Long responders to estramustine monophosphate. Report of two cases and literature review. / Repondedores a largo plazo a Estramustina monofosfato. A propósito de dos casos. Revisión bibliográfica.

OBJECTIVE: Estramustine is an stable estradiol and nitrogenated mustard conjugatewith antymicotic properties. Currently, with the appearance of chemotherapy and new molecules, estramustin acetate is not a drug of choice for castration resistant prostate cancer. METHODS: We describe two patients with castration resistant prostate cancer under treatment with estramustine acetate and complete biochemical response and stable disease. We review the literature to elucidate if the drug should be stopped and changed for the new molecules that have demonstrated survival increase. RESULTS: To our knowledge, there are not data in the literature to either solve the questions posed or shed light regarding cumulative toxicity due to prolongued use of estramustine acetate. CONCLUSIONS: We recognize that these clinical cases do not translate that estramustine acetate is a first line treatment for patients with CRPC. Nevertheless, they translate the heterogeneity of CRPC. It would be interesting to investigate the combination of new agents with estramustine acetate as well as the search of biomarkers that enable selection of candidates who could respond to estramustine acetate.

OBJETIVO: La estramustina es un conjugado estable de estradiol y una mostaza nitrogenada que tiene propiedades antimitóticas. Actualmente, con la aparición de la quimioterpia y las nuevas moléculas, el acetato de estramustina -no es un fármaco de elección en el cáncer de próstata resistente a castración.MÉTODO: Describimos dos pacientes con cáncer de próstata resistente a la castración en tratamiento con acetato de estramustina, y con una respuesta bioquímica completa y enfermedad estable. Revisamos la literatura para dilucidar si se debería retirar el acetato de estramustina y cambiar por las nuevas moléculas que han demostrado un aumento de supervivencia. RESULTADO: Hasta donde llega nuestro conocimiento, no hay datos en la literatura que resuelvan las dudas planteadas y tampoco que aporten luz en cuanto a la toxicidad acumulada por el uso prolongado del acetato de estramustina.CONCLUSIÓN: Somos conscientes de que estos casos clínicos no traducen que el acetato de estramustina sea un tratamiento de primera línea para los pacientes con cáncer de próstata resistente a la castración. Sin embargo, traducen la heterogeneidad del CPRC. Sería interesante investigar la combinación de los nuevos agentes con el acetato de estramustina así como la búsqueda de biomarcadores que permitan la selección de los candidatos que podrían responder al acetato de estramustina.

Long responders to estramustine monophosphate. Report of two cases and literature review / Repondedores a largo plazo a Estramustina monofosfato. A propósito de dos casos. Revisión bibliográfica

Objective: Estramustine is an stable estradiol and nitrogenated mustard conjugatewith antymicotic properties. Currently, with the appearance of chemotherapy and new molecules, estramustin acetate is not a drug of choice for castration resistant prostate cancer. Methods: We describe two patients with castration resistant prostate cancer under treatment with estramustine acetate and complete biochemical response and stable disease. We review the literature to elucidate if the drug should be stopped and changed for the new molecules that have demonstrated survival increase. Results: To our knowledge, there are not data in the literature to either solve the questions posed or shed light regarding cumulative toxicity due to prolongued use of estramustine acetate. Conclusions: We recognize that these clinical cases do not translate that estramustine acetate is a first line treat ment for patients with CRPC. Nevertheless, they translate the heterogeneity of CRPC. It would be interesting to investigate the combination of new agents with estramustine acetate as well as the search of biomarkers that enable selection of candidates who could respond to estramustine acetat. Conclusions: We recognize that these clinical cases do not translate that estramustine acetate is a first line treat

