Neoadjuvant and adjuvant treatments in muscle-invasive bladder cancer: Where are we?

OBJECTIVES: Fifty percent of muscle-invasive bladder cancer (MIBC) patients succumb from metastatic disease despite radical cystectomy (RC). Neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (ACT) randomized clinical trials (RCT) investigated whether peri-operative chemotherapy improves survival. More recently, immune checkpoint inhibitors (ICI) are explored as peri-operative single agent, ICI-ICI or ICI-chemotherapy combinations. Our goal is to provide the status of neoadjuvant and adjuvant treatment in MIBC. METHODS: The literature on NAC and ACT trials in MIBC was reviewed. RESULTS: Since the 1980s, NAC RCTs were performed in cisplatin-fit patients, mainly using cisplatin combination chemotherapy. Meta-analyses indicated a small, but significant 5% improvement in overall survival in T2-T4N0M0 MIBC patients. Mostly MVAC or gemcitabine-cisplatin (GC) regimens were used without clear benefit of one regimen over the other. NAC value in N+MIBC is not established and predictive value of associated~25-40% complete downstaging (pathologically confirmed complete regression, pCR) not unequivocally demonstrated. Adjuvant cisplatin-based chemotherapy RCTs were smaller, some prematurely stopped for poor accrual, and underpowered to demonstrate clear statistical evidence for a 5% overall survival advantage in pT3-T4N1-3M0 MIBC. Novel neoadjuvant immune checkpoint inhibitors, alone or with chemotherapy, phase 2 trials demonstrate down staging and encouraging clinical results. CONCLUSIONS: Neoadjuvant MVAC or GC in cT2-T4N0 MIBC patients fit for cisplatin is still recommended based on OS benefit shown in meta-analyses, butreal-world adherence to NAC is low as ~40-50% ofpatients are unfit for cisplatin. The value of neoadjuvant treatment in node-positive MIBC is not clearly demonstrated requiring more accurate clinical staging and prospective studies. Adjuvant cisplatin-based chemotherapy may be considered in selected, chemo-naïve pT3-T4N+patients. Results from prospective checkpoint inhibitor immunotherapy RCTs are needed before immunotherapy becomes a recommended alternative for peri-operative treatment. Molecular tumour subtyping will support selecting novel agents for neoadjuvant or adjuvant strategies.

OBJETIVOS: El 50% de los tumores vesicales invasivos acaban siendo metastáticos todos y con la cistectomía radical. Los ensayos prospectivos randomizados de quimioterapia neoadyuvante y adyuvante investigaron si la quimioterapia perioperatoria mejoraba la supervivencia. Recientemente, los inhibidores de checkpoint han sido estudiados como única terapia perioperatoria o en combinaciones con quimioterapia. Nuestro objetivo es determinar el estado del tratamiento neoadyuvante y adyuvante en cáncer de vejiga musculo invasivo.MÉTODOS: Se revisó la literatura en quimioterapia neoadyuvante y adyuvante para cáncer de vejiga músculoinfiltrante. RESULTADOS: Desde 1980, los ensayos de quimioterapia neoadyuvante se realizaron en pacientes que podían tolerar cisplatino usando combinaciones de quimioterapia de cisplatino. Un metanálisis indicó una pequeña pero significante ventaja del 5% en supervivencia global para pacientes T2-4 N-M0 con cáncer de vejiga músculo invasivo. Principalmente los regímenes MVAC oGC han sido utilizados, sin demostrar beneficio de un régimen sobre otro. El valor de la quimioterapia neoadyuvante en pacientes con ganglios positivos no esta establecido pero una infragradación del 25 al 40% se ha demostrado. Los ensayos de quimioterapia adyuvante fueron mas pequeños, algunos terminaron antes de finalizar el reclutamiento y con poca potencia estadística para demostrar un 5% de ventaja de supervivencia global en pT3-T4N1-3M0. Los nuevos immunomoduladores neoadyuvantes, solos o en combinación con quimioterapia han demostrado resultados esperanzadores en términos de infragradación. CONCLUSIONES: La quimioterapia neoadyuvante con MVAC o GC en cT2-4N0 de vejiga en pacientes que pueden recibir cisplatino se recomienda en base a un beneficio en supervivencia global demostrado en un metanálisis, pero la adherencia en el mundo real a la quimioterapia neoadyuvante es tan baja como que del 40-50% de los pacientes no puede recibir cisplatino. El valor de la quimioterapia neoadyuvante en pacientes con ganglios positivos y cáncer de vejiga musculoinvasivo no esta claramente demostrado; requiere un estadiaje clínico mas eficaz y estudio prospectivos. La quimioterapia adyuvante se puede considerar en pacientes seleccionados, sobretodo los que no han recibido quimioterapia previa pT3-4 N+. Los resultados de estudios prospectivos con inmunoterapia son necesarios antes de que se pueda recomendar la quimioterapia como alternativa en el tratamiento perioperatorio. La clasificación molecular nos ayudara a seleccionar los pacientes que pueden beneficiarse de terapias neoadyuvantes y adyuvantes.

[Prognostic factors in renal cancer with venous thrombus survival analysis.] / Factores pronósticos en cáncer renal con trombo en vena. Análisis de supervivencia.

OBJECTIVES: To analyze surgery for renal cancer with venous thrombus at different levels, perioperative complications and prognostic factors associated to overall, cancer-specific and disease-free survival. MATERIAL AND METHODS: Retrospective analysis of 42 cases of renal cancer with venous thrombus performed between 2005 and 2015. The level reached by the thrombus was established according to the Mayo Clinic classification. Postoperative complications were staged according to Clavien-Dindo classification. RESULTS: Most frequent in males. Mean age 65.7 years. 16.6% were tumors with level II thrombus. Subcostal approach was performed in 58.9%. Extracorporeal circulation with cardiac arrest and hypothermia was established in 2 patients. Resection of metastatic disease was performed in 3 patients during radical nephrectomy. Reoperation was 2.3% while, perioperative mortality was 4.7%. 30% presented with metastases at diagnosis. Twenty patients progressed at 15.5 months (3-55). Overall survival was 60 months. The cancer-specific mortality was 75%. Disease-free survival was 30% at 55 months. CONCLUSIONS: Surgical treatment of renal cancer with venous thrombus requires a multidisciplinary management. The surgical technique varies according to the level reached by the venous thrombus. Tumor stage is the most important prognostic factor. Thrombus level influences prognosis, with longer survival for patients with tumor thrombus confined to the renal vein (pT3a) in comparison to tumors with thrombus in the atrium (pT3c).

[Prostatic abscess: report of a case]. / Absceso prostático: a propósito de un caso.

OBJECTIVES: To report one case of prostatic abscess which required emergency surgical treatment because of its aggressive evolution. METHODS: We describe the case of a 61-year-old male patient who was diagnosed of prostatic abscess in the emergency room, and initially underwent conservative treatment with antibiotics and urinary diversion. Due to clinical impairment to septicemia and upper urinary tract involvement we decided to perform a surgical perineal drainage. RESULTS: The septic clinical picture resolved immediately, but he presented a prostatic-perineal fistula in the intermediate postoperative period which resolved with prolonged urinary diversion by cystotomy catheter. HIV serologies were performed considering the aggressiveness of picture; they were positive. CONCLUSIONS: We emphasize this case because of the great aggressiveness that presented, possibly due to factors such as diabetes and immunosuppression (HIV). Provided the great variety of presentations of this disease, a high degree of suspicion must be exercised for its diagnosis, and once the diagnosis is got immediate treatment is recommended. We review etiopathogenic factors, clinical findings, diagnosis and therapeutic options.