Transcriptomic analysis of micropapillary high grade T1 urothelial bladder cancer.

No consensus currently exist on the optimal treatment of patients with high-risk nonmuscle invasive (HGT1) micropapillary variant of bladder cancer (MPBC). Transcripsome analysis may allow stratification of MPBC-HGT1 enabling prediction of recurrence and guide therapeutic management for individual patients. Whole transcriptome RNA-Sequencing of tumors from 23 patients with MPBC-HGT1 and 64 conventional urothelial carcinomas (cUC) (reference set) was performed. Differentially expressed genes between MPBC-HGT1 and cUC-HGT1 were explored. Cox proportional hazard models and Kapplan-Meier methods were used to assess the relation between time to progression (TTP) and individual gene expression adjusting for clinical covariates. Over 3000 genes were differentially expressed in MPBC-HGT1 as compared with cUC-HGT1 and a 26-gene signature is characteristic of MPBC within HGT1. A set of three genes; CD36, FAPB3 and RAETE1; were significantly associated with TTP. High expression of FABP3 and CD36 were associated with shorter TTP (p = 0.045 and p = 0.08) as was low expression of RAET1E (p = 0.01). Our study suggest that a 26-gene signature can define MPBC-HGT1 within conventional urothelial carcinomas. A prognostic risk index of three genes (FABP3, CD36 and RAET1E) was found to be associated with shorter TTP and may help classify a group of patients with MPBC-HGT1 with high-risk of early progression. These observations might have implications in terms of radical cystectomy recommendation in MPBC patients.

Genomic Predictors of Good Outcome, Recurrence, or Progression in High-Grade T1 Non-Muscle-Invasive Bladder Cancer.

High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non-muscle-invasive bladder cancer with unpredictable outcome and poorly understood risk factors. Here, we examined the association of somatic mutation profiles with nonrecurrent disease (GO, good outcome), recurrence (R), or progression (PD) in a cohort of HGT1 patients. Exome sequencing was performed on 62 HGT1 and 15 matched normal tissue samples. Both tumor only (TO) and paired analyses were performed, focusing on 95 genes known to be mutated in bladder cancer. Somatic mutations, copy-number alterations, mutation load, and mutation signatures were studied. Thirty-three GO, 10 R, 18 PD, and 1 unknown outcome patients were analyzed. Tumor mutational burden (TMB) was similar to muscle-invasive disease and was highest in GO, intermediate in PD, and lowest in R patients (P = 0.017). DNA damage response gene mutations were associated with higher TMB (P < 0.0001) and GO (P = 0.003). ERCC2 and BRCA2 mutations were associated with GO. TP53, ATM, ARID1A, AHR, and SMARCB1 mutations were more frequent in PD. Focal copy-number gain in CCNE1 and CDKN2A deletion was enriched in PD or R (P = 0.047; P = 0.06). APOBEC (46%) and COSMIC5 (34%) signatures were most frequent. APOBEC-A and ERCC2 mutant tumors (COSMIC5) were associated with GO (P = 0.047; P = 0.0002). pT1b microstaging was associated with a genomic cluster (P = 0.05) with focal amplifications of E2F3/SOX4, PVRL4, CCNE1, and TP53 mutations. Findings were validated using external public datasets. These findings require confirmation but suggest that management of HGT1 bladder cancer may be improved via molecular characterization to predict outcome. SIGNIFICANCE: Detailed genetic analyses of HGT1 bladder tumors identify features that correlate with outcome, e.g., high mutational burden, ERCC2 mutations, and high APOBEC-A/ERCC2 mutation signatures were associated with good outcome.

Differential Expression of PD-L1 in High Grade T1 vs Muscle Invasive Bladder Carcinoma and its Prognostic Implications.

