Proteome-based classification of Nonmuscle Invasive Bladder Cancer.

DNA/RNA-based classification of bladder cancer (BC) supports the existence of multiple molecular subtypes, while investigations at the protein level are scarce. Here, we aimed to investigate if Nonmuscle Invasive Bladder Cancer (NMIBC) can be stratified to biologically meaningful groups based on the proteome. Tissue specimens from 117 patients at primary diagnosis (98 with NMIBC and 19 with MIBC), were processed for high-resolution proteomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomics output was subjected to unsupervised consensus clustering, principal component analysis (PCA) and investigation of subtype-specific features, pathways, and gene sets. NMIBC patients were optimally stratified to three NMIBC proteomic subtypes (NPS), differing in size, clinicopathologic and molecular backgrounds: NPS1 (mostly high stage/grade/risk samples) was the smallest in size (17/98) and overexpressed proteins reflective of an immune/inflammatory phenotype, involved in cell proliferation, unfolded protein response and DNA damage response, whereas NPS2 (mixed stage/grade/risk composition) presented with an infiltrated/mesenchymal profile. NPS3 was rich in luminal/differentiation markers, in line with its pathological composition (mostly low stage/grade/risk samples). PCA revealed a close proximity of NPS1 and conversely, remoteness of NPS3 to the proteome of MIBC. Proteins distinguishing these two extreme subtypes were also found to consistently differ at the mRNA levels between high and low-risk subtypes of the UROMOL and LUND cohorts. Collectively, our study identifies three proteomic NMIBC subtypes and following a cross-omics validation in two independent cohorts, shortlists molecular features meriting further investigation for their biomarker or potentially therapeutic value.

Open radical prostatectomy after transurethral resection: perioperative, functional, oncologic outcomes.

INTRODUCTION: To demonstrate any differences in the perioperative, functional and oncologic outcomes after radical retropubic prostatectomy (RRP) among those patients having previously performed transurethral resection of prostate (TURP) and those not. MATERIALS AND METHODS: A total of 35 patients were diagnosed with prostate cancer (T1a and T1b) after TURP, underwent RRP and completed a 1 year follow up (group A). They were matched with a cohort of another 35 men (group B) in terms of age, body mass index (BMI), prostatic specific antigen (PSA), Gleason score, prostate volume (before surgery), pathological stage and neurovascular bundle-sparing technique. That was a retrospective study completed between September 2011 and March 2014. RESULTS: Not a significant difference was demonstrated among the two groups of patients concerning the functional and oncologic results. On the other hand, previous prostate surgery made the operation procedure more demanding. Besides, operative time and blood loss (though not translated in transfusion rates) were higher among patients in group A. Besides, catheter removal in group A patients was performed later than their counterparts of group B. CONCLUSIONS: RRP after TURP is a relatively safe procedure and in the hands of experienced surgeons, a previously performed TURP, does not seem to compromise oncologic outcomes of the operation. Continence is preserved, though erectile function seems to be compromised compared with patients undergoing RRP without prior TURP. Moreover, defining the prostate and bladder neck margins can be challenging and the surgeon has to be aware of the difficulties that might confront.

