External validation of nomograms including MRI features for the prediction of side-specific extraprostatic extension.

BACKGROUND: Prediction of side-specific extraprostatic extension (EPE) is crucial in selecting patients for nerve-sparing radical prostatectomy (RP). Multiple nomograms, which include magnetic resonance imaging (MRI) information, are available predict side-specific EPE. It is crucial that the accuracy of these nomograms is assessed with external validation to ensure they can be used in clinical practice to support medical decision-making. METHODS: Data of prostate cancer (PCa) patients that underwent robot-assisted RP (RARP) from 2017 to 2021 at four European tertiary referral centers were collected retrospectively. Four previously developed nomograms for the prediction of side-specific EPE were identified and externally validated. Discrimination (area under the curve [AUC]), calibration and net benefit of four nomograms were assessed. To assess the strongest predictor among the MRI features included in all nomograms, we evaluated their association with side-specific EPE using multivariate regression analysis and Akaike Information Criterion (AIC). RESULTS: This study involved 773 patients with a total of 1546 prostate lobes. EPE was found in 338 (22%) lobes. The AUCs of the models predicting EPE ranged from 72.2% (95% CI 69.1-72.3%) (Wibmer) to 75.5% (95% CI 72.5-78.5%) (Nyarangi-Dix). The nomogram with the highest AUC varied across the cohorts. The Soeterik, Nyarangi-Dix, and Martini nomograms demonstrated fair to good calibration for clinically most relevant thresholds between 5 and 30%. In contrast, the Wibmer nomogram showed substantial overestimation of EPE risk for thresholds above 25%. The Nyarangi-Dix nomogram demonstrated a higher net benefit for risk thresholds between 20 and 30% when compared to the other three nomograms. Of all MRI features, the European Society of Urogenital Radiology score and tumor capsule contact length showed the highest AUCs and lowest AIC. CONCLUSION: The Nyarangi-Dix, Martini and Soeterik nomograms resulted in accurate EPE prediction and are therefore suitable to support medical decision-making.

The current role of precision surgery in oligometastatic prostate cancer.

Oligometastatic prostate cancer (omPCa) is a novel intermediate disease state characterized by a limited volume of metastatic cells and specific locations. Accurate staging is paramount to unmask oligometastatic disease, as provided by prostate-specific membrane antigen-positron emission tomography. Driven by the results of prospective trials employing conventional and/or modern staging modalities, the treatment landscape of omPCa has rapidly evolved over the last years. Several treatment-related questions comprising the concept of precision strikes are under development. For example, beyond systemic therapy, cohort studies have found that cytoreductive radical prostatectomy (CRP) can confer a survival benefit in select patients with omPCa. More importantly, CRP has been consistently shown to improve long-term local symptoms when the tumor progresses across disease states due to resistance to systemic therapies. Metastasis-directed treatments have also emerged as a promising treatment option due to the visibility of oligometastatic disease and new technologies as well as treatment strategies to target the novel PCa colonies. Whether metastases are present at primary cancer diagnosis or detected upon biochemical recurrence after treatment with curative intent, targeted yet decisive elimination of disseminated tumor cell hotspots is thought to improve survival outcomes. One such strategy is salvage lymph node dissection in oligorecurrent PCa which can alter the natural history of progressive PCa. In this review, we will highlight how refinements in modern staging modalities change the classification and treatment of (oligo-)metastatic PCa. Further, we will also discuss the current role and future directions of precision surgery in omPCa.

Radical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery.

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design setting and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

Contrast-enhanced CT texture analysis for the prediction of delayed graft function following kidney transplantation from cadaveric donors.

OBJECTIVE: Delayed graft function (DGF) is a common complication after transplantation of deceased donor kidneys. The aim of this study was to investigate the feasibility of using computed tomography texture analysis (CT-TA) of the donor kidney to predict delayed graft function (DGF) following kidney transplantation from cadaveric donors. MATERIALS AND METHODS: We made a retrospective review of all consecutive DBD and DCD kidney donors admitted to our institution and their corresponding KTRs between December 2014 and January 2019. We extracted 15 image features from unenhanced CT and contrast-enhanced CT corresponding to first order and second order Haralick textural features. Predictors of DGF were evaluated by univariable and multivariable analysis. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) to predict DGF was calculated for the predictors. RESULTS: A total of 115 patients were included in the study. DGF occurred in 15 patients (13%). Recipient body mass index (BMI) (P=0.003) and Skewness (P=0.05) represented independent predictors in the multivariate model. The combination of both clinical and textural features in a bivariate model reached a ROC-AUC of 0.79 (95% CI: 0.64-0.94) in predicting the probability of DGF. CONCLUSION: Results from this preliminary study suggest that CT texture analysis might be a promising quantitative imaging tool to help physician predict DFG after kidney transplantation from cadaveric donors. LEVEL OF EVIDENCE: 4/5.