PURPOSE: PD-L1 is expressed on tumor cells and tumor immune cell infiltrates. In metastatic bladder cancer increased tumor immune cell infiltrate PD-L1 positivity correlated with better overall survival. However, to our knowledge in high grade T1 bladder tumors positivity on tumor cells and tumor immune cell infiltrates, and correlation with outcomes or pathological features remain unknown. MATERIALS AND METHODS: Formalin fixed, paraffin embedded tumor samples from 140 patients with clinically annotated, high grade T1 bladder tumors were retrieved. All patients were initially diagnosed with high grade T1 bladder tumors by transurethral resection, subsequently received bacillus Calmette-Guérin and had a median followup of 7.4 years. PD-L1 positivity on initial transurethral resection was evaluated by immunohistochemistry using a mouse monoclonal antiPD-L1 antibody (405.9A11). Tumor cell PD-L1 positivity was defined as staining of 5% of the tumor cell membrane. Tumor immune cell infiltrate PD-L1 positivity was scored based on the extent of infiltrate and the percent of positive cells. The Fisher exact test was used to assess associations of PD-L1 positivity with disease outcomes, carcinoma in situ presence and the difference between high grade T1 bladder tumors and muscle invasive bladder cancer. RESULTS: Among 140 patients with high grade T1 bladder tumors tumor cells and tumor immune cell infiltrate PD-L1 positivity was seen in 6 (4%) and 48 (34.3%), respectively. In a subset of 106 patients with adequate followup PD-L1 positivity did not correlate with disease outcomes on tumor cells (p = 0.3) or on tumor immune cell infiltrates (p = 0.47). PD-L1 positivity also did not correlate with the presence of carcinoma in situ. Tumor cell PD-L1 positivity was significantly less in high grade T1 bladder tumors than in muscle invasive bladder cancer (p <0.001). CONCLUSIONS: PD-L1 is widely expressed on tumor immune cell infiltrates but not on tumor cells in high grade T1 bladder tumors. We did not find a correlation between PD-L1 positivity and outcomes or carcinoma in situ presence. Tumor cell PD-L1 positivity is significantly lower in high grade T1 bladder tumors than in muscle invasive bladder cancer.

Role of Inflammation in the Perioperative Management of Urothelial Bladder Cancer With Squamous-Cell Features: Impact of Neutrophil-to-Lymphocyte Ratio on Outcomes and Response to Neoadjuvant Chemotherapy.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) might reflect an increased neutrophilic inflammatory response, and urothelial tumors with squamous-cell features (SqD) have been linked to inflammation. We hypothesized that NLR could be prognostic in these patients. PATIENTS AND METHODS: In patients with SqD muscle-invasive bladder cancer treated with curative intent, NLR and relationships with outcomes were analyzed by Cox regression, log-rank, and Kaplan-Meier analysis. RESULTS: Fifty patients presented SqD (median follow-up, 29 months). The ideal NLR cutoff (by receiver operating characteristic curves) was 5. Thirty-seven patients had NLR < 5 and 13 had NLR ≥ 5. The 5-year progression-free survival, cancer-specific survival (CSS), and overall survival were 46.8%, 48.4%, and 45% for NLR < 5 cases, and 10.3%, 10.3%, and 11.7% for NLR ≥ 5 cases (all P < .05). On multivariate analysis, NLR was prognostic (hazard ratio = 4.26, 6.21, and 4.08 for progression-free survival, CSS, and overall survival). Neoadjuvant chemotherapy (NAC) was of significant benefit in NLR < 5 patients, with a CSS of 91.2 months (n = 3) versus 38.1 months (n = 24) for those treated with up-front radical cystectomy (P = .009); Kaplan-Meier curves were also significantly different. These differences did not reach statistical significance for patients with NLR ≥ 5. For the 19 patients treated with NAC, NLR was also predictive of response to NAC. CONCLUSION: Inflammation, measured by NLR, is potentially prognostic in the perioperative management of SqD. NLR identifies 2 risk groups. Patients displaying low NLR had a 4-fold survival improvement and were highly responsive to NAC. NLR might be a good prognostic tool. Its role as a predictor of response to NAC deserves future study, along with its role as a selection criterion for therapies other than chemotherapy.

Low Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts for Good Outcomes in Patients Receiving Neoadjuvant Chemotherapy Before Radical Cystectomy for Muscle Invasive Bladder Cancer.