OBJETIVO: La estramustina es un conjugado estable de estradiol y una mostaza nitrogenada que tiene propiedades antimitóticas. Actualmente, con la aparición de la quimioterpia y las nuevas moléculas, el acetato de estramustina -no es un fármaco de elección en el cáncer de próstata resistente a castración. MÉTODO: Describimos dos pacientes con cáncer de próstata resistente a la castración en tratamiento con acetato de estramustina, y con una respuesta bioquímica completa y enfermedad estable. Revisamos la literatura para dilucidar si se debería retirar el acetato de estramustina y cambiar por las nuevas moléculas que han demostrado un aumento de supervivencia. RESULTADO: Hasta donde llega nuestro conocimiento, no hay datos en la literatura que resuelvan las dudas planteadas y tampoco que aporten luz en cuanto a la toxicidad acumulada por el uso prolongado del acetato de estramustina. CONCLUSIÓN: Somos conscientes de que estos casos clínicos no traducen que el acetato de estramustina sea un tratamiento de primera línea para los pacientes con cáncer de próstata resistente a la castración. Sin embargo, traducen la heterogeneidad del CPRC. Sería interesante investigar la combinación de los nuevos agentes con el acetato de estramustina así como la búsqueda de biomarcadores que permitan la selección de los candidatos que podrían responder al acetato de estramustina

Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy.

BACKGROUND: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. METHODS: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference's nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. RESULTS: We detect 28% of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20% at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95%:0.68-0.79) and 0.786 for HGPCa (C.I.95%:0.71-0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40% could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31% for the threshold probability of 40%. CONCLUSIONS: PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40% should be counseled to undergo an IBx if opportunistic screening is required.

Biopsia dinámica de ganglio centinela en cáncer de pene. Indicaciones, técnica y resultados en un centro oncológico español / Dynamic sentinel node biopsy in penile cancer. Indications, technique and results in a spanish oncological center

OBJETIVO: El cáncer de pene tiene una diseminación predominantemente linfática. La afectación metastásica de los ganglios linfáticos condiciona el pronóstico de esta enfermedad y la linfadenectomía inguinal tiene tanto valor pronóstico como terapéutico. Los pacientes de riesgo alto e intermedio con ganglios no palpables se beneficiarán de un diagnóstico preciso mediante la biopsia selectiva de ganglio centinela (BDGC) con una mínima agresividad quirúrgica. MÉTODOS: Revisión retrospectiva de nuestra experiencia en biopsia dinámica de ganglio centinela en cáncer de pene desde noviembre de 1999 a julio de 2014. RESULTADOS: Hemos realizado este procedimiento en 33 pacientes, técnicamente con éxito en 29 (88%). Los pacientes no sometidos a linfadenectomía por BDGC positiva han sido seguidos una media de 60.4 meses (mediana 59, rango 5-145). En 20 pacientes se realizó BDGC de manera simultánea al tratamiento quirúrgico de la lesión primaria y en 13 con posterioridad. El tiempo transcurrido en estos casos fue de 5,5 meses (mediana 5, rango: 2-12). En 6 (18,8%) de los 29 pacientes biopsiados con éxito, se observó metástasis en alguno de sus ganglios identificados como centinela. Dos pacientes fueron Falsos Negativos (6,25%). La Sensibilidad (S), Especificidad (E), Valor Predictivo Positivo (VPP) y Valor Predictivo Negativo (VPN) de las BDGC llevadas a cabo con éxito ha sido de: 66, 100, 100 y 93%, respectivamente. Conclulsión: La BDCG permite un correcto estadiaje ganglionar evitando la morbilidad de la linfadenectomía inguinal. La tasa de fracaso técnico y de Falsos Negativos (FN) es baja y puede considerarse como técnica diagnóstica de elección en cáncer de pene de riesgo alto e intermedio con ganglios impalpables

OBJECTIVE: Penile cancer has a predominantly lymphatic dissemination. Lymph nodes metastatic involvement conditions disease prognosis and inguinal lymph node dissection has both prognostic and therapeutic value. High and intermediate risk patients with non-palpable lymph nodes will benefit of a precise diagnosis by means of selective sentinel node biopsy with minimal surgical aggressiveness. Methos: Retrospective review of our experience on dynamic sentinel node biopsy in penile cancer from November 1999 to July 2014. RESULTS: We performed this procedure in 33 patients, technically successful in 29 (88%). The patients who did not undergo lymph node dissection due to positive sentinel node biopsy have been followed a mean of 60.4 months (Median 59, range 5-145). 20 patients underwent simultaneous sentinel node biopsy and surgical treatment of the primary lesion and in 13 it was performed posteriorly. In these cases the time lapse was 5.5 months (median 5, range 2-12). In 6 (18.9%) of the 29 patients successfully biopsied, metastasis was founded in any of the lymph nodes identified as sentinel. Two patients were false negative (6,25%). Sensitivity (S), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of successfully performed sentinel node biopsies were 66, 100, 100 and 93%, respectively. CONCLUSION: Sentinel node biopsy enables a correct lymph node staging avoiding the morbidity of inguinal lymph node dissection. The rate of technical failure and false negative results is low and it may be considered the diagnostic technique of choice in high and intermediate risk penile cancer with non-palpable lymph nodes