Impact of PI-QUAL on PI-RADS and cancer yield in an MRI-TRUS fusion biopsy population.

PURPOSE: To test the inter-reader agreement of the Prostate Imaging Quality (PI-QUAL) score for multiparametric prostate MRI and its impact on diagnostic performance in an MRI-ultrasound fusion biopsy population. PATIENTS AND METHODS: Pre-biopsy multiparametric (T2-weighted, DWI, and DCE) prostate MRIs (mpMRI) of 50 patients undergoing transrectal ultrasound-guided MRI-fusion (MRI-TRUS) biopsy were included. Two radiologists independently assigned a PI-QUAL score to each patient and assessed the diagnostic quality of individual sequences. PI-RADS categories were assigned to six regions per prostate (left and right: base/mid-glandular/apex). Inter-reader agreement was calculated using Cohen's kappa and diagnostic performance was compared by the area under the receiver operating characteristics curve (AUC). RESULTS: In 274 diagnostic areas, the malignancy rate was 62.7% (22.5% clinically significant prostate cancer, ISUP ≥ 2). Inter-reader agreement for the diagnostic quality was poor for T2w (kappa 0.19), fair for DWI and DCE (kappa 0.23 and 0.29) and moderate for PI-QUAL (kappa 0.51). For PI-RADS category assignments, inter-reader agreement was very good (kappa 0.86). Overall diagnostic performance did not differ between studies with a PI-QUAL score > 3 compared to a score ≤ 3 (p = 0.552; AUC 0.805 and 0.839). However, the prevalence of prostate cancer was significantly lower when the PI-QUAL score was ≤ 3 (16.7% vs. 30.2%, p = 0.008). CONCLUSION: PI-QUAL has only a limited impact on PI-RADS diagnostic performance in patients scheduled for MRI-TRUS fusion biopsy. However, the lower cancer prevalence in the lower PI-QUAL categories points out a risk of false-positive referrals and unnecessary biopsies if prostate imaging quality is low.

Outcome of immune checkpoint inhibitors in metastatic renal cell carcinoma across different treatment lines.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have led to a paradigm change in the management of metastatic renal cell carcinoma (mRCC). Prospective trials have focused on ICI treatment in the first or second line. The aim of this analysis is to evaluate the benefit of ICI across different treatment lines. PATIENTS AND METHODS: This is a single-center retrospective study that included mRCC patients who received ICIs in various treatment lines. Objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Ninety-four patients were eligible for full evaluation. Patients were classified as International mRCC Database Consortium (IMDC) risk group categorization as good, intermediate and poor risk in 26.8%, 61.6% and 14.8% of cases, respectively. They were treated with ICI monotherapy, dual ICI therapy and ICI + tyrosine kinase inhibitor in 59%, 20% and 21% of cases, respectively. ORR, median PFS and OS for the entire cohort was 39.4%, 9.67 months [95% confidence interval (CI) 6.9-12.4 months] and 23.6 months (95% CI 13.3-33.9 months), respectively. The ORR by treatment line was 33% in first, 40.4% in the second, 35% in the third and 43.5% in the fourth line and beyond. Median PFS by treatment line was 8.6, 10.3, 7.9 and 7.23 months, respectively. The median OS was not reached in first-line treatment and was 26.2, 18.1 and 20.7 months in the second, third and fourth line and beyond, respectively. CONCLUSIONS: ICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.

Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients.

INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.

Sarcopenic Obesity and its Prognostic Impact on Urological Cancers: A Systematic Review.

