systematic cores was 6 (2-15) and 12 (6-18), respectively. The overall PCa detection rate of comPbx was 52%. FusPbx detected more PCa than sysPbx (47% vs 43%; P = 0.15). The detection rate of significant PCa was 38% for fusPbx and 35% for sysPbx (P = 0.296). The rate of missed significant PCa was 14% in fusPbx and 21% in sysPbx. ComPbx detected significantly more significant PCa than fusPbx and sysPbx alone (44% vs 38% vs 35%; P < 0.005). In patients presenting with Prostate Imaging Reporting and Data System (PI-RADS) 4 and 5 lesions there was a higher detection rate of significant PCa than in patients presenting with PI-RADS ≤3 lesions in comPbx (61% vs 14%; P < 0.005). CONCLUSIONS: For biopsy-naïve men with tumour-suspicious lesions in mpMRI, the combined approach outperformed both fusPbx and sysPbx in the detection of overall PCa and significant PCa. Thus, biopsy-naïve patients may benefit from sysPbx in combination with mpMRI targeted fusPbx.

Predicting 90-day and long-term mortality in octogenarians undergoing radical cystectomy.

BACKGROUND: Radical cystectomy bears a considerable perioperative mortality risk particularly in elderly patients. In this study, we searched for predictors of perioperative and long-term competing (non-bladder cancer) mortality in elderly patients selected for radical cystectomy. METHODS: We stratified 1184 consecutive patients who underwent radical cystectomy for high risk superficial or muscle-invasive urothelial or undifferentiated carcinoma of bladder into two groups (age < 80 years versus 80 years or older). Multivariable and cox proportional hazards models were used for data analysis. RESULTS: Whereas Charlson score and the American Society of Anesthesiologists (ASA) physical status classification (but not age) were independent predictors of 90-day mortality in younger patients, only age predicted 90-day mortality in patients aged 80 years or older (odds ratio per year 1.24, p = 0.0422). Unlike in their younger counterparts, neither age nor Charlson score or ASA classification were predictors of long-term competing mortality in patients aged 80 years or older (hazard ratios 1.07-1.10, p values 0.21-0.77). CONCLUSIONS: This data suggest that extrapolations of perioperative mortality or long-term mortality risks of younger patients to octogenarians selected for radical cystectomy should be used with caution. Concerning 90-day mortality, chronological age provided prognostic information whereas comorbidity did not.

Gender and Mortality after Radical Cystectomy: Competing Risk Analysis.

BACKGROUND: Data on the impact of gender on mortality after radical cystectomy is conflicting. We investigated a large single center sample with long-term follow-up in order to determine the relationship between gender and outcome. PATIENTS AND METHODS: A total of 1,184 consecutive patients who underwent radical cystectomy for high risk superficial or muscle-invasive urothelial or undifferentiated bladder cancer between 1993 and 2015 were stratified by gender. Demographic data was compared using Mann-Whitney U test, chi-square test, or Fisher exact test. Cox proportional hazard models were used for the analysis of competing risks and logit models were used for the prediction of the receipt of adjuvant cisplatin-based chemotherapy. RESULTS: Female patients were older, healthier, less frequently current smokers and had more extravesical tumors. In the multivariate analyses, female gender was an independent predictor of (lower) non-bladder cancer (competing) mortality (hazards ratio [HR] 0.68, 95% CI 0.49-0.95, p = 0.0248) but no predictor of bladder cancer-specific mortality (HR in the full model 1.20, 95% CI 0.94-1.54, p = 0.15). Gender was no predictor of the receipt of adjuvant cisplatin-based chemotherapy. CONCLUSIONS: Female gender was associated with an increased risk of extravesical disease but was no independent predictor of bladder cancer-specific mortality. Anatomical differences might be a plausible explanation for these observations.

Evaluation of Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy in Patients with Low-Risk Prostate Cancer Under Active Surveillance Undergoing Surveillance Biopsy.

