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Minimally Invasive Surgery

Survival After Minimally Invasive vs Open Radical Hysterectomy for Early-Stage Cervical CancerA Systematic Review and Meta-analysis

Educational Objective
To learn the risk of recurrence and death associated with minimally invasive vs open radical hysterectomy for early-stage cervical cancer
1 Credit CME
JAMA Oncology
Published Online: June 11, 2020
Original Investigation
Roni Nitecki, MD1;
Pedro T. Ramirez, MD1;
Michael Frumovitz, MD, MPH1;
Kate J. Krause, MLIS2;
Ana I. Tergas, MD, MPH3;
Jason D. Wright, MD3;
J. Alejandro Rauh-Hain, MD, MPH1;
Alexander Melamed, MD, MPH3
Author Affiliations
  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston
  • 2Research Medical Library, The University of Texas MD Anderson Cancer Center, Houston
  • 3Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University Vagelos College of Physicians and Surgeons, New York, New York
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Key Points

Question  Are the findings of high-quality observational studies consistent with the results of a randomized clinical trial that found that minimally invasive hysterectomy was associated with a higher risk of recurrence and death compared with open surgery?

Findings  In this systematic review and meta-analysis of 15 high-quality studies comprising 9499 patients, minimally invasive radical hysterectomy was associated with shorter overall and disease-free survival among women with operable cervical cancer compared with open surgery.

Meaning  These results provide evidence to support the survival benefit associated with open radical hysterectomy for early-stage cervical cancer; these findings are consistent with a recent randomized clinical trial.

Abstract

Importance  Minimally invasive techniques are increasingly common in cancer surgery. A recent randomized clinical trial has brought into question the safety of minimally invasive radical hysterectomy for cervical cancer.

Objective  To quantify the risk of recurrence and death associated with minimally invasive vs open radical hysterectomy for early-stage cervical cancer reported in observational studies optimized to control for confounding.

Data Sources  Ovid MEDLINE, Ovid Embase, PubMed, Scopus, and Web of Science (inception to March 26, 2020) performed in an academic medical setting.

Study Selection  In this systematic review and meta-analysis, observational studies were abstracted that used survival analyses to compare outcomes after minimally invasive (laparoscopic or robot-assisted) and open radical hysterectomy in patients with early-stage (International Federation of Gynecology and Obstetrics 2009 stage IA1-IIA) cervical cancer. Study quality was assessed with the Newcastle-Ottawa Scale and included studies with scores of at least 7 points that controlled for confounding by tumor size or stage.

Data Extraction and Synthesis  The Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist was used to abstract data independently by multiple observers. Random-effects models were used to pool associations and to analyze the association between surgical approach and oncologic outcomes.

Main Outcomes and Measures  Risk of recurrence or death and risk of all-cause mortality.

Results  Forty-nine studies were identified, of which 15 were included in the meta-analysis. Of 9499 patients who underwent radical hysterectomy, 49% (n = 4684) received minimally invasive surgery; of these, 57% (n = 2675) received robot-assisted laparoscopy. There were 530 recurrences and 451 deaths reported. The pooled hazard of recurrence or death was 71% higher among patients who underwent minimally invasive radical hysterectomy compared with those who underwent open surgery (hazard ratio [HR], 1.71; 95% CI, 1.36-2.15; P < .001), and the hazard of death was 56% higher (HR, 1.56; 95% CI, 1.16-2.11; P = .004). Heterogeneity of associations was low to moderate. No association was found between the prevalence of robot-assisted surgery and the magnitude of association between minimally invasive radical hysterectomy and hazard of recurrence or death (2.0% increase in the HR for each 10-percentage point increase in prevalence of robot-assisted surgery [95% CI, −3.4% to 7.7%]) or all-cause mortality (3.7% increase in the HR for each 10-percentage point increase in prevalence of robot-assisted surgery [95% CI, −4.5% to 12.6%]).

Conclusions and Relevance  This systematic review and meta-analysis of observational studies found that among patients undergoing radical hysterectomy for early-stage cervical cancer, minimally invasive radical hysterectomy was associated with an elevated risk of recurrence and death compared with open surgery.

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Cervical Cancer Minimally Invasive Surgery Oncology Surgery Surgical Oncology Gynecologic Cancer Gynecology Women's Health Obstetrics and Gynecology
Article Information

Accepted for Publication: April 8, 2020.

Corresponding Author: Alexander Melamed, MD, MPH, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University Vagelos College of Physicians and Surgeons, 161 Ft Washington Ave, New York, NY 10032 (am5195@cumc.columbia.edu).

Published Online: June 11, 2020. doi:10.1001/jamaoncol.2020.1694

Author Contributions: Dr Melamed had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Rauh-Hain and Melamed are co–senior authors and contributed equally to this work.

Concept and design: Nitecki, Ramirez, Tergas, Rauh-Hain, Wright, Melamed.

Acquisition, analysis, or interpretation of data: Nitecki, Ramirez, Frumovitz, Krause, Rauh-Hain, Wright, Melamed.

Drafting of the manuscript: Nitecki, Ramirez, Krause, Rauh-Hain, Wright, Melamed.

Critical revision of the manuscript for important intellectual content: Nitecki, Ramirez, Frumovitz, Tergas, Rauh-Hain, Melamed.

Statistical analysis: Nitecki, Rauh-Hain, Wright, Melamed.

Administrative, technical, or material support: Ramirez, Krause, Tergas, Rauh-Hain.

Supervision: Frumovitz, Rauh-Hain, Melamed.

Conflict of Interest Disclosures: Dr Ramirez reported receiving honoraria from Johnson & Johnson and receiving research funding from Pacira. Dr Frumovitz reported receiving grants and personal fees from Stryker, grants from AstraZeneca, and personal fees from Genentech. Dr Wright reported serving as a consultant for Clovis Oncology and Tesaro and receiving research funding from Merck.

Funding/Support: This study was supported by a National Cancer Institute Cancer Center Support Grant (P30 48CA016672), a National Institutes of Health T32 grant (5T32 CA101642) (Dr Nitecki), and a National Institutes of Health K grant (K08CA234333) (Dr Rauh-Hain).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Editorial support was provided by Bryan Tutt, MA, in Scientific Publications Services, Research Medical Library, The University of Texas MD Anderson Cancer Center. He was not compensated for his contributions.

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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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