PURPOSE: Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and significance of sarcopenic obesity are not well understood. We systematically reviewed data on the prevalence and prognostic impact of sarcopenic obesity for patients with renal cell carcinoma, urothelial carcinoma and prostate cancer undergoing treatment. MATERIALS AND METHODS: We searched EMBASE®, PubMed®/MEDLINE® and Scopus® for relevant original articles and abstracts published between January 2010 and February 2021. Primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival. The secondary outcome was the prevalence of sarcopenic obesity. RESULTS: A total of 15 studies comprising 3,866 patients were included. Of the 10 studies that evaluated survival outcomes, the association between sarcopenic obesity and survival was mixed. One of 10 studies showed a significant association of sarcopenic obesity with OS (HR 0.7, 95% CI 0.51-0.98; p=0.04). One additional study showed reported a trend for shorter OS (p=0.05) associated with sarcopenic obesity. Others reported that it is an adverse prognostic factor for CSS (HR 5.0, 95% CI 1.4-16.7; p=0.01). All other studies did not demonstrate that sarcopenic obesity was of prognostic relevance with regard to OS, CSS and progression-free survival. Overall, its mean prevalence was 27% (range 11-63). CONCLUSIONS: There is considerable heterogeneity in methods used to define sarcopenic obesity in the literature, and current data are limited. Future studies are needed to further understand the relationship of obesity and sarcopenia on the clinical trajectory of patients with urological cancer.

Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET/MRI.

PURPOSE: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. METHODS: Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. RESULTS: The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. CONCLUSION: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

The prognostic value of serum MMP-7 levels in prostate cancer patients who received docetaxel, abiraterone, or enzalutamide therapy.

OBJECTIVES: The rapidly changing treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) calls for biomarkers to guide treatment decisions. We recently identified MMP-7 as a potential serum marker for the prediction of response and survival in mCRPC patients who received docetaxel (DOC) chemotherapy. Here, we aimed to test this finding in an independent patient cohort and in addition to explore the prognostic potential of serum MMP-7 in abiraterone (ABI) or enzalutamide (ENZA) treated patients. METHODS AND MATERIALS: MMP-7 levels were measured in 836 serum samples from 320 mCRPC patients collected before and during DOC (n = 95), ABI (n = 140), or ENZA (n = 85) treatment by using the ELISA method. Results were correlated with clinical and follow-up data. RESULTS: MMP-7 baseline levels were similar between the 3 treatment groups. In the ABI and ENZA cohorts, baseline MMP-7 levels were lower in patients with prior radical prostatectomy (P = 0.058 and P = 0.041, respectively). Baseline MMP-7 levels above the median were associated with shorter overall survival for the DOC (P = 0.001) and ENZA (P = 0.006) cohorts. Multivariable analyses in the DOC and ENZA cohorts revealed that high pretreatment MMP-7 level is an independent risk factor for patients' survival. In addition, in DOC-treated patients with high baseline MMP-7 level, marker decrease at the third DOC cycle was associated with improved survival. Patients with high baseline MMP-7 levels had better survival when treated with ABI compared to DOC or ENZA. CONCLUSIONS: We confirmed the prognostic value of pretreatment MMP-7 serum level and its changes as independent predictors of survival in DOC-treated mCRPC patients. In addition, high MMP-7 was a negative predictor in ENZA-treated but not in ABI-treated patients. These results warrant further research to confirm the predictive value of serum MMP-7 and to explore the potential mechanistic involvement of MMP-7 in DOC and ENZA resistance of mCRPC patients.

Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.

The effect of maternal sleep deprivation on differentiation of mesenchymal stem cells in the presence of neonates brain cerebrospinal fluid of Wistar rats.