Comparison of efficacy and satisfaction profile, between penile prosthesis implantation and oral PDE5 inhibitor tadalafil therapy, in men with nerve-sparing radical prostatectomy erectile dysfunction.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Erectile dysfunction after nerve-sparing radical retropubic prostatectomy constitutes a challenge to the urologist. The mainstay of medical treatment after radical prostatectomy to restore spontaneous erectile function remains phosphodiesterase (PDE5) inhibitors, despite the fact that data from animal studies suggesting that PDE5 inhibitors can prevent smooth muscle apoptosis and fibrosis have not yet been extrapolated to humans because of a lack of standardized protocols. If the above treatment fails, second-line therapies such as intraurethral prostaglandins, penile injection therapy and vacuum devices are offered. When less invasive therapies are ineffective, interventions that preserve sexual function such as penile prosthesis implantation become the treatment of choice. Our study reveals the alternative of penile prosthesis implantation as first-line treatment in erectile dysfunction after nerve-sparing radical prostatectomy. It also highlights its superiority to the oral PDE5 inhibitor treatment, regarding the erection, frequency, firmness, maintenance and penetration ability. This suggests that a concept of an early penile intervention in the future would be promising for those patients who wish to remain sexually active without depending on oral formulations with doubtful and delayed results. OBJECTIVE: To evaluate the outcome of penile prosthesis surgery in comparison to oral phosphodiesterase type 5 (PDE5) inhibitor administration, in men with erectile dysfunction after nerve-sparing radical prostatectomy, as early penile intervention therapy. PATIENTS AND METHODS: A total of 174 patients treated by nerve-sparing retropubic radical prostatectomy (RRP) for clinically localized prostate cancer, between January 2006 and September 2009 enrolled in the study, 153 patients fulfilled the inclusion criteria, and 69 (45%) patients presented with post-RRP erectile dysfunction 6 months after primary surgery. Fifty-four patients were disease-free and subdivided into two arms according to treatment modality, either tadalafil three times/week or penile prosthesis implantation. All patients were evaluated using the International Index of Erectile Function (IIEF) questionnaire preoperatively and at 6, 12 and 24 month postoperatively. Repeated measurements analysis of variance was conducted to evaluate the effect of time and group on IIEF total score. RESULTS: There was a significant reduction in IIEF score from preoperative values to the first measurement after surgery in both treatment groups. The overall degree of change from the first time point immediately after surgery to 2 years was greater in the penile prosthesis group than the tadalafil group (20.4 ± 1.3 vs 8.1 ± 2.4, P < 0.001). CONCLUSIONS: The efficacy and satisfaction results of both treatment types are considered acceptable. However, regarding the erection frequency, firmness, penetration ability, maintenance and erection confidence it seems that penile prosthesis implantation is superior to oral treatment. The concept of early penile intervention should be considered and is promising for all patients with post-RRP erectile dysfunction.

Incidental prostate cancer in patients who underwent radical cystectomy for high risk non muscle invasive bladder cancer: Is it clinically significant?

INTRODUCTION AND OBJECTIVE: Non muscle invasive, high-risk, bladder cancer is an entity which is usually treated with radical cystectomy. Incidental prostate cancer refers to prostate cancer detected in radical cystectomy specimens in patients with no signs of the disease. Objective of this study is to report the prevalence, characteristics, and clinical significance of incidental prostate cancer in non-muscle invasive bladder cancer patients treated with radical cystectomy in our department. MATERIAL AND METHODS: We retrospectively reviewed data from 41 patients who underwent radical cystectomy for non-muscle invasive, high risk, bladder cancer during the years 2016-2020 in our department. Prostate cancer was described as clinically significant when there were positive surgical margins, extraprostatic extension, Gleason score >6, or tumor volume ⩾0.5 cm3. Two groups of patients were formed according to the presence or absence of clinically significant prostate cancer. RESULTS: Incidental prostate cancer in the cystectomy specimens was detected in 21 of the 35 patients investigated. Clinically significant prostate cancer was detected in five patients. Positive surgical margins and extraprostatic extension were present in one patient, respectively. Gleason score was more than six in four of the five patients and PCa tumor volume was above 0.5 cm3 in three patients. Two patients with clinically significant prostate cancer were diagnosed with biochemical recurrence during their follow up. CONCLUSIONS: In non-muscle invasive, high-risk patients undergoing radical cystectomy, clinically significant incidental PCa is an important issue as it may affect prognosis, quality of life, metastasis free survival, and overall survival.

Clinical impact of ERG and PTEN status in prostate cancer patients underwent radical prostatectomy.

