Esophageal cancer - French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFP, RENAPE, SNFCP, AFEF, SFR).

INTRODUCTION: This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022. RESULTS: EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study.

BACKGROUND: Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. PATIENTS AND METHODS: This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. RESULTS: Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P = 0.025) and absence of peritoneal metastases (P = 0.009). CONCLUSIONS: Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

Prognosis and molecular characteristics of IBD-associated colorectal cancer: Experience from a French tertiary-care center.

BACKGROUND: Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France. METHODS: We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center. RESULTS: Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p = 0.05) and OS (74 vs 44 months; p = 0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis.

Incidencia del carcinoma transicional del tracto urinario superior en España / Incidence of upper tract urothelial carcinoma in Spain

INTRODUCCIÓN Y OBJETIVOS: El objetivo primario del presente estudio es conocer la incidencia real de los tumores transicionales del tracto urinario superior (TTUS) en nuestro medio. MATERIAL Y MÉTODOS: Estudio epidemiológico prospectivo y multicéntrico desarrollado en 31 centros hospitalarios españoles a través de la Plataforma de Investigación de Estudios Multicéntricos (PIEM) de la Asociación Española de Urología (AEU). El reclutamiento se inició el 01 de mayo de 2017, finalizando el 30 de abril de 2018. La base de datos final incluyó 402 casos válidos. El manejo estadístico de los datos se realizó mediante el software SPSS V 23 y EPIDAT V 3.4. RESULTADOS: Incidencia ajustada por edad a la población española de 3,27 casos/100.000 habitantes/año (2,93-3,61, IC 95%); para la población europea fue de 3,3 (2,96-3,66, IC 95%). La edad media al diagnóstico fue de 70 años, siendo el 77% de los pacientes varones. El diagnóstico fue incidental en el 34% de los casos. La localización más frecuente fue la pielocalicial (54%), seguida por el uréter distal (22%). La ureterorrenoscopia previa al tratamiento definitivo se realizó en 114 pacientes, modificando la indicación inicial del tratamiento en el 58% de los casos. La nefrectomía radical fue el tratamiento empleado en 311 pacientes; en 76 casos (20% del total) el tratamiento fue conservador. Se registraron complicaciones en el 69% de los casos tratados, la mayoría Clavien 1 y 2 (86% de todas las complicaciones). La mortalidad postoperatoria global fue de 1,76%, asociada únicamente a la realización de nefroureterectomía. CONCLUSIONES: La incidencia ajustada por edad de los TTUS es de 3,27 en España y de 3,3 en Europa. La ureterorrenoscopia como elemento de diagnóstico permite modificar la indicación inicial del tratamiento en el 58% de los pacientes

INTRODUCTION AND OBJECTIVES: The incidence of upper urinary tract tumors is currently unknown. The aim of this study is to determine the real incidence of upper tract urothelial carcinoma (UTUC) in Spain. MATERIAL AND METHODS: A descriptive, prospective and multicenter epidemiological study was conducted in 31 Spanish facilities by means of the Platform for Multicenter Studies of the Spanish Association of Urology. Recruitment was opened from May 1st, 2017 to April 30th, 2018. The original database was exported directly from the electronic Data Collection Logbook on December 15th, 2018, with a total of 404 cases registered (402 valid cases after depuration). Statistical analysis was performed using IBM SPSS software V 23 and EPIDAT V 3.4. RESULTS: The incidence adjusted to Spanish population from raw data was 3.27 cases per 100.000 inhabitants per year (2.93 - 3.61 95% CI) and 3,3 cases per 100.000 inhabitants per year (2.96-3.66 95%CI) when adjusted to European population by age. The mean age at diagnosis was 70 years, and 77% of patients were male. Thirty-four percent of patients had an incidental diagnosis. Tumors were most commonly located in the pyelocalyceal system (54%), followed by the distal ureter (22%). Prior ureteroscopy was performed in 114 patients: this technique modified the subsequent treatment indication in 58% of cases. Radical nephroureterectomy was performed in 311 patients. Kidney-sparing surgery was the elected treatment in 76 patients (20%). Complications were found in 69% of cases, most of them classified as Clavien 1 and 2 (86% of all complications). Postoperative mortality rate was 1.7%. CONCLUSIONS: UTUC adjusted incidence rate in Spain is 3.27 and 3.3 in Europe. Prior URS modified the treatment indication in 18% of patients. We found a 69% complication rate and a 1.7% mortality rate

Incidence of upper tract urothelial carcinoma in Spain. / Incidencia del carcinoma transicional del tracto urinario superior en España.

