Estimands for Clinical Effectiveness of Risk-Reducing Early Salpingectomy in Women With High Risk of Ovarian Cancer

作者：Jacqueline Sia, Emily F. Lane, Caitlin T. Fierheller, Samuel Oxley, Ashwin Kalra, Michail Sideris, Wei Xia, Lea Mansour, Annika Idahl, Holly Fraser, Subhasheenee Ganesan, Priyanka Deshmukh, Raji Ganesan, Helen Hanson, Ertan Sarıdoğan, Hisham Hamed, W. Glenn McCluggage, Rosa Legood, Peter Sasieni, D. Gareth Evans, Usha Menon, Adam R. Brentnall, Ranjit Manchanda, PROTECTOR team, Emma J. Crosbie, Sudha Sundar, Munaza Ahmed, Naveena Singh, Asma Faruqi, Gareth Bryson, Gareth Rowlands, Rupali Arora, Giorgia Trevisan, Laura Casey, Jacqueline McDermott, T. R. E. Pilkington, Nataliya Piletska, Aarti Sharma, Gautam Mehra, Adam N. Rosenthal, Ian Harley, Michelle L. MacKintosh, Sadaf Ghaem‐Maghami, Omer Devaja, Janos Balega, Timothy J. Duncan, Iain Cameron, Claire Newton, Sonali Kaushik, Angela F. Brady, Bianca de Souza, Supratik Chattopadhyay, Natalia Povolotskaya, Rema Iyer, Lucy Side, Katie Snape, Amal Singh, Anil Tailor, Manon van Seters, Katherine Edey, Siân Taylor, Monika Oktaba, S. Kodiathodi, Partha Pratim Sengupta, Scott Fegan, Karin Williamson, Andrew Phillips, Mark Willett, Tony Chalhoub, R O’Donnell, S. A. Rao, Nicholas Matthews, Beena Abdul, C. Gnanachandran, Claire Park, Jane Borley, Richard Hutson, John D. Dalton, Richard Peevor, Atiyah Kamran, Mahalakshmi Gurumurthy, Kalpana Ragupathy, Helen Bolton, Jenifer Sassarini, Mithila Prasad, Monica Tryczynska, Roula Elboraei, Gisela Reig, Kelly Kohut, Victor Ohwo, Victoria Barker, Halimah Alazzani, Neil Ryan, Nazish Zulfiqar, Mohamed Abdelaziz, Georgina McArdle, Hyun Joo Doh, Kathryn Baxter, Irene Ray, Thu Thu Khaing, Maria Marks, Helena Misiura · 发表于：JAMA Network Open · 年份：2025 · DOI：10.1001/jamanetworkopen.2025.32195 · 被引用次数：4 · 研究领域：Ovarian cancer diagnosis and treatment、Menopause: Health Impacts and Treatments、BRCA gene mutations in cancer

Importance: Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking. Objective: To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements. Design, Setting, and Participants: In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohort study (N = 1250 recruited from January 1, 2019, to December 31, 2024) evaluating RRES and DO for OC surgical prevention. Participants were premenopausal women 30 years or older at increased OC risk due to BRCA1/BRCA2 pathogenic variants. Participants could choose RRES, RRSO, or no surgery at entry. Sample size requirements used initial data (eg, age and BRCA1/2 distribution) from PROTECTOR (analysis undertaken from January 1, 2024, to December 31, 2025). Main Outcomes and Measures: Incidence of OC after (not at) RRES and before or at DO in women with normal histologic analysis findings at surgery. The proportion of cancers prevented was estimated as the completement of the observed (O) to expected (E; assumi...