OBJECTIVES: Phosphate and tensin homolog gene (PTEN) acts as a regulator of PI3-KAkt molecular pathway. ETS Related gene (ERG), an oncogene located in chromosome 21q22.2, is involved in prostate cancer (PCa) by serine 2 (TMPRSS2), a protein encoded by TMPRSS2 gene. The aim of this study is to evaluate the clinical impact of PTEN loss and ERG rearrangement in terms of oncologic results in patients diagnosed with localized PCa who underwent radical prostatectomy. MATERIALS AND METHODS: Prospective data were collected from a total of 74 patients who underwent open radical retropubic prostatectomy for localized PCa and immunohistochemical study was performed in tissue samples. The primary antibodies for anti-ERG antibody as well as anti-PTEN antibody were obtained from DAKO. ERG was considered positive if at least 20% of the evaluated cells were stained at least with medium intensity. PTEN protein loss was considered when the intensity of cytoplasmic and nuclear staining was mild or entirely negative across > 10% of tumor cells. RESULTS: Homogenous loss of PTEN was associated with higher clinical International Society of Urological Pathology (ISUP) grade (p = 0.018) while no statistical significant association was present regarding the presence of ERG rearrangement with either ISUPc or ISUPp. After a median follow up of 34 months, 24 patients developed biochemical recurrence. No statistical significant correlation of ERG status with biochemical recurrence was noted while PTEN was associated with biochemical recurrence development in a statistical significant way. Lastly the combination of PTEN loss with ERG rearrangement presence was detected more often in higher ISUPc and ISUPp as well as biochemical recurrence development, although in a non statistical significant way. CONCLUSIONS: Homogenous and heterogenous PTEN loss was associated with biochemical recurrence. No association of ERG and biochemical recurrence was noted. The combination of PTEN loss and ERG rearrangement presented a trend for higher ISUPc and ISUPp as well as biochemical recurrence but not in a statistical significant way.

Outcomes of radical cystectomy in pT4 bladder cancer frail patients: Α high-volume single center study.

Objectives: This study aims to evaluate the effect of frailty in patients undergoing radical cystectomy (RC) for locally advanced bladder cancer. Methods: In this retrospective, single center study we evaluated 51 patients with pT4 bladder cancer treated with radical cystectomy between 2016-2020. Patient frailty was assessed with the Clinical Frailty Scale (CFS). Furthermore, six separate parameters (early mortality index within 30 days after surgery, death after one year, length of stay, respiratory complications, readmission index, total hospital charges) were also evaluated. The patients were categorized on three groups (Group 1, 2, 3) based on the CFS. Results: A total of 51 pT4 RC patients were included in the study. Mean age was 75.6 years. Early mortality rate at 30 days after surgery was low all the groups. One year mortality rate was higher in Group 2 (22%) and 3 (69%). The length of stay and the number of patients with respiratory complications were also higher in the frailer groups. 30 days readmission rate was 22% in Group 2 and 38% in Group 3. Conclusions: Preoperative frailty is associated with worse postoperative results after RC. CFS is an objective tool for patient risk stratification and can predict postoperative complications and mortality.

Conservative management of grade 4 and 5 renal injuries: A high-volume trauma center experience.

INTRODUCTION: Traumatic renal injuries represent a major public health issue concerning mostly young men. Over the last decades there is growing debate regarding the management of high-grade renal injuries due to the emerging role of conservative treatment. The aim of this study is to present our experience in the conservative management of patients presenting with grade 4 or grade 5 renal injuries in our department. MATERIAL AND METHODS: In this retrospective, single center study we evaluated data from a total of 57 hemodynamically stable patients who were managed conservatively for grade 4 or grade 5 renal injuries from 2015 to 2019 in our high-volume trauma center. Grading was based on contrast enhanced abdominal computed tomography (CT) scans. Patients managed with immediate nephrectomy due to hemodynamic instability and patients who underwent immediate laparotomy due to concomitant injuries or penetrating wounds were excluded from the study. RESULTS: A total of 54 patients diagnosed either with grade 4 or grade 5 renal trauma were finally successfully managed conservatively and included in the study. Median age was 34 years. Most patients presented with grade 4 renal trauma while five patients presented with grade 5 renal injury. Concomitant injuries not requiring surgical intervention were present in 48 patients. Continuous renal bleeding was detected in 15 patients (27.8%) and subsequent arterial embolization was performed with no further intervention required. Urine leak was diagnosed in 12 patients treated either by double j stent or by nephrostomy tube. CONCLUSIONS: Grade 4 and selected cases of grade 5 renal trauma can be treated conservatively with close monitoring and CT scan protocols in hemodynamic stable patients. In cases of continuous bleeding, arterial embolization can be performed. In cases of severe urine leak conservative management is also feasible either by inserting a double j stent or a nephrostomy tube.

Novel treatments in BCG failure. Where do we stand today? / Nuevos tratamientos en fallo a BCG. ¿Dónde estamos?

