Prognostic factors of renal cell carcinoma.

Renal cell carcinoma represents 23% of all adult malignancies and its incidence in the Czech Republic is one of the highest worldwide. Until late stages this disease often remains asymptomatic, which makes its diagnosis difficult. Despite an increasing proportion of small, incidentally detected tumours on imaging, approximately one third of patients are still diagnosed with advanced disease. Moreover, a relapse occurs in up to 40% of patients after surgery for localized tumour. Increased availability of imaging investigations allowing an early detection of kidney carcinoma and advances in systemic treatment have favourably affected the outcome of patients with this type of tumour. Nevertheless, mortality of renal cell carcinoma remains the highest among urological malignancies. The individual course of the disease and its response to systemic treatment are difficult to predict. A number of prognostic factors of renal cell carcinoma have been identified, of which TNM classification and tumour grade remain the most important. Recently, several multivariate prognostic models have become available, allowing a more accurate prediction of the disease course. In localized disease, they are useful in identifying patients at higher risk of recurrence and allow optimization of follow-up after surgery. In metastatic disease, they are routinely used to stratify patients into risk groups for targeted treatment. There has been a long-term effort to identify a suitable biomarker useful for an early detection and assessment of the prognosis of renal cell carcinoma. At the same time, such a biomarker could improve the accuracy of established prognostic systems. This text presents an overview of prognostic factors of renal cell carcinoma, including a summary of potential biomarkers.

New trends in prostate cancer diagnostics.

The ever-increasing incidence of prostate cancer is driving research and clinicians efforts to manage the disease more precisely. Leaving aside the progress we are making in the field of prostate cancer treatment, we can notice the pressure on accurate diagnosis in everyday practice. We often meet patients who are in the so-called gray zone and we are not sure whether to indicate a prostate biopsy or continue to monitor the patient. For diagnostics, we use a number of more or less proven methods that we have at our disposal. No clinical urologist wants to send their patient for a prostate biopsy unnecessarily. However, if the patient is finally planned for a prostate biopsy, there is no 100% certainty that we will detect the cancer. For this reason, there is an effort to develop other methods that would refine the collection of histological material and thus increase the capture of those patients who need treatment. The aim of this review is to show modern approaches to diagnostics and outline the direction in which diagnostics will go in the coming years.

Management of BCG failure in non-muscle-invasive bladder cancer the present and the future.

Bladder neoplasms are still among the most common cancer types in the Czech Republic. Even though the majority (more than 90%) of bladder tumours are of urothelial origin, the group is vastly heterogeneous in terms of biological behaviour and thus also progression of the disease. Adequate adjuvant treatment is the cornerstone of the therapy in high-risk patients for disease recurrence, particularly those with a high risk of progression to a muscle-invasive disease (T2 and higher). Intravesical BCG immunotherapy still remains such a therapy. It is a standard therapy with well-established efficacy as regards the recurrence rate and a reduced risk of progression. Nevertheless, radical cystectomy is recommended in patients in whom this therapy fails. Considering the non-negligible morbidity and mortality associated with this type of surgery, intensive research efforts have been put forth to develop new bladder preserving strategies. This article outlines the main bladder preserving strategies that are currently explored.

Histologic tumor necrosis rate as a predictor of recurrence after surgical treatment for localized clear cell renal cell carcinoma.

