bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–09–27
twelve papers selected by
Lara Paracchini, Humanitas Research
  1. Projected Benefit of Bilateral Salpingo-Oophorectomy by Age in BRCA Carriers.
  2. Galleri cancer test fails to meet main aim in NHS trial, but FDA still endorses it.
  3. Remove the Fallopian Tubes If the Opportunity Arises, ACOG Says in New Ovarian Cancer Prevention Guidance.
  4. Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial.
  5. Clinical impact of ENIGMA-based variant reclassification on genotype-phenotype analyses in BRCA1- and BRCA2-associated hereditary breast and ovarian cancer.
  6. Recommendations of the American Cancer Society workshop on design, conduct, analysis, and reporting of multicancer early detection trials with late-stage incidence end points and post-trial ongoing evaluation-The Peachtree Consensus.
  7. Prognostic and therapeutic implications of BRCA1 and BRCA2 mutations in ovarian cancer.
  8. Tubo-Ovarian Cancer Risk Reduction Counseling for BRCA1/2 Carriers.
  9. Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study.
  10. Breast-Ovarian Hereditary Cancer Syndrome: Beyond BRCA1 and BRCA2.
  11. Liquid Biopsy and Multi-Cancer Early Detection Tests for Cancer Screening: A Scoping Review.
  12. Some answers, more questions for multi-cancer early detection tests.
  1. JAMA Surg. 2026 Sep 23.
    Projected Benefit of Bilateral Salpingo-Oophorectomy by Age in BRCA Carriers.
    Hereditary Ovarian Cancer Clinical Study Group
       Importance: Women with a BRCA1 or BRCA2 variant face a high lifetime risk of ovarian cancer and are often advised to undergo preventive surgery (bilateral salpingo-oophorectomy [BSO]) before cancer develops. The recommended age of BSO is 35 years for BRCA1 carriers and is 45 years for BRCA2 carriers, but some women choose to delay surgery until the age of menopause; there is no standard upper age at which surgery is no longer advised.
    Objective: To estimate the residual lifetime risk of ovarian cancer among BRCA carriers by current age and projected age at BSO.
    Design, Setting, and Participants: This was a prospective cohort study in an international cohort of BRCA carriers monitored for incident ovarian cancer. A life table analysis used age-specific ovarian cancer incidence rates and competing mortality rates to estimate lifetime risk of ovarian cancer among women with a BRCA1 or BRCA2 pathogenic variant with both ovaries intact and no prior ovarian cancer at baseline. Patients were recruited between 1995 and 2024 across 24 international centers, and the mean (SD) follow-up was 4.4 (3.9) years.
    Exposure: Timing of BSO, defined as immediate BSO, delayed BSO, or no BSO.
    Main Outcome and Measures: Residual lifetime risk of ovarian cancer.
    Results: The cohort consisted of 4286 BRCA1 and 1427 BRCA2 carriers between the ages of 30 and 74 years at baseline (mean [SD] age, 42.0 [10.8] years). There were 249 incident ovarian cancers in the follow-up period. The lifetime risk of ovarian cancer was 55.0% (95% CI, 48.8-61.9) for a BRCA1 carrier and 24.1% (95% CI, 15.1-36.6) for a BRCA2 carrier. A 30-year-old BRCA1 carrier with BSO delayed to age 50 years had a projected residual ovarian cancer risk of 23.9% (95% CI, 20.7-27.4). At age 75 years, the residual risk of ovarian cancer was estimated to be 8.4% (95% CI, 1.7-22.7) for a BRCA1 carrier and 3.7% (95% CI, 0.1-22.7) for a BRCA2 carrier.
    Conclusions and Relevance: The residual risk of ovarian cancer for older women in good health is sufficiently high to consider preventive surgery. BRCA1 carriers who defer BSO until age 50 years may face a substantial risk of developing ovarian cancer.
    DOI:  https://doi.org/10.1001/jamasurg.2026.4356
  2. BMJ. 2026 Sep 25. 394 e100975
    Galleri cancer test fails to meet main aim in NHS trial, but FDA still endorses it.