OBJECTIVES: Most patients at first diagnosis of bladder cancer (BC) present with non muscle invasive disease (NMIBC). BCG intravesical therapy after transurethral resection of the bladder tumor is the gold standard in intermediate and high risk NMIBC patients. However, it is estimated that approximately 50% of these patients will present with BCG failure which increases their risk for progression to muscle invasive disease. Currently, the best option for these patients is radical cystectomy. Thus, it is of great interest to pursue new, therapeutic options for BCG failure patients to avoid the necessity of radical cystectomy. We hereby review novel treatment modalities for BCG failure patients. METHODS: This is a narrative review. Keywords for the search were BCG failure, BCG unresponsive, BCG refractory, BCG relapsing and BCG intolerance. Evidence was identified through a search for publications with a ''BCG unresponsive'' tag through 2020. Studies were selected if they contained clinical data on BCG unresponsive therapeutics with near-term availability. Clinical trial landscape evaluation for emerging therapies was performed by searching ClinicalTrials.gov for recruiting/ open interventional trials in 2020. RESULTS: Novel treatment modalities for BCG failure include intravesical chemotherapy, BCG re-challenge or combination of BCG with IFN-α2ß, valrubicin, radiotherapy, electromotive drug administration, vicinium, chemohyperthermia, photodynamic therapy, gene therapy, vaccine therapy and immunotherapy. For patients in whom BCG has once failed a repeat course of BCG or BCG plus interferon appears to be a reasonable practice. Likewise, single agent gemcitabine may be considered a treatment modality. However, after 2 or more BCG failures, especially in patients with earlier relapses or cancer persistence, single agent intravesical chemotherapy with valrubicin, gemcitabine or docetaxel appears to be less active than doublet/triplet intravesical chemotherapy or mitomycin chemothermotherapy. Gene therapy or conjugated antibodies may play a role upon further relapse. Single agent pembrolizumab is unlikely to be used as first line, but may be useful, along with multiple new immunotherapeutics, as part of a multimodal approach towards BCG unresponsive disease. CONCLUSIONS: Results from ongoing trials will provide us useful information about many of the existing regimens and probably new drugs will soon be available for this group of patients.

OBJETIVOS: La mayoría de pacientes al primer diagnóstico de cáncer de vejiga se presentan como canceres no musculo-invasivos. El tratamiento con BCG intravesical después de resección transuretral de vejiga es el tratamiento de elección en los pacientes de riesgo intermedio y alto. Aunque, se estima que aproximadamente el 50% de estos pacientes presentaran un fallo a BCG, que incrementa su riesgo de progresión a enfermedad musculo-invasiva. Actualmente, la mejor opción para estos pacientes es la cistectomía radical. Por tanto, es de alto interés la investigación de nuevos tratamientos para pacientes con fallo a BCG para evita rla cistectomía radical. Hemos revisado las nuevas modalidades de tratamiento en pacientes con fallo a BCG.MÉTODOS: Es una revisión narrativa. Las palabras clave para la búsqueda fueron BCG failure, BCG unresponsive, BCG refractory, BCG relapsing y BCG intolerance. La evidencia se identifico a través de una búsqueda para las publicaciones con BCG un responsive hasta 2020. Los estudios fueron seleccionados si contenían datos clínicos con tratamiento para BCG unresponsive. La evaluación de ensayos clínicos para terapias emergentes se realizó a través de clinicaltrials.gov para ensayos abierto o en recrutamiento, intervencionales en 2020. RESULTADOS: Las nuevas modalidades de tratamiento para el fallo de la BCG incluyen quimioterapia intravesical, reemplace de BCG o combinación de BCG con INF-α2ß, valrubicina, radioterapia, administración electromotiva del tratamiento (EMDA), vicinium, quimiohipertermia, terapia fotodinámica, terapia genética, terapia por vacunas e immunoterapia. Para pacientes en que la BCG ha fallado una vez, el reemplace de BCG o BCG junto interferón parece ser una opción razonable. De la misma forma, gemcitabina sola puede ser utilizada como modalidad de tratamiento. Aunque, después de 2 o mas fallos a BCG, especialmente en pacientes con fallos precoces o persistencia de cáncer, el tratamiento único intravesical con quimioterapia de valrubicina, gemcitabina o docetaxel parece ser menos activa que los dobletes/tripletes de quimioterapia intravesical o mitomicina quimiotermoterapia. La terapiagénica o anticuerpo conjugados parece que juegan un papel en futuras recurrencias. La administración de pembolizumabúnicamente, es poco probable que se utilice como primera línea, pero parece ser útil, junto con los nuevos immunoterápicos como parte de un tratamiento multimodal para la enfermedad refractaria a BCG. CONCLUSIONES: Los resultados de los ensayos clínicos en funcionamiento nos dará información útil de muchos de los regímenes existentes y probablemente nuevas drogas que pronto estarán preparadas para usar en este grupo de pacientes.