INTRODUCTION: Coagulative tumor necrosis (TN) is a potential negative prognostic marker in clear cell renal cell carcinoma (ccRCC). Our study assessed the significance of the TN rate in histological specimens in terms of the risk of recurrence in patients after surgical treatment for localized disease. METHODS: Our study included 149 subjects surgically treated for ccRCC from 2011 to 2014. Mean postoperative follow-up was 538 days. Presence of TN was assessed by a physician - pathologist in histological specimens. The following findings were described: without necrosis (79 samples), TN rate below 50% (46 samples) and TN rate higher or equal to 50% of the specimen (24 samples). The Kaplan-Meier method, log-rank test and Cox regression analysis were used to evaluate the disease-free survival (DFS). RESULTS: Seventeen patients experienced recurrence - with no TN detected in 3, TN rate below 50% in 6 and TN rate above 50% in 8 patients. There was a significant difference in DSF in patients with proven TN compared to patients without TN (HR 3.83; CI95% 1.489.94%; p=0.006; in multivariate analysis: p=0.031). Evaluation according to the proportion of TN showed a significant difference in DFS in patients with the TN rate below or equal to 50% compared to patients without TN (HR 16.27; CI95% 4.0066.15; p=0.0001; in multivariate analysis: p=0.041). The difference of DSF between patients without TN and with the TN rate higher than 50%, and patients with the TN rate below 50% and higher than 50% was not statistically significant. CONCLUSION: Our study confirmed TN as a risk factor of disease recurrence. Additionally, a higher TN rate is associated with a significantly higher risk of recurrence.

Risk of biochemical recurrence in patients with a positive surgical margin after radical prostatectomy.

INTRODUCTION: Serum prostate specific antigen (PSA) is an irreplaceable marker in the detection and follow-up of patients with prostate cancer. In our analysis we addressed factors that could indicate the likelihood of biochemical recurrence (BCR) early after radical prostatectomy. We mainly focused on the positive surgical margin (R1). METHODS: Retrospective evaluation and analysis of the database of patients with prostate cancer after radical prostatectomy from 2001 to 2019. In total 1529 patients were enrolled in the study. The median follow-up was 48 months. The age of the patients ranged from 49 to 76 years. We used pre-operative PSA values, and the monitoring of the dynamics of 3rd generation PSA progression (detection limit 0.003 ng/ml) at month 1 and month 3 after surgery and then in 3-month intervals. We monitored the surgical margin positivity (R0 negative, R1 positive) and the Gleason score (GS) based on histological samples and we analysed the relationship to biochemical recurrence of the disease. RESULTS: The pre-operative PSA value did not show a direct relationship to the R1 risk. Patient values in the groups R1 and R0 differed only by 1.159 ng/ml (p=NS). The 3rd generation PSA value at month 1 after surgery was 50.82% higher in R1 patients (p>0.001). 50% of patients with R1 (29.5% patients of the total) did develop BCR during the follow-up period, while in patients with R0 (70.5% patients of the total) this proportion was 30% (p>0.001). Among those with GS 67, 47% developed BCR. The GS 810 group relapsed in 75% of the cases (p>0.001). CONCLUSION: According to our analysis 33% of the patients reached the stage of biochemical recurrence. We demonstrated a direct dependency between the risk of recurrence and the final Gleason score. The presence of R1 should not be viewed as a direct indication for adjuvant radiotherapy.

Penile amputation for sarcoma.

Penile cancer is uncommon among other urological malignancies, squamous cell carcinoma being the most common type of penile cancer. This case report presents a patient with rapidly progressive angiosarcoma who underwent penile amputation.

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.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy.

PURPOSE: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG. METHODS: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups. RESULTS: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024) CONCLUSIONS: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.

Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG: not as bad as previously thought.

PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen. CONCLUSIONS: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.

MicroRNAs in urine supernatant as potential non-invasive markers for bladder cancer detection.

