Advertisement

Trachelectomy for reproductive-aged women with early-stage cervical cancer: minimally invasive surgery versus laparotomy

Published:February 22, 2019DOI:https://doi.org/10.1016/j.ajog.2019.02.038

      Background

      A recent trial demonstrated decreased survival in women with early-stage cervical cancer who underwent radical hysterectomy via minimally invasive surgery compared with laparotomy; however, outcomes following trachelectomy have yet to be studied.

      Objective

      To examine trends, characteristics, and survival of reproductive-aged women with early-stage cervical cancer who underwent minimally invasive trachelectomy.

      Study Design

      This is a retrospective study examining the National Cancer Database between 2010 and 2015. Women aged <50 years who underwent trachelectomy for stage IA2-IB cervical cancer were grouped by mode of surgery. Clinicopathologic characteristics and outcomes were compared between minimally invasive surgery and laparotomy groups.

      Results

      A total of 246 women were included, 144 (58.5%, 95% confidence interval, 52.4%–64.7%) of whom had trachelectomy with a minimally invasive surgery approach. Median age was similar between the minimally invasive surgery and laparotomy groups (median, 31 vs 29 years, P = .20). There was a significant increase in the use of minimally invasive surgery from 29.3% in 2010 to 75.0% in 2015 (P < .001). Specifically, minimally invasive surgery became the dominant approach for trachelectomy by year 2011 (54.8%). Hospitals registered in the West (75.0% vs 25.0%) were more likely, whereas those registered in the Midwest (46.9% vs 53.1%) were less likely, to perform minimally invasive surgery (P = .02). Median follow-up was 37 months (interquartile range, 23–51) for the minimally invasive surgery group and 40 months (interquartile range, 26–67) for the laparotomy group. During follow-up, there were 11 (5.3%) deaths, 4 (3.5%) in the minimally invasive surgery group and 7 (7.6%) in the laparotomy group (P = .25).

      Conclusion

      Minimally invasive surgery has become the dominant modality for trachelectomy in reproductive-aged women with stage IA2-IB cervical cancer after year 2011. Survival of women with stage IA2-IB cervical cancer who underwent trachelectomy is generally good regardless of surgical modality. Although our study showed no difference in survival between the minimally invasive surgery and laparotomy approaches, effects of MIS on survival remain unknown and further study is warranted.

      Key words

      Related editorial, page 417.
      The incidence of cervical cancer has decreased over the past several decades, and it is now the 13th most common female malignancy in the United States.
      • Siegel R.L.
      • Miller K.D.
      • Jemal A.
      Cancer statistics, 2018.
      However, young women continue to be disproportionately affected. Between 2012 and 2014, it was estimated that 1 in 368 women younger than the age of 50 years was diagnosed with cervical cancer in the United States.
      • Siegel R.L.
      • Miller K.D.
      • Jemal A.
      Cancer statistics, 2018.
      Cervical cancer continues to be the second-leading cause of female cancer-related death among women 20–39 years of age.
      • Siegel R.L.
      • Miller K.D.
      • Jemal A.
      Cancer statistics, 2018.

      Why was the study conducted?

      • Recent studies have shown that women with early-stage cervical cancer who underwent minimally invasive surgery for radical hysterectomy had poorer survival compared with those with laparotomy; however, outcomes following minimally invasive trachelectomy have yet to be studied.

      Key findings

      • An analysis of National Cancer Database examining women aged <50 years with stage IA2-IB cervical cancer who underwent trachelectomy found that the minimally invasive surgery approach has significantly increased from 29.3% to 75.0% between 2010 and 2015.

      What does this add to what is known?