    Elisabeth Mahase.
      
    DOI:  https://doi.org/10.1136/bmj-2026-100975
  3. JAMA. 2026 Sep 25.
    Remove the Fallopian Tubes If the Opportunity Arises, ACOG Says in New Ovarian Cancer Prevention Guidance.
    Linda Rodgers.
      
    DOI:  https://doi.org/10.1001/jama.2026.19503
  4. Nat Med. 2026 Sep 22.
    Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial.
    Richard D Neal, Saoirse Dolly, Peter Johnson, Helen Jones, Sir Harpal Kumar, Lennard Y W Lee, Yujin Lee, Wei Liang, Thomas Round, Rebecca Smittenaar, Jane Warwick, Peter Sasieni, Charles Swanton.
      The NHS-Galleri trial was a randomized controlled trial evaluating a multi-cancer early detection (MCED) test added to usual care. We reported elsewhere that the primary endpoint of a reduction in the incidence of stage III/IV cancer diagnoses in the intervention arm versus control arm was not met. Here we report prespecified secondary test performance endpoints among evaluable intervention arm participants across three annual screening rounds. These analyses were descriptive; there was no hypothesis testing. Participants aged 50-77 years (N = 142,250) were randomized 1:1 into intervention (MCED) or control arms. Intervention arm participants with positive MCED results were referred to National Health Service (NHS) standard-of-care pathways for diagnostic workup, with referrals informed by the predicted cancer signal origin (CSO). Positive test results were returned for 722 of 70,325 (1.03%), 518 of 64,498 (0.80%) and 561 of 62,323 (0.90%) participants in rounds 1-3, respectively. In aggregate, 937 participants had MCED-detected primary cancers. Respective by-round cancer detection rates were 0.60%, 0.40% and 0.41%; positive predictive values were 58.0% (419/722), 50.4% (261/518) and 45.8% (257/561); and negative predictive values were 98.98% (68,895/69,603), 98.90% (63,278/63,980) and 98.86% (61,058/61,762). Across rounds, specificity ranged from 99.50% to 99.60%; episode sensitivity ranged from 26.7% to 37.2% for all cancers and from 47.6% to 63.4% for 12 prespecified types; and CSO accuracy ranged from 91.1% to 93.6%. These data provide insights on the performance of the MCED test in population screening within the NHS setting. ClinicalTrials.gov: NCT05611632 ; ISRCTN: ISRCTN91431511 .
    DOI:  https://doi.org/10.1038/s41591-026-04652-8
  5. Breast Cancer. 2026 Sep 25.
    Clinical impact of ENIGMA-based variant reclassification on genotype-phenotype analyses in BRCA1- and BRCA2-associated hereditary breast and ovarian cancer.
    Said Furkan Yildirim, Pervin Demir, Hakan Kosku, Bulent Yalcin, Ahmet Cevdet Ceylan.
       BACKGROUND: Accurate interpretation of BRCA1 and BRCA2 variants is essential for meaningful genotype-phenotype correlations and informed clinical decision-making. However, general frameworks such as the ACMG 2015 criteria frequently result in high rates of variants of uncertain significance (VUS), which may generate misleading clinicopathological associations and complicate genetic counseling.
    METHODS: We conducted a retrospective analysis of 3,706 individuals tested for BRCA1/2 variants due to BRCA-related malignancies in a large Turkish cohort. Variants were initially classified according to ACMG 2015 criteria and subsequently re-evaluated using ENIGMA consensus recommendations. Clinicopathological data were compared between variant categories before and after reclassification.
    RESULTS: Pathogenic or likely pathogenic variants were detected in 6.7% of patients, while 3.8% were initially classified as VUS. Following ENIGMA-guided reclassification, a substantial proportion of VUS, particularly missense variants lacking functional impact, were reclassified as benign or likely benign. Clinicopathological differences observed between ACMG-defined pathogenic and VUS groups-including age at onset, tumor distribution, receptor status, and progression-free survival-were eliminated after ENIGMA-based reassessment, revealing biological heterogeneity within the VUS category. Post-reclassification analyses allowed more precise distinction of benign variant profiles, refining genotype-phenotype interpretations.