Urinary bladder carcinoma contributes to 4% of newly diagnosed oncological diseases in the Czech Republic. Biomarkers for its early non-invasive detection are therefore highly desirable. Urine seems to be an ideal source of such biomarkers due to the content of cell-free nucleic acids, especially microRNAs (miRNAs).To find potential biomarkers among miRNAs in urine supernatant, we examined in total 109 individuals (36 controls and 73 bladder cancer patients) in three phases. In the first - discovery - phase, microarray cards with 381 miRNAs were used for miRNA analysis of 13 controls and 46 bladder cancer patients. In the second - verification - phase, the results of this first phase were verified on the same groups of subjects by single-target qPCR assays for the selected miRNAs. For the third - validation - phase, new independent samples of urine supernatant (23 controls and 27 bladder cancer patients) were analyzed using single-target qPCR assays for 13 verified in the previous phase. The results of all phases were normalized to miR-191, miR-28-3p, and miR-200b, which were selected as suitable for our study by the qBase+®.We found that miR-125b, miR-30b, miR-204, miR-99a, and miR-532-3p are significantly down-regulated in patients' urine supernatant. In our experiments, the analysis of miR-125 levels provided the highest AUC (0.801) with 95.65% specificity and 59.26% sensitivity, the analysis of miR-99a lead to AUC (0.738) with 82.61% specificity and 74.07% sensitivity. We demonstrate that levels of these miRNAs could potentially serve as promising diagnostic markers for the non-invasive diagnostics of bladder cancer.

Wilms tumor gene 1 (WT1), TP53, RAS/BRAF and KIT aberrations in testicular germ cell tumors.

PURPOSE: Wilms tumor gene 1 (WT1), a zinc-finger transcription factor essential for testis development and function, along with other genes, was investigated for their role in the pathogenesis of testicular germ cell tumors (TGCT). METHODS: In total, 284 TGCT and 100 control samples were investigated, including qPCR for WT1 expression and BRAF mutation, p53 immunohistochemistry detection, and massively parallel amplicon sequencing. RESULTS: WT1 was significantly (p < 0.0001) under-expressed in TGCT, with an increased ratio of exon 5-lacking isoforms, reaching low levels in chemo-naïve relapsed TGCT patients vs. high levels in chemotherapy-pretreated relapsed patients. BRAF V600E mutation was identified in 1% of patients only. p53 protein was lowly expressed in TGCT metastases compared to the matched primary tumors. Of 9 selected TGCT-linked genes, RAS/BRAF and WT1 mutations were frequent while significant TP53 and KIT variants were not detected (p = 0.0003). CONCLUSIONS: WT1 has been identified as a novel factor involved in TGCT pathogenesis, with a potential prognostic impact. Distinct biologic nature of the two types of relapses occurring in TGCT has been demonstrated. Differential mutation rate of the key TGCT-related genes has been documented.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

Cancer incidence and mortality in the Czech Republic.

BACKGROUND: The Czech Republic ranks among the countries with the highest cancer burden in Europe as well as worldwide. The purpose of this study is to summarize longterm trends in the cancer burden and to provide up-to-date estimates of incidence and mortality rates after 2011. DATA AND METHODS: The Czech National Cancer Registry (CNCR) was instituted in 1977 and contains information collected over a 34-year period of standardized registration covering 100% of cancer diagnoses within the entire Czech population. The CNCR analysis is supported by demographic data and by the Death Records Database. An overview of the epidemiology of malignant tumors in the Czech population is available online at www.svod.cz. RESULTS: All neoplasms, including nonmelanoma skin cancer, reached a crude incidence rate of almost 802 cases per 100,000 men and 681 cases per 100,000 women in 2011. The annual mortality rate exceeded 258 deaths per 100,000 individuals; in other words, more than 27,000 individuals die of cancer each year. The overall incidence of malignancies has increased with a growth index of +27.6% during the last decade (2001- 2011), while the mortality rate has been stabilized over the time span (growth index in 2001- 2011: - 5.0%). Consequently, the prevalence has significantly increased in the observed period and exceeded 475,000 cases in 2011. In addition to demographic aging of the Czech population, the cancer burden has also increased due to the growing incidence of multiple primary tumors (recently more than 15% of the total incidence). The most frequent diagnoses include colorectal cancer, lung cancer, breast cancer, and prostate cancer. Although some neoplasms are increasingly diagnosed at an early stage (e. g. the proportion of stage I or II was 75.3% for female breast cancer and 84.2% for skin melanoma), the numbers of early diagnosed cases are generally insufficient, even in the case of highly prevalent cancers such as colorectal carcinoma (only 46.1% of incident cases are diagnosed at stage I or II, according to recent data). CONCLUSION: Population-based data on malignant tumors are available in the Czech Republic. The data survey can help us define national cancer management priorities. The current priority is to achieve a sustained reduction of cases diagnosed at an advanced stage and reduction of the significant regional differences in diagnostic efficiency.

