A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).

Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.

Cribado de cáncer de pulmón: Supervivencia en un amplio programa de detección precoz en España (I-ELCAP) / Lung Cancer Screening: Survival in an Extensive Early Detection Program in Spain (I-ELCAP)

Introducción y objetivo: El cáncer de pulmón (CP) se diagnostica habitualmente en estadios avanzados con una supervivencia media a cinco años del 12%. Ensayos como el National Lung Screening Trial (NLST) y el NEderlands Leuvens longkanker Screenings ONderzoek (NELSON) demuestran una reducción de la mortalidad que justifican la implantación del cribado en población de riesgo. Nuestro objetivo es presentar los resultados de supervivencia del programa de cribado de CP más amplio de España con tomografía computarizada de baja dosis (TCBD). Métodos: Se analizaron los datos del programa Internacional de Detección Precoz de CP (IELCAP) en Valencia, España. Este programa reclutó fumadores o exfumadores con una edad entre 40- 80 años. Se comparan los resultados con otros programas de similar tamaño. Resultados: Un total de 8.278 participantes fueron reclutados con al menos dos rondas de seguimiento, hasta noviembre de 2020 (62,8% varones), realizando una media de seis rondas de cribado por individuo. Diagnosticamos 239 tumores en 12 años de seguimiento. El adenocarcinoma fue el tumor más frecuente con un 61,3% en estadio I. Las tasas de prevalencia e incidencia fueron de 1,5% y 1,4%, respectivamente, con una tasa de detección anual de 0,17. Las tasas de supervivencia cáncer específica a cinco años fueron del 90 y del 80,1% a 10 años. La adherencia fue de 96,84%. Conclusión: La experiencia del programa más amplio de España demuestra que la supervivencia se mejora cuando se realiza en equipos multidisciplinares con experiencia en CP y es similar a programas similares. (AU)

Introduction: Lung cancer (LC) is usually diagnosed at advanced stages with only a 12% 5-year survival. Trials as NLST and NELSON show a mortality decrease, which justifies implementation of lung cancer screening in risk population. Our objective was to show survival results of the largest LC screening program in Spain with low dosage computed tomography (LDCT). Methods: Clinical records from International Early Lung Cancer Detection Program (IELCAP) at Valencia, Spain were analysed. This program recruited volunteers, ever-smokers aged 40-80 years, since 2008. Results are compared to those from other similar sizeable programs. Results: A total of 8278 participants were screened with at least two-rounds until November 2020. A mean of 6 annual screening rounds were performed. We detected 239 tumours along 12-year follow-up. Adenocarcinoma was the most common histology, being 61.3% at stage I. The lung cancer prevalence and incidence proportion was 1.5% and 1.4%, respectively with an annual detection rate of 0.17. One-year survival and 10-year survival were 90% and 80.1%, respectively. Adherence was 96.84%. Conclusion: Largest lung cancer screening in Spain shows that survival is improved when is performed in multidisciplinary team experienced in management of LC, and is comparable to similar screening programs. (AU)

[Translated article] Lung Cancer Screening: Survival in an Extensive Early Detection Program in Spain (I-ELCAP) / Cribado de cáncer de pulmón: supervivencia en un amplio programa de detección precoz en España (I-ELCAP)

Introduction: Lung cancer (LC) is usually diagnosed at advanced stages with only a 12% 5-year survival. Trials as NLST and NELSON show a mortality decrease, which justifies implementation of lung cancer screening in risk population. Our objective was to show survival results of the largest LC screening program in Spain with low dosage computed tomography (LDCT). Methods: Clinical records from International Early Lung Cancer Detection Program (IELCAP) at Valencia, Spain were analysed. This program recruited volunteers, ever-smokers aged 40-80 years, since 2008. Results are compared to those from other similar sizeable programs. Results: A total of 8278 participants were screened with at least two-rounds until November 2020. A mean of 6 annual screening rounds were performed. We detected 239 tumours along 12-year follow-up. Adenocarcinoma was the most common histology, being 61.3% at stage I. The lung cancer prevalence and incidence proportion was 1.5% and 1.4%, respectively with an annual detection rate of 0.17. One-year survival and 10-year survival were 90% and 80.1%, respectively. Adherence was 96.84%. Conclusion: Largest lung cancer screening in Spain shows that survival is improved when is performed in multidisciplinary team experienced in management of LC, and is comparable to similar screening programs. (AU)