    CONCLUSIONS: ENIGMA-guided variant interpretation enhances analytical precision, reduces false-positive associations, and improves clinical utility in hereditary breast and ovarian cancer genetics, offering a more reliable framework for genetic counseling and risk assessment in populations with diverse variant spectra.
    Keywords:  BRCA; ENIGMA; Genotype-phenotype correlation; Reclassification; Variant spectrum
    DOI:  https://doi.org/10.1007/s12282-026-01913-9
  6. Cancer. 2026 Oct 01. 132(19): e70628
    Recommendations of the American Cancer Society workshop on design, conduct, analysis, and reporting of multicancer early detection trials with late-stage incidence end points and post-trial ongoing evaluation-The Peachtree Consensus.
    Ruth Etzioni, Larry Kessler, Deb Schrag, Peter Sasieni, Hilary A Robbins, Hormuzd A Katki, Stephen W Duffy, Roman Gulati, Diana Buist, Sean Tunis, Rebecca Landy, Jane Lange, Alpa V Patel, William L Dahut, Robert A Smith.
       BACKGROUND: In a new era of multicancer early detection (MCED), late-stage incidence has been proposed as an end point for the evaluation of test efficacy, marking a departure from the established end point of cancer mortality.
    METHODS: The American Cancer Society convened a panel of 15 academic researchers with expertise in cancer screening evaluation to develop principles assuring the validity and interpretability of MCED trials with late-stage incidence end points and advancing implementation of tests with potential for meaningful clinical utility.
    RESULTS: The definition of late-stage cancer is critical and affects study design, interpretation, and outcomes. The authors of the Peachtree Consensus recommend considering cancer-type-specific definitions of late stage and paying attention to comparability of staging intensity in both trial arms. The duration of screening and the follow-up interval after the last screen should be chosen based on the preclinical early stage and late-stage durations of the target cancer types. The authors also recommend reporting aggregate results and results for individual cancer types as numbers permit and summarizing relative and absolute benefits. Predicted mortality reductions should be calculated to contextualize a late-stage result and the inputs and assumptions involved should be reported. Given a significant late-stage reduction suggestive of meaningful clinical benefit, the authors support launching consortium and demonstration studies while continuing to track trial mortality outcomes.
    CONCLUSIONS: Trials with late-stage incidence end points that are conducted using these principles should support the development of evidence-based screening guidelines as well as the creation of accessible data resources for observational and modeling studies.
    Keywords:  cancer screening; late‐stage incidence; multicancer early detection; randomized trials; surrogate end points
    DOI:  https://doi.org/10.1002/cncr.70628
  7. Front Oncol. 2026 ;16 1899836
    Prognostic and therapeutic implications of BRCA1 and BRCA2 mutations in ovarian cancer.
    Weronika Pawul, Paulina Opoka, Agata Dusza, Bernard Blajerski, Julia Orzelska, Natalia Gierulska, Krzysztof Kułak, Rafał Tarkowski.
       Introduction: Ovarian cancer remains one of the leading causes of cancer-related mortality among women because of its asymptomatic early course, delayed diagnosis, and frequent presentation at advanced stages. Germline and somatic mutations in the BRCA1 and BRCA2 genes significantly increase the risk of ovarian cancer by impairing homologous recombination DNA repair, resulting in genomic instability. Beyond their role in carcinogenesis, BRCA mutations have become important prognostic and predictive biomarkers, influencing treatment response and clinical outcomes. This review summarizes current evidence regarding the impact of BRCA1/2 status on prognosis and therapeutic strategies in ovarian cancer.
    Methods: A literature review was conducted using the PubMed and Scopus databases. English-language articles published between 2016 and 2026 were identified using combinations of the keywords ovarian cancer, BRCA1, BRCA2, PARP inhibitors, homologous recombination deficiency, and treatment. Original studies, systematic reviews, meta-analyses, and relevant clinical trials were included.