      • Survival of women who underwent trachelectomy in this population is generally good regardless of surgical modality, exhibiting 4-year rates of 92%–95%. Although there was no difference in survival between the minimally invasive surgery and laparotomy approaches, effects of minimally invasive surgery on survival remains unknown, and further study is warranted.
      Unique treatment considerations exist in this population of young women with cervical cancer, as many face the dilemma of deciding between definitive cancer treatment with hysterectomy vs uterine preservation for reproductive function. In conjunction with national trends toward delayed childbearing, fertility-preserving treatment options in this population are becoming increasingly important.
      Birth: Final data for 2015
      National vital statistics reports.
      CDC National Vital Statistics Data Brief 152.
      One treatment option for such women is fertility-sparing trachelectomy.
      National Comprehensive Cancer Network Clinical Practice Guideline in Oncology
      Cervical Cancer.
      Mounting evidence has demonstrated the oncologic safety and subsequent favorable pregnancy outcomes in reproductive-aged women with early-stage cervical cancer who desire fertility preservation.
      • Cui R.R.
      • Chen L.
      • Tergas A.I.
      • et al.
      Trends in use and survival associated with fertility-sparing trachelectomy for young women with early-stage cervical cancer.
      • Ebisawa K.
      • Takano M.
      • Fukuda M.
      • et al.
      Obstetric outcomes of patients undergoing total laparoscopic radical trachelectomy for early stage cervical cancer.
      • Kasuga Y.
      • Nishio H.
      • Miyakoshi K.
      • et al.
      Pregnancy outcomes after abdominal radical trachelectomy for early-stage cervical cancer: a 13-year experience in a single tertiary-care center.
      • Machida H.
      • Mandelbaum R.S.
      • Mikami M.
      • et al.
      Characteristics and outcomes of reproductive-aged women with early-stage cervical cancer: trachelectomy versus hysterectomy.
      • Nishio H.
      • Fujii T.
      • Kameyama K.
      • et al.
      Abdominal radical trachelectomy as a fertility-sparing procedure in women with early-stage cervical cancer in a series of 61 women.
      • Pareja R.
      • Rendon G.J.
      • Sanz-Lomana C.M.
      • Monzon O.
      • Ramirez P.T.
      Surgical, oncological, and obstetrical outcomes after abdominal radical trachelectomy—a systematic literature review.
      A previous study in the United States has shown that ∼40% of women aged <40 years who underwent definitive surgical treatment with radical hysterectomy actually expressed interest for fertility preservation and nearly one half were indeed candidates for fertility-sparing trachelectomy based on their surgical–pathologic factors.
      • Sonoda Y.
      • Abu-Rustum N.R.
      • Gemignani M.L.
      • et al.
      A fertility-sparing alternative to radical hysterectomy: how many patients may be eligible?.
      In the past several years, there has been a significant recent increase in the use of trachelectomy in this population in the United States.
      • Cui R.R.
      • Chen L.
      • Tergas A.I.
      • et al.
      Trends in use and survival associated with fertility-sparing trachelectomy for young women with early-stage cervical cancer.
      • Machida H.
      • Mandelbaum R.S.
      • Mikami M.
      • et al.
      Characteristics and outcomes of reproductive-aged women with early-stage cervical cancer: trachelectomy versus hysterectomy.
      • Matsuo K.
      • Machida H.
      • Mandelbaum R.S.
      • et al.
      Trachelectomy for stage IB1 cervical cancer with tumor size >2 cm: trends and characteristics in the United States.
      One clinical entity that has not been addressed in the literature regarding trachelectomy for cervical cancer is the oncologic safety of minimally invasive surgery (MIS) as compared with laparotomy and radical vaginal trachelectomy, which remains unknown. Given the results of a recent randomized trial and an observational study that demonstrated decreased survival with MIS radical hysterectomy in women with early-stage cervical cancer, this clinical question is of great importance.
      • Melamed A.
      • Margul D.J.
      • Chen L.
      • et al.
      Survival after minimally invasive radical hysterectomy for early-stage cervical cancer.
      • Ramirez P.T.
      • Frumovitz M.
      • Pareja R.
      • et al.
      Minimally invasive versus abdominal radical hysterectomy for cervical cancer.
      We examined trends, characteristics, and survival of reproductive-aged women with early-stage cervical cancer who underwent trachelectomy with a MIS approach.

      Materials and Methods

      Data source

      This is a retrospective study examining the National Cancer Database (NCDB). This database is a nationwide tumor registry that collects >1 million invasive cancer cases, representing approximately 70% of all new invasive cancers in the United States.
      • Bilimoria K.Y.
      • Stewart A.K.
      • Winchester D.P.
      • Ko C.Y.
      The National Cancer Data Base: a powerful initiative to improve cancer care in the United States.
      Nearly 1500 Commission on Cancer–affiliated institutions participate in the database through a partnership between the Commission on Cancer of the American College of Surgeons and the American Cancer Society Society.
      • Bilimoria K.Y.
      • Stewart A.K.
      • Winchester D.P.
      • Ko C.Y.
      The National Cancer Data Base: a powerful initiative to improve cancer care in the United States.
      Information extracted from the NCDB included patient demographics, tumor characteristics, treatment type, cancer staging, follow-up, and survival outcome. The study used publicly available deidentified data thus was deemed exempt by the Columbia University institutional review board (ethical committee exemption: AAAN2900).