Introducción y objetivo: El cáncer de pulmón (CP) se diagnostica habitualmente en estadios avanzados con una supervivencia media a cinco años del 12%. Ensayos como el National Lung Screening Trial (NLST) y el NEderlands Leuvens longkanker Screenings ONderzoek (NELSON) demuestran una reducción de la mortalidad que justifican la implantación del cribado en población de riesgo. Nuestro objetivo es presentar los resultados de supervivencia del programa de cribado de CP más amplio de España con tomografía computarizada de baja dosis (TCBD). Métodos: Se analizaron los datos del programa Internacional de Detección Precoz de CP (IELCAP) en Valencia, España. Este programa reclutó fumadores o exfumadores con una edad entre 40- 80 años. Se comparan los resultados con otros programas de similar tamaño. Resultados: Un total de 8.278 participantes fueron reclutados con al menos dos rondas de seguimiento, hasta noviembre de 2020 (62,8% varones), realizando una media de seis rondas de cribado por individuo. Diagnosticamos 239 tumores en 12 años de seguimiento. El adenocarcinoma fue el tumor más frecuente con un 61,3% en estadio I. Las tasas de prevalencia e incidencia fueron de 1,5% y 1,4%, respectivamente, con una tasa de detección anual de 0,17. Las tasas de supervivencia cáncer específica a cinco años fueron del 90 y del 80,1% a 10 años. La adherencia fue de 96,84%. Conclusión: La experiencia del programa más amplio de España demuestra que la supervivencia se mejora cuando se realiza en equipos multidisciplinares con experiencia en CP y es similar a programas similares. (AU)

Lung Cancer Screening: Survival in an Extensive Early Detection Program in Spain (I-ELCAP). / Cribado de cáncer de pulmón: Supervivencia en un amplio programa de detección precoz en España (I-ELCAP).

INTRODUCTION: Lung cancer (LC) is usually diagnosed at advanced stages with only a 12% 5-year survival. Trials as NLST and NELSON show a mortality decrease, which justifies implementation of lung cancer screening in risk population. Our objective was to show survival results of the largest LC screening program in Spain with low dosage computed tomography (LDCT). METHODS: Clinical records from International Early Lung Cancer Detection Program (IELCAP) at Valencia, Spain were analysed. This program recruited volunteers, ever-smokers aged 40-80 years, since 2008. Results are compared to those from other similar sizeable programs. RESULTS: A total of 8278 participants were screened with at least two-rounds until November 2020. A mean of 6 annual screening rounds were performed. We detected 239 tumours along 12-year follow-up. Adenocarcinoma was the most common histology, being 61.3% at stage I. The lung cancer prevalence and incidence proportion was 1.5% and 1.4%, respectively with an annual detection rate of 0.17. One-year survival and 10-year survival were 90% and 80.1%, respectively. Adherence was 96.84%. CONCLUSION: Largest lung cancer screening in Spain shows that survival is improved when is performed in multidisciplinary team experienced in management of LC, and is comparable to similar screening programs.

A Tetra-Panel of Serum Circulating miRNAs for the Diagnosis of the Four Most Prevalent Tumor Types.