Expression of proto-oncogene c-Myc in patients with urinary bladder transitional cell carcinoma.

BACKGROUND: c-Myc is a proto-oncogene located on human chromosome 8. It encodes a transcriptional factor which regulates the expression of approximately 10% to 15% of human genes, playing a crucial role in cell growth, differentiation, cellular metabolism, apoptosis, and cell transformation. The aim of this study is to correlate the expression of c-Myc in patients suffering from urinary bladder transitional cell carcinoma with tumor grade, stage, and lymph node metastases. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue samples were obtained from 54 consecutive patients who underwent transurethral resection of bladder tumor or radical cystectomy (RC) as treatment for urinary bladder transitional cell carcinoma. Immunohistochemistry was performed using c-Myc monoclonal antibody and c-Myc expression was then analyzed for correlation with tumor stage, grade, and lymph node metastases. RESULTS: From a total of 54 patients, 42 (77.8%) had c-Myc positive staining and 12 (22.2%) were c-Myc negative. In the c-Myc positive group, 28 patients (66.7%) had low grade tumors and 33 (78.6%) presented with non-muscle-invasive disease (p < 0.05). In the c-Myc negative group, 10 patients (83.3%) had high-grade disease and 8 (66.7%) presented with muscle-invasive disease (p < 0.05). Lymph node metastases were evaluated in 17 patients who underwent RC. Of these, 5 had lymph node metastases, 4 of whom had c-Myc negative staining (p < 0.05). CONCLUSIONS: In our study, c-Myc negative staining was associated with higher grade and higher stage disease. On the contrary, most c-Myc positive tumors were low grade and non-muscle-invasive disease. In patients who underwent RC, c-Myc negative staining was associated with lymph node metastases.

Association of metabolic syndrome with prostate cancer diagnosis and aggressiveness in patients undergoing transrectal prostate biopsy.

INTRODUCTION AND OBJECTIVE: Even though the only established risk factors for prostate cancer (PCa) are age, ethnic origin and family history, there are data suggesting that environmental factors, such as the presence of metabolic syndrome (MetS), may also play a role in the etiology of the disease. The aim of this study is to correlate MetS with PCa diagnosis and Gleason score (GS) in patients undergoing transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: This is a prospective, single-center study including 378 patients who underwent transrectal ultrasound guided prostate biopsy in our department during the years from 2018 to 2019. Patients were divided into two groups according to the presence of PCa. Group A included 197 patients diagnosed with PCa while Group B consisted of 181 patients without PCa in their biopsy result. Multiple variables such as the presence of MetS and its components were evaluated in correlation to the presence of PCa and PCa characteristics. Statistical analysis was performed using the IBM SPSS Statistics v.23 program. RESULTS: Mean PSA value was 8.7 ng/dl in the PCa group and 7.1 ng/dl in the non PCa group, respectively. MetS was diagnosed in 108 patients (54.8%) with PCa and 80 patients (44.2%) without PCa and the difference was statistically significant. Hypertriglyceridemia was the MetS component with statistically higher frequency in PCa patients. Furthermore, the prevalence of MetS was higher in higher Gleason score PCa (GS ≥ 4+3) patients vs lower Gleason score PCa (GS ≤ 3+4) patients. More specifically, MetS, hypertriglyceridemia, and low HDL levels were independent factors associated with higher Gleason score PCa (GS ≥ 4+3). CONCLUSIONS: Patients suffering from MetS who undergo prostate biopsy present with higher rates of PCa diagnosis and higher GS in comparison with patients with a normal metabolic profile.

