Accuracy of the European Association of Urology (EAU) NMIBC 2021 scoring model in predicting progression in a large cohort of HG T1 NMIBC patients treated with BCG.

BACKGROUND: Recently, the European Association of Urology Guidelines Panel updated the prognostic factor risk groups model for non-muscle-invasive bladder cancer (NMIBC) with the introduction of a new group of patients at very high risk (VHR). Furthermore, three additional clinical risk factors (i.e., age>70 years, multiple papillary tumors; tumor diameter >3 cm) were proposed. However, the new scoring model was created by analyzing data from patients who did not receive BCG intravesical therapy. METHODS: This is a retrospective multicenter study analyzing data of 920 patients with HGT1 NMIBC that underwent ReTUR e following BCG intravesical therapy. Patients were stratified into risk groups according to the 2021 new EAU NMIBC prognostic factor risk groups model. This study aimed to identify variables related to disease progression in a large cohort of HGT1 NMIBC patients who underwent both Re-TURB and BCG intravesical immunotherapy. RESULTS: Median follow-up was 51 months (IQR 41-75), according to EAU NMIBC 2021 scoring model 179 (19.5%) patients were at VHR. Progression-free survival at 5 years was 68.2% and 59.9% for the whole sample and the VHR group, respectively. At multivariable regression model size >3 cm, multifocal tumor, concomitant CIS and LVI were identified as independently associated with disease progression. CONCLUSIONS: Although patients at VHR are more likely to experience disease progression during follow-up, the European Association of Urology (EAU) NMIBC 2021 scoring model appears to be suboptimal in patients who underwent ReTUR and intravesical BCG therapy.

Association of statin use and oncological outcomes in patients with first diagnosis of T1 high grade non-muscle invasive urothelial bladder cancer: results from a multicenter study.

BACKGROUND: We aimed to test the hypothesis that the immune-modulatory effect of statins may improve survival outcomes in patients with non-muscle invasive bladder cancer (NMIBC). We focused on a cohort of patients diagnosed with high risk NMIBC, that were treated with intravesical BCG immunotherapy. METHODS: We included patients at first diagnosis of T1 high grade NMIBC after transurethral resection of bladder (TURB). All procedures were performed at 18 different tertiary institutions between January 2002 and December 2012. Univariable and multivariable models were used to test differences in terms of residual tumor, disease recurrence, disease progression and overall mortality (OM) rates. RESULTS: Overall, 1510 patients with T1 high grade NMIBC at TURB were included in our analyses. Of these, 402 (26.6%) were statin users. At multivariable analysis, statin use was associated with a higher rate of high-grade BC at re-TURB (OR: 1.37, 95%CI: 1.04-1.78; P=0.022), while at follow-up it was not independently associated with OM (HR: 0.71, 95%CI: 0.50-1.03; P=0.068) and disease progression rates (HR: 0.97, 95%CI: 0.79-1.19; P=0.753). Conversely, statin use has been shown to be independently associated with a lower risk of recurrence (HR:0.80, 95%CI: 0.67-0.95; P=0.009). The median recurrence-free survival was 47 (95%CI 40-49) months for those classified as non-statin users vs. 53 (95%CI 48-68) months in those classified as statin users. CONCLUSIONS: Statin daily intake do not compromise oncological outcomes in high risk NMIBC patients treated with BCG. Moreover, statin may have a beneficial effect on recurrence rates in this cohort of patients.

A treatment strategy to help select patients who may not need secondary intervention to remove symptomatic ureteral stones after previous stenting.

