Normal Risk Ovarian Screening Study - 21-Year Update

Q: What screening strategy does NROSS evaluate?

NROSS evaluates a two-stage strategy in postmenopausal women where significantly rising CA-125 triggers transvaginal sonography (TVS), and abnormal TVS leads to surgery. ROCA risk thresholds determine when each step occurs.

Q: How were CA-125 results managed according to ROCA risk?

Women with ROCA risk unchanged and <1:2,000 returned in one year. Intermediate risk led to repeat CA-125 in 3 months, and risk increases above 1:500 triggered TVS referral.

Q: What were the key outcomes reported in this 21-year update?

Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors, with a majority of ovarian and borderline cases in early stage (I-II). Screening reduced late-stage (III-IV) disease compared with controls and achieved PPVs of 50% for ovarian cancer and 74% for any cancer.

Sep 21, 2026

Uploaded by Olivia Brown

Clinical trials often use multiple end points that mature at different times, so initial publications may precede planned co-primary or secondary analyses. Clinical Trial Updates consolidate additional findings from studies already reporting the primary end point, enabling broader dissemination of results. This update reports the Normal Risk Ovarian Screening Study (NROSS), a two-stage strategy using serial CA-125 with ROCA to trigger transvaginal sonography and surgery to detect ovarian and related cancers, emphasizing stage shift and diagnostic performance.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages9

Reading Time23 min

AccessFree to download

Abstract

Purpose

Methods

ROCA Analysis

Results

Conclusion

Introduction

Methods

Study Sites and Organization

ROCA Analysis

Clinical Trial Updates Normal Risk Ovarian Screening Study: 21-Year Update Chae Young Han, PhD1 ; Karen H. Lu, MD2 ; Gwen Corrigan, BSN1 ; Alexandra Perez, CMA1; Sharlene D. Kohring, HSD1; Joseph Celestino, BS2; Deepak Bedi, MD3 ; Enrique Bedia, MD4 ; Therese Bevers, MD5; David Boruta, MD2; Matthew Carlson, MD6; Laura Holman, MD7; Leroy Leeds, MD8,†; Cara Mathews, MD9 ; Georgia McCann, MD10; Richard G. Moore, MD11 ; Matthew Schlumbrecht, MD12 ; Brian Slomovitz, MD12,13; Dan Tobias, MD13; Yvette Williams-Brown, MD14 ; Michael W. Bevers, MD2; Jinsong Liu, MD15 ; Terrie G. Gornet, BS15; Beverly C. Handy, MD15; Zhen Lu, MD1; Jacob S. Bedia, BS16; Steven J. Skates, PhD16 ; and Robert C. Bast Jr, MD1 DOI [https://doi.org/10.1200/JCO.23.00141](https://doi.org/10.1200/JCO.23.00141) ABSTRACT Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where signiﬁcantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer. METHODS A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study ([ClinicalTrials.gov](ClinicalTrials.gov) identiﬁer: NCT00539162) . Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually. RESULTS Thirty-four patients were referred for operations detecting 15 ovarian cancersand two borderline tumors with 12 in early stage (I-II) . In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancersand two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74%(17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50%(17 of 34) for detecting ovarian cancer and 74%(25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV. CONCLUSION While the NROSS trial was not powered to detect reduced mortality, the high speciﬁcity, PPV, and marked stage shift support further development of this strategy. ACCOMPANYING CONTENT Editorial, p. 1091 Data Supplement Accepted November 3, 2023 Published January 9, 2024 J Clin Oncol 42:1102-1109 © 2024 by American Society of Clinical Oncology View Online Article Creative Commons Attribution Non-Commercial No Derivatives 4.0 License INTRODUCTION Poor outcomes in ovarian cancer relate to late detection with 70%-75% of cases diagnosed in advanced stage (III or IV) where the cure rate is less than 30% .1 Although computer algorithms suggest that mortality could be reduced by 10%-30% if ovarian cancers were detected at an earlier stage,2 only 25%-30% of patients are currently diagnosed in stage I or II. Neither serum biomarkers nor transvaginal sonography (TVS) alone are sufﬁciently speciﬁc nor sensitive to detect early-stage ovarian cancer.3 A two-stage strategy with rising cancer antigen (CA)-125 followed by TVS has shown more promise. To assess the ri

FAQs

What screening strategy does NROSS evaluate?

NROSS evaluates a two-stage strategy in postmenopausal women where significantly rising CA-125 triggers transvaginal sonography (TVS), and abnormal TVS leads to surgery. ROCA risk thresholds determine when each step occurs.

How were CA-125 results managed according to ROCA risk?

Women with ROCA risk unchanged and <1:2,000 returned in one year. Intermediate risk led to repeat CA-125 in 3 months, and risk increases above 1:500 triggered TVS referral.

What were the key outcomes reported in this 21-year update?

Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors, with a majority of ovarian and borderline cases in early stage (I-II). Screening reduced late-stage (III-IV) disease compared with controls and achieved PPVs of 50% for ovarian cancer and 74% for any cancer.

Sep 21, 2026

Uploaded by Olivia Brown