      Study population

      Women <50 years of age who were diagnosed with stage IA2-IB cervical cancer between 2010 and 2015 who underwent trachelectomy either with MIS or laparotomy were eligible for the study. Stage was grouped according to International Federation of Gynecology and Obstetrics system and defined using the American Joint Committee on Cancer (AJCC) clinical stage if available, Collaborative Staging Site-Specific Factor 1 if AJCC clinical stage was unknown, and AJCC pathologic stage when the former 2 were unknown. The age cutoff was of 50 years was chosen based on the World Health Organization for reproductive age.
      Infertility definitions and terminology.
      The inclusion of cancer stage IA2 and IB disease was chosen per the guideline recommendation for fertility-sparing trachelectomy only in early-stage cervical cancer.
      National Comprehensive Cancer Network Clinical Practice Guideline in Oncology
      Cervical Cancer.
      Women ≥50 years as well as those with cancer in situ, absence of diagnostic confirmation, or cervical cancer stage other than IA2-IB were excluded. Patients who had multiple tumors and cervical cancer not as the first were excluded. Women who did not undergo surgery or who had surgery other than trachelectomy, unknown surgery type, or trachelectomy with unknown surgical modality were also excluded from the study.

      Study definition

      MIS trachelectomy in this study refers to conventional laparoscopic trachelectomy or robotic-assisted trachelectomy, and the codes in the database were unable to distinguish vaginal radical trachelectomy. The starting time point of 2010 was chosen based on the rationale that the first case entry of MIS trachelectomy was recorded in the database in 2010. MIS trachelectomy cases resulted in laparotomy conversion was grouped as the MIS group (intention-to-treat). Of note, the extent of trachelectomy (simple vs radical) was not distinguishable via the procedure codes in the database.

      Clinical information

      The following abstracted data variables were categorized based on a previous study.
      • Cui R.R.
      • Chen L.
      • Tergas A.I.
      • et al.
      Trends in use and survival associated with fertility-sparing trachelectomy for young women with early-stage cervical cancer.
      Demographic information of interest included age (in years), race/ethnicity (white, black, Hispanic, other, or unknown), year of diagnosis, insurance type (private, Medicare, Medicaid, uninsured, other government or unknown), median household income (<$38,000, $38,000–47,999, $48,000–62,999, ≥$63,000), education (measured as percentage of adults in the patient’s zip code who did not graduate from high school and grouped as ≥21%, 13%–20%, 7.0%–12.9%, <7%), and urban–rural location (metropolitan, urban, rural, or unknown).
      Charlson Comorbidity Index for medical comorbidities was based on the Deyo classification (0, 1, or ≥2). Hospital information included facility type per the Commission on Cancer criteria (academic/research, community cancer programs, comprehensive community cancer programs, or integrated network cancer program), and geographic location (Northeast, Midwest, South, West).
      Tumor characteristics included stage (IA2, IB1, IB2, or IB not otherwise specified), histology (squamous, adenocarcinoma, or others), grade (well-, moderately, poorly differentiated, or unknown), lymphovascular space invasion (absent, present, or unknown), and tumor size (<1, 1–2, >2 cm, or unknown). Information for regional lymph node status included performance of lymph node dissection for assessment (not examined, examined, or unknown) and presence of lymph node metastasis (no vs yes).
      For survival outcome, overall survival, defined as the time interval between the cervical cancer diagnosis and death from any reason (all-cause), was collected. Cases deemed alive at the last follow-up were censored.

      Statistical consideration

      The primary objective of analysis was to examine performance and characteristics related to MIS trachelectomy. The secondary objective was to examine survival after MIS trachelectomy. Continuous variables were reported with the median and interquartile range, and statistical difference was assessed with Wilcoxon rank-sum test. Categorical variables were reported as frequencies per group, and statistical difference was assessed with χ2 test. A trend curve depicting MIS use per calendar year was constructed, and statistical difference was assessed with the Cochran–Armitage trend test. The Kaplan–Meier method was used to plot survival curves, and statistical difference was assessed with the log-rank test.
      Multivariable analyses to assess the independent prognostic factors for as well as factors contributing to MIS use were not preplanned in this study, as we estimated that trachelectomy with a MIS approach is a relatively new treatment modality and study size as well as survival events would not be adequate to perform adjusted models. All hypothesis testing was 2-sided, and a P < .05 was considered statistically significant. SAS 9.4 (SAS Institute, Cary, NC) was used for all analyses.