Does radical prostatectomy result in lower urinary tract symptom improvement in high-risk and locally advanced prostate cancer? A Single-center experience.

PURPOSE: Radical prostatectomy represents the most popular method of prostate cancer treatment, including cases with high-risk and locally advanced cancer. Besides, men with this disease often experience lower urinary tract symptoms (LUTS) and report high International Prostate Symptom Scores (IPSS), pathological post-void residual (PVR) urine volumes and low levels of maximum urinary flow rates (Qmax). In this study we assessed the effect of radical prostatectomy on the above parameters in patients with high-risk and locally advanced disease. METHODS: A number of 240 individuals were enrolled in the study. Patients that required any post-operative manipulation up to the completion of 12 months after surgery were excluded. All patients were assessed pre- and post-operatively at 3, 6 and 12 months. Evaluation included IPSS, Qmax and PVR. RESULTS: Mean age was 66.8 years. Mean PSA value was 12.7 ng/ml and mean Gleason score was 7.9. At baseline 41.3% of the patients had Qmax ⩽10 and 42.5% had IPSS >8. There was a significant increase in Qmax during the follow-up (median value was 12 at baseline and increased to 21 at 12 months). Also, IPSS and PVR decreased significantly during the follow-up. IPSS median value decreased from 9 at baseline to 5 at 12 months. Improvement was observed in all grades of symptoms.

Oncology and complications.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.

Transurethral resection versus open bladder cuff excision in patients undergoing nephroureterectomy for upper urinary tract carcinoma: Operative and oncological results.

OBJECTIVES: To evaluate the impact of distal ureter management on oncological results after open nephroureterectomy (ONU) comparing transurethral resection of the intramural ureter to conventional open excision, as controversy still exists about the method of choice for managing the distal ureter and bladder cuff during ONU. PATIENTS AND METHODS: We retrospectively collected data from 378 patients who underwent ONU for upper urinary tract transitional cell carcinoma (UUT-TCC) from 1988 to 2009. Patients were divided into two subgroups according to the type of operation performed. Group A comprised 192 patients who had ONU with open resection of the bladder cuff from 1988 to 1997. Group B comprised 186 patients in whom transurethral resection of the intramural ureter plus single incision ONU was performed between 1998 and 2009. The mean operative time, hospital stay, duration of catheterisation, bladder recurrence rates, and cancer-specific survival (CSS) were assessed. RESULTS: The total operative time was statistically significantly less in the endoscopic group (Group B). For catheterisation, patients treated with an open approach (Group A) had a statistically significantly shorter duration of postoperative catheterisation. There was no statistical difference between Groups A and B for the bladder recurrence rate (Group A 24% vs 27% in Group B, P = 0.51). There was no difference in CSS at the 5-year follow-up. CONCLUSIONS: ONU with transurethral resection of the intramural ureter up to the extravesical fat followed by ureter extraction is an oncologically safe and technically feasible operation.

Novel treatments in bcg failure. Where do we stand today? / Nuevos tratamientos en el fracaso de bcg. ¿Dónde estamos hoy?

Objetives: Most patients at first diagnosis of bladder cancer (BC) present with nonmuscleinvasive disease (NMIBC). BCG intravesical therapyafter transurethral resection of the bladder tumor is thegold standard in intermediate and high risk NMIBC patients. However, it is estimated that approximately 50%of these patients will present with BCG failure whichincreases their risk for progression to muscle invasive disease. Currently, the best option for these patients is radical cystectomy. Thus, it is of great interest to pursue new,therapeutic options for BCG failure patients to avoid thenecessity of radical cystectomy. We hereby review novel treatment modalities for BCG failure patients.Methods: This is a narrative review. Keywords for thesearch were BCG failure, BCG unresponsive, BCG refractory, BCG relapsing and BCG intolerance. Evidencewas identified through a search for publications with a ’BCG unresponsive’’ tag through 2020. Studies wereselected if they contained clinical data on BCG unresponsive therapeutics with near-term availability. Clinicaltrial landscape evaluation for emerging therapies wasperformed by searching ClinicalTrials.gov for recruiting/open interventional trials in 2020.Results: Novel treatment modalities for BCG failureinclude intravesical chemotherapy, BCG re-challengeor combination of BCG with IFN-α2β, valrubicin, radiotherapy, electromotive drug administration, vicinium,chemohyperthermia, photodynamic therapy, gene therapy, vaccine therapy and immunotherapy. For patients inwhom BCG has once failed a repeat course of BCG orBCG plus interferon appears to be a reasonable practice. Likewise, single agent gemcitabine may be considered a treatment modality. However, after 2 or moreBCG failures, especially in patients with earlier relapsesor cancer persistence, single agent intravesical chemotherapy with valrubicin, gemcitabine or docetaxel...(AU)