INTRODUCTION AND OBJECTIVES: The incidence of upper urinary tract tumors is currently unknown. The aim of this study is to determine the real incidence of upper tract urothelial carcinoma (UTUC) in Spain. MATERIAL AND METHODS: A descriptive, prospective and multicenter epidemiological study was conducted in 31 Spanish facilities by means of the Platform for Multicenter Studies of the Spanish Association of Urology. Recruitment was opened from May 1st, 2017 to April 30th, 2018. The original database was exported directly from the electronic Data Collection Logbook on December 15th, 2018, with a total of 404 cases registered (402 valid cases after depuration). Statistical analysis was performed using IBM SPSS software v 23 and EPIDAT v 3.4. RESULTS: The incidence adjusted to Spanish population from raw data was 3.27 cases per 100.000 inhabitants per year (2.93 - 3.61 95% CI) and 3,3 cases per 100.000 inhabitants per year (2.96-3.66 95%CI) when adjusted to European population by age. The mean age at diagnosis was 70 years, and 77% of patients were male. Thirty-four percent of patients had an incidental diagnosis. Tumors were most commonly located in the pyelocalyceal system (54%), followed by the distal ureter (22%). Prior ureteroscopy was performed in 114 patients: this technique modified the subsequent treatment indication in 58% of cases. Radical nephroureterectomy was performed in 311 patients. Kidney-sparing surgery was the elected treatment in 76 patients (20%). Complications were found in 69% of cases, most of them classified as Clavien 1 and 2 (86% of all complications). Postoperative mortality rate was 1.7%. CONCLUSIONS: UTUC adjusted incidence rate in Spain is 3.27 and 3.3 in Europe. Prior URS modified the treatment indication in 18% of patients. We found a 69% complication rate and a 1.7% mortality rate.

Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study.

BACKGROUND AND AIMS: The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. METHODS: A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. RESULTS: A total of 52 patients [male 65%, Crohn's disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4-7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%-96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%-94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%-100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. CONCLUSIONS: In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.

Development and internal validation of a diagnostic score for gastric linitis plastica.

BACKGROUND: There is no consensual definition for gastric linitis plastica (GLP). We aim to construct a diagnostic score to distinguish this rare tumor from usual gastric adenocarcinomas. METHODS: In this retrospective study, all patients who had gastrectomy for cancer between 2007 and 2017 in French tertiary centers were included. The outcome was a diagnosis of GLP based on pathological review of the surgical specimen. The diagnostic score was created by using variables that were most frequently associated with GLP using penalized logistic regression on multiply imputed datasets. We used discrimination measures to assess the performances of the score. Internal validation was performed using bootstrapping methods to correct for over-optimism. RESULTS: 220 patients including 71 linitis plastica (female 49%, median age 57 years) were analyzed. The six parameters retained in the diagnosis score were the presence of large folds and/or parietal thickening on at least one segment, pangastric infiltration and presence of gastric stenosis on the upper endoscopy, circumferential thickening on at least one segment and thickening of the third hyperechogenic layer on endoscopic ultrasound and the presence of signet ring cells on endoscopic biopsies. The area under the ROC curve (AUC) was 0.967 with a sensitivity of 94% [89.9-97.3] and a specificity of 88.7% [81.7-95.8] for a threshold of 2.75. After internal validation, the corrected AUC was 0.959. CONCLUSION: It is the first study validating a pre-therapeutic diagnostic score (Saint Louis linitis score) with an excellent ability to discriminate GLP from non-GLP adenocarcinomas. An external validation is necessary to confirm our data.

