A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide.

BACKGROUND: There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). METHODS: We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical-molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. RESULTS: Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort. CONCLUSIONS: TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers.

[Lymphoepithelioma-like bladder tumor. A rare variant.] / Tumor vesical linfoepitelioma-like. Una variante infrecuente.

INTRODUCTION: Lymphoepitheliomalikedifferentiation is a rare histological variant of urothelialbladder carcinoma, therefore its prognosis and treatmentare not clearly defined. A retrospective study of 5cases in the last 10 years in our center was performed. CASE REPORT: cystectomy was performed in 4 of5 because they were non-metastatic muscle-invasivetumors at diagnosis, in the 5th TURB + BCG because itwas non-muscle-invasive. 2 patients received chemotherapyand 1 adjuvant radiotherapy, and 1 immunotherapyafter relapse. 2 had a pure lymphoepithelioma-like pattern, 2 predominant and 1 focal. DISCUSSION: In predominant or pure forms, agood response to treatment with TURB and adjuvantchemotherapy has been described, even superior tocystectomy, as it is a variant with a very favorable responseto platinum. Immunotherapy is currently onlyindicated as second-line treatment. CONCLUSIONS: adjuvant treatment plays an importantrole as it is a highly chemosensitive variant, but more studies are needed to define the best therapeuticstrategy.

INTRODUCCIÓN: La diferenciaciónlinfoepitelioma-like es una variante histológica pocofrecuente del carcinoma urotelial vesical, por lo que supronóstico y tratamiento no está claramente definido.Se presenta un estudio retrospectivo de 5 casos en losúltimos 10 años en nuestro centro.DESCRIPCIÓN DE CASOS: en 4 de los casos se realizócistectomía por ser tumores músculo-invasivosno metastásicos al diagnóstico, en el 5º RTU + BCGpor ser no músculo-invasivo. 2 pacientes recibieronquimioterapia y 1 radioterapia en adyuvancia, y 1 inmunoterapiatras recidiva. 2 presentaban un patrónlinfoepitelioma-like puro, 2 predominante y 1 focal.DISCUSIÓN: en formas predominantes o puras seha descrito buena respuesta al tratamiento con RTU yquimioterapia adyuvante, incluso superiores a cistectomía,por ser una variante con respuesta muy favorableal platino. La inmunoterapia actualmente solo estáindicada como tratamiento en segunda línea. CONCLUSIONES: el tratamiento adyuvante tiene unpapel importante por ser una variante muy quimiosensible,pero son necesarios más estudios para definirla mejor estrategia terapéutica.

Tumor vesical linfoepitelioma-like. Una variante infrecuente / Lymphoepithelioma-like bladder tumor. A rare variant

INTRODUCCIÓN: La diferenciaciónlinfoepitelioma-like es una variante histológica pocofrecuente del carcinoma urotelial vesical, por lo que supronóstico y tratamiento no está claramente definido.Se presenta un estudio retrospectivo de 5 casos en losúltimos 10 años en nuestro centro.DESCRIPCIÓN DE CASOS: en 4 de los casos se realizó cistectomía por ser tumores músculo-invasivosno metastásicos al diagnóstico, en el 5º RTU + BCGpor ser no músculo-invasivo. 2 pacientes recibieronquimioterapia y 1 radioterapia en adyuvancia, y 1 inmunoterapia tras recidiva. 2 presentaban un patrónlinfoepitelioma-like puro, 2 predominante y 1 focal.DISCUSIÓN: en formas predominantes o puras seha descrito buena respuesta al tratamiento con RTU yquimioterapia adyuvante, incluso superiores a cistectomía, por ser una variante con respuesta muy favorable al platino. La inmunoterapia actualmente solo estáindicada como tratamiento en segunda línea. CONCLUSIONES: el tratamiento adyuvante tiene unpapel importante por ser una variante muy quimiosensible, pero son necesarios más estudios para definir la mejor estrategia terapéutica.(AU)

INTRODUCTION: Lymphoepitheliomalike differentiation is a rare histological variant of urothelial bladder carcinoma, therefore its prognosis and treatment are not clearly defined. A retrospective study of 5cases in the last 10 years in our center was performed.CASE REPORT: cystectomy was performed in 4 of5 because they were non-metastatic muscle-invasivetumors at diagnosis, in the 5th TURB + BCG because itwas non-muscle-invasive. 2 patients received chemotherapy and 1 adjuvant radiotherapy, and 1 immunotherapy after relapse. 2 had a pure lymphoepithelioma-like pattern, 2 predominant and 1 focal.DISCUSSION: In predominant or pure forms, agood response to treatment with TURB and adjuvantchemotherapy has been described, even superior tocystectomy, as it is a variant with a very favorable response to platinum. Immunotherapy is currently onlyindicated as second-line treatment.CONCLUSIONS: adjuvant treatment plays an important role as it is a highly chemosensitive variant, but more studies are needed to define the best therapeutic strategy. (AU)

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study.