PURPOSE: The pretreatment neutrophil-to-lymphocyte ratio (NLR) has been associated with cancer prognosis, influencing progression and chemosensitivity. We aimed to define the role of the NLR in predicting the outcomes to neoadjuvant chemotherapy (NAC) in patients with muscle invasive bladder cancer (MIBC). PATIENTS AND METHODS: The data from patients treated with NAC and radical cystectomy for MIBC from 2007 to 2015 at a tertiary care center were reviewed. The clinicopathologic pretreatment, including the NLR, and post-treatment predictors were documented. The NLR was evaluated as a continuous variable on uni- and multivariate analysis and dichotomized in Kaplan-Meier curves. The relationships with outcomes (progression-free survival [PFS], cancer-specific survival [CSS], and overall survival [OS]) were analyzed using Cox regression analysis and log-rank tests. The pathologic response (PR) included any downstaging from the baseline clinical stage to the final pathologic stage. RESULTS: Of 205 patients with MIBC, 75 underwent NAC (median follow-up, 31 months) with a 5-year PFS, CSS, and OS rate of 56%, 60%, and 52%, respectively, and a PR of 38.6%. On multivariate analysis, the PR, PFS, CSS, and OS were predicted by the NLR (hazard ratio > 0.8, 1.25, 1.27, and 1.12, respectively; P < .05 for all). The NLR with age and clinical stage predicted the PR. A NLR threshold of 2.26 better predicted CSS (P < .05) and OS (P = .055). The limitations included the retrospective design and modest number of cases. CONCLUSION: We have provided initial evidence that a low NLR helps understand the value of the underlying immune system in predicting a good outcome to NAC. The NLR is a simple and accessible biomarker that is easy to implement in clinical practice. In addition to established prognosticators and newer genomic predictors, the NLR could improve therapeutic algorithms and help in decision-making regarding the need for NAC, which is currently underused, in MIBC patients.

Association of tumour microRNA profiling with outcomes in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy.

BACKGROUND: Tumour expression of selected microRNAs (miRs) correlates with cisplatin efficacy in multiple cancers. We investigated the role of selected miRs in patients receiving cisplatin-based therapy for advanced urothelial carcinoma (UC). METHODS: RNA was extracted from formalin-fixed paraffin-embedded tumour from 83 advanced UC patients who received cisplatin. A miR panel based on relevance for platinum sensitivity and UC was studied by quantitative reverse transcription quantitative PCR (RT-qPCR). Association of progression-free survival (PFS) with miR expression was analysed using cox regression. Selected TFs were chosen by association with the panel of miRs using the Transcription Regulation algorithm (GeneGo MetaCore+MetaDrug version 6.23 build 67496). Bladder cancer (BC) cell lines were used to investigate the previously described role of miR-21 mediating cisplatin sensitivity. RESULTS: The 83 patients had a median PFS of 8 months. In multivariate analysis, higher levels of E2F1 (P=0.01, HR: 1.95 (1.14, 3.33)), miR-21 (P=0.01, HR: 2.01 (1.17, 3.45)) and miR-372 (P=0.05, HR: 1.70 (1.00, 2.89)) were associated with a shorter PFS. In the 8 BC cell lines, miR-21 was not shown to be necessary nor sufficient for modulating cisplatin sensitivity. CONCLUSIONS: In metastatic UC patients treated with cisplatin-based therapy, high primary tumour levels of E2F1, miR-21 and miR-372 are associated with poor PFS independent of clinical prognostic factors. The in vitro study could not confirm miR-21 levels role in modulating platinum sensitivity.

Precision and predictive medicine in urothelial cancer: are we making progress?

Therapy for urothelial carcinoma appears poised for a breakthrough on the basis of information regarding molecular subtypes and promising activity of PD-1/PD-L1 inhibitors. Precision medicine may be possible using rational marker-driven trial designs with enriched information from tumor genotyping and extreme responders.

High-risk nonmuscle invasive bladder cancer.