      Results

      The study selection schema is shown in Figure 1. There are 246 women aged <50 years with stage IA2-IB cervical cancer who underwent trachelectomy via a MIS or laparotomy approach represented the study population. Among the 246 women, 144 (58.5%, 95% confidence interval [CI], 52.4%–64.7%) underwent MIS trachelectomy and 102 (41.5%) women underwent laparotomy. Of the 144 MIS patients, there are 96 (66.7%) robotic assisted, 46 (31.9%) laparoscopic, and 2 (1.4%) laparoscopic converted to open.
      Figure thumbnail gr1
      Figure 1Study schema
      Cohort selection criteria from the National Cancer Database.
      Matsuo et al. Trachelectomy for reproductive-aged women with early-stage cervical cancer: minimally invasive surgery versus laparotomy. Am J Obstet Gynecol 2019.
      The trend in use of MIS for trachelectomy was examined between 2010 and 2015 (Figure 2). There was a significant increase in the use of MIS during the study period from 29.3% in 2010 to 75.0% in 2015 (P < .001). Specifically, although MIS accounted for less than one third of trachelectomies performed in 2010 (29.3%; 95% CI, 15.3%–43.2%), by 2011, MIS became the dominant approach for trachelectomy (54.8%; 95% CI, 39.7%–69.8%). By 2015, nearly three quarters of all the trachelectomies at the NCDB sites were performed with MIS (75.0%; 95% CI, 61.6%–88.4%). MIS with robotic approach increased from 38.1% to 60.0% between 2011 and 2015.
      Figure thumbnail gr2
      Figure 2Trend of trachelectomy use between 2010 and 2015
      Cochran–Armitage trend test for P-value. Dots represent observed value and bars represent 95% confidence interval for minimally invasive trachelectomy.
      Matsuo et al. Trachelectomy for reproductive-aged women with early-stage cervical cancer: minimally invasive surgery versus laparotomy. Am J Obstet Gynecol 2019.
      Patient demographics based on treatment modality are shown in Table 1. Age at cervical cancer diagnosis was similar between the 2 groups (median, MIS vs laparotomy, 31 vs 29, P = .20). Percentages between the 2 groups for race/ethnicity, insurance type, household income, education, hospital, and type differed but did not show statistical difference (all, P > .05). Hospital location was significantly associated with MIS use, and the hospitals in the West (MIS vs laparotomy, 75.0% vs 25.0%) were more likely, whereas those registered in Midwest (46.9% vs 53.1%) were less likely, to perform MIS trachelectomy (P = .02). The vast majority of women in the study also underwent regional lymphadenectomy (94.1% in laparotomy vs 95.8% in patients undergoing MIS).
      Table 1Patient demographics (N = 246)
      CharacteristicLaparotomyMIS
      Intention-to-treat analysis, including 2 cases converted to laparotomy
      P value
      n(%)n(%)
      Number102(41.5)144(58.5)
      Age
       Median (IQR)29(27-35)31(28-36).20
      Race/ethnicity.34
       White69(40.6%)101(59.4%)
       Black12(63.2%)
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
       Hispanic11(40.7%)16(59.3%)
       Other
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      18(66.7%)
       Unknown
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Year of diagnosis<.001
       201029(70.7%)12(29.3%)
       201119(45.2%)23(54.8%)
       201215(33.3%)30(66.7%)
       201317(50.0%)17(50.0%)
       201412(27.3%)32(72.7%)
       201510(25.0%)30(75.0%)
      Insurance.46
       Uninsured
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
       Private79(40.3%)117(59.7%)
       Medicaid14(53.8%)12(46.2%)
       Medicare
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
       Other
      Including government or unknown.
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Income.82
       <$38,00014(42.4%)19(57.6%)
       $38,000–$47,99921(45.7%)25(54.3%)
       $48,000–$62,99926(37.1%)44(62.9%)
       ≥$63,00041(42.3%)56(57.7%)
      Education.47
       ≥21%15(41.7%)21(58.3%)
       13%–20%30(46.9%)34(53.1%)
       7.0%–12.9%25(34.2%)48(65.8%)
       <7%32(43.8%)41(56.2%)
      Urban rural.61
       Metropolitan92(42.2%)126(57.8%)
       Urban
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      14(63.6%)
       Rural
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
       Unknown
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Comorbidity.56
       097(42.2%)133(57.8%)
       1
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      10(66.7%)
       ≥2
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Facility type.23
       Community cancer
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
       Comprehensive community cancer25(39.1%)39(60.9%)
       Academic/research6646.2%)77(53.8%)
