Factores pronósticos en el tratamiento adyuvante del cáncer de vejiga

El cáncer de vejiga es el cuarto tumor más frecuente en hombres. En este estudio se recogen 70 pacientes diagnosticados de carcinoma urotelial resecables en el Hospital Germans Trias y Pujol(1994 -2011). El objetivo es analizar que factores pronósticos determinan la realización del tratamiento adyuvante.La edad fue un factor pronóstico: menores de 70 años alcanzaban una mediana de supervivencia de 77 meses.Pacientes sin afectación ganglionar tenían una mediana de supervivencia de 77 meses frente a 26 meses (con afectación ganglionar)siendo significativo.La afectación linfovasular también evidenció peor supervivencia siendo significativa.En nuestra serie la quimioterapia adyuvante en cáncer de vejiga aporta un beneficio cuando existe afectación ganglionar y linfovascular.El càncer de bufeta és el quart tumor més freqüent en homes. En aquest estudi es recullen 70 pacients diagnosticats de carcinoma urotelial ressecables a l'Hospital Germans Trias i Pujol (1994 -2011). L'objectiu és analitzar quins factors pronòstics determinen la realització del tractament adyuvante.La edat va ser un factor pronòstic: menors de 70 anys arribaven a una mitjana de supervivència de 77 meses.Pacientes sense afectació ganglionar tenien una mitjana de supervivència de 77 mesos enfront de 26 mesos (amb afectació ganglionar) sent significativo.La afectació linfovasular també va evidenciar pitjor supervivència sent significativa.En nostra sèrie la quimioteràpia adjuvant en càncer de bufeta aporta un benefici quan hi ha afectació ganglionar i limfovascular

Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial

[Background] There are limited data on toxicity and surgical safety associated with neoadjuvant programmed death ligand 1 (PD-L1) inhibitors prior to radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC).[Objective] To present a comprehensive safety analysis of the largest neoadjuvant series, with focus on timing and severity of toxicity and surgical complications occurring after neoadjuvant atezolizumab in patients with MIBC enrolled in the ABACUS trial.[Design, setting, and participants] ABACUS (NCT02662309) is an open-label, multicenter, phase II trial for patients with histologically confirmed (T2-T4aN0M0) MIBC, awaiting RC. Patients either were ineligible or refused cisplatin-based neoadjuvant chemotherapy.[Intervention] Two cycles of neoadjuvant atezolizumab (1200 mg, every 3 wk) followed by RC.[Outcome measurements and statistical analysis] Description of atezolizumab toxicity profile in the neoadjuvant setting, impact on surgery, and delayed immune-mediated adverse events (AEs) were assessed.[Results and limitations] Ninety-five patients received treatment. Of them, 44% (42/95) had atezolizumab-related AEs during the neoadjuvant period (fatigue [20%], decreased appetite [6%], and transaminases increased [6%]). Treatment-related grade 3–5 AEs occurred in 11% (10/95) of patients during the study. Of the patients, 21% (20/95) received only one cycle of atezolizumab due to AEs; 92% (87/95) underwent RC. No surgery was delayed due to atezolizumab-related toxicities. Surgical complications occurred in 62% (54/87) of patients. Of these patients, 43% (37/87) and 20% (17/87) had minor (grade 1–2) and major (grade 3–5) complications, respectively. Thirteen of 87 (15%) patients had post-RC atezolizumab-related AEs, including adrenal insufficiency and transaminases increased. Three deaths occurred during the period of study-related interventions (one non–treatment-related aspiration pneumonia, one immune-related myocardial infarction, and one cardiogenic shock after RC). Not all surgical safety parameters were available.[Conclusions] Two cycles of neoadjuvant atezolizumab are well tolerated and do not seem to impact surgical complication rates. Owing to the long half-life, AEs may occur in the postoperative period, including endocrine abnormalities requiring attention and intervention.[Patient summary] Here, we report a comprehensive dataset of patients receiving neoadjuvant immune checkpoint inhibitors before radical cystectomy. Treatment with neoadjuvant atezolizumab is safe and does not seem to complicate surgery significantly.Queen Mary University of London was the Sponsor of the study. Roche granted QMUL funding for the study. J. Bull and M. Jacobson also provided financial support for aspects of the biomarker analysis. We acknowledge Cancer Research UK, the UK Experimental Cancer Medicine Network, and La Roche-Hoffmann for funding.Peer reviewe