Please also verify that the expansion of HGT1 is OK as set: The risk of progression for high-grade T1 (HGT1) cancer has been recently established at 21% using updated information on large series and a meta-analysis. These outcomes are better than those classically expected supporting the rule of thirds for HGT1. The main limitation of this subgroup is that most studies are retrospective observational studies, which, compared with randomized controlled trials, are subject to various selection biases, carrying a higher risk of uncontrolled confounding factors, with potential preferential reporting of positive findings.

A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Although the main treatment is radical nephroureterectomy (NU), oncologic outcomes are not comparable to lower tract urothelial cancers. Identifying prognostic factors can help guide management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC. METHODS: A comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed. RESULTS: Preoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits. Minimally invasive surgery has equivalent oncologic and better peri-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease. CONCLUSION: Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy.

Improving selection criteria for early cystectomy in high-grade t1 bladder cancer: a meta-analysis of 15,215 patients.

PURPOSE: High-grade T1 (HGT1) bladder cancer is the highest risk subtype of non-muscle-invasive bladder cancer, with highly variable prognosis, poorly understood risk factors, and considerable debate about the role of early cystectomy. We aimed to address these questions through a meta-analysis of outcomes and prognostic factors. METHODS: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and American Society of Clinical Oncology abstracts were searched for cohort studies in HGT1. We pooled data on recurrence, progression, and cancer-specific survival from 73 studies. RESULTS: Five-year rates of recurrence, progression, and cancer-specific survival were 42% (95% CI, 39% to 45%), 21% (95% CI, 18% to 23%), and 87% (95% CI, 85% to 89%), respectively (56 studies, n = 15,215). In the prognostic factor meta-analysis (33 studies, n = 8,880), the highest impact risk factor was depth of invasion (T1b/c) into lamina propria (progression: hazard ratio [HR], 3.34; P < .001; cancer-specific survival: HR, 2.02; P = .001). Several other previously proposed factors also predicted progression and cancer-specific survival (lymphovascular invasion, associated carcinoma in situ, nonuse of bacillus Calmette-Guérin, tumor size > 3 cm, and older age; HRs for progression between 1.32 and 2.88, P ≤ .002; HRs for cancer-specific survival between 1.28 and 2.08, P ≤ .02). CONCLUSION: In this large analysis of outcomes and prognostic factors in HGT1 bladder cancer, deep lamina propria invasion had the largest negative impact, and other previously proposed prognostic factors were also confirmed. These factors should be used for prognostication and patient stratification in future clinical trials, and depth of invasion should be considered for inclusion in TNM staging criteria. This meta-analysis can also help define selection criteria for early cystectomy in HGT1 bladder cancer, particularly for patients with deep lamina propria invasion combined with other risk factors.

Molecular determinants of response to cisplatin-based neoadjuvant chemotherapy.

PURPOSE OF REVIEW: Neoadjuvant chemotherapy followed by cystectomy improves survival compared with surgery alone. To prevent overtreatment is of outmost importance to define molecular predictors of response for patient selection. We present the currently available data outlining a variety of potential markers to aid for a personalized decision-making process. RECENT FINDINGS: Apart from p53, other markers of cell cycle regulation and apoptosis such as p21WAF1/CIP1 (p21) gene, Bcl-2, mouse double minute-2 and pRB have also been related to survival. The clinical relevance of epidermal growth factor receptor and HER2 expression has also been investigated with no success. Regarding Ki67, overexpressing tumors may potentially benefit from neoadjuvant therapy and conversely overexpression of vascular endothelial growth factor and bFGF have been linked to resistance to cisplatin-induced apoptosis. The role of multidrug resistance gene 1 and excision repair cross-complementing rodent repair deficiency complementation group 1 supports that enhanced DNA repair in the tumor decreases the benefit of platinum-based treatment. A 20-gene expression model has shown to predict lymph node involvement, helping on decision-making. A gene expression profiling has been proposed as predictive for response to neoadjuvant chemotherapy. SUMMARY: Predictive markers will eventually aid in the selection of patients that most likely benefit from preoperative treatment. In the coming years, a panel of markers will become available to achieve the predicted goal.

Variant forms of bladder cancer: basic considerations on treatment approaches.

