Jordi Ponce

Evaluation of Somatic Mutations in Urine Samples as a Noninvasive Method for the Detection and Molecular Classification of Endometrial Cancer

Abstract Purpose: Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive procedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate patients with endometrial cancer from controls. Experimental Design: Overall, 72 samples were analyzed using next-generation sequencing (NGS) with molecular identifiers targeting 47 genes. We evaluated urine supernatant samples from women with endometrial cancer (n = 19) and age-matched controls (n = 20). Cell pellets from urine and plasma samples from seven cases were sequenced; further, we also evaluated paired tumor samples from all cases. Finally, immunohistochemical markers for molecular profiling were evaluated in all tumor samples. Results: Overall, we were able to identify mutations in DNA from urine supernatant samples in 100% of endometrial cancers. In contrast, only one control (5%) showed variants at a variant allele frequency (VAF) ≥ 2% in the urine supernatant samples. The molecular classification obtained by using tumor samples and urine samples showed good agreement. Analyses in paired samples revealed a higher number of mutations and VAF in urine supernatants than in urine cell pellets and blood samples. Conclusions: Evaluation of somatic mutations using urine samples may offer a user-friendly and reliable tool for endometrial cancer detection and molecular classification. The diagnostic performance for endometrial cancer detection was very high, and cases could be molecularly classified using these noninvasive and self-collected samples. Additional multicenter evaluations using larger sample sizes are needed to validate the results and understand the potential of urine samples for the early detection and prognosis of endometrial cancer.

A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets

PURPOSE Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival. METHODS We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86). RESULTS We describe the Women's cancer risk IDentification – quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC), a three-marker test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology. CONCLUSION The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.

Predicting Ovarian-Cancer Burden in Catalonia by 2030: An Age–Period–Cohort Modelling

Ovarian cancer is the most lethal gynaecological cancer in very-high-human-development-index regions. Ovarian cancer incidence and mortality rates are estimated to globally rise by 2035, although incidence and mortality rates depend on the region and prevalence of the associated risk factors. The aim of this study is to assess changes in incidence and mortality of ovarian cancer in Catalonia by 2030. Bayesian autoregressive age–period–cohort models were used to predict the burden of OC incidence and mortality rates for the 2015–2030 period. Incidence and mortality rates of ovarian cancer are expected to decline in Catalonia by 2030 in women ≥ 45 years of age. A decrease in ovarian-cancer risk was observed with increasing year of birth, with a rebound in women born in the 1980s. A decrease in mortality was observed for the period of diagnosis and period of death. Nevertheless, ovarian-cancer mortality remains higher among older women compared to other age groups. Our study summarizes the most plausible scenario for ovarian-cancer changes in terms of incidence and mortality in Catalonia by 2030, which may be of interest from a public health perspective for policy implementation.

SUCCOR 10 years: a decade's perspective on radical hysterectomy outcomes in cervical cancer.

Interest in long-term outcomes of radical hysterectomy for cervical cancer has increased, especially after the LACC trial findings, which showed worse outcomes for minimally invasive surgery. However, limited information is available on 10-year oncological outcomes, particularly, recurrence and survival. The primary objective of this study was to analyze the 10-year oncological outcomes of patients with International Federation of Gynecology and Obstetrics 2009 stage IB1 cervical cancer treated with radical hysterectomy performed via minimally invasive or open approaches. This retrospective, multi-center, observational study updates the data from the SUCCOR cohort. Patients diagnosed between January 2013 and December 2014 with tumors ≤4 cm without extra-cervical metastasis and treated with radical hysterectomy as the primary treatment were included, and a 10-year follow-up after surgery was successfully conducted. A total of 556 patients were analyzed. The median age was 46 years (range; 18-82). The most common final International Federation of Gynecology and Obstetrics 2009 stage was IB1, 474 patients (85%), and the most common histology was squamous carcinoma, 376 patients (67.6%). The 5-year disease-free survival was 93%, and the 10-year disease-free survival was 90%. The overall survival was 97% at 5 years and 89% at 10 years. During follow-up, 9% (n = 49) of patients experienced recurrences, 78% (n = 38) within the first 5 years. Comparing surgical approaches, 10-year disease-free survival was 92% for minimally invasive surgery and 88% for open surgery (p = .12). Similarly, 10-year overall survival was 92% for minimally invasive surgery and 88% for open surgery (p = .12). Post-recurrence disease-specific survival was 47% at 60 months and 39% at 96 months. The 2-year survival after recurrence was 80% for late recurrences (>5 years) versus 69% for early recurrences. The overall survival after radical hysterectomy at 5-years was 97% in patients with early-stage cervical cancer. The recurrence rate at 10 years was 9%. No differences in 10-year survival were observed between the surgical approaches.

