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MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?
  1. Roni Nitecki1,
  2. Pedro T Ramirez2,
  3. Pavel Dundr3,
  4. Kristyna Nemejcova3,
  5. Reitan Ribeiro4,
  6. Mariano Tamura Vieira Gomes5,
  7. Ronaldo Luis Schmidt6,
  8. Lucio Bedoya7,
  9. David Ortiz Isla8,
  10. Rene Pareja9,
  11. Gabriel Jaime Rendón Pereira10,
  12. Aldo Lopez11,
  13. David Kushner12 and
  14. David Cibula13
  1. 1Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2Obstetrics and Gynecology, Houston Methodist Hospital, Houston, Texas, USA
  3. 3Pathology, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic
  4. 4Surgery, Hospital Erasto Gaertner, Curitiba, Hospital, Brazil
  5. 5Gynecologic Oncology, Albert Einstein Hospital, São Paulo, Brazil
  6. 6Gynecologic Oncology, Cancer Hospital of Barretos, Barretos, São Paulo, Brazil
  7. 7Gynecologic Oncology, Hospital Misercordia, Cordoba, Argentina
  8. 8Gynecologic Oncology, Instituto Nacional de Cancerologia, Mexico City, Mexico
  9. 9Gynecologic Oncology, Clinica Astorga, Medellin, and Instituto Nacional de Cancerología, Bogotá, Medellin, Colombia
  10. 10Gynecologic Oncology, Instituto de Cancerologia - Clínica Las Américas - AUNA, Medellin, Colombia
  11. 11Gynecologic Surgery, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru
  12. 12Gynecologic Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
  13. 13Department of Obstetrics and Gynecology, General University Hospital in Prague, First Faculty of Medicine, Charles University, Prague, Czech Republic
  1. Correspondence to Dr Roni Nitecki, Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; rnitecki{at}


Objective The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial.

Methods Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells).

Results The study included 20 patients with median age of 42 (range 30–68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4–32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node.

Conclusions There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

  • uterine cervical neoplasms
  • pathology
  • lymph nodes
  • lymphatic metastasis
  • neoplasm micrometastasis

Data availability statement

Data are available upon reasonable request. Data are available upon IRB approval.

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Data availability statement

Data are available upon reasonable request. Data are available upon IRB approval.

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  • Correction notice This article has been corrected since it was first published. Affiliation 13 has been updated.

  • Contributors Substantial contributions to the conception or design of the work: all authors. Drafting the work or revising it critically for important intellectual content: all authors. Final approval of the version to be published: all authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors. Guarantor: DC.

  • Funding This work was supported by grants from the National Institutes of Health National Cancer Institute (RN: P30 CA016672; RN 5T32 CA101642), the LACC trial lead institution (MD Anderson Cancer Center), by a research grant from the First Faculty of Medicine, Charles University, by the Ministry of Health. Czech Republic (research project MH CZ DRO-VFN 64165) and by the Central and Eastern European Gynecologic Oncology Group (CEEGOG).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.