PURPOSE: This study aimed at evaluating whether removal of the ureteral stent the day before scheduled secondary intervention facilitates spontaneous ureteral stone passage and thus can spare the pre-stented patient this surgery. METHODS: Retrospective analysis of a single-centre consecutive series of 216 patients after previous stenting due to a symptomatic ureteral stone from 01/2013 to 01/2018. Indwelling stents were removed under local anaesthesia. Patients were told to filter their urine overnight. Multivariate analysis was performed to assess predictive factors for spontaneous stone passage. RESULTS: 34% (74/216) of patients had spontaneous stone passage while the stent was indwelling. Of the remaining 142 patients, 41% (58/142) had spontaneous stone passage within 24 h after stent removal. Only 84/216 (39%) patients needed secondary intervention. Multivariate logistic regression analysis of all 216 patients showed a significant association between spontaneous stone passage and smaller stone size (p < 0.001), distal stone location (p = 0.046) and stent dwell time (p = 0.02). Predictive factors for spontaneous stone passage after stent removal were smaller size (p < 0.001), distal location (p = 0.001), and stone movement while the stent was indwelling (p = 0.016). A treatment strategy was established that helps select patients suitable for conservative management. CONCLUSIONS: The majority (61%) of ureteral stones passed spontaneously after pre-stenting; 34% while the stent was indwelling, 27% within 24 h after stent removal. Besides distal stone location, stone size (< 6 mm) and stone movement (≥ 5 cm) while the stent is indwelling indicate patients who are likely to pass their ureteral stone spontaneously after stent removal. The treatment strategy (decision tree) presented here helps identify those patients. TRIAL REGISTRATION: https://doi.org/10.1186/ISRCTN12112914 .

Prognostic Value of Concomitant Carcinoma In Situ in the Radical Cystectomy Specimen: A Systematic Review and Meta-Analysis.

PURPOSE: We investigated the prognostic impact of concomitant carcinoma in situ in radical cystectomy specimens. MATERIALS AND METHODS: We performed a systematic review and meta-analysis using MEDLINE®, Scopus®, Web of Science™ and The Cochrane Library to identify eligible studies published until October 2017. Studies were eligible for analysis if they compared patients with concomitant carcinoma in situ in radical cystectomy specimens for bladder cancer to patients without concomitant carcinoma in situ to determine its value to prognosticate overall mortality, recurrence-free survival, cancer specific mortality and ureteral involvement using multivariable analysis. The protocol for this systematic review was registered in PROSPERO (Prospective Register of Systematic Reviews, CRD42018086539) and is available in full on the University of York website. RESULTS: Overall 23 studies published between 2006 and 2017 including a total of 20,647 patients were selected for the systematic review and meta-analysis. Concomitant carcinoma in situ was reported in 39.4% of radical cystectomy specimens. In studies analyzing all patients the presence of concomitant carcinoma in situ was not associated with overall mortality (pooled HR 0.92, 0.77-1.10), recurrence-free survival (pooled HR 1.06, 0.99-1.13) or cancer specific mortality (pooled HR 1.00, 0.93-1.07). It was associated with ureteral involvement (pooled OR 4.51, 2.59-7.84). On subanalysis of studies restricted to patients with organ confined bladder cancer at radical cystectomy concomitant carcinoma in situ was associated with worse recurrence-free survival (pooled HR 1.57, 1.12-2.21) and cancer specific mortality (pooled HR 1.51, 1.001-2.280). CONCLUSIONS: Concomitant carcinoma in situ is significantly associated with ureteral involvement in patients treated with radical cystectomy. In patients with organ confined disease concomitant carcinoma in situ in the radical cystectomy specimen is a prognosticator of recurrence-free survival and cancer specific mortality.

High-throughput detection of low abundance sialylated glycoproteins in human serum by TiO2 enrichment and targeted LC-MS/MS analysis: application to a prostate cancer sample set.

Glycopeptide enrichment can be a strategy to allow the detection of peptides belonging to low abundance proteins in complex matrixes such as blood serum or plasma. Though several glycopeptide enrichment protocols have shown excellent sensitivities in this respect, few reports have demonstrated the applicability of these methods to relatively large sample cohorts. In this work, a fast protocol based on TiO2 enrichment and highly sensitive mass spectrometric analysis by Selected Reaction Monitoring (SRM) has been applied to a cohort of serum samples from prostate cancer and benign prostatic hyperplasia patients in order to detect low abundance proteins in a single LC-MS/MS analysis in nanoscale format, without immunodepletion or peptide fractionation. A peptide library of over 700 formerly N-glycosylated peptides was created by data dependent analysis. Then, 16 medium to low abundance proteins were selected for detection by single injection LC-MS/MS based on selected-reaction monitoring. Results demonstrated the consistent detection of the low-level proteins under investigation. Following label-free quantification, four proteins (Adipocyte plasma membrane-associated protein, Periostin, Cathepsin D and Lysosome-associated membrane glycoprotein 2) were found significantly increased in prostate cancer sera compared to the control group. Graphical abstract ᅟ.