Prognostic factors in patients treated with second-line chemotherapy for advanced gastric cancer: results from the randomized prospective phase III FFCD-0307 trial.

AIM: The aim of this study was to determine prognostic factors in patients treated with second-line therapy (L2) for locally advanced or metastatic gastric and gastro-esophageal junction (GEJ) adenocarcinoma in a randomized phase III study with predefined L2. METHODS: In the FFCD-0307 study, patients were randomly assigned to receive in L1 either epirubicin, cisplatin, and capecitabine (ECX arm) or fluorouracil, leucovorin, and irinotecan (FOLFIRI arm). L2 treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). Chi square tests were used to compare the characteristics of patients treated in L2 with those of patients who did not receive L2. Prognostic factors in L2 for progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox model. RESULTS: Among 416 patients included, 101/209 (48.3%) patients in the ECX arm received FOLFIRI in L2, and 81/207 (39.1%) patients in the FOLFIRI arm received ECX in L2. Patients treated in L2, compared with those who only received L1 had : a better ECOG score (0-1: 90.4% versus 79.7%; p = 0.0002), more frequent GEJ localization (40.8% versus 27.6%; p = 0.005), and lower platelet count (median: 298000 versus 335000/mm3; p = 0.02). In multivariate analyses, age < 60 years at diagnosis (HR 1.49, 95% CI 1.09-2.03, p = 0.013) and ECOG score 2 before L2 (HR 2.62, 95% CI 1.41-4.84, p = 0.005) were the only significant poor prognostic factors for OS. CONCLUSION: Age ≥ 60 years at diagnosis and ECOG score 0/1 before L2 were the only favorable prognostic factors for OS.

Multidisciplinary development of the Geriatric Core Dataset for clinical research in older patients with cancer: A French initiative with international survey.

BACKGROUND: To define a core set of geriatric data to be methodically collected in clinical cancer trials of older adults, enabling comparison across trials. PATIENTS AND METHODS: Following a consensus approach, a panel of 14 geriatricians from oncology clinics identified seven domains of importance in geriatric assessment. Based on the international recommendations, geriatricians selected the mostly commonly used tools/items for geriatric assessment by domain (January-October 2015). The Geriatric Core Dataset (G-CODE) was progressively developed according to RAND appropriateness ratings and feedback during three successive Delphi rounds (July-September 2016). The face validity of the G-CODE was assessed with two large panels of health professionals (55 national and 42 international experts) involved both in clinical practice and cancer trials (March-September 2017). RESULTS AND DISCUSSION: After the last Delphi round, the tools/items proposed for the G-CODE were the following: (1) social assessment: living alone or support requested to stay at home; (2) functional autonomy: Activities of Daily Living (ADL) questionnaire and short instrumental ADL questionnaire; (3) mobility: Timed Up and Go test; (4) nutrition: weight loss during the past 6 months and body mass index; (5) cognition: Mini-Cog test; (6) mood: mini-Geriatric Depression Scale and (7) comorbidity: updated Charlson Comorbidity Index. More than 70% of national experts (42 from 20 cities) and international experts (31 from 13 countries) participated. National and international surveys showed good acceptability of the G-CODE. Specific points discussed included age-year cut-off, threshold of each tool/item and information about social support, but no additional item was proposed. CONCLUSION: We achieved formal consensus on a set of geriatric data to be collected in cancer trials of older patients. The dissemination and prospective use of the G-CODE is needed to assess its utility.

Fulguración ambulatoria con láser Holmium: Un procedimiento seguro para el tratamiento de la recidiva del carcinoma vesical no músculo infiltrante / Outpatient Holmium laser fulguration: A safe procedure for treatment of recurrence of nonmuscle invasive bladder cancer