[Dynamic sentinel node biopsy in penile cancer. Indications, technique and results in a Spanish oncological center]. / BIOPSIA DINÁMICA DE GANGLIO CENTINELA EN CÁNCER DE PENE. INDICACIONES, TÉCNICA Y RESULTADOS EN UN CENTRO ONCOLÓGICO ESPAÑOL.

OBJECTIVE: Penile cancer has a predominantly lymphatic dissemination. Lymph nodes metastatic involvement conditions disease prognosis and inguinal lymph node dissection has both prognostic and therapeutic value. High and intermediate risk patients with non-palpable lymph nodes will benefit of a precise diagnosis by means of selective sentinel node biopsy with minimal surgical aggressiveness. METHODS: Retrospective review of our experience on dynamic sentinel node biopsy in penile cancer from November 1999 to July 2014. RESULTS: We performed this procedure in 33 patients, technically successful in 29 (88%). The patients who did not undergo lymph node dissection due to positive sentinel node biopsy have been followed a mean of 60.4 months (Median 59, range 5-145). 20 patients underwent simultaneous sentinel node biopsy and surgical treatment of the primary lesion and in 13 it was performed posteriorly. In these cases the time lapse was 5.5 months (median 5, range 2-12). In 6 (18.9%) of the 29 patients successfully biopsied, metastasis was founded in any of the lymph nodes identified as sentinel. Two patients were false negative (6,25%). Sensitivity (S), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of successfully performed sentinel node biopsies were 66, 100, 100 and 93%, respectively. CONCLUSION: Sentinel node biopsy enables a correct lymph node staging avoiding the morbidity of inguinal lymph node dissection. The rate of technical failure and false negative results is low and it may be considered the diagnostic technique of choice in high and intermediate risk penile cancer with non-palpable lymph nodes.

[Spontaneous enterocutaneous and rectovaginal fistula: potential complications during therapy with anti-angiogenic drugs in renal cancer]. / Fistula rectovaginal y enterocutánea espontáneas: potenciales complicaciones durante la terapia con fármacos antiangiogénicos en cancer renal.

We present two cases of enterovaginal and enterocutaneous fistulae associated to treatment with pazopanib, which is an angiogenesis inhibitor for the treatment of metastatic renal cancer. The times from drug administration and the first appearance of a fistula were 6 and 16 months, respectively. None of the cases had a history of surgery or radiotherapy in the area where the complication was observed. Enterovaginal and enterocutaneous fistula represent less than 1% of all published complications caused by the use of antiangiogenic drugs. However, they must be taken into account as the reported mortality rate is close to 30%. Given its low incidence, we believe that sharing this data is a great way to help specialists who have to treat these patients to take the necessary precautions and decide on an adequate approach.

Effectiveness of hexaminolevulinate fluorescence cystoscopy for the diagnosis of non-muscle-invasive bladder cancer in daily clinical practice: a Spanish multicentre observational study.

OBJECTIVE: To assess the sensitivity and specificity of blue-light cystoscopy (BLC) with hexaminolevulinate as an adjunct to white-light cystoscopy (WLC) vs WLC alone for the detection of non-muscle-invasive bladder cancer (NMIBC), in routine clinical practice in Spain. PATIENTS AND METHOD: An intra-patient comparative, multicentre, prospective, observational study. Adults with suspected or documented primary or recurrent NMIBC at eight Spanish centres were included in the study. All patients were examined with WLC followed by BLC with hexaminolevulinate. We evaluated the detection rate of bladder cancer lesions by WLC and BLC with hexaminolevulinate, overall and by tumour stage and compared with histological examination of the biopsied lesions. Sensitivity and specificity was calculated. RESULTS: In all, 1,569 lesions were identified from 283 patients: 621 were tumour lesions according to histology and 948 were false-positives. Of the 621 tumour lesions, 475 were detected by WLC (sensitivity 76.5%, 95% confidence interval [CI] 73.2-79.8) and 579 were detected by BLC (sensitivity 93.2%, 95% CI 91.0-95.1; P < 0.001). There was a significant improvement in the sensitivity in the detection of all types of NMIBC lesions with BLC compared with WLC. Of 219 patients with tumours, 188 had NMIBC [highest grade: carcinoma in situ (CIS), n = 36; Ta, n = 87; T1, n = 65). CIS lesions were identified more with BLC (n = 27) than with WLC [n = 19; sensitivity: BLC 75.0% (95% CI 57.8-87.9) vs WLC 52.8% (95% CI 35.5-69.6); P = 0.021]. Results varied across centres. CONCLUSIONS: This study shows that improvement in diagnosis of NMIBC, mainly CIS and Ta tumours, obtained with BLC with hexaminolevulinate as an adjunct to WLC vs WLC alone can be shown in routine clinical practice.