Long-term oncologic and functional outcomes after robot-assisted partial nephrectomy in elderly patients.

BACKGROUND: The aim of this study was to assess the long-term oncologic and functional outcomes in elderly patients having undergone robot-assisted partial nephrectomy (RAPN) for renal cancer (RC). METHODS: Sixty-one patients out of 323 who underwent RAPN for localized RC between July 2009 and March 2016 in our high-volume robotic surgery center (>800 procedures/year), had 70 years or more. Inclusion criteria of the study were age ≥70 years; pathological confirmed RCC and ASA Score ≤3. All patients were stratified according to PADUA classification system in three groups: <7 points, 8-9 points, >10 points. Trifecta was defined as a warm ischemia time (WIT) less then 25 min, negative surgical margins and no perioperative complications. RESULTS: A total of 52 patients were included; median follow-up was 47 months. Median age was 74 yrs. (IQR 72-76.5). Complication rate was 15.4%. Trifecta failure was associated to PADUA Score (P=0.02), and tumor diameter (P=0.04). Renal function was altered in 10 (19.2%) patients before surgery and at last follow-up in 11 (21.1%) patients (CKD stage>2) The DFS, OS and CSS were 89.33%, 90.06% and 94.4%, respectively. CONCLUSIONS: In a high-volume center, robot-assisted approach is feasible and safe in surgical fit elderly patients with good long-term oncologic outcomes.

Prognostic value of modified Glasgow Prognostic Score in non-muscle-invasive bladder cancer.

PURPOSE: To investigate the prognostic value of preoperative modified Glasgow Prognostic Score (mGPS) in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of bladder with or without intravesical therapy. MATERIAL AND METHODS: We retrospectively reviewed our medical records to identify 1,096 consecutive patients with NMIBC treated with transurethral resection of bladder. The mGPS of each patient was calculated on the basis of preoperative serum C-reactive protein and albumin. Univariable and multivariable Cox regression analyses were performed to investigate the association of mGPS with recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: The mGPS of 0, 1, and 2 was observed in 764 (69.7%), 299 (27.3%), and 33 (3.0%) patients, respectively. On univariable analysis, mGPS 2 was associated with worse RFS (Hazard Ratio [HR]: 1.60, 95%; CI: 1.01-2.54). However, on multivariable analyses, which adjusted for the effects of established clinicopathologic features, mGPS 2 did not maintain its independent association with RFS (HR: 1.41, 95% CI: 0.88-2.26). On multivariable analysis, mGPS 1 and 2 were both independently associated with worse PFS compared to mGPS 0 (HR: 2.06, 95% CI: 1.37-3.12 and HR: 3.31, 95% CI: 1.40-7.87, respectively). The inclusion of mGPS improved the discrimination of a standard prognostic model for PFS from 71.6% to 73.8%. In subgroup analyses, mGPS 1 was associated with PFS (HR 2.09, 95% CI: 1.24-3.52) on multivariable analysis in patients with the European Association of Urology high-risk group. Additionally, in patients treated with bacillus Calmette-Guérin, mGPS 2 was associated with disease PFS (HR10.1, 95% CI: 2.61-38.8). CONCLUSIONS: The mGPS independently predicts PFS in patients with NMIBC. Inclusion of mGPS in prognostic models might help identify patients who are more likely to fail standard therapy and experience disease progression and, therefore, may benefit from intensified therapy such as radical cystectomy or inclusion in clinical trials of novel immunotherapeutics.

Clinical value of cholinesterase in the prediction of biochemical recurrence after radical prostatectomy.