Introducción y objetivo: Los tumores vesicales no musculo-invasivos presentan una elevada tasa de recurrencias y una baja tasa de progresión. El objetivo del estudio es evaluar la efectividad, seguridad y factibilidad de la fulguración con láser Holmium en régimen ambulatorio en tumores seleccionados. Material y método: Estudio prospectivo, longitudinal, de cohortes (enero de 2009 hasta diciembre de 2016). Se realizaron 79 procedimientos de fulguración con láser Holmium + instilación posterior de MMC en régimen ambulatorio en 59 pacientes con historia de neoplasia vesical de bajo riesgo y recidivas papilares de pequeño tamaño. Se realiza un análisis descriptivo de los datos y se analiza el tiempo libre de recidiva mediante curvas de Kaplan-Meier. Resultados: Todos los procedimientos se completaron en el día y sólo un paciente precisó ingreso posterior por hematuria. El 87.2% de los pacientes presentó dolor con EVA ≤ 3. Se objetivó recidiva tras el 49.4% de los procedimientos (27.3% a los 12 meses). La mediana de seguimiento fue de 17 meses (rango 2-65). La aparición de recidiva fue significativamente más precoz tras la segunda fulguración que tras la primera (mediana: 10 meses vs 56 meses). Conclusiones: La fulguración con láser Holmium + instilación posterior de MMC en régimen ambulatorio es una alternativa segura y factible a la RTUv en pacientes con tumores seleccionados. Probablemente sea recomendable realizar una RTUv en los pacientes con recidiva tras fulguración, dado que posiblemente el riesgo de progresión en estos pacientes es superior

Background and Objective: Nonmuscle invasive bladder cancer has a high recurrence rate and a low progression rate. The aim of this study was to assess the effectiveness, safety and feasibility of Holmium laser fulguration in an outpatient regimen for selected tumours. Material and Method: A prospective, longitudinal cohort study was conducted between January 2009 and December 2016. Seventy-nine Holmium laser fulguration procedures with subsequent instillation of mitomycin C were performed in an outpatient regimen on 59 patients with a history of low-risk bladder cancer and recurrence of small papillary tumours. We performed a descriptive data analysis and analysed the relapse-free time using Kaplan-Meier curves. Results: All procedures were completed in one day, and only one patient required subsequent hospitalisation due to haematuria. Some 87.2% of the patients presented pain with a visual analogue score ≤3. Recurrence occurred after 49.4% of the procedures (27.3% at 12 months). The median follow-up time was 17 months (range, 2-65). The onset of recurrence was significantly earlier after the second fulguration than after the first (median, 10 months vs. 56 months). Conclusions: Holmium laser fulguration and subsequent mitomycin C instillation in an outpatient regimen is a safe and feasible alternative to transurethral resection of bladder tumours in selected patients. Transurethral resection of the bladder tumour is recommended for patients with recurrence after fulguration, given the possibly higher risk of progression in these patients

Geriatric analysis from PRODIGE 20 randomized phase II trial evaluating bevacizumab + chemotherapy versus chemotherapy alone in older patients with untreated metastatic colorectal cancer.

BACKGROUND: Older patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older. PATIENTS AND METHODS: Patients underwent a geriatric assessment at randomization and at each evaluation. The predictive value of geriatric and oncologic factors was determined for the primary composite end-point assessing safety and efficacy of treatment (BEV or CT) simultaneously and also progression-free survival (PFS) and overall survival (OS). RESULTS: 102 patients were randomized (51 BEV and 51 CT; median age 80 years [range 75-91]). On multivariate analysis, baseline normal independent activity of daily living (IADL) score and no previous cardiovascular disease predicted the primary end-point. High (versus low) baseline Köhne score predicted short PFS and baseline Spitzer quality of life (QoL) score <8, albumin level ≤35 g/L, CA19.9 >2 LN levels above normal and high baseline Köhne score predicted short OS. Survival without deteriorated QoL and autonomy was similar with BEV and CT. On subgroup analyses, the benefit of bevacizumab seemed to be maintained in patients with baseline impaired IADL or nutritional status. CONCLUSION: Normal IADL score was associated with a good efficacy and safety of both BEV and CT. Köhne criteria may be relevant prognostic factors in older patients. Adding bevacizumab to chemotherapy does not impair patient autonomy or QoL.

Seguimiento a largo plazo del cabestrillo AdVance(R)/AdVanceXP(R). ¿Qué piensa el cirujano?, ¿qué piensa el paciente? / Long-term follow-up of the AdVance(R)/AdVanceXP(R) sling. What are the surgeons' impressions? What are the patients'?