INTRODUCTION: Targeted biopsy of tumour-suspicious lesions detected in multiparametric magnetic resonance imaging (mpMRI) plays an increasing role in the active surveillance (AS) of patients with low-risk prostate cancer (PCa). The aim of this study was to compare MRI/ultrasound-fusion biopsy (fusPbx) with systematic biopsy (sysPbx) in patients undergoing biopsy for AS. METHODS: Patients undergoing mpMRI and transperineal fusPbx combined with transrectal sysPbx (comPbx) as surveillance biopsy were investigated. The detection of Gleason score upgrading and reclassification according to Prostate Cancer Research International Active Surveillance criteria were evaluated. RESULTS: Eighty-three patients were enrolled. PCa upgrading was detected in 39% by fusPbx and in 37% by sysPbx (p = 1.0). The percentage of patients who were reclassified in fusPbx and sysPbx (p = 0.45) were 64 and 59% respectively. ComPbx detected more frequently tumour upgrading than fusPbx (71 vs. 64%, p = 0.016) and sysPbx (71 vs. 59%, p < 0.001) and more patients had to be reclassified after comPbx than after fusPbx or sysPbx alone. CONCLUSIONS: The combination of fusPbx and sysPbx outperforms both modalities alone with regard to the detection of upgrading and reclassification in patients under AS. Because a high missing rate of significant PCa still exists in both biopsy modalities, a combination of fusPbx and sysPbx should be recommended in these patients.

Evaluation of Prostate Imaging Reporting and Data System Classification in the Prediction of Tumor Aggressiveness in Targeted Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy.

OBJECTIVES: The study aimed to evaluate the prediction of Prostate Imaging Reporting and Data System (PI-RADS) with respect to the prostate cancer (PCa) detection rate and tumor aggressiveness in magnetic resonance imaging (MRI)/ultrasound-fusion-biopsy (fusPbx) and in systematic biopsy (sysPbx). MATERIALS AND METHODS: Six hundred and twenty five patients undergoing multiparametric MRI were investigated. MRI findings were classified using PI-RADS v1 or v2. All patients underwent fusPbx combined with sysPbx (comPbx). The lesion with the highest PI-RADS was defined as maximum PI-RADS (maxPI-RADS). Gleason Score ≥7 (3 + 4) was defined as significant PCa. RESULTS: The overall PCa detection rate was 51% (n = 321; 39% significant PCa). The detection rate was 43% in fusPbx (n = 267; 34% significant PCa) and 36% in sysPbx (n = 223; 27% significant PCa). Nine percentage of significant PCa were detected by sysPbx alone. A total of 1,162 lesions were investigated. The detection rate of significant PCa in lesions with PI-RADS 2, 3, 4, and 5 were 9% (18/206), 12% (56/450), 27% (98/358), and 61% (90/148) respectively. maxPI-RADS ≥4 was the strongest predictor for the detection of significant PCa in comPbx (OR 2.77; 95% CI 1.81-4.24; p < 0.005). CONCLUSIONS: maxPI-RADS is the strongest predictor for the detection of significant PCa in comPbx. Due to a high detection rate of additional significant PCa in sysPbx, fusPbx should still be combined with sysPbx.

Testicular cancer patients undergoing cisplatin based chemotherapy exhibit temporary olfactory threshold scores changes.

Testicular cancer is the most frequent malignant disease in young males between 15 and 35 years. Platinum based chemotherapy regimen is the therapy of choice in advanced disease. This treatment has also adverse effects caused by the cytostatic active substances, such as olfactory dysfunctions. The aim of this study was, therefore, to monitor olfactory function of testicular cancer patients during and 6 months after chemotherapy. A total of 17 patients (mean age 31.06 ± 10.26 years), which underwent chemotherapy (mean 2.47 cycles ± 0.5) were enrolled in this study. Odor threshold, discrimination and identification were assessed by means of the "Sniffin' Sticks" prior to and on day 42, 90 and 180 after chemotherapy has been completed. Furthermore, patients' ratings of olfactory function and depressive symptoms were evaluated. Threshold scores were significantly lower on day 90 (8.0 ± 2.51) compared to baseline (10.4 ± 2.20) (p = 0.014) and recovered almost completely on day 180 (9.65 ± 3.26). Odor discrimination and identification did not show significant changes during therapy. The decrease of the olfactory function during/immediately after chemotherapy was underlined by the subjectively perceived impaired olfactory function during this time. In addition almost every fourth patient presented with a depressed mood at the beginning of chemotherapy. Patients should be informed about possible transient olfactory impairment during/immediately after chemotherapy.