PURPOSE: To evaluate the predictive and prognostic role as well as the clinical impact on decision-making of serum cholinesterase (ChoE) levels in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer. MATERIALS AND METHODS: We conducted a retrospective analysis of our multi institutional database. Preoperative ChoE was evaluated as continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with biochemical recurrence (BCR)-free survival. We assessed its association with perioperative clinicopathologic characteristics and outcomes. Multivariable models established its independent prognostic value for BCR. Cox proportional hazard coefficients were used to build nomograms for the prediction of early and late BCR. Decision curve analysis was used to assess the clinical impact on decision making of preoperative ChoE. RESULTS: In all, 6,041 patients were available for the analysis. Decreased ChoE was associated with higher biopsy Gleason score, preoperative PSA levels, pathologic Gleason score, pathological stage, lymph node metastasis, positive surgical margin, and lymphovascular invasion at radical prostatectomy (all P < 0.01). Preoperative ChoE ≤ 6.52 U/ml was associated with higher probability of BCR (HR 1.72, 95% CI 1.48-1.99, P < 0.001). Preoperative and postoperative multivariable models that adjusted for the effects of established clinicopathologic features confirmed its independent association with BCR. In decision curve analysis inclusion of preoperative ChoE did not improve the net benefit of preoperative and postoperative models for the prediction of BCR. CONCLUSIONS: Despite independent association with clinicopathologic features and BCR, preoperative serum ChoE has no impact on clinical decision making. Future studies should investigate the possible relationship between ChoE activity and neoplastic cell transformation with a rational for targeting.

Prognostic Value of Serum Cholinesterase in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Serum cholinesterase (ChE) has been reported to be a prognostic factor in several cancers, but its relationship with oncologic outcomes of non-muscle-invasive bladder cancer (NMIBC) has not yet been well-studied. MATERIALS AND METHODS: We retrospectively assessed 1117 patients with NMIBC undergoing transurethral resection of the bladder. Cox regression analyses were performed to elucidate the association between preoperative ChE and oncologic outcomes such as recurrence-free survival (RFS) and progression-free survival. RESULTS: The median preoperative ChE level was 5.51 kU/L (interquartile range, 4.95-7.01), and the optimal cut-off value of ChE obtained from receiver operator characteristic analysis was 5.55 kU/L. The 5-year RFS in patients with low and normal ChE levels were 41.1% and 70.0%, respectively (P < .001). The 5-year progression-free survival in patients with low and normal ChE levels were 93.2% and 91.4%, respectively (P = .053). On multivariable analysis, ChE was significantly associated with shorter RFS (P < .001). ChE as a continuous variable and low ChE levels improved the C-index for prediction of disease recurrence by 4.0% and 2.7% to 72.4% and 71.1%, respectively. In patients stratified into the European Association of Urology high-risk category, serum ChE was also a strong predictor of disease recurrence (hazard ratio, 4.14; 95% confidence interval, 2.90-5.89). Moreover, in the European Association of Urology high-risk patients treated with bacillus Calmette-Guérin immunotherapy, serum ChE was still strongly correlated with worse RFS (hazard ratio, 5.46; 95% confidence interval, 2.91-10.2). CONCLUSIONS: Decreased ChE is associated with shorter RFS in patients with NMIBC undergoing transurethral resection of the bladder. Preoperative ChE could improve patients' risk stratification and selection for adjuvant therapy. The mechanisms underlying this association needs further elucidation to design potential targets for intervention.

Robotic assisted simple prostatectomy: recent advances.

PURPOSE OF REVIEW: Robotic assisted simple prostatectomy (RASP) represents a minimally invasive evolution of traditional open simple prostatectomy for the surgical treatment of severe lower urinary tract symptoms (LUTS) because of benign prostatic enlargement (BPE). Aim of the present review is to summarize the most recent evidence on this novel procedure, and to better define its current role in the surgical armamentarium for the treatment of BPE. RECENT FINDINGS: Several studies demonstrated that RASP can be safely and effectively performed in centers with sufficient expertise. The procedure can duplicate its open counterpart with the advantage of lower perioperative morbidity, and ultimately faster patient recovery. Overall, the status of RASP seems to be well beyond that of an 'investigational' procedure, and guidelines should be amended accordingly.Nevertheless, it remains to be determined what the place of the RASP procedure in the surgical armamentarium for the treatment of symptomatic BPE will be. Over the most recent years, few comparative studies have been reported, allowing in part to draw some conclusions. RASP seems to be attractive when compared with open simple prostatectomy as it can offer less blood loss, and shorter hospital stay. However, its advantages over transurethral enucleation techniques - such as HoLEP - remain unclear. There are some specific indications, such as the presence of concomitant bladder diverticula or stones, for example, where a robotic approach could represent an appealing solution. Ultimately, further research should look at a cost analysis to determine which technique can be more cost effective. Last, the issue of the learning curve for the different procedures for symptomatic BPE remain to be further scrutinized. SUMMARY: RASP offers potential advantages over other available techniques for the treatment of large prostate glands. In centers, wherever a solid robotic program is already in place, this procedure is likely to be increasingly implemented.