Evaluation of DNA Methylation Markers for Endometrial Cancer Risk-stratification Using Patient-collected Urine and Vaginal Samples and Clinician-collected Cervical Samples From Women With Postmenopausal Bleeding

The goal of this observational study is to investigate the clinical utility of DNA-methylation testing in urine and vaginal samples collected by patients and cervical samples collected by clinicians, to determine the risk of endometrial cancer in symptomatic women with postmenopausal bleeding. The study aims to answer the following research questions: * What is the diagnostic accuracy of DNA methylation testing in urine, vaginal and cervical samples compared to traditional TVUS for endometrial cancer detection? * What is the 2-year risk of EC among women testing negative on TVUS and/or DNA methylation tests or those testing positive on methylation only? Researchers will compare DNA methylation testing in patient-collected urine and vaginal samples as well as in clinician-collected cervical samples, with the traditional diagnostic pathway for women with PMB, which includes TVUS evaluation, and when indicated by abnormal TVUS findings, endometrial biopsy according to clinical guidelines. Participants will * take a urine and vaginal sample * have a cervical sample collected by a clinician * undergo TVUS evaluation according to clinical guidelines * If TVUS shows thickened endometrium (≥ 5 mm) and/or irregularity, an endometrial biopsy will be collected according to clinical guidelines * fill out a questionnaire regarding acceptability and preferences of sampling methods and complete a lifestyle questionnaire.

The Clinical Utility of DNA Methylation Testing in Patient-collected Urine and Vaginal Samples to Detect Endometrial Cancer: a Case-control Study

The goal of this observational case-control study is to investigate the use of DNA-methylation testing in patient-collected urine and vaginal samples to detect endometrial cancer. The study aims to answer the following questions: * Can DNA methylation testing in vaginal and full-void urine samples distinguish endometrial cancer cases from healthy controls? Researchers will compare patient-collected urine and vaginal samples from patients with diagnosed endometrial cancer (cases) to gynaecologically and oncologically healthy controls (controls). Participants will * take a urine and vaginal sample at the hospital. * answer a questionnaire regarding acceptability and preferences of self-sampling methods. * answer a lifestyle questionnaire.

Clinical Studies of Endometrial Cytology and Cervical Methylation Assays in Endometrial Cancer Screening and Fertility-Preservation Evaluation

The current study aims to assess high-risk patients using both liquid-based cytology and cervical methylation testing. The results will be compared with the traditional hysteroscopic pathological findings to determine the sensitivity and specificity of these methods for early detection of endometrial cancer, thereby evaluating their potential application in early screening. Primary Objectives： 1. To evaluate the sensitivity, specificity, and accuracy of endometrial cytology for screening endometrial cancer. 2. To assess the sensitivity, specificity, and accuracy of methylation testing for screening endometrial cancer. 3. To perform further molecular testing on tissue samples obtained from endometrial cytology and cervical methylation tests, aiming to explore early screening-sensitive indicators. Secondary Objectives： 1. To determine the value of endometrial cytology in evaluating the efficacy of fertility-sparing treatments for endometrial cancer. 2. To assess the value of methylation testing in evaluating the efficacy of fertility-sparing treatments for endometrial cancer.