OBJECTIVE: Cerebrospinal fluid (CSF) contains proliferation, differentiation and maturation signals that are essential factors for brain development. Due to presence of such factors this fluid has proliferative and differentiation potential. A previous study showed that maternal sleep deprivation (MSD) decrease the number of newborn neurons in development of hippocampus. Also, it impairs hippocampus-dependent spatial learning and memory in the young offspring rat. MSD can change CSF factors. In the present study, the effect of MSD-CSF on differentiation of mesenchymal stem cells to neural cells was examined, and expression of Nestin, Neun, and NeurD1 that are neurogenic markers was investigated. MATERIAL AND METHODS: In this study, bone marrow mesenchymal stem cells were aspirated from the femur and tibia of young male Wistar rats. Then cell suspension was cultured in DMEM medium supplemented with 10 % FBS and 1 % antibiotics. Pregnant rats were subjected to sleep deprivation for 6 h by gentle handling during 4th, 7th, and 18th day of pregnancy. CSF was collected from cisterna magna of neonate rats. CSF was added to culture media with a 5 % ratio (v/v). Then cell viability was determined with MTT assay. Total cellular RNA was extracted, cDNA was synthesized and NeuN, Nestin, NeuroD1 and IL-6 genes were analyzed by Real-time PCR. RESULTS: Real time-PCR analysis showed that expression of Neun and NeurD1gene decreased compared with culture in normal CSF (N-CSF), and also showed that expression of Nestin did not decrease, inflammatory gene (IL-6) showed high expression compared to culture with N-CSF. CONCLUSION: Based on our results, MSD-CSF could inhibit neurogenesis process in mesenchymal stem cells and also, this result suggests that MSD can suppress neural differentiation and decrease of neurogenesis gene expression. Overall these findings suggest that insomnia and sleep loss may active inflammatory responses in the brain and change CSF-markers (Fig. 3, Ref. 34).

Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.

Absolute basophil count is associated with time to recurrence in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p < 0.1, have been selected for the development of a multivariable model. RESULTS: A total of 1045 patients with primary T1 HG/G3 were included. A total of 678 (64.9%) recurrences, 303 (29.0%) progressions and 150 (14.3%) deaths were observed during follow-up. Multivariate analysis showed that logarithmic transformation of basophils count was associated with a 30% increment in the hazard of recurrence per unit increase of logarithmic basophils count (HR 1.30; 95% confidence interval 1.09-1.54; p = 0.0026). Basophil count modeled by quartiles was also significantly associated with time to recurrence [second vs. lower quartile HR 1.42 (1.12-1.79); p = 0.003, third vs. lower quartile HR 1.26 (1.01-1.57); p = 0.041; upper vs. lower quartile HR 1.36 (1.1-1.68); p = 0.005]. The limitations of a retrospective study are applicable. CONCLUSION: Baseline basophil count may predict recurrence in BCG-treated HG/G3 T1 bladder cancer patients. External validation is warranted.

Can the addition of clinical information improve the accuracy of PI-RADS version 2 for the diagnosis of clinically significant prostate cancer in positive MRI?

AIM: To report prostate cancer (PCa) prevalence in Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) categories and investigate the potential to avoid unnecessary, magnetic resonance imaging (MRI)-guided in-bore biopsies by adding clinical and biochemical patient characteristics. MATERIALS AND METHODS: The present institutional review board-approved, prospective study on 137 consecutive men with 178 suspicious lesions on 3 T MRI was performed. Routine data collected for each patient included patient characteristics (age, prostate volume), clinical background information (prostate-specific antigen [PSA] levels, PSA density), and PI-RADS v2 scores assigned in a double-reading approach. RESULTS: Histopathological evaluation revealed a total of 93/178 PCa (52.2%). The mean age was 66.3 years and PSA density was 0.24 ng/ml2 (range, 0.04-0.89 ng/ml). Clinically significant PCa (csPCa, Gleason score >6) was confirmed in 50/93 (53.8%) lesions and was significantly associated with higher PI-RADS v2 scores (p=0.0044). On logistic regression analyses, age, PSA density, and PI-RADS v2 scores contributed independently to the diagnosis of csPCa (p=7.9×10-7, p=0.097, and p=0.024, respectively). The resulting area under the receiver operating characteristic curve (AUC) to predict csPCa was 0.76 for PI-RADS v2, 0.59 for age, and 0.67 for PSA density. The combined regression model yielded an AUC of 0.84 for the diagnosis of csPCa and was significantly superior to each single parameter (p≤0.0009, respectively). Unnecessary biopsies could have been avoided in 50% (64/128) while only 4% (2/50) of csPCa lesions would have been missed. CONCLUSIONS: Adding age and PSA density to PI-RADS v2 scores improves the diagnostic accuracy for csPCa. A combination of these variables with PI-RADS v2 can help to avoid unnecessary in-bore biopsies while still detecting the majority of csPCa.