Rethinking prognostic factors in locally advanced or metastatic urothelial carcinoma in the immune checkpoint blockade era: a multicenter retrospective study.

BACKGROUND: Few studies have investigated the safety and efficacy of anti-PD-(L)1 antibodies in metastatic urothelial carcinoma (mUC) in daily clinical practice. Knowledge about the influence of baseline clinical and analytical factors on therapy outcomes is scarce. PATIENTS AND METHODS: We conducted a multicenter retrospective study involving 119 previously treated or untreated mUC patients under anti-PD-(L)1 therapy in a real-world scenario. The objectives of this study were to confirm the safety and efficacy of anti-PD-(L)1 monotherapy and to identify pretreatment factors influencing therapy outcomes. In addition, an independent prognostic model for overall survival (OS) was developed and internally validated. RESULTS: Median OS was 7.8 months [95% confidence interval (CI), 5.4-10.4], median progression-free survival (PFS) was 2.80 months (95% CI, 2.4-3.4), disease control rate (DCR) was 40% (95% CI, 31-49), and overall response rate (ORR) was 24% (95% CI, 15-31). Presence of peritoneal metastases was associated with poor OS [hazard ratio (HR) = 2.40, 95% CI, 1.08-5.33; P = 0.03]. Use of proton-pump inhibitors (PPI) was associated with poor OS (HR = 1.83, 95% CI, 1.11-3.02; P = 0.02) and PFS (HR = 1.94, 95% CI, 1.22-3.09; P = 0.005), and lower DCR (OR = 0.38, 95% CI, 0.17-0.89; P = 0.03) and ORR (OR = 0.18, 95% CI, 0.02-1.60; P = 0.002). The three risk category prognostic model developed included Eastern Cooperative Oncology Group performance status, PPI use, albumin level, presence of liver metastases, and presence of peritoneal metastases variables and was associated with higher risk of death (HR = 3.00, 95% CI, 1.97-4.56; P = 0.0001). CONCLUSIONS: This study confirms anti-PD-(L)1 monotherapy as a safe and effective treatment option in daily clinical practice for mUC patients. It also describes the presence of peritoneal metastases as an independent prognostic factor for OS and underlines the association between PPI use and worse therapeutic outcomes. Finally, it proposes a new easy-to-use risk-assessment model for OS prediction.

Latest progress in molecular biology and treatment in genitourinary tumours.

The management of genitourinary cancer, including bladder, prostate, renal and testicular cancer, has evolved dramatically in recent years due to a better understanding of tumour genetic mutations, alterations in molecular pathways, and to the development of new kinds of drugs such as targeted therapies and immunotherapies. In the field of immunotherapy, new drugs focused on stimulating, enhancing and modulating the immune system to detect and destroy cancer, have been recently discovered. Research in oncology moves quickly and new data of great relevance for clinical practice are communicated every year. For this reason, a group of experts, focused exclusively on the treatment of genitourinary tumours and who get together every year in the BestGU conference to assess the latest progress in this field have summarized the most important advances in a single review, along with a critical assessment of whether these results should alter daily clinical practice.

Chemotherapy management for unfit patients with metastatic castration-resistant prostate cancer.

Administration of chemotherapy in prostate cancer depends on patient fitness. In unfit patients, physiological impairment determines the optimum treatment. Although no consensus on assessing patient fitness currently exists, this article proposes an algorithm combining the available information for administering chemotherapy, and in particular docetaxel, in unfit patients. It was constructed by reviewing factors that can influence treatment, such as performance status, taxane-related comorbidities and nutritional status. Geriatric scales for prostate cancer patients and alternative treatment regimens for this population are also reviewed. In summary, patients require overall assessment to optimise treatment. Use of docetaxel should be restricted in unfit patients, and other options must be evaluated, because of high toxicity and low efficacy.

Abordaje del paciente con cáncer renal: ¿existe la colaboración entre urología y oncología? / Approach of the patient with renal cancer: Is there a collaboration between urology and oncology?

No disponible

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).

A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).

BACKGROUND: Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. PATIENTS AND METHODS: This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. RESULTS: Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. CONCLUSION: This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. TRIAL NUMBER: NCT01830231.

Comprehensive overview of the efficacy and safety of sorafenib in advanced or metastatic renal cell carcinoma after a first tyrosine kinase inhibitor

We performed a literature search that shed light on the signaling pathways involved in the sorafenib activity as first- or subsequent-line treatment, taking into account its toxicity profile. Sorafenib appears to have better tolerability when compared with other agents in the same indication. Cross-resistance between tyrosine kinase inhibitors (TKIs) may be limited, even after failure with a previous VEGFR inhibitor, but the optimal sequence with TKIs remains to be determined. Randomized trials of second-line treatment options have showed either modest or no differences in terms of progression-free and overall survival (OS). Direct comparison between sorafenib and axitinib demonstrated differences in terms of PFS in favor of axitinib, but not in terms of OS as second-line treatment. In contrast, a phase III study showed a benefit in OS, favoring sorafenib when compared with temsirolimus. In conclusion, after using other VEGF inhibitor such as sunitinib, sorafenib is active and safe for the treatment of patients with advanced or metastatic RCC (AU)

Comprehensive overview of the efficacy and safety of sorafenib in advanced or metastatic renal cell carcinoma after a first tyrosine kinase inhibitor.