Variant forms of bladder cancer are non-urothelial neoplasms or urothelial carcinomas mixed with other histologies. Compared to pure urothelial carcinoma, they all present with a high stage and grade. Prognosis is variable and there is a lack of evidence regarding the ideal treatment approach, because of their relative infrequency and the noninclusion in bladder cancer randomized trials. Despite this, basic recommendations can be extracted from case series. In the present report, existent literature about variant forms of bladder cancer is reviewed with focus on the most frequent: squamous cell, adenocarcinoma, small cell, micropapillary, sarcomatoid, and lymphoepithelioma-like.

Preoperative prediction of pathologically insignificant prostate cancer in radical prostatectomy specimens: the role of prostate volume and the number of positive cores.

INTRODUCTION: To determine clinical and biopsy features with predictive capacity to identify pathologically insignificant prostate cancer (pIPCa). MATERIAL AND METHODS: pIPCa was defined as cancer volume <0.5 cm(3) and a Gleason score (GS) of or=45 cm(3) to d'Amico's criteria. This allows to preoperatively distinguish between patients that most probably would benefit from radical treatment and patients that might be offered active surveillance.

Risk factors for positive findings in patients with high-grade T1 bladder cancer treated with transurethral resection of bladder tumour (TUR) and bacille Calmette-Guérin therapy and the decision for a repeat TUR.

OBJECTIVE: To determine factors predictive of positive findings at the 3-month follow-up evaluation (after transurethral resection of bladder tumour [TUR] and bacille Calmette-Guérin [BCG] therapy) in patients with initial high-grade (HG)T1 bladder cancer, and to assess the depth of lamina propria (LP) invasion and effectiveness of BCG therapy. PATIENTS AND METHODS: In all, 138 patients with initial HGT1-transitional cell carcinoma (TCC) were prospectively assigned, after TUR + BCG and according to depth of LP invasion, to a postBCG-TUR (T1b) or cystoscopy/cytology (T1a) at 3 months. Any finding at 3 months was considered positive. The predictive value of 11 clinical and pathological variables was assessed by chi-squared, Mann-Whitney U and multivariate logistic regression. RESULTS: Of the 138 patients (14 women, mean age 69 years), 42% had T1a and 58% T1b TCC. Tumour size and carcinoma in situ (CIS) were significantly associated with positive findings and present in 26% (36/138) of the patients. The postBCG-TUR (T1b cases), was positive in 31% (25/80), including seven infiltrating tumours. On multivariate analysis, again a tumour size of >3 cm (odds ratio, OR, 7.02) and associated CIS (OR 5.4) were significantly related to a positive postBCG-TUR. A secondary finding was that at 20.3 months; patients with T1a TCC, who did not undergo a repeat TUR, did not have increased progression; only 3% (two of 58) had progressed compared with 21% (17/80) of those with T1b/c TCC (P < 0.002). CONCLUSIONS: In initial HGT1-TCC, tumour size and CIS were predictive factors of positive findings at 3 months after the initial TUR + BCG therapy. Patients with HGT1-TCC invading the LP (T1b TCC) had a seven times higher risk of a positive repeat TUR if the initial tumour was >3 cm and a five-fold increased risk if associated with CIS. The repeat TUR after BCG therapy allowed confirmation of complete resection and pathological evaluation of the BCG response. Although data are still preliminary, the strategy of performing a repeat TUR only in cases with LP involvement, i.e. T1b TCC, did not increase the risk of progression in cases with T1a TCC.