Objetivos: Analizar la seguridad, la eficacia y la calidad de vida del paciente con incontinencia urinaria de esfuerzo masculina tras una prostatectomía radical, tratados con el cabestrillo AdVance(R) y AdvanceXP(R). Pacientes y método: Se han incluido en el estudio 92 pacientes con incontinencia urinaria de esfuerzo tras una prostatectomía radical tratados mediante cabestrillo AdVance(R) y AdVanceXP(R) entre mayo de 2008 y diciembre de 2015. Se realizó en todos los casos test de reposición perineal con coaptación esfinteriana ≥ 1,5cm. Se definió incontinencia urinaria de esfuerzo leve como el uso de 1-2 absorbentes/24 h; moderada: 3-5 absorbentes/24 h, y grave más de 5 absorbentes/24 h. Como curación se definió la ausencia total de uso de absorbentes, mejoría cuando la reducción fue mayor del 50% en el número de estos y fracaso cuando la reducción fue menor del 50%, no se obtuvo mejoría o se produjo un empeoramiento de la incontinencia. Se realizaron controles a los 3, 12 y 36 meses tras la cirugía. El índice de calidad de vida utilizado fue el International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Las complicaciones se reflejaron según la clasificación de Clavien-Dindo. Resultados: El grado de incontinencia preoperatoria fue de tipo leve en el 23,9%, moderada en el 67,4% y grave en el 8,7%. El uso medio de absorbentes preoperatorio fue de 3,1 (rango 1-6, IC 95%). La puntuación media preoperatoria del test ICIQ-SF fue de 16,5 (15-20). La coaptación esfinteriana ≥ 1,5cm mediante el test de reposicionamiento perineal estaba presente en 87 pacientes (94,6%). El seguimiento medio desde la inserción del cabestrillo fue de 42,1 meses. El porcentaje de pacientes curados a los 3 meses fue del 89,1%, a los 12 meses del 70,7% y a los 36 meses del 70,4%. La puntuación del ICQ-SF a los 3, 12 y 36 meses mostró una mejoría significativa (p < 0,001) respecto a la puntuación preoperatoria. Conclusiones: Los sistemas Advance(R) y AdvanceXP(R) se muestran eficaces en el tiempo en cuanto a la continencia urinaria y la satisfacción del paciente

Objectives: To analyse the safety, efficacy and quality of life of patients with male stress urinary incontinence after radical prostatectomy treated with the AdVance(R) and AdvanceXP(R) slings. Patients and method: The study included 92 patients with stress urinary incontinence after radical prostatectomy treated with the AdVanc(R) and AdVanceXP(R) sling between May 2008 and December 2015. A perineal repositioning test was performed in all cases with sphincter coaptation of ≥ 1.5 cm. Mild stress urinary incontinence was defined as the use of 1-2 absorbers/24 h; moderate was defined as 3-5 absorbers/24 h; and severe was defined as more than 5 absorbers/24 h. Healing was defined as the total absence of using pads; improvement was defined as a reduction > 50% in the number of pads; and failure was defined as a reduction < 50, no improvement or worsened incontinence. Check-ups were conducted at 3, 12 and 36 months after the surgery. We employed the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) for the quality of life index. The complications are listed according to the Clavien-Dindo classification. Results: The degree of preoperative incontinence was mild in 23.9%, moderate in 67.4% and severe in 8.7% of the patients. The mean use of preoperative pads was 3.1 (range 1-6, 95% CI). The mean preoperative ICIQ-SF score was 16.5 (15-20). Sphincter coaptation ≥ 1.5cm using the perineal repositioning test was present in 87 patients (94.6%). The mean follow-up from insertion of the sling was 42.1 months. Some 89.1% of the patients were healed at 3 months, 70.7% were healed at 12 months, and 70.4% were healed at 36 months. The ICIQ-SF score at 3, 12 and 36 months showed significant improvement (P < .001) compared with the preoperative score. Conclusions: The Advance(R) and AdvanceXP(R) system are effective over time in terms of urinary continence and patient satisfaction

Outpatient Holmium laser fulguration: A safe procedure for treatment of recurrence of nonmuscle invasive bladder cancer. / Fulguración ambulatoria con láser Holmium: Un procedimiento seguro para el tratamiento de la recidiva del carcinoma vesical no músculo infiltrante.