Feasibility of radical transurethral resection as monotherapy for selected patients with muscle invasive bladder cancer.

PURPOSE: We proved the feasibility of radical transurethral bladder tumor resection in selected patients with muscle invasive bladder cancer with a minimum followup of more than 15 years and investigated the impact of patient age on survival. A followup schedule was developed based on progression and recurrence during this period. MATERIALS AND METHODS: A phase II nonrandomized trial was designed including patients with muscle invasive bladder cancer with negative biopsies of tumor bed who were apparently healthy after undergoing complete transurethral bladder tumor resection. Patients with positive biopsies, or with macroscopically residual tumor, hydronephrosis or metastasis were excluded from study. In this trial 133 patients fulfilled the inclusion criteria and had a minimum followup of more than 15 years. RESULTS: Cancer specific survival was 81.9%, 79.5% and 76.7%, and progression-free survival with bladder preservation was 75.5%, 64.9% and 57.8% at 5, 10 and 15 years, respectively. Patient age had a negative impact on overall survival on univariate (HR 0.842, p = 0.049) and multivariate analyses (HR 1.062, p = 0.000), and according to median and quartile age stratifications (p = 0.000 and p = 0.000, respectively). However, age did not have a negative impact on cancer specific survival even when following the same stratifications. Although progression and recurrence were concentrated during the first 3 years (70% and 65%, respectively), both steadily increased afterward. A followup schedule was developed according to this sequence of events. CONCLUSIONS: Radical transurethral bladder tumor resection is a reliable therapeutic approach for patients with muscle invasive bladder cancer after complete tumor resection and with negative biopsies of the tumor bed. These results are consistent in all age ranges.

Clinical implications of TMPRSS2-ERG gene fusion expression in patients with prostate cancer treated with radical prostatectomy.

PURPOSE: Molecular prognostic factors may be useful tools for prostate cancer that complement classic clinicopathological factors. Genetic rearrangements between TMPRSS2 and ETS have been described for prostate cancer but their clinical significance is still unclear. We analyzed the association of the TMPRSS2-ERG fusion gene with prostate cancer outcome in patients treated with radical prostatectomy. MATERIAL AND METHODS: We analyzed prostate cancer samples from 226 patients treated with radical prostatectomy from 1996 to 2002 with a median followup of 84 months (range 9 to 153). TMPRSS2-ERG fusion gene expression was determined by reverse transcriptase-polymerase chain reaction. Clinicopathological and molecular variables were related to biochemical and clinical progression-free survival by the Kaplan-Meier proportional risk log rank test. A Cox proportional hazards model using stepwise selection was used to identify independent predictors of poor outcome. RESULTS: TMPRSS2-ERG fusion was detected in 114 cases (50.4%). We noted no association between fusion gene status and prostate cancer clinicopathological characteristics. However, when patients were grouped by TMPRSS2-ERG fusion gene status, different clinicopathological prognostic factors defined each group for biochemical and clinical progression-free survival. Prostate specific antigen, specimen Gleason score and margin status were independent prognostic factors in patients with prostate cancer expressing the fusion gene. In the nonexpressing TMPRSS2-ERG group the prognostic factors were cT, Gleason score and margins. CONCLUSIONS: TMPRSS2-ERG fusion gene status classifies patients with prostate cancer treated with radical prostatectomy into groups defined by different prognostic factors. This could be the basis for designing more refined treatment strategies.