Direct comparison of multiparametric magnetic resonance imaging (MRI) results with final histopathology in patients with proven prostate cancer in MRI/ultrasonography-fusion biopsy.

OBJECTIVE: To compare multiparametric magnetic resonance imaging (mpMRI) of the prostate and histological findings of both targeted MRI/ultrasonography-fusion prostate biopsy (PBx) and systematic PBx with final histology of the radical prostatectomy (RP) specimen. PATIENTS AND METHODS: A total of 105 patients with prostate cancer (PCa) histopathologically proven using a combination of fusion Pbx and systematic PBx, who underwent RP, were investigated. All patients had been examined using mpMRI, applying the European Society of Urogenital Radiology criteria. Histological findings from the RP specimen were compared with those from the PBx. Whole-mount RP specimen and mpMRI results were directly compared by a uro-pathologist and a uro-radiologist in step-section analysis. RESULTS: In the 105 patients with histopathologically proven PCa by combination of fusion PBx and systematic PBx, the detection rate of PCa was 90% (94/105) in fusion PBx alone and 68% (72/105) in systematic PBx alone (P = 0.001). The combination PBx detected 23 (22%) Gleason score (GS) 6, 69 (66%) GS 7 and 13 (12%) GS ≥8 tumours. Fusion PBx alone detected 25 (26%) GS 6, 57 (61%) GS 7 and 12 (13%) GS ≥8 tumours. Systematic PBx alone detected 17 (24%) GS 6, 49 (68%) GS 7 and 6 (8%) GS ≥8 tumours. Fusion PBx alone would have missed 11 tumours (4% [4/105] of GS 6, 6% [6/105] of GS 7 and 1% [1/105] of GS ≥8 tumours). Systematic PBx alone would have missed 33 tumours (10% [10/105] of GS 6, 20% [21/105] of GS 7 and 2% [2/105] of GS ≥8 tumours). The rates of concordance with regard to GS between the PBx and RP specimen were 63% (n = 65), 54% (n = 56) and 75% (n = 78) in fusion, systematic and combination PBx (fusion and systematic PBx combined), respectively. Upgrading of the GS between PBx and RP specimen occurred in 33% (n = 34), 44% (n = 46) and 18% (n = 19) in fusion, systematic and combination PBx, respectively. γ-correlation for detection of any cancer was 0.76 for combination PBx, 0.68 for fusion PBx alone and 0.23 for systematic PBx alone. In all, 84% (n = 88) of index tumours were identified by mpMRI; 86% (n = 91) of index lesions on the mpMRI were proven in the RP specimen. CONCLUSIONS: Fusion PBx of tumour-suspicious lesions on mpMRI was associated with a higher detection rate of more aggressive PCa and a better tumour prediction in final histopathology than systematic PBx alone; however, combination PBx had the best concordance for the prediction of GS. Furthermore, the additional findings of systematic PBx reflect the multifocality of PCa, therefore, the combination of both biopsy methods would still represent the best approach for the prediction of the final tumour grading in PCa.

Prediction of cancer-specific survival after radical cystectomy in pT4a urothelial carcinoma of the bladder: development of a tool for clinical decision-making.

OBJECTIVE: To externally validate the pT4a-specific risk model for cancer-specific survival (CSS) proposed by May et al. (Urol Oncol 2013; 31: 1141-1147) and to develop a new pT4a-specific nomogram predicting CSS in an international multicentre cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) PATIENTS AND METHODS: Data from 856 patients with pT4a UCB treated with RC at 21 centres in Europe and North-America were assessed. The risk model proposed by May et al., which includes female gender, presence of positive lymphovascular invasion (LVI) and lack of adjuvant chemotherapy administration as adverse predictors for CSS, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver-operating characteristic-derived area under the curve. A nomogram for predicting CSS in pT4a UCB after RC was developed after internal validation based on multivariable Cox proportional hazards regression analysis evaluating the impact of clinicopathological variables on CSS. Decision-curve analyses were applied to determine the net benefit derived from the two models. RESULTS: The estimated 5-year-CSS after RC was 34% in our cohort. The risk model devised by May et al. predicted individual 5-year-CSS with an accuracy of 60.1%. In multivariable Cox proportional hazards regression analysis, female gender (hazard ratio [HR] 1.45), LVI (HR 1.37), lymph node metastases (HR 2.54), positive soft tissue surgical margins (HR 1.39), neoadjuvant (HR 2.24) and lack of adjuvant chemotherapy (HR 1.67, all P < 0.05) were independent predictors of an adverse CSS rate and formed the features of our nomogram with a predictive accuracy of 67.1%. Decision-curve analyses showed higher net benefits for the use of the newly developed nomogram in our cohort over all thresholds. CONCLUSIONS: The risk model devised by May et al. was validated with moderate discrimination and was outperformed by our newly developed pT4a-specific nomogram in the present study population. Our nomogram might be particularly suitable for postoperative patient counselling in the heterogeneous cohort of patients with pT4a UCB.