    Results: The available evidence demonstrates that patients carrying BRCA1 or BRCA2 mutations generally experience improved progression-free survival and, in many studies, prolonged overall survival compared with non-carriers. This survival advantage is largely attributed to increased sensitivity to platinum-based chemotherapy and the efficacy of PARP inhibitors, which exploit synthetic lethality in homologous recombination-deficient tumors. The literature also emphasizes the importance of universal BRCA testing to optimize treatment selection, identify candidates for maintenance PARP inhibitor therapy, and facilitate genetic counseling. In addition, emerging mechanisms of resistance to PARP inhibitors remain a significant therapeutic challenge.
    Conclusion: BRCA1/2 mutation status is a key biomarker in the management of ovarian cancer, supporting personalized treatment strategies and improving patient outcomes. Further research is needed to identify novel predictive biomarkers, overcome therapeutic resistance, and develop more effective targeted therapies.
    Keywords:  BRCA 1/2 mutation; BRCA1/2; HRD (homologous recombination deficiency); PARPi; PARPi resistance; genetic testing; ovarian cancer; treatment
    DOI:  https://doi.org/10.3389/fonc.2026.1899836
  8. JAMA Surg. 2026 Sep 23.
    Tubo-Ovarian Cancer Risk Reduction Counseling for BRCA1/2 Carriers.
    Christina Curtin, Ying L Liu, Kara C Long.
      
    DOI:  https://doi.org/10.1001/jamasurg.2026.4347
  9. Nat Med. 2026 Sep 22.
    Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study.
    Nima Nabavizadeh, Charles McDonnell, Dax Kurbegov, Marc Matrana, Shirish Gadgeel, Raymond H Kim, Gretchen Stipec, Kevin C Oeffinger, Michael J Demeure, James W Lillard, Rebecca Kaltman, Jennifer Tran, Alan Roth, Sami Tahhan, Andrew Poklepovic, Donald Richards, Margarita Lopatin, Celine Marquez, Margaret McCusker, Karthik V Giridhar.
      Early cancer detection improves survival; however, most cancer types do not have guideline-recommended screening. We previously reported the first PATHFINDER study that established feasibility of cancer screening with a blood-based multi-cancer early detection (MCED) test that predicts cancer signal origin (CSO) to guide diagnostic workup. The prospective, interventional PATHFINDER 2 study expands clinical evidence for the MCED test by evaluating co-primary endpoints of MCED performance metrics and safety in participants aged 50 years or older without clinical suspicion of cancer. Performance measures included cancer detection rate, positive and negative predictive values, episode sensitivity, specificity and CSO prediction accuracy. Safety was evaluated in terms of number and type of invasive procedures performed and adverse events due to diagnostic testing, after 12 months of follow-up. Endpoints were analyzed descriptively; no hypothesis testing was performed. Between December 2021 and July 2024, 35,878 participants were enrolled. Among 32,007 performance-analyzable participants, cancer detection rate was 0.54% (95% confidence interval (CI): 0.47-0.63%), positive predictive value was 60.3% (95% CI: 54.5-65.8%), negative predictive value was 99.2% (95% CI: 99.1-99.3%) and specificity was 99.64% (95% CI: 99.57-99.70%). Episode sensitivity was 39.3% (95% CI: 34.9-44.0%; all cancers) and 69.8% (95% CI: 62.8-76.0%; prespecified 12-cancer subgroup). Positive and negative likelihood ratios were 108.9 (95% CI: 87.6-135.2) and 0.61 (95% CI: 0.56-0.66), respectively, and the number needed to screen to detect one cancer was 185 (95% CI: 159-215). CSO prediction accuracy was 91.3%. Among 35,335 safety-analyzable participants, 213 (0.6%) had invasive procedure(s) after a positive MCED test; 90.5% were nonsurgical. No serious study-related adverse events were reported by the time of this analysis. These results provide insights into performance and safety of the MCED test in an intended-use population. Randomized trials and longer follow-up are needed to assess the clinical utility of MCED tests. ClinicalTrials.gov identifier: NCT05155605 .
