7d4ec8fb67840ff3215711be1bd6442f cancers-17-03487.pdf 1acbbca3d48f0996f4923e72c36cad45b1ad9e8e cancers-17-03487.pdf ad6429c5da7bc00ff247fd94b037a0e7fc31fa5fa50171c3180d8ea2e8bfe665 cancers-17-03487.pdf Title: Surgical Staging in Locally Advanced Cervical Cancer: Precision, Risks, and the ‘Helmet’ Analogy Subject: Background/Objectives: This study aims to critically appraise the role of para-aortic surgical staging in locally advanced cervical cancer (LACC) in the era of advanced imaging, and to outline how selective surgery and biomarkers could be integrated within modern, quality-assured treatment pathways. Methods: Narrative review of randomized trials, large databases, and prospective/retrospective series comparing para-aortic lymphadenectomy with imaging-based staging; focused appraisal of Uterus-11, NCDB analyses, and ongoing prospective trials (PAROLA with Senti-PAROLA as one of its sub-studies and PALDISC). Emerging technologies (PET/MRI, radiomics/AI) and molecular assays (OSNA, HPV-ctDNA) were also assessed. Results: PET/CT remains the standard for distant staging, but sensitivity for low-volume nodal disease (<5 mm) is poor; in pelvic-positive/para-aortic-negative patients, occult para-aortic metastases approach ~21%. Para-aortic surgical staging modifies radiotherapy planning in ~18% of cases and can act as a de-escalation tool by avoiding unnecessary extended-field CRT (EF-CRT) when para-aortic nodes are negative. Uterus-11 showed no overall survival difference versus CT-based staging, but suggested benefit in FIGO 2009 stage IIB; its design (CT comparator, optimistic assumptions, limited power) constrains inference. Minimally invasive extraperitoneal/transperitoneal staging is feasible with low morbidity in expert centers, yet real-world management may worsen outcomes. The role of systemic intensification in node-positive disease remains undefined: PALN-positive patients were excluded from the INTERLACE trial. In the KEYNOTE-826 study, subgroup analyses according to nodal status were not reported, although the benefit of pembrolizumab remained consistent irrespective of bevacizumab use. Sentinel para-aortic mapping and biomarkers (e.g., HPV-ctDNA) may refine selection and reduce morbidity. Conclusions: Surgical staging is the most accurate method to detect occult para-aortic disease. Its routine use is not justified, but it may benefit selected high-risk patients, particularly where decisions on EF-CRT or systemic therapy hinge on para-aortic status. Future practice should integrate advanced imaging, selective surgery, and biomarkers within accredited centers, guided by large collaborative trials conducted under international quality frameworks such as ESGO/ESTRO/ESP guidelines. Keywords: uterine cervical neoplasms; lymph node excision; para-aortic lymph nodes;neoplasm staging; positron-emission tomography and computed tomography;chemoradiotherapy; biomarkers; tumor; minimally invasive surgical procedures Author: Mikel Gorostidi, Martina Ángeles, Blanca Gil-Ibáñez, Arantxa Lekuona, Alejandra Martinez and Ignacio Zapardiel Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Thu Oct 30 09:45:49 2025 CET ModDate: Thu Oct 30 10:00:32 2025 CET Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 508663 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JBYGON+URWPalladioL-Roma Type 1 Custom yes yes yes 71 0 KRHXWX+VnURWPalladioL Type 1 Custom yes yes yes 72 0 QCVICL+URWPalladioL-Ital Type 1 Custom yes yes yes 73 0 BLRBEL+URWPalladioL-Bold Type 1 Custom yes yes yes 74 0 XQBIYI+CMSY10 Type 1 Builtin yes yes yes 158 0 JFJCCE+PalatinoLinotype TrueType WinAnsi yes yes no 221 0 JFJCCA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 222 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-04-25 04:44:09 CEST RepresentationInformation: cancers-17-03487.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-04-24 16:22:05 CEST Size: 508663 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 396 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Available Evidence and Its Limitations Item: Title: Safety, Timing and Real-World Considerations Item: Title: The “Helmet” Analogy Item: Title: Refining Surgical Staging: From OSNA to Biomarkers Item: Title: Conclusions Item: Title: References Info: Title: Surgical Staging in Locally Advanced Cervical Cancer: Precision, Risks, and the ‘Helmet’ Analogy Author: Mikel Gorostidi, Martina Ángeles, Blanca Gil-Ibáñez, Arantxa Lekuona, Alejandra Martinez and Ignacio Zapardiel Subject: Background/Objectives: This study aims to critically appraise the role of para-aortic surgical staging in locally advanced cervical cancer (LACC) in the era of advanced imaging, and to outline how selective surgery and biomarkers could be integrated within modern, quality-assured treatment pathways. Methods: Narrative review of randomized trials, large databases, and prospective/retrospective series comparing para-aortic lymphadenectomy with imaging-based staging; focused appraisal of Uterus-11, NCDB analyses, and ongoing prospective trials (PAROLA with Senti-PAROLA as one of its sub-studies and PALDISC). Emerging technologies (PET/MRI, radiomics/AI) and molecular assays (OSNA, HPV-ctDNA) were also assessed. Results: PET/CT remains the standard for distant staging, but sensitivity for low-volume nodal disease (<5 mm) is poor; in pelvic-positive/para-aortic-negative patients, occult para-aortic metastases approach ~21%. Para-aortic surgical staging modifies radiotherapy planning in ~18% of cases and can act as a de-escalation tool by avoiding unnecessary extended-field CRT (EF-CRT) when para-aortic nodes are negative. Uterus-11 showed no overall survival difference versus CT-based staging, but suggested benefit in FIGO 2009 stage IIB; its design (CT comparator, optimistic assumptions, limited power) constrains inference. Minimally invasive extraperitoneal/transperitoneal staging is feasible with low morbidity in expert centers, yet real-world management may worsen outcomes. The role of systemic intensification in node-positive disease remains undefined: PALN-positive patients were excluded from the INTERLACE trial. In the KEYNOTE-826 study, subgroup analyses according to nodal status were not reported, although the benefit of pembrolizumab remained consistent irrespective of bevacizumab use. Sentinel para-aortic mapping and biomarkers (e.g., HPV-ctDNA) may refine selection and reduce morbidity. Conclusions: Surgical staging is the most accurate method to detect occult para-aortic disease. Its routine use is not justified, but it may benefit selected high-risk patients, particularly where decisions on EF-CRT or systemic therapy hinge on para-aortic status. Future practice should integrate advanced imaging, selective surgery, and biomarkers within accredited centers, guided by large collaborative trials conducted under international quality frameworks such as ESGO/ESTRO/ESP guidelines. 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