Identification of tissue microRNAs predictive of sunitinib activity in patients with metastatic renal cell carcinoma

PURPOSE: To identify tissue microRNAs predictive of sunitinib activity in patients with metastatic renal-cell-carcinoma (MRCC) and to evaluate in vitro their mechanism of action in sunitinib resistance. METHODS: We screened 673 microRNAs using TaqMan Low-density-Arrays (TLDAs) in tumors from MRCC patients with extreme phenotypes of marked efficacy and resistance to sunitinib, selected from an identification cohort (n = 41). The most relevant differentially expressed microRNAs were selected using bioinformatics-based target prediction analysis and quantified by qRT-PCR in tumors from patients presenting similar phenotypes selected from an independent cohort (n = 101). In vitro experiments were conducted to study the role of miR-942 in sunitinib resistance. RESULTS: TLDAs identified 64 microRNAs differentially expressed in the identification cohort. Seven candidates were quantified by qRT-PCR in the independent series. MiR-942 was the most accurate predictor of sunitinib efficacy (p = 0.0074). High expression of miR-942, miR-628-5p, miR-133a, and miR-484 was significantly associated with decreased time to progression and overall survival. These microRNAs were also overexpressed in the sunitinib resistant cell line Caki-2 in comparison with the sensitive cell line. MiR-942 overexpression in Caki-2 up-regulates MMP-9 and VEGF secretion which, in turn, promote HBMEC endothelial migration and sunitinib resistance. CONCLUSIONS: We identified differentially expressed microRNAs in MRCC patients presenting marked sensitivity or resistance to sunitinib. MiR-942 was the best predictor of efficacy. We describe a novel paracrine mechanism through which high miR-942 levels in MRCC cells up-regulates MMP-9 and VEGF secretion to enhance endothelial migration and sunitinib resistance. Our results support further validation of these miRNA in clinical confirmatory studies

Factores pronósticos en el tratamiento adyuvante del cáncer de vejiga

El cáncer de vejiga es el cuarto tumor más frecuente en hombres. En este estudio se recogen 70 pacientes diagnosticados de carcinoma urotelial resecables en el Hospital Germans Trias y Pujol(1994 -2011). El objetivo es analizar que factores pronósticos determinan la realización del tratamiento adyuvante.La edad fue un factor pronóstico: menores de 70 años alcanzaban una mediana de supervivencia de 77 meses.Pacientes sin afectación ganglionar tenían una mediana de supervivencia de 77 meses frente a 26 meses (con afectación ganglionar)siendo significativo.La afectación linfovasular también evidenció peor supervivencia siendo significativa.En nuestra serie la quimioterapia adyuvante en cáncer de vejiga aporta un beneficio cuando existe afectación ganglionar y linfovascular.El càncer de bufeta és el quart tumor més freqüent en homes. En aquest estudi es recullen 70 pacients diagnosticats de carcinoma urotelial ressecables a l'Hospital Germans Trias i Pujol (1994 -2011). L'objectiu és analitzar quins factors pronòstics determinen la realització del tractament adyuvante.La edat va ser un factor pronòstic: menors de 70 anys arribaven a una mitjana de supervivència de 77 meses.Pacientes sense afectació ganglionar tenien una mitjana de supervivència de 77 mesos enfront de 26 mesos (amb afectació ganglionar) sent significativo.La afectació linfovasular també va evidenciar pitjor supervivència sent significativa.En nostra sèrie la quimioteràpia adjuvant en càncer de bufeta aporta un benefici quan hi ha afectació ganglionar i limfovascular

Toxicity and Surgical Complication Rates of Neoadjuvant Atezolizumab in Patients with Muscle-invasive Bladder Cancer Undergoing Radical Cystectomy: Updated Safety Results from the ABACUS Trial

International audienc

Publisher Correction: Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial (Nature Medicine, (2019), 25, 11, (1706-1714), 10.1038/s41591-019-0628-7)

In the version of this article initially published, the labels in the key to Fig. 1f (red bars, Down in responders; blue bars, Up in responders) were incorrect. The correct labels are as follows: red bars, Up in responders; blue bars, Down in responders. Also, the histopathology images in Fig. 2a were incorrect. The correct images are now provided. The errors have been corrected in the HTML and PDF versions of the article