Epidemiología de la incontinencia urinaria en el cáncer de próstata. Incidencia, calidad de vida y aspectos farmacoeconómicos / Epidemiology of urinary incontinence in prostate cancer. Incidence, quality of life and farmacoeconomic features

OBJETIVO: Presentar datos recientes sobre la epidemiología de la incontinencia urinaria en el cáncer de próstata (CaP). Asimismo hacer un repaso de su incidencia, del impacto en la calidad de vida y de los aspectos farmacoeconómicos relacionados.MÉTODO: Se ha realizado una revisión de la literatura referente a las complicaciones de los distintos métodos de tratamiento del CaP incluyendo la prostatectomia radical -PR- (abierta, laparoscópica y robótica), la radioterapia externa, la braquiterapia, la crioterapia y los ultrasonidos de alta-intensidad (high-intensity focused ultrasound –HIFU-).RESULTADOS: La falta de uniformidad en la definición de incontinencia, la manera de evaluarla y la manera de reportarla hacen que la interpretación de los resultado funcionales y del impacto en la calidad de vida tras cualquiera de los tratamientos del CaP sea dispar y difícil de interpretar. En líneas generales se ha documentado que la incontinencia urinaria post tratamiento afecta con mayor frecuencia a los pacientes tratados mediante cirugía radical. Sin embargo, se constata también que la preservación de bandeletas neurovasculares, los realización de los procedimientos en hospitales con gran volumen de pacientes y por cirujanos con un elevado número de casos y el desarrollo de la PR robótica parecen afectar positvamente el rendimiento global de la técnica. En la radioterapia externa, la incontinencia moderada es menos frecuente pero la asociación de dolor rectal y diarrea, que llegan a desarrollar hasta el 40% de los pacientes, agrava la sintomatología miccional. En la braquiterapia transperineal los síntomas irritativos y obstructivos se asocian en especial a disfunción eréctil desarrollada a largo plazo así como a morbilidad rectal. En el caso de la crioterapia y del HIFU los estudios son series de casos y no hay estudios randomizados que comparen estas terapias como tratamiento primario del CaP localizado(AU)

CONCLUSIONES: Cada modalidad de tratamiento para el CaP se asocia a un patrón distinto de cambios en los dominios de calidad de vida relacionados con la función urinaria, sexual, intestinal y hormonal. Dos factores son claves cuando se evalúa la incontinencia; la documentación del grado de continencia previa al procedimiento y el uso de métodos de evaluación validados y autoadministrados. Aunque las mejoras técnicas en todos los procedimientos deberían contribuir a disminuir el impacto de las complicaciones, no hay que olvidar la tendencia a asociar tratamientos –terapias multimodales- tienen un perfil de complicaciones mas elevado. Por lo que deben reservarse para aquellos pacientes en los que se haya demostrado un beneficio(AU)

OBJECTIVES: To present recent data on the epidemiology of urinary incontinence in prostate cancer (PCa). To review the incidence of urinary incontinence, its impact on quality of life and related pharmacoeconomic features.METHODS: We performed a bibliographic review about the complications of the various therapeutic options for PCa including radical prostatectomy (RP) (open, laparoscopic and robotic), external beam radiotherapy, brachytherapy, cryotherapy, and high intensity focused ultrasound (HIFU).RESULTS: The lack of uniformity for urinary incontinence definition, for its evaluation, and for the way to report it makes the interpretation of functional results and impact on quality of life after any treatment option difficult and uneven. Generally, we documented that urinary incontinence after treatment appears more often in patients undergoing radical surgery. Nevertheless, we stated that neurovascular bundle preservation, performance of the procedure in high volume centers, by high volume surgeons, and development of robotic surgery may positively influence the global outcomes of this technique. Moderate incontinence is less frequent after external beam radiotherapy, but the association of rectal pain and diarrhea, in up to 40% of the patients, worsens voiding symptoms. Irritative and obstructive voiding symptoms after perineal brachytherapy are especially associated with long term erectile dysfunction as well as rectal morbidity. In the case of cryotherapy and HIFU the available studies are case series and there are not randomized studies comparing them with the primary treatment of localized PCa(AU)

CONCLUSIONS: Each treatment modality for PCa is associated with a different pattern of changes in the urinary, sexual, intestinal and hormonal related quality of life domains. Two key factors when evaluating incontinence are information about continence before the procedure and the use of validated, self-administered evaluation means. Although technical improvements in all procedures should contribute to diminish the impact of complications, we should not forget the trend to the association of therapies- multimodal therapy- has a higher complication profile. Therefore, they should be reserved for patients in whom a benefit has been proved(AU)