    DOI:  https://doi.org/10.1038/s41591-026-04618-w
  10. Curr Oncol. 2026 Sep 14. pii: 556. [Epub ahead of print]33(9):
    Breast-Ovarian Hereditary Cancer Syndrome: Beyond BRCA1 and BRCA2.
    Evgeny Imyanitov, Anna Sokolenko.
      Although BRCA1 and BRCA2 remain the backbone for germline DNA testing of patients with breast cancer (BC) or ovarian cancer (OC), there are a number of other genes with proven or potential clinical significance. PALB2 is associated with an elevated risk of BC, whereas pathogenic variants (PVs) in RAD51C, RAD51D, and BRIP1 are mainly relevant to OC development. Some germline findings are helpful in guiding therapeutic decisions: for example, PALB2, RAD51C, and RAD51D germline PVs render tumors sensitive to PARP inhibitors (PARPi), whereas cancers arising in PTEN heterozygotes are likely to be responsive to AKT down-regulators. CHEK2, ATM, BLM, and NBN PVs result in only a two-fold or even lower excess of cancer risk. However, the incorporation of these genes in DNA testing panels may occasionally lead to the identification of individuals with biallelic germline inactivation; these patients have a severe disease phenotype and thus require intensive medical intervention. The accumulation of data on "non-BRCA" BC- and OC-predisposing genes is complicated due to the rarity of their alterations, significant interethnic variations in population frequency of relevant PVs, heterogeneity of disease subtypes, etc. The use of extended gene panels, which pool together both clinically validated cancer-associated genes and "candidate" genes with potential but unproven significance, is likely to be a prevailing diagnostic approach in the next few years; therefore, proper attitudes towards accumulation and interpretation of genetic data are important.
    Keywords:  NCCN guidelines; breast cancer; germline pathogenic variant; non-BRCA genes; ovarian cancer
    DOI:  https://doi.org/10.3390/curroncol33090556
  11. Clin Genet. 2026 Sep 25.
    Liquid Biopsy and Multi-Cancer Early Detection Tests for Cancer Screening: A Scoping Review.
    Tessa Robinson, Marian Saab, Lily Thao Nguyen, Pooja Kochar, Olivia Meggetto, Jill Tinmouth, Meghan J Walker.
      Liquid biopsy constitutes a range of tests that use biological fluids to detect cancer. Research is now targeting their use for cancer screening. This is the first review of the evidence on liquid biopsy tests across a range of analytical parameters, biomarkers, and cancer types for cancer screening. A scoping review was conducted using JBI methodology for scoping reviews. MEDLINE and targeted websites were searched for studies published in 2014 or later on the use of liquid biopsy and multi-cancer early detection tests for screening. A total of 104 studies were included, covering a wide range of study designs. Several types of biomarkers (e.g., cell-free DNA, circulating tumor DNA) and analytical parameters were used. Most studies addressed test performance outcomes, while fewer addressed clinical outcomes, implementation considerations, and cost-effectiveness. No empirical studies on cancer-specific mortality were found. A large body of literature was identified that covered a range of cancer types, biomarkers, analytical parameters, and outcomes. Critical gaps in the literature were demonstrated, including evidence on clinical outcomes such as cancer-specific mortality and potential harms that currently preclude the implementation of liquid biopsy tests for cancer screening. Findings of this review can be used to guide the necessary future research.
    Keywords:  cancer screening; cancer screening tests; liquid biopsy; multi‐cancer early detection; scoping review
    DOI:  https://doi.org/10.1111/cge.70249
  12. Nat Med. 2026 Sep 22.
    Some answers, more questions for multi-cancer early detection tests.
    Catherine R Marinac, Timothy R Rebbeck, Elizabeth K O'Donnell.
      
    DOI:  https://doi.org/10.1038/s41591-026-04688-w
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