       Integrated network cancer10(28.6%)25(71.4%)
      Facility location.02
       Northeast29(45.3%)35(54.7%)
       Midwest26(53.1%)23(46.9%)
       South33(42.9%)44(57.1%)
       West14(25.0%)42(75.0%)
      Regional nodes.47
       Not examined
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
       Examined96(41.0%)138(59.9%)
       Unknown
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Age was compared using Wilcoxon rank-sum test; the other categorical variables were compared using χ2 tests.
      IQR, interquartile range; MIS, minimally invasive surgery.
      Matsuo et al. Trachelectomy for reproductive-aged women with early-stage cervical cancer: minimally invasive surgery versus laparotomy. Am J Obstet Gynecol 2019.
      a Intention-to-treat analysis, including 2 cases converted to laparotomy
      b Suppress reporting because some cell sizes were <10
      c Including government or unknown.
      Tumor characteristics were compared between the 2 groups (Table 2). In both groups, the majority of tumors were stage 1B1 (MIS vs laparotomy, 74.3% vs 76.1%) and ≤2 cm in size (51.4% vs 48.1%). Notably, tumors >2 cm accounted for nearly one third of cases in this study population (29.9% vs 31.4%) but tumors assigned as stage IB2 disease were rare in this study population (<3%). Nearly 1 in 6 tumors had no information for tumor size (16.3%). Overall, cancer stage, histologic subtype, tumor size, presence of lymphovascular space invasion, and presence of regional lymph node metastasis were all similar between the MIS and laparotomy groups (all, P > .05).
      Table 2Tumor characteristics (N = 246)
      CharacteristicLaparotomyMIS
      Intention-to-treat analysis, including 2 cases converted to laparotomy
      P value
      n(%)n(%)
      Number102(41.5)144(58.5)
      Stage.21
       1A212(48.0%)13(52.0%)
       1B173(40.6%)107(59.4%)
       1B2
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
       1B NOS17(47.2%)19(52.8%)
      Histology.41
       Squamous cell51(45.9%)60(54.1%)
       Adenocarcinoma40(37.0%)68(63.0%)
       Other11(40.7%)16(59.3%)
      Grade.16
       Well differentiated23(54.8%)19(45.2%)
       Moderately differentiated43(36.4%)75(63.6%)
       Poorly differentiated29(44.6%)36(55.4%)
       Unknown
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      14(66.7%)
      Tumor size, cm.80
       <121(44.7%)26(55.3%)
       1–228(36.8%)48(63.2%)
       >232(42.7%)43(57.3%)
       Unknown21(43.8%)27(56.3%)
      LVSI.68
       Absent55(39.6%)84(60.4%)
       Present33(42.3%)45(57.7%)
       Unknown14(48.3%)15(51.7%)
      Regional nodal metastasis
      Regional nodal metastasis no/yes were compared restricting to patients with nodes examined.
      .28
       No86(40.0%)129(60.0%)
       Yes10(52.6%)
      Suppress reporting because some cell sizes were <10
      Suppress reporting because some cell sizes were <10
      Categorical variables were compared using χ2 tests.
      LVSI, lymphovascular space invasion; MIS, minimally invasive surgery; NOS, not otherwise specified.
      Matsuo et al. Trachelectomy for reproductive-aged women with early-stage cervical cancer: minimally invasive surgery versus laparotomy. Am J Obstet Gynecol 2019.
      a Intention-to-treat analysis, including 2 cases converted to laparotomy
      b Suppress reporting because some cell sizes were <10
      c Regional nodal metastasis no/yes were compared restricting to patients with nodes examined.
      The median follow-up for the cohort was 37 months (interquartile range, 23–51) for the MIS group and 40 months (interquartile range, 26–67) for the laparotomy group, corresponding to 4301 and 3857 person-months at risk, respectively. During the follow-up period, among 206 patients with survival data, there were 11 (5.3%) deaths recorded; 4 (3.5%) deaths occurred in the MIS group and ranged from 12-30 months after diagnosis, and 7 (7.6%) deaths occurred in the laparotomy group with a range of 13-49 months after the cervical cancer diagnosis (unadjusted hazard ratio, 0.50; 95% CI, 0.15–1.70, P = .25; Figure 3). The 4-year overall survival rates were estimated as 95.7% (95% CI, 88.7–98.4) for the MIS group and 92.3% (95% CI, 83.5–96.5) for the laparotomy group, respectively. Survival estimates of other clinicopathologic factors are shown in Supplemental Table 1.
      Figure thumbnail gr3
      Figure 3Overall survival based on treatment modality
      Colored areas represent 95% confidence intervals.
      MIS, minimally invasive surgery.
      Matsuo et al. Trachelectomy for reproductive-aged women with early-stage cervical cancer: minimally invasive surgery versus laparotomy. Am J Obstet Gynecol 2019.