We performed a literature search that shed light on the signaling pathways involved in the sorafenib activity as first- or subsequent-line treatment, taking into account its toxicity profile. Sorafenib appears to have better tolerability when compared with other agents in the same indication. Cross-resistance between tyrosine kinase inhibitors (TKIs) may be limited, even after failure with a previous VEGFR inhibitor, but the optimal sequence with TKIs remains to be determined. Randomized trials of second-line treatment options have showed either modest or no differences in terms of progression-free and overall survival (OS). Direct comparison between sorafenib and axitinib demonstrated differences in terms of PFS in favor of axitinib, but not in terms of OS as second-line treatment. In contrast, a phase III study showed a benefit in OS, favoring sorafenib when compared with temsirolimus. In conclusion, after using other VEGF inhibitor such as sunitinib, sorafenib is active and safe for the treatment of patients with advanced or metastatic RCC.

Choroid plexus carcinoma: a rare condition and its therapeutic management.

Choroid plexus carcinomas are rare tumours, found chiefly during childhood. The commonest pattern of progression is via the neural axis. We present the case of a patient with unusual metastatic dissemination, affecting lungs and bones two years after diagnosis, and the approach adopted towards him.

Choroid plexus carcinoma: a rare condition and its therapeutic management

Choroid plexus carcinomas are rare tumours, found chiefly during childhood. The commonest pattern of progression is via the neural axis. We present the case of a patient with unusual metastatic dissemination, affecting lungs and bones two years after diagnosis, and the approach adopted towards him (AU)

Factores que influyen en la prescripción de los médicos de atención primaria / No disponible

Objetivo: Analizar cuantitativa y cualitativamente la prescripción farmacéutica realizada por los médicosde atención primaria del Área de Salud de León. Estudiar qué características personales del médico y delcentro de salud explican las variaciones en la prescripción.Diseño: Estudio observacional.Emplazamiento: Centros de Atención Primaria del Área de Salud de León.Participantes: Se analiza la prescripción de 270 médicos generales de atención primaria durante el periodoenero-diciembre del 2001.Intervenciones: Se utiliza como variable de respuesta: el gasto medio por envase de pensionista, el gasto porpoblación ajustada, el porcentaje de medicamentos genéricos, el porcentaje de medicamentos hipnóticos y elporcentaje de medicamentos de utilidad terapéutica baja. Se recogen como variables explicativas: la formaciónen Medicina Familiar y Comunitaria, el sexo del médico y el centro de salud urbano o rural.Resultados: El gasto medio por envase de pensionista es mayor en el medio urbano que en el rural, sin diferenciassignificativas en el resto de las variables. El gasto por población ajustada y el porcentaje de medicamentosde utilidad terapéutica baja es mayor en el medio rural que en el urbano. El porcentaje de medicamentos genéricosprescritos es mayor entre los médicos con formación en Medicina Familiar y Comunitaria que trabajan en el medio rural. En el porcentaje de medicamentos hipnóticos prescritos no se encontraron diferencias dignas de mención.Conclusiones: Se estima que las diferencias por sexo en el análisis cuantitativo fueron de poca importancia. Eltipo de centro de salud se ha identificado, entre las variables estudiadas, como la que mejor explica la prescripción. En cuanto a la formación del médico, sólo tiene importancia en la prescripción de medicamentos genéricos

Objective: The quantitative and qualitative analysis of the practice of drug prescription on the part of primarycare physicians in the Health Area of León in Spain. The determination of the particular characteristicsof the physician and the health center that explain the variations in prescription.Study design: Observational study.Setting: Primary care centers in the Health Area of León.Participants: We analyzed the prescriptions of 270 primary care general practitioners from January toDecember 2001.Interventions: We utilized the mean expenditure per package or bottle corresponding to retirees, the populationadjusted expenditure, the percentage of generic drugs prescribed, the percentage of hypnotics and the percentage of medications of limited therapeutic value as response variables. The explanatory variables were: training in family and community medicine, sex of the physician and whether the center was urban or rural.Results: The mean expenditure per package or bottle corresponding to retirees was higher in the urban settingthan in the rural setting, whereas there were no significant differences in the remaining explanatoryvariables. The population-adjusted expenditure and the percentage of drugs of limited therapeutic value werehigher in the rural setting than in the urban setting. The percentage of generic drugs prescribed was higheramong physicians with training in family and community medicine working in the rural setting. Therewere no noteworthy differences in the percentages of hypnotic drugs prescribed.Conclusions: We consider the gender differences in the quantitative analysis to be of little importance.Among all the variables studied, that which best explains the prescription pattern is the setting of the health center. The training of the physician has an effect only on the prescription of generic drugs

Tratamiento de las dislipemias en atención primaria / No disponible

Las dislipemias constituyen unas de las enfermedades más importantes en la clínica actual por su relacióndirecta con la patología coronaria. En toda situación de hipercolesterolemia es conveniente evaluar el riesgocardiovascular global del paciente, para poder fijar el objetivo a alcanzar. La modificación del estilo de vidaes el primer paso en cualquier plan terapéutico. Si no se alcanzan los objetivos fijados deberá comenzarse eltratamiento farmacológico, siendo las estatinas los fármacos de primera elección

Dyslipidemias are among the most serious diseases in current clinical practice because of their direct relationship to coronary heart disease. In patients with hypercholesterolemia, the overall cardiovascular riskshould be evaluated in order to establish the desired objective. The modification of lifestyle is the first step in any therapeutic plan. If the established objectives are not achieved, drug treatment should be introduced, with statins as the drugs of first choice