The purpose of this study is to clinically validate a series of circulating miRNAs that distinguish between the 4 most prevalent tumor types (lung cancer (LC); breast cancer (BC); colorectal cancer (CRC); and prostate cancer (PCa)) and healthy donors (HDs). A total of 18 miRNAs and 3 housekeeping miRNA genes were evaluated by qRT-PCR on RNA extracted from serum of cancer patients, 44 LC, 45 BC, 27 CRC, and 40 PCa, and on 45 HDs. The cancer detection performance of the miRNA expression levels was evaluated by studying the area under the curve (AUC) of receiver operating characteristic (ROC) curves at univariate and multivariate levels. miR-21 was significantly overexpressed in all cancer types compared with HDs, with accuracy of 67.5% (p = 0.001) for all 4 tumor types and of 80.8% (p < 0.0001) when PCa cases were removed from the analysis. For each tumor type, a panel of miRNAs was defined that provided cancer-detection accuracies of 91%, 94%, 89%, and 77%, respectively. In conclusion, we have described a series of circulating miRNAs that define different tumor types with a very high diagnostic performance. These panels of miRNAs would constitute the basis of different approaches of cancer-detection systems for which clinical utility should be validated in prospective cohorts.

Diagnóstico precoz del cáncer de pulmón: utilidad de la tomografía computarizada de baja dosis de radiación / Lung Cancer Screening: Use of Low-Dose Computed Tomography

Introducción: El pronóstico del cáncer de pulmón (CP) está relacionado directamente con el estadio de la enfermedad al diagnóstico. Material y métodos: Realizamos TC de baja dosis (TCBD) a personas asintomáticas ≥ 50 años, fumadores o exfumadores de ≥ 10 paquetes-año, sin antecedentes oncológicos. Seguimos un algoritmo de evaluación según el tamaño y la morfología de los nódulos. En los CP diagnosticados se estableció el tratamiento adecuado y el seguimiento fue de 5 años. Resultados: Estudiamos 4.951 personas (65,4% varones) con una media de edad de 56,89 ± 5,26 años; 550 presentaron nódulos. De 3.891 nódulos detectados, 692 (19,57%) fueron considerados positivos, hallando 38 tumores (36 CP). En el estudio anual, 224 sujetos mostraban algún nódulo, siendo 288 (7,91%) positivos (13 CP). En el 80% el control se realizó con TCBD y se indicó biopsia en el 5,8% (basal) y 7,6% (anual) de los nódulos positivos. La prevalencia fue del 0,89 y la incidencia del 0,1%. La sensibilidad, la especificidad, el VPP y el VPN en el estudio basal fueron del 92,31, del 89,54, del 6,55 y del 99,93%, respectivamente, y en el anual, del 76,92, del 95,7, del 4,52 y del 99,94%, respectivamente. Se detectaron 52 tumores (49 CP), 25 (52,08%) en estadio I. La supervivencia global de los CP fue del 58,5% a los 5 años, y la supervivencia cáncer específica, del 67,1% (75,8% en los pacientes quirúrgicos). Conclusiones: La TCBD integrada en un programa elaborado de detección y evaluación de nódulos es una herramienta útil para diagnosticar CP en estadio precoz

Introduction: The prognosis of lung cancer (LC) correlates directly with the stage of the disease at the time of diagnosis. Material and methods: We performed low-dose CT (LDCT) in asymptomatic individuals ≥ 50 years old, smokers or former smokers of ≥ 10 pack-years, with no history of cancer. We followed an evaluation algorithm, according to the size and morphology of the nodules. The appropriate treatment for the LC diagnosis was given and patients were followed up for 5 years. Results: We studied 4,951 individuals (65.4% males) with an average age of 56.89 ± 5.26 years; 550 presented nodules. Of the 3,891 nodules detected, 692 (19.57%) were considered positive, and 38 tumors (36 LC) were identified. In the annual follow-up, nodules were found in 224 subjects, 288 (7.91%) of which were positive (13 LC). In 80%, the study was performed with LDCT, and biopsy was indicated in 5.8% (baseline) and in 7.6% (annual) of the positive nodules. Prevalence was 0.89 and incidence was 0.1%. The sensitivity, specificity, PPV and NPV in the baseline study were 92.31, 89.54, 6.55 and 99.93%, respectively, and in the annual study, they were 76.92, 95.7, 4.52 and 99.94%, respectively. A total of 52 tumors were detected (49 LC), 25 (52.08%) in stage I. The 5-year overall survival rate for LC was 58.5% and cancer-specific survival was 67.1% (75.8% in surgical patients). Conclusion: LDCT integrated into an elaborate nodule detection and evaluation program is a useful tool for diagnosing early-stage LC