¿Qué pacientes con incontinencia de esfuerzo tras prostatectomía radical se benefician de la indicacion de INVANCE®? / Which parients with stress urinary incontinence after radical prostatectomy benefit from the indication of an Invance®

OBJETIVO: La incontinencia urinaria de esfuerzo post-prostatectomía radical es una de las secuelas más preocupantes para el paciente y su urólogo. El motivo de este trabajo es valorar las indicaciones de la malla suburetral Invance®, detallando nuestra valoración preoperatoria e indicación, técnica quirúrgica y correlación entre los hallazgos preoperatorios y los resultados funcionales.MÉTODOS: Entre febrero 2006 y enero de 2009 se intervinieron 27 pacientes. Todos tenían más de un año de seguimiento tras la prostatectomía, estudio urodinámico y cistoscopia preoperatoria. Se valoró la continencia con el número de compresas/día y el cuestionario ICIQ-UI SF. A través de una incisión perineal se colocaron tres tornillos de titanio con sutura de polipropileno en cada rama isquiopubiana, a los que se fijó una malla de polipropileno y silicona (Invance®) que comprimía la uretra bulbar.Se dividió a los pacientes en dos grupos: buen pronóstico (1-2 compresas/día y sin alteración de la fase de llenado) y mal pronóstico (3 compresas/día, antecedente de radioterapia o cervicotomía y alteración del estudio urodinámico). Se consideró curación cuando los pacientes no precisaban compresas y mejoría si había descendido el número/día(AU)

RESULTADOS: La mediana de seguimiento tras Invance® fue de 18 meses (4-38). Nueve pacientes usaban una compresa/día, 10 pacientes usaban dos y ocho usaban tres compresas/día. En seis casos se realizó previamente cervicotomía y tres pacientes habían recibido radioterapia.De forma global, 20 pacientes (74%) estaban curados y cinco (19%) habían mejorado. El porcentaje de curación en el grupo de buen pronóstico fue del 100% y del 61% en el de mal pronóstico (p= 0.03).No se observó ninguna complicación intraoperatoria. Durante el postoperatorio inmediato, un paciente precisó sonda de cistostomía durante 10 días. Siete pacientes (26%) manifestaron molestias perineales y no se observaron casos de urgencia de novo, erosión uretral o explante por infección.CONCLUSIONES: Invance® es una técnica eficaz, que garantiza una tasas elevadas de continencia en pacientes seleccionados. Se trata de una cirugía reproducible y con un seguimiento a medio plazo, no se ha observado pérdida de continencia y el riesgo de erosión es nulo según nuestra experiencia. Los pacientes con escape leve-moderado, sin alteración del estudio urodinámico ni radioterapia son los candidatos ideales(AU)

OBJECTIVES: Stress urinary incontinence alter radical prostatectomy is one of the most worrisome sequelae for the patient and urologist. The aim of this paper is to evaluate the indications of the suburethral mesh Invance®, giving details on our preoperative evaluation and indication, surgical technique, and the correlation between preoperative findings and functional results.METHODS: Between February 2006 and January 2009 27 patients underwent surgery. All of them had more than one year of follow up after prostatectomy, urodynamic study and preoperative cystoscopy. Continence was evaluated by the number of pads/day and the ICIQ-UI SF questionnaire. Through a perineal incision three titanium screws with a polipropylene suture were inserted in each ischiopubic rami, and a silicon/polipropylene mesh (Invance ®) is affixed to them, compressing the bulbar urethra. Patients were divided into two groups: good prognosis (1-2 pads/day without urodynamic anomalies in the filling phase) and bad prognosis (3 pads/day, history of radiotherapy or bladder neck incision, and urodynamic anomalies). Cure was defined as a patient not needing pads, and improvement was defined as decrease in the number of pads per day(AU)

RESULTS: Median follow up after Invance ® was 18 months (4-38). Nine patients used one pad/day, 10 used two, and eight used three pads /day. Six cases had underwent previous bladder neck incision and three radiotherapy.Globally, 20 patients (74%) were cured and five (19%) had improved. Cure rate was 100% in the good prognosis group and 61% in the bad prognosis group (p=0.03).No intraoperative complications were registered. During the immediate postoperative period, one patient required cystostomy tube for 10 days. Seven patients (26%) presented perineal discomfort; neither de novo urgency nor urethral erosion nor sling explants due to infection were registered.CONCLUSIONS: Invance ® is a safe technique that guarantees a high continence rate in selected patients. It is a reproducible operation and, with a midterm follow up, no loss of continence has been observed, and the risk of urethral erosion is null in our experience. Patients with mild-moderate incontinence, without urodynamic anomalies nor previous radiotherapy are the ideal candidates(AU)

[Which patients with stress urinary incontinence after radical prostatectomy benefit from the indication of an Invance?]. / ?Qué pacientes con incontinencia de esfuerzo tras prostatectomía radical se benefician de la indicación de Invance?