Age, American Society of Anesthesiologists physical status classification and Charlson score are independent predictors of 90-day mortality after radical cystectomy.

PURPOSE: Radical cystectomy (RC) is a major surgical procedure accompanied with meaningful complications and countable perioperative mortality. To identify the risk factors predicting the perioperative morbidity and mortality is essential. The study aimed to identify relevant, patient-specific factors associated with 90-day mortality following RC, which may serve as a foundation for improving healthcare delivery to patients with bladder cancer. METHODS: We investigated a sample of 1015 consecutive patients in order to identify predictors of 90-day mortality after RC. Beside tumor-related parameters, ASA classification, NYHA, Canadian Cardiovascular Society classification of angina pectoris, Charlson score, age, gender and the single conditions contributing to the Charlson score were included in the multivariable analyses. The patient data were collected retrospectively, except the ASA score that was obtained prospectively. RESULTS: We identified a model containing the parameters age (OR 1.05, p = 0.023), ASA classification of 3-4 (OR 6.19, p < 0.001) and Charlson score (OR 1.22, p = 0.003) to predict 90-day mortality. Among the single conditions to the Charlson score, moderate or severe renal disease (OR 3.94, p < 0.001) and liver disease (OR 3.24, p = 0.037) were most closely related to 90-day mortality. CONCLUSIONS: Age, ASA classification and Charlson score as well as moderate or severe renal disease and liver disease appear to be independent predictors of 90-day mortality after RC. Given the highly significant association of ASA score with 90-day mortality and the relative ease and width disposability of this measure, this classification should be, after external validation, incorporated into daily clinical practice in treatment of patients planned to RC.

Impact of Adjuvant Intravesical Bacillus Calmette-Guérin Treatment on Patients with High-Grade T1 Bladder Cancer.

PURPOSE: To evaluate the impact of adjuvant intravesical bacillus Calmette-Guérin (BCG) treatment in patients with high-grade transitional cell carcinoma of bladder. PATIENTS AND METHODS: A total of 207 consecutive patients who underwent transurethral resection for high-grade T1 transitional cell carcinoma of bladder at our institution between January 1, 2005 and December 31, 2012. Of those patients, 77 underwent early cystectomy without BCG instillation and were excluded from the analysis. The overall survival and cancer-specific mortality were compared in 2 different therapy options groups (group of patients who received adjuvant BCG instillation vs. the group of patients who did not receive BCG therapy). Overall mortality was estimated by the Kaplan-Meier method, univariate comparisons were made with the log rank test. The cumulative incidence of deaths from bladder cancer (BC) was determined by univariate and multivariate competing risk analysis. Cox proportional hazard models for competing risks were used to study the combined effects of the variables on BC-specific mortality. RESULTS: The 5-year overall survival in patients with BCG instillation vs. patients who did not receive BCG therapy was 74 vs. 28% (p = 0.0016). In the univariate analysis, the adjuvant intravesical BCG treatment was associated with decreased cancer-specific mortality (p = 0.0062). In the multivariable analysis, the age and the BCG instillation were independent factors of overall survival (hazard ratio 0.26, 95% CI 0.15-0.46, p < 0.0001) and cancer-specific mortality (hazard ratio 0.29, 95% CI 0.12-0.71, p = 0.0067). CONCLUSION: Dispensing from adjuvant intravesical BCG treatment is associated with increased overall- and disease-specific mortality in patients with T1 high-grade transitional cell carcinoma of bladder. This observation confirms that adjuvant BCG instillation is a crucial part of treatment in this patient population.