Objetivos: La mayoría de pacientes alprimer diagnóstico de cáncer de vejiga se presentancomo canceres no musculo-invasivos. El tratamiento conBCG intravesical después de resección transuretral devejiga es el tratamiento de elección en los pacientes deriesgo intermedio y alto. Aunque, se estima que aproximadamente el 50% de estos pacientes presentaran unfallo a BCG, que incrementa su riesgo de progresióna enfermedad musculo-invasiva. Actualmente, la mejoropción para estos pacientes es la cistectomía radical.Por tanto, es de alto interés la investigación de nuevostratamientos para pacientes con fallo a BCG para evitarla cistectomía radical. Hemos revisado las nuevas modalidades de tratamiento en pacientes con fallo a BCG.Métodos: Es una revisión narrativa. Las palabrasclave para la búsqueda fueron BCG failure, BCG unresponsive, BCG refractory, BCG relapsing y BCG intolerance. La evidencia se identifico a través de unabúsqueda para las publicaciones con BCG unresponsive hasta 2020. Los estudios fueron seleccionadossi contenían datos clínicos con tratamiento para BCGunresponsive. La evaluación de ensayos clínicos paraterapias emergentes se realizó a través de clinicaltrials.gov para ensayos abierto o en recrutamiento, intervencionales en 2020.Resultados: Las nuevas modalidades de tratamientopara el fallo de la BCG incluyen quimioterapia intravesical, reemplace de BCG o combinación de BCGcon INF-α2β, valrubicina, radioterapia, administraciónelectromotiva del tratamiento (EMDA), vicinium, quimiohipertermia, terapia fotodinámica, terapia genética,terapia por vacunas e immunoterapia. Para pacientesen que la BCG ha fallado una vez, el reemplace deBCG o BCG junto interferón parece ser una opciónrazonable. De la misma forma, gemcitabina sola puedeser utilizada como modalidad de tratamiento. Aunque,después de 2 o mas fallos a BCG, especialmente enpacientes con fallos precoces o persistencia de cáncer...(AU)

Evaluation of urine tumor-associated trypsin inhibitor, CYFRA 21-1, and urinary bladder cancer antigen for detection of high-grade bladder carcinoma.

OBJECTIVES: To assess the value of urine tumor-associated trypsin inhibitor (TATI), CYFRA 21-1, which measures cytokeratin 19 fragment, and urinary bladder carcinoma antigen (UBC) for the detection of high-grade bladder carcinoma. METHODS: A total of 160 individuals were enrolled in the present study. Of these, 80 were patients with proven primary high-grade urothelial bladder cancer (group 1), 40 were healthy volunteers (group 2), and 40 had history of benign urologic disease (group 3). All were evaluated with respect to urinary TATI, CYFRA 21-1, and UBC levels. All these markers were evaluated using commercial kits. Cytology was also performed. RESULTS: The TATI measurements were significant greater in group 1 compared with groups 2 and 3. The cutoff point used for TATI, CYFRA 21-1, and UBC was 22, 2.8, and 12 microg/L, respectively. The overall sensitivity was 85.7% for TATI, 61.9% for CYFRA 21-1, 50% for UBC, and 42.8% for cytology. TATI was significantly more sensitive in Stage Ta (80%) than was CYFRA 21-1 (32%), UBC (12%), and cytology (20%). TATI was also more sensitive compared with other tumor markers for Stage T1 but not for Stage T2 or T3. CONCLUSIONS: The results of our study have shown that TATI is a promising urinary tumor marker for high-grade urothelial bladder cancer. It is more sensitive than CYFRA 21-1, UBC, and cytology for Stage Ta and T1 bladder cancer.