OBJECTIVES: Stress urinary incontinence alter radical prostatectomy is one of the most worrisome sequelae for the patient and urologist. The aim of this paper is to evaluate the indications of the suburethral mesh Invance, giving details on our preoperative evaluation and indication, surgical technique, and the correlation between preoperative findings and functional results. METHODS: Between February 2006 and January 2009 27 patients underwent surgery. All of them had more than one year of follow up after prostatectomy, urodynamic study and preoperative cystoscopy. Continence was evaluated by the number of pads/day and the ICIQ-UI SF questionnaire. Through a perineal incision three titanium screws with a polipropylene suture were inserted in each ischiopubic rami, and a silicon/polipropylene mesh (Invance) is affixed to them, compressing the bulbar urethra. Patients were divided into two groups: good prognosis (1-2 pads/day without urodynamic anomalies in the filling phase) and bad prognosis (3 pads/day, history of radiotherapy or bladder neck incision, and urodynamic anomalies). Cure was defined as a patient not needing pads, and improvement was defined as decrease in the number of pads per day. RESULTS: Median follow up after Invance was 18 months (4-38). Nine patients used one pad/day, 10 used two, and eight used three pads /day. Six cases had underwent previous bladder neck incision and three radiotherapy. Globally, 20 patients (74% ) were cured and five (19% ) had improved. Cure rate was 100% in the good prognosis group and 61% in the bad prognosis group (p=0.03). No intraoperative complications were registered. During the immediate postoperative period,one patient required cystostomy tube for 10 days. Seven patients (26% ) presented perineal discomfort; neither de novo urgency nor urethral erosion nor sling explants due to infection were registered. CONCLUSIONS: Invance is a safe technique that guarantees a high continence rate in selected patients. It is a reproducible operation and, with a midterm follow up, no loss of continence has been observed, and the risk of urethral erosion is null in our experience. Patients with mild-moderate incontinence, without urodynamic anomalies nor previous radiotherapy are the ideal candidates.

Bladder preservation in selected patients with muscle-invasive bladder cancer by complete transurethral resection of the bladder plus systemic chemotherapy: long-term follow-up of a phase 2 nonrandomized comparative trial with radical cystectomy.

BACKGROUND: Many phase 2 bladder-sparing programmes using transurethral resection of the bladder (TURB) plus chemotherapy or radio-chemotherapy have been undertaken, but some controversies remain. OBJECTIVE: To determine the efficacy of complete TURB plus three cycles of cisplatin-based chemotherapy in selected patients with muscle-invasive bladder cancer (MIBC). DESIGN, SETTING, AND PARTICIPANTS: A phase 2 nonrandomized trial was designed that included patients with MIBC who underwent complete TURB with positive biopsies of the tumour bed. Patients with negative biopsies of the tumour bed, with macroscopically residual tumour, with hydronephrosis, or with distant metastasis were excluded from this trial. Patients included in this trial were offered three cycles of systemic chemotherapy or radical cystectomy (RC). Clinical response (cR) was denoted by either no tumour or the presence of Ta1-Tis bladder tumour at 3-mo evaluation; clinical non-response (cNR) was denoted by cases of muscle-invasive tumour or distant metastasis. Of 146 patients who entered this trial, 75 choose the bladder-sparing programme and 71 chose RC. MEASUREMENTS: At 5 yr and 10 yr, the cancer-specific survival (CSS) rate was 64.5% and 59.8%, respectively, with no significant difference compared to the RC arm (p=0.544). The progression-free survival with bladder preserved was 52.6% and 34.5%, respectively. In multivariate analysis, cR was the only predictive factor for survival (p=0.001) and bladder preservation (p=0.000). RESULTS AND LIMITATIONS: This was not a randomized trial, and patients were included over 16 yr. However, no modifications were made to the therapy schedule except from chemotherapy schemes considered standard at the time. CONCLUSIONS: Patients with microscopic residual cancer after complete TURB seem to be good candidates for the bladder-sparing programme using three cycles of systemic chemotherapy, with CSS comparable to RC.