BACKGROUND AND OBJECTIVE: Nonmuscle invasive bladder cancer has a high recurrence rate and a low progression rate. The aim of this study was to assess the effectiveness, safety and feasibility of Holmium laser fulguration in an outpatient regimen for selected tumours. MATERIAL AND METHOD: A prospective, longitudinal cohort study was conducted between January 2009 and December 2016. Seventy-nine Holmium laser fulguration procedures with subsequent instillation of mitomycin C were performed in an outpatient regimen on 59 patients with a history of low-risk bladder cancer and recurrence of small papillary tumours. We performed a descriptive data analysis and analysed the relapse-free time using Kaplan-Meier curves. RESULTS: All procedures were completed in one day, and only one patient required subsequent hospitalisation due to haematuria. Some 87.2% of the patients presented pain with a visual analogue score ≤3. Recurrence occurred after 49.4% of the procedures (27.3% at 12 months). The median follow-up time was 17 months (range, 2-65). The onset of recurrence was significantly earlier after the second fulguration than after the first (median, 10 months vs. 56 months). CONCLUSIONS: Holmium laser fulguration and subsequent mitomycin C instillation in an outpatient regimen is a safe and feasible alternative to transurethral resection of bladder tumours in selected patients. Transurethral resection of the bladder tumour is recommended for patients with recurrence after fulguration, given the possibly higher risk of progression in these patients.

RAS mutation analysis in circulating tumor DNA from patients with metastatic colorectal cancer: the AGEO RASANC prospective multicenter study.

Background: RAS mutations are currently sought for in tumor samples, which takes a median of almost 3 weeks in western European countries. This creates problems in clinical situations that require urgent treatment and for inclusion in therapeutic trials that need RAS status for randomization. Analysis of circulating tumor DNA might help to shorten the time required to determine RAS mutational status before anti-epidermal growth factor receptor antibody therapy for metastatic colorectal cancer. Here we compared plasma with tissue RAS analysis in a large prospective multicenter cohort. Patients and methods: Plasma samples were collected prospectively from chemotherapy-naive patients and analyzed centrally by next-generation sequencing (NGS) with the colon lung cancer V2 Ampliseq panel and by methylation digital PCR (WIF1 and NPY genes). Tumoral RAS status was determined locally, in parallel, according to routine practice. For a minimal κ coefficient of 0.7, reflecting acceptable concordance (precision ± 0.07), with an estimated 5% of non-exploitable data, 425 subjects were necessary. Results: From July 2015 to December 2016, 425 patients were enrolled. For the 412 patients with available paired plasma and tumor samples, the κ coefficient was 0.71 [95% confidence interval (CI), 0.64-0.77] and accuracy was 85.2% (95% CI, 81.4% to 88.5%). In the 329 patients with detectable ctDNA (at least one mutation or one methylated biomarker), the κ coefficient was 0.89 (95% CI, 0.84-0.94) and accuracy was 94.8% (95% CI, 91.9% to 97.0%). The absence of liver metastases was the main clinical factor associated with inconclusive circulating tumor DNA results [odds ratio = 0.11 (95% CI, 0.06-0.21)]. In patients with liver metastases, accuracy was 93.5% with NGS alone and 97% with NGS plus the methylated biomarkers. Conclusion: This prospective trial demonstrates excellent concordance between RAS status in plasma and tumor tissue from patients with colorectal cancer and liver metastases, thus validating plasma testing for routine RAS mutation analysis in these patients. Clinical Trial registration: Clinicaltrials.gov, NCT02502656.

Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

Background: [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. Patients and methods: In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Results: Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13 €, P < 0.033). Conclusion: 18FDG-PET/CT, when added every 6 months, increased costs without decreasing treatment failure rates in patients in remission of CRC. The control group had very close follow-up, and any additional improvement (if present) would be small and hard to detect. ClinicalTrials.gov identifier: NCT00624260.