Robot-assisted partial nephrectomy: systematic review of functional results.

PURPOSE OF REVIEW: Various ischemia type during partial nephrectomy for renal cell cancer (RCC) resulted in different postoperative functional outcomes. Our objective was to systematically review the contemporary literature on robot-assisted partial nephrectomy (RPN) and investigate the association of ischemia type and tumor complexity with postoperative functional outcomes of the operated kidney and overall. RECENT FINDINGS: Forty-five of the 99 reports identified were selected for qualitative analysis. All included studies were observational and nonrandomized. Overall, we found that patients undergoing RPN with zero ischemia and selective artery clamping had a lower decrease in glomerular filtration rates of the operated kidney in comparison to both warm and cold ischemia. This association seems also to play a role in patients with bilateral kidneys harboring complex tumors. SUMMARY: Zero ischemia and selective artery clamping provide the best functional outcomes following robotic partial nephrectomy. This seems to be of particular relevance in patients with single kidney or tumors of high complexity. Whether these changes are statistically or clinically significant cannot be determined within this systematic review.

Role of survivin expression in predicting biochemical recurrence after radical prostatectomy: a multi-institutional study.

OBJECTIVE: To assess the association of survivin expression with clinicopathological features and biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. METHODS: Survivin expression was evaluated by immunohistochemistry on a tissue microarray of RP cores from 3 117 patients. Survivin expression was considered altered when at least 10% of the tumour cells stained positive. The association of altered survivin expression with BCR was evaluated using Cox proportional hazards regression models. RESULTS: Survivin expression was altered in 1 330 patients (42.6%). Altered expression was associated with higher Gleason score on RP (P = 0.001), extracapsular extension (P = 0.019), seminal vesicle invasion (P < 0.001) and lymph node metastases (P = 0.009). The median (interquartile range) follow-up was 38 (21-66) months. Patients with altered survivin expression had a shorter BCR-free survival time than those with normal expression (5-year BCR-free survival estimates: 74.7 vs 79.0%; P = 0.008). Altered survivin expression did not retain its prognostic value, however, after adjustment for the effect of established clinicopathological factors (P = 0.73). Subgroup analyses also showed no independent prognostic value of survivin. CONCLUSIONS: Survivin expression is commonly altered in patients undergoing RP. Altered survivin expression is associated with the clinicopathological features of biologically and clinically aggressive PCa. Survivin expression was associated with BCR only in univariable analysis, limiting its value in daily clinical decision-making.

Urothelial cancer of the upper urinary tract: emerging biomarkers and integrative models for risk stratification.

INTRODUCTION: The aim of this review was to provide an overview of current biomarkers and risk stratification models in urothelial cancer of the upper urinary tract (UTUC). EVIDENCE ACQUISITION: A non-systematic Medline/PubMed literature search was performed using the terms "biomarkers", "preoperative models", "postoperative models", "risk stratification", together with "upper tract urothelial carcinoma". Original articles published between January 2003 and August 2015 were included based on their clinical relevance. Additional references were collected by cross referencing the bibliography of the selected articles. EVIDENCE SYNTHESIS: Various promising predictive and prognostic biomarkers have been identified in UTUC thanks to the increasing knowledge of the different biological pathways involved in UTUC tumorigenesis. These biomarkers may help identify tumors with aggressive biology and worse outcomes. Current tools aim at predicting muscle invasive or non-organ confined disease, renal failure after radical nephroureterectomy and survival outcomes. These models are still mainly based on imaging and clinicopathological feature and none has integrated biomarkers. Risk stratification in UTUC is still suboptimal, especially in the preoperative setting due to current limitations in staging and grading. Identification of novel biomarkers and external validation of current prognostic models may help improve risk stratification to allow evidence-based counselling for kidney-sparing approaches, perioperative chemotherapy and/or risk-based surveillance. CONCLUSIONS: Despite growing understanding of the biology underlying UTUC, management of this disease remains difficult due to the lack of validated biomarkers and the limitations of current predictive and prognostic tools. Further efforts and collaborations are necessaryry to allow their integration in daily practice.