The optimum timing of radical cystectomy for patients with recurrent high-risk superficial bladder tumour.

OBJECTIVE: To establish the optimum time of radical cystectomy (RC) for patients with recurrent high-risk superficial bladder tumours after the failure of intravesical therapy. PATIENTS AND METHODS: Among 318 patients with transitional cell carcinoma treated with RC and with no neoadjuvant therapy, there were 46 with clinical stage Ta, T1 or Tis refractory to transurethral resection associated with intravesical therapy. These patients had at least one of: (i) high-risk superficial bladder tumours after failure of two consecutive induction courses of intravesical therapy; (ii) superficial bladder tumours with prostatic stromal invasion; (iii) superficial bladder tumours with mucosa/ducts involvement after failure of one course of intravesical therapy; (iv) uncontrolled superficial tumours with transurethral resection associated or not with intravesical therapy. Progression and cause-specific survival of these patients were compared to those with muscle-invasive tumours. Univariate and multivariate analyses of predictive factors for cause-specific survival were also used in patients with superficial tumours. The incidence of significant prognostic factors was compared in both superficial and muscle-invasive tumours, as were the progression pattern and survival. RESULTS: The progression-free and cause-specific survival of patients with superficial tumours was 54% and 67%, respectively, with no significant difference from those with muscle-invasive tumours. In multivariate analysis, positive lymph-nodes and prostatic stromal invasion were significant and independent variables for survival. The incidence of positive lymph nodes was 15% vs 30% (P < 0.05) and of stromal invasion was 32% vs 1.5% (P < 0.001) in patients with superficial and muscle-invasive tumours, respectively. Accounting for the progression pattern in patients with superficial tumours, extravesical urothelial recurrence prevailed over local or distant recurrences (30% vs 15%), whereas in patients with muscle-invasive tumours the opposite occurred (5% vs 33%, respectively). The cause-specific survival of patients with superficial tumour and prostatic stromal invasion was one of three, and in those who developed extravesical urothelial recurrence was 28.5%. CONCLUSION: In patients with recurrent high-risk superficial bladder cancer after intravesical therapy, our criteria for RC were inappropriate, and patients had a survival rate similar to those with muscle-invasive tumours. RC might have been used too late, as there was a high incidence of prostatic stromal invasion and extravesical urothelial recurrence after RC. Both events seem to be responsible of the low cause-specific survival. Predictive factors for progression are needed to indicate early RC in patients with recurrent high-risk superficial tumours. From a previous analysis the pathological pattern of the clinical lack of response (T1, G3, bladder carcinoma in situ and prostate involvement) to intravesical therapy evaluated at 3 months might be important for predicting progression, and an early RC at that time might be useful.

Disruption of basement membrane, extracellular matrix metalloproteinases and E-cadherin in renal-cell carcinoma.

UNLABELLED: A retrospective study was performed to determine the prognostic value of Basement Membrane (BM) integrity, Matrix Metalloproteinases (MMPs) and E-Cadherin expression in renal cell carcinoma (RCC). MATERIALS AND METHODS: An immunohistochemical study on laminin and collagen IV, MMPs 1 and 2, and E-Cadherin was carried out on 71 RCCs. BM fragmentation was considered taking 75% as a cut-off. MMP 1 and MMP2 immunostaining, as well as E-Cadherin was considered taking 25% as a cut-off. RESULTS: An inverse relationship was seen between E-Cadherin with laminin, collagen IV and MMPs. More than 75% loss of laminin, collagen IV and E-Cadherin, as well as higher expression of MMPs, were associated with symptoms, tumoral size and worse grade. Loss of collagen IV and E-Cadherin were of prognostic value. CONCLUSION: Both BM and E-Cadherin are good prognostic markers. MMPs patterns show a relationship between BM proteins and E-Cadherin, but evaluation is more time-consuming and provide no better prognostication; consequently they are not useful in routine clinical applications.