Magnetic resonance imaging as an assessment tool following intervention with an AdVance XP suburethral sling for postprostatectomy urinary incontinence.

AIMS: The aim of this study was to compare magnetic resonance imaging (MRI) parameters in patients with mild incontinence after radical prostatectomy, who had undergone treatment with a suburethral sling. The objective was to compare patients who had been successfully treated with unsuccessful patients. METHODS: This observational cohort study at a single institution evaluated consecutive patients treated with an AdVance XP sling. MRI was performed using a 1.5 Tesla system. Preoperative urodynamic assessment and flexible cystoscopy were performed. The qualitative analysis was based on sling indentation (complete vs incomplete). The quantitative analysis comprised the following three parameters: the sling-pubis distance, the thickness of the proximal urethral bulb, and the sling backward distance (SBD), defined as the distance between the prolongation of a line through the major axis of the pubis (the line-segment joining the vertices of the pubis) and the sling indentation. The primary outcome was pad count at 3 months; cure as zero pads. A logistic univariate regression model was employed to assess the potential predictors of successful outcomes. An adjusted multivariate logistic regression model using the significant univariate factors was developed. RESULTS: Of the 83 patients enrolled, the univariate analysis revealed a relationship between failure and adverse urodynamics and between success and sling indentation, thickness of the proximal bulb and SBD. Only the association with SBD persisted in the multivariate analysis. CONCLUSIONS: MRI revealed a strong relationship between proper positioning of the sling (small SBD) and continence outcome. These data have important implications for a second surgery following initial sling failure.

Lung Cancer Screening: Use of Low-Dose Computed Tomography. / Diagnóstico precoz del cáncer de pulmón: utilidad de la tomografía computarizada de baja dosis de radiación.

INTRODUCTION: The prognosis of lung cancer (LC) correlates directly with the stage of the disease at the time of diagnosis. MATERIAL AND METHODS: We performed low-dose CT (LDCT) in asymptomatic individuals ≥50years old, smokers or former smokers of ≥10 pack-years, with no history of cancer. We followed an evaluation algorithm, according to the size and morphology of the nodules. The appropriate treatment for the LC diagnosis was given and patients were followed up for 5years. RESULTS: We studied 4,951 individuals (65.4% males) with an average age of 56.89±5.26years; 550 presented nodules. Of the 3,891 nodules detected, 692 (19.57%) were considered positive, and 38 tumors (36LC) were identified. In the annual follow-up, nodules were found in 224 subjects, 288 (7.91%) of which were positive (13LC). In 80%, the study was performed with LDCT, and biopsy was indicated in 5.8% (baseline) and in 7.6% (annual) of the positive nodules. Prevalence was 0.89 and incidence was 0.1%. The sensitivity, specificity, PPV and NPV in the baseline study were 92.31, 89.54, 6.55 and 99.93%, respectively, and in the annual study, they were 76.92, 95.7, 4.52 and 99.94%, respectively. A total of 52 tumors were detected (49LC), 25 (52.08%) in stageI. The 5-year overall survival rate for LC was 58.5% and cancer-specific survival was 67.1% (75.8% in surgical patients). CONCLUSION: LDCT integrated into an elaborate nodule detection and evaluation program is a useful tool for diagnosing early-stage LC.

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole.

BACKGROUND: Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. METHODS: We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. RESULTS: Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). CONCLUSIONS: Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.