The prognostic value of T1 bladder cancer substaging: a single institution retrospective study.

OBJECTIVE: To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer. SUBJECTS AND METHODS: 200 patients were treated between the years 2002 and 2009. Tumours with depth of invasion above the muscularis mucosae level were categorised as pT1a and those with depth of invasion up to or beyond the muscularis mucosae as pT1b. RESULTS: Categorisation for pT1a and pT1b was performed in 176 of 200 patients (88%). In 10 patients a muscle-invasive tumour was found in re-transurethral resection samples. 131 (79%) of 166 analysed patients had pT1a tumour and 35 (21%) had pT1b tumour. During the follow-up, in 101 (61%) patients the tumour had recurred and in 27 (16.3%) the tumour had progressed. Of all the investigated parameters, T1 substaging (p < 0.0001), grade (p = 0.0003) and the number of bacillus Calmette-Guérin instillations (p = 0.0490) were significant in predicting progression. The only significant factor for disease-specific survival was T1 substaging in univariable (p = 0.0008) and multivariable (hazard ratio 4.407) analysis. T1 substaging (p = 0.0149) and tumour multiplicity (p = 0.0448) have a statistically significant prognostic value with respect to overall survival. CONCLUSIONS: Deep invasion of the lamina propria is a significant adverse prognostic factor for tumour progression, disease-specific survival and overall survival.

Prediction of recurrence in low and intermediate risk non-muscle invasive bladder cancer by real-time quantitative PCR analysis: cDNA microarray results.

The aim of the study was to define specific genetic profile in Ta and T1 urinary bladder carcinoma patients with and without recurrence by gene expression microarrays. Eleven patients with the time to recurrence shorter than one year (patients with recurrence) and 11 patients with time to recurrence longer than 4 years (patients without recurrence) were enrolled. Data from microarrays were subjected to a panel of statistical analyses to identify bladder cancer recurrence-associated gene signatures. Initial screening using the GeneSpring and Bioconductor software tools revealed a putative set 47 genes differing in gene expression in both groups. After the validation, 33 genes manifested significant differences between both groups. The significant expression was observed in the group of patients without recurrence by 30 genes of which the highest differences were detected by ANXA1, ARHGEF4, FLJ32252, GNE, NINJ1, PRICKLE1, PSAT1, RNASE1, SPTAN1, SYNGR1, TNFSF15, TSPAN1, and WDR34. These genes code for signal transduction, vascular remodeling and vascular endothelial growth inhibition mainly. In the group with recurrence, 3 genes had significant differences, the highest differences were identified by two genes (PLOD2 and WDR72). Loci of genes with significant changes of gene expression were located on characteristic chromosomes for bladder cancer: 7 loci on chromosome 9, 8 loci on chromosomes 1, 2, 3, 12,14,15,16, and 22. We have selected and validated 15 genes that are differentially expressed in superficial bladder cancer. We hope that this cohort of genes will serve as a promising pool of candidate biomarkers for early stage bladder cancer. Our results indicate that it may be possible to identify patients with a low and high risk of disease recurrence at an early stage using a molecular profile.

Guía clínica del carcinoma urotelial de vejiga no músculo-invasivo de la Asociación Europea de Urología. Actualización de 2011 / EAU Guidelines on Non-Muscle-Invasive Urothelial Carcinoma of the Bladder, the 2011 Update