Histologically Proven Bronchial Neuroendocrine Tumors in MEN1: A GTE 51-Case Cohort Study.

OBJECTIVE: To evaluate the natural history of MEN1-related bronchial endocrine tumors (br-NETs) and to determine their histological characteristics, survival and causes of death. br-NETs frequency ranges from 3 to 13% and may reach 32% depending on the number of patients evaluated and on the criteria required for diagnosis. METHODS: The 1023-patient series of symptomatic MEN1 patients followed up in a median of 48.7 [35.5-59.6] years by the Groupe d'étude des Tumeurs Endocrines was analyzed using time-to-event techniques. RESULTS: br-NETs were found in 51 patients (4.8%, [95% CI 3.6-6.2%]) and were discovered by imaging in 86% of cases (CT scan, Octreoscan, Chest X-ray, MRI). Median age at diagnosis was 45 years [28-66]. Histological examination showed 27 (53%) typical carcinoids (TC), 16 (31%) atypical carcinoids (AC), 2 (4%) large cell neuroendocrine carcinomas (LCNEC), 3(6%) small cell neuroendocrine carcinomas (SCLC), 3(6%) TC associated with AC. Overall survival was not different from the rest of the cohort (HR 0.29, [95% CI 0.02-5.14]). AC tended to have a worse prognosis than TC (p = 0.08). Seven deaths were directly related to br-NETs (three AC, three SCLC and one LCNEC). Patients who underwent surgery survived longer (p = 10-4) and were metastasis free, while 8 of 14 non-operated patients were metastatic. There were no operative deaths. CONCLUSIONS: Around 5% of MEN1 patients develop br-NETs. br-NETs do not decrease overall survival in MEN1 patients, but poorly differentiated and aggressive br-NETs can cause death. br-NETs must be screened carefully. A biopsy is essential to operate on patients in time.

Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results.

Background: Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population. Patients and methods: Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria. Results: About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT). Conclusion: Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.

Long-term follow-up of the AdVance®/AdVanceXP® sling. What are the surgeons' impressions? What are the patients'? / Seguimiento a largo plazo del cabestrillo AdVance®/AdVanceXP®. ¿Qué piensa el cirujano?, ¿qué piensa el paciente?

OBJECTIVES: To analyse the safety, efficacy and quality of life of patients with male stress urinary incontinence after radical prostatectomy treated with the AdVance® and AdvanceXP® slings. PATIENTS AND METHOD: The study included 92 patients with stress urinary incontinence after radical prostatectomy treated with the AdVance® and AdVanceXP® sling between May 2008 and December 2015. A perineal repositioning test was performed in all cases with sphincter coaptation of≥1.5cm. Mild stress urinary incontinence was defined as the use of 1-2 absorbers/24h; moderate was defined as 3-5 absorbers/24h; and severe was defined as more than 5 absorbers/24h. Healing was defined as the total absence of using pads; improvement was defined as a reduction>50% in the number of pads; and failure was defined as a reduction<50, no improvement or worsened incontinence. Check-ups were conducted at 3, 12 and 36 months after the surgery. We employed the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) for the quality of life index. The complications are listed according to the Clavien-Dindo classification. RESULTS: The degree of preoperative incontinence was mild in 23.9%, moderate in 67.4% and severe in 8.7% of the patients. The mean use of preoperative pads was 3.1 (range 1-6, 95% CI). The mean preoperative ICIQ-SF score was 16.5 (15-20). Sphincter coaptation≥1.5cm using the perineal repositioning test was present in 87 patients (94.6%). The mean follow-up from insertion of the sling was 42.1 months. Some 89.1% of the patients were healed at 3 months, 70.7% were healed at 12 months, and 70.4% were healed at 36 months. The ICIQ-SF score at 3, 12 and 36 months showed significant improvement (P<.001) compared with the preoperative score. CONCLUSIONS: The Advance® and AdvanceXP® system are effective over time in terms of urinary continence and patient satisfaction.