BACKGROUND: Axitinib monotherapy obtained approval in pre-treated mRCC patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified. PATIENTS AND METHODS: Retrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months vs. disease progression/refractory patients [RP]). A multivariate logistic-regression model was used to analyse clinical factors. Efficacy and safety were also analysed. RESULTS: In total, 157 patients who received axitinib in second or subsequent line were evaluated (91 LR and 66 RP). Older age at start of axitinib and haemoglobin levels > LLN were independent predictive factors for LR in multivariate analyses. In LR patients, median (m) PFS was 18.1 months, median overall survival was 36.0 months and objective response rate (ORR) was 45.5%. In 59 LR patients receiving axitinib in second-line, mPFS was 18.7 months, mOS was 44.8 months and ORR was 43.9%. mOS was significantly longer in second line compared to subsequent lines (44.8 vs. 26.5 months; P = .009). In LR vs. RP, mPFS with sunitinib in first-line was correlated with mPFS with axitinib in second-line (27.2 vs. 10.9 months P < .001). The safety profile was manageable and consistent with known data. CONCLUSIONS: This study confirms the long-term benefits of axitinib in a selected population, helping clinicians to select the best sequential approach and patients who could obtain a greater benefit from axitinib.

Recommendations from the Spanish Oncology Genitourinary Group for the treatment of patients with renal cell carcinoma.

Clear-cell renal cell carcinoma (RCC) is the most common kidney cancer. New treatment options of localized RCC recently incorporated include laparoscopic surgery, nephron-sparing surgery, ablative techniques and active surveillance. But 50 % of patients may develop disease recurrence attributable to subclinical metastases. In these cases, and considering the low benefits of chemotherapy, new targeted therapies such as tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors have been developed as first- and second-line treatment. Both sunitinib and pazopanib are TKIs that constitute the first-line treatment option in patients with metastatic RCC. As second-line treatment, sequential therapy with a second TKI or a mTOR inhibitor is recommended. This review has collected together a series of recommendations issued by the Spanish Oncology Genitourinary Group with the aim of facilitating the treatment of these patients. Each recommendation is accompanied by the level of evidence and grade of recommendation on the basis of the available data.

Correlation between age and weight loss after bariatric surgery.

BACKGROUND: Conflicting evidence exists regarding age as a predictive factor in excess weight loss after bariatric surgery. The objective of this cross-sectional study is to evaluate differences in excess BMI loss (%EBMIL) 1 year after surgery in patients older and younger than 45 years. METHODS: Adult obese patients fulfilling selection criteria underwent either Roux-en-Y gastric bypass or sleeve gastrectomy and were grouped according to age < and ≥45 years with follow-up at least 1 year. Both groups were compared in terms of excess BMI loss (%EBMIL) and other clinical outcomes. Possible relationship between %EBMIL, age, surgical technique, and presence of comorbidities such as diabetes mellitus, hypertension (HT), and dyslipidemia (DL) was searched. RESULTS: Three hundred thirty-seven patients (72.5 % female), 196 (50.1 %) younger than 45 years and 141 (49.9 %) with age ≥45 years. There was significant difference between age group and %EBMIL 12 months after surgery (p < 0.001), showing better results in younger patients. No differences were found in terms of gender, preoperative body mass index (BMI), surgical technique, nor presence of DL. Using multiple regression, we found significant interaction effect between age group (p < 0.001), presence of HT (p = 0.001), and %EBMIL at follow-up. CONCLUSIONS: Patients younger than 45 years lose greater amount of excess BMI than older patients after bariatric surgery. This tendency might be useful as a preoperative weight loss predictor in bariatric patients.

[Spontaneous closure of a residual fistula after surgical closure of a traumatic aorto-right ventricular fístula. Report of one case]. / Cierre espontáneo de fístula residual post cierre quirúrgico de fístula aorto-ventricular derecha traumática: Caso clínico.

We report a 16-year-old boy, who suffered a right vent ride penetrating injury caused by a sharp blade that evolved to cardiac tampon. He underwent surgery and was discharged four days later. Thirteen days later, a cardiac murmur was found. An echocardiography showed an aorta-right ventricular fistula. Surgical closure was performed through an aortotomy on cardiopulmonary by pass. The control echocardiography showed a small residual fistula, which closed spontaneously three months later.