      Comments

      Our findings suggest that in the United States, MIS has been rapidly adopted for women who undergo trachelectomy for cervical cancer. Although our power is limited, there was no difference in survival between MIS and open trachelectomy in contrast to recent studies demonstrating inferior survival for minimally invasive compared with open radical hysterectomy.
      Our analysis demonstrated that the performance of MIS trachelectomy in young women with early-stage cervical cancer has significantly increased over a short period of 6 years. By 2015, the vast majority of trachelectomies were performed using a minimally invasive approach. This increase clearly reflects the recent practice patterns among US gynecologic oncologists in that MIS is considered the preferred approach over laparotomy for radical trachelectomy.
      • Churchill S.J.
      • Armbruster S.
      • Schmeler K.M.
      • et al.
      Radical trachelectomy for early-stage cervical cancer: a survey of the society of gynecologic oncology and gynecologic oncology fellows-in-training.
      The use of fertility-sparing trachelectomy, regardless of surgical approach, for women aged <45 years with stage IA2-IB1 (≤2 cm) cervical cancer has increased from 2.0% to 6.8% between 1998 and 2014 in the United States.
      • Machida H.
      • Mandelbaum R.S.
      • Mikami M.
      • et al.
      Characteristics and outcomes of reproductive-aged women with early-stage cervical cancer: trachelectomy versus hysterectomy.
      This increase was most pronounced in women <30 years of age.
      • Cui R.R.
      • Chen L.
      • Tergas A.I.
      • et al.
      Trends in use and survival associated with fertility-sparing trachelectomy for young women with early-stage cervical cancer.
      Our study demonstrates that the majority of these procedures are now performed with a minimally invasive approach, particularly with use of the robotic platform. This increased use of MIS for trachelectomy parallels the trends observed for radical hysterectomy for early-stage cervical cancer in the United States. Specifically, use of MIS for radical hysterectomy has significantly increased from 2% to 58% between 2006 and 2013.
      • Melamed A.
      • Margul D.J.
      • Chen L.
      • et al.
      Survival after minimally invasive radical hysterectomy for early-stage cervical cancer.
      • Wright J.D.
      • Herzog T.J.
      • Neugut A.I.
      • et al.
      Comparative effectiveness of minimally invasive and abdominal radical hysterectomy for cervical cancer.
      It is speculated that the increasing use of MIS in the surgical treatment of early-stage cervical cancer, including trachelectomy, is influenced by the results of studies on the use of MIS in the surgical treatment of endometrial cancer and other solid tumors.
      • Janda M.
      • Gebski V.
      • Davies L.C.
      • et al.
      Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage i endometrial cancer: a randomized clinical trial.
      • Walker J.L.
      • Piedmonte M.R.
      • Spirtos N.M.
      • et al.
      Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2.
      • Veldkamp R.
      • Kuhry E.
      • Hop W.C.
      • et al.
      Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial.
      • Leung K.L.
      • Kwok S.P.
      • Lam S.C.
      • et al.
      Laparoscopic resection of rectosigmoid carcinoma: prospective randomised trial.
      • Huscher C.G.
      • Mingoli A.
      • Sgarzini G.
      • et al.
      Laparoscopic versus open subtotal gastrectomy for distal gastric cancer: five-year results of a randomized prospective trial.
      • Vinuela E.F.
      • Gonen M.
      • Brennan M.F.
      • Coit D.G.
      • Strong V.E.
      Laparoscopic versus open distal gastrectomy for gastric cancer: a meta-analysis of randomized controlled trials and high-quality nonrandomized studies.
      Previously, multiple phase III randomized trials reported comparable oncologic outcomes and decreased perioperative complication rates with MIS hysterectomy compared to laparotomy for endometrial cancer.
      • Janda M.
      • Gebski V.
      • Davies L.C.
      • et al.
      Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage i endometrial cancer: a randomized clinical trial.
      • Walker J.L.
      • Piedmonte M.R.
      • Spirtos N.M.
      • et al.
      Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2.
      Although prospective data specifically examining MIS use for cervical cancer have been lacking, a sizable body of evidence has previously demonstrated noninferiority of survival with MIS approach until recent.
      • Obermair A.
      • Gebski V.
      • Frumovitz M.
      • et al.
      A phase III randomized clinical trial comparing laparoscopic or robotic radical hysterectomy with abdominal radical hysterectomy in patients with early stage cervical cancer.
      • Nam J.H.
      • Park J.Y.
      • Kim D.Y.
      • Kim J.H.
      • Kim Y.M.
      • Kim Y.T.
      Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study.
      • Sert B.M.
      • Boggess J.F.
      • Ahmad S.
      • et al.
      Robot-assisted versus open radical hysterectomy: a multi-institutional experience for early-stage cervical cancer.
      • Shazly S.A.
      • Murad M.H.
      • Dowdy S.C.
      • Gostout B.S.
      • Famuyide A.O.
      Robotic radical hysterectomy in early stage cervical cancer: a systematic review and meta-analysis.
      • Wang Y.Z.
      • Deng L.
      • Xu H.C.
      • Zhang Y.
      • Liang Z.Q.
      Laparoscopy versus laparotomy for the management of early stage cervical cancer.
      In 2018, Ramirez et al reported the results of a phase III trial examining oncologic outcomes following MIS radical hysterectomy vs laparotomy for women with early-stage cervical cancer (LACC trial).
      • Ramirez P.T.
      • Frumovitz M.
      • Pareja R.
      • et al.
      Minimally invasive versus abdominal radical hysterectomy for cervical cancer.
      Of note, the study is known to be the first randomized controlled trial examined the efficacy of MIS radical hysterectomy for early-stage cervical cancer. This trial was designed with a noninferiority hypothesis based on previous nonrandomized studies
      • Nam J.H.
      • Park J.Y.
      • Kim D.Y.
      • Kim J.H.
      • Kim Y.M.
      • Kim Y.T.
      Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study.
      • Sert B.M.
      • Boggess J.F.
      • Ahmad S.
      • et al.
      Robot-assisted versus open radical hysterectomy: a multi-institutional experience for early-stage cervical cancer.
      • Shazly S.A.
      • Murad M.H.
      • Dowdy S.C.
      • Gostout B.S.
      • Famuyide A.O.
      Robotic radical hysterectomy in early stage cervical cancer: a systematic review and meta-analysis.
      • Wang Y.Z.
      • Deng L.
      • Xu H.C.
      • Zhang Y.
      • Liang Z.Q.
      Laparoscopy versus laparotomy for the management of early stage cervical cancer.
      ; however, the results showed that MIS radical hysterectomy was associated with a nearly 4-fold increased risk of recurrence and 6-fold increase in all-cause mortality compared with laparotomy.
      • Ramirez P.T.
      • Frumovitz M.
      • Pareja R.
      • et al.
      Minimally invasive versus abdominal radical hysterectomy for cervical cancer.
      Although there is an expert opinion that disease-free survival rate of 97% among the laparotomy group in their trial is greater and the survival in the MIS group (86%) is what seems expected compared with the historical controls (80%–88%),
      • Leitao Jr., M.M.
      The LACC trial: has minimally invasive surgery for early-stage cervical cancer been dealt a knockout punch?.
      another population-based observational study that examined multiple US tumor registries also showed the similar results to the LACC trial in that MIS radical hysterectomy was associated with ∼50% increased risk of all-cause mortality compared with the laparotomy approach.
      • Melamed A.
      • Margul D.J.
      • Chen L.
      • et al.
      Survival after minimally invasive radical hysterectomy for early-stage cervical cancer.
      Their analysis even found that there is a trend of decreasing a 4-year survival rate for ∼1% per year annually in women undergoing radical hysterectomy for cervical cancer, which began concurrently with the rapid increasing use of MIS radical hysterectomy that started in 2006.
      • Melamed A.
      • Margul D.J.
      • Chen L.
      • et al.
      Survival after minimally invasive radical hysterectomy for early-stage cervical cancer.
      These 2 studies call into question the use of MIS for radial hysterectomy but did not examine outcomes of women who underwent MIS trachelectomy.
      Given the concerning results of these 2 studies and the rapid adoption of MIS approaches for trachelectomy in addition to radical hysterectomy, there is clearly a need to document the safety of MIS for trachelectomy. To date, available evidence related to MIS trachelectomy is limited in that these are small sample sizes, lack in a comparator with laparotomy, are retrospective, and have short follow-up periods.
      • Api M.
      • Boza A.
      • Ceyhan M.
      Robotic versus laparoscopic radical trachelectomy for early-stage cervical cancer: case report and review of literature.
      • Johansen G.
      • Lonnerfors C.
      • Falconer H.
      • Persson J.
      Reproductive and oncologic outcome following robot-assisted laparoscopic radical trachelectomy for early stage cervical cancer.
      • Park J.Y.
      • Joo W.D.
      • Chang S.J.
      • et al.
      Long-term outcomes after fertility-sparing laparoscopic radical trachelectomy in young women with early-stage cervical cancer: an Asan Gynecologic Cancer Group (AGCG) study.
      • Vieira M.A.
      • Rendon G.J.
      • Munsell M.
      • et al.
      Radical trachelectomy in early-stage cervical cancer: a comparison of laparotomy and minimally invasive surgery.
      • Yoo S.E.
      • So K.A.
      • Kim S.A.
      • et al.
      Surgical and obstetrical outcomes after laparoscopic radical trachelectomy and pelvic lymphadenectomy for early cervical cancer.
      In the current analysis there was no statistical difference in survival for women who underwent open and minimally invasive trachelectomy. But, as expected, our results are underpowered due to small sample size and few survival events to draw any clinically meaningful conclusions.
      Our study demonstrated that the majority of MIS trachelectomies were performed with the robotic-assisted approach. We did not examine trends or outcomes of robotic-assisted MIS trachelectomy specifically as the number was few. Because the recent trial evaluating outcomes following MIS radical hysterectomy predominately consisted of hysterectomies performed via conventional laparoscopy (>80%) but not robotic approach,
      • Ramirez P.T.
      • Frumovitz M.
      • Pareja R.
      • et al.
      Minimally invasive versus abdominal radical hysterectomy for cervical cancer.
      it is of interest to see whether outcomes differ between conventional laparoscopic vs robotic-assisted approaches. A recent review reported comparable outcomes between the 2 modalities, but sample size remains limited, and further study is warranted.
      • Api M.
      • Boza A.
      • Ceyhan M.
      Robotic versus laparoscopic radical trachelectomy for early-stage cervical cancer: case report and review of literature.
      A strength of this study is that our sample size is likely among the largest in the literature examining MIS trachelectomy for cervical cancer. However, we also acknowledge a number of weaknesses in this study. First, this is a retrospective study likely with several unobserved confounding factors that influenced the decision to perform trachelectomy as well as the surgical approach for the procedure. Surgeon’s level of experience with MIS trachelectomy is likely one of the most important factors affecting outcomes. In addition, the database does not include information regarding the use of intra-uterine manipulators as well as vaginal colpotomy type, both of which are potential factors affecting tumor spread following MIS.
      • Kong T.W.
      • Chang S.J.
      • Piao X.
      • et al.
      Patterns of recurrence and survival after abdominal versus laparoscopic/robotic radical hysterectomy in patients with early cervical cancer.
      • Rakowski J.A.
      • Tran T.A.
      • Ahmad S.
      • et al.
      Does a uterine manipulator affect cervical cancer pathology or identification of lymphovascular space involvement?.
      Some surgeons also advocate for the use of neoadjuvant chemotherapy before trachelectomy or a vaginal trachelectomy approach, both of which were not assessed in this study either due to small cases (n = 2 for neoadjuvant therapy) or nonspecific coding (vaginal trachelectomy).
      • Dursun P.
      • LeBlanc E.
      • Nogueira M.C.
      Radical vaginal trachelectomy (Dargent's operation): a critical review of the literature.
      • Pareja R.
      • Rendon G.J.
      • Vasquez M.
      • Echeverri L.
      • Sanz-Lomana C.M.
      • Ramirez P.T.
      Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: a literature review and analysis of oncological and obstetrical outcomes.
      • Plante M.
      Bulky early-stage cervical cancer (2-4 cm lesions): upfront radical trachelectomy or neoadjuvant chemotherapy followed by fertility-preserving surgery: which is the best option?.
      • Ramirez P.T.
      • Schmeler K.M.
      • Soliman P.T.
      • Frumovitz M.
      Fertility preservation in patients with early cervical cancer: radical trachelectomy.
      Although radical vaginal trachelectomy is performed infrequently in the United States, we recognize the inability to subclassify these patients as an important limitation of the study. As an intrauterine manipulator is not used and intraperitoneal tumor exposure does not occur, the potential risk of tumor dissemination may be mitigated in women who undergo radical vaginal trachelectomy.
      • Sideri M.
      Surgery for cervical neoplasia.
      If lymphadenectomy was assessed with laparoscopic/robotic approach, then, cases with radical vaginal trachelectomy would have been classified in the MIS group.
      Second, we could not examine perioperative complications or reproductive outcomes following MIS trachelectomy, which in addition to survival, are important outcomes related to trachelectomy. Third, we did not specify the type of trachelectomy as radical vs simple as the coding in the database does not specify the 2 modalities; however, we believe our study population most likely consists of women who underwent radical trachelectomy, as this is the standard trachelectomy approach for stage IA2-IB cervical cancer.
      National Comprehensive Cancer Network Clinical Practice Guideline in Oncology
      Cervical Cancer.
      Recurrence information is not available in this database, and the detailed association for oncologic outcome was not assessable.
      Lastly, given the favorable prognosis for this population of women, our study lacks the power to determine modest differences in survival. As an example, assuming a 1-to-1 case mix for open and minimally invasive trachelectomy (α-level of 0.05 and a power of 80%) and an increased mortality for laparotomy as described in recent studies,
      • Melamed A.
      • Margul D.J.
      • Chen L.
      • et al.
      Survival after minimally invasive radical hysterectomy for early-stage cervical cancer.
      • Ramirez P.T.
      • Frumovitz M.
      • Pareja R.
      • et al.
      Minimally invasive versus abdominal radical hysterectomy for cervical cancer.
      we estimated that a total sample size of 39,350, 6670, and 1842 of cases would be needed to detect a 10%, 25%, and 50% difference in 4-year mortality, respectively (Table 3). Conversely, assuming that MIS trachelectomy is associated with decreased mortality, we estimated total sample sizes are 35,900, 5322, and 1152 cases to detect 10%, 25%, and 50% difference in mortality, respectively.
      Table 3Sample size estimation
      HypothesisIncrease in mortalityDecrease in mortality
      