Contexto y objetivo: Presentar la guía clínica de la Asociación Europea de Urología (EAU) de 2011 del carcinoma de vejiga no músculo-invasivo (CVNMI). Adquisición de la evidencia: Se ha realizado una revisión sistemática de la literatura publicada entre 2004 y 2010 acerca del diagnóstico y el tratamiento del CVNMI. Se actualizaron las guías clínicas previas, y se asignó un nivel de evidencia (NE) y un grado de recomendación (GR). Síntesis de la evidencia: Los tumores en estadio Ta, T1 o carcinoma in situ (CIS) se agrupan como CVNMI. El diagnóstico depende de la cistoscopia y de la evaluación histológica del tejido obtenido por resección transuretral (RTU) en los tumores papilares o por biopsias de vejiga múltiples en el CIS. En las lesiones papilares, una completa RTU es esencial para el pronóstico del paciente. Cuando la primera resección es incompleta o cuando se detecta un tumor de alto grado o T1, se debe realizar una segunda RTU a las 2-6 semanas. En los tumores papilares, el riesgo tanto de recurrencia como de progresión se puede calcular de manera individual mediante los sistemas de puntuación y tablas de riesgo. La estratificación de los pacientes en grupos de riesgo bajo, intermedio y alto (separando la recidiva y la progresión) es fundamental para recomendar un tratamiento adyuvante. Para los pacientes con bajo riesgo de recurrencia y progresión se recomienda una instilación inmediata de quimioterapia. Los pacientes con riesgo intermedio o alto de recurrencia y riesgo intermedio de progresión deben recibir una instilación inmediata de quimioterapia seguida de un mínimo de un año con inmunoterapia intravesical con bacilo de Calmette-Guérin (BCG) o más instilaciones de quimioterapia. Los tumores papilares con alto riesgo de progresión y CIS deben recibir BCG intravesical durante un año. Se puede ofrecer una cistectomía a los pacientes de más alto riesgo, y por lo menos se recomienda a los pacientes en los que ha fallado la BCG. Conclusión: La versión reducida de esta guía clínica de la EAU presenta una información actualizada sobre el diagnóstico y el tratamiento del CVNMI para la incorporación a la práctica clínica (AU)

Context and objective: To present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC).Evidence acquisition: Literature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient’s prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression maybe estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups (separately for recurrence and progression) is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice (AU)

Positron emission tomography and clinical predictors of survival in primary extragonadal germ cell tumors.

BACKGROUND: Primary extragonadal germ cell tumors (EGTs) are an uncommon malignancy -accounting for 2-4% of all germ cell neoplasms in adult males. Their prognosis is worse than that for testicular germ cell tumors because of their relative chemoresistance and frequent presentation with widely disseminated metastases. We have studied the role of fluorodeoxyglucose positron emission tomography (FDG-PET) for outcome prediction of patients with EGTs. PATIENTS AND METHODS: We have retrospectively analysed 36 men with germ cell tumors originating in the mediastinum or the retroperitoneum. All patients were treated between 1994 and 2010. Negative result of testicular ultrasonographic examination and/or testicular biopsy was required for diagnosis of EGT. Platinum-based systemic therapy was used in all cases, and resectable residual tumor masses were removed surgically. RESULTS: Overall survival at one and three years was 81% (95% confidence interval [CI]: 68-94%) and 55% (CI: 38-71%), respectively. None of the patients who had positive FDG-PET findings after first line chemotherapy survived at three years after diagnosis. In contrast, 69% and 20% of patients with positive tumor markers, and 90% and 67% of patients with negative tumor markers after first line chemotherapy survived at one and three years, respectively. Negative FDG-PET after completion of treatment was also a powerful predictor of long-term survival with 100% patients surviving three years and 89% surviving five years after diagnosis. CONCLUSIONS: Negative FDG-PET after first-line chemotherapy or after the completion of systemic treatment and resection of residual tumor masses strongly predicts long-term event-free survival in patients with EGTs.

[EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update]. / Guía clínica del carcinoma urotelial de vejiga no músculo-invasivo de la Asociación Europea de Urología. Actualización de 2011.

CONTEXT AND OBJECTIVE: To present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION: Literature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. EVIDENCE SYNTHESIS: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups (separately for recurrence and progression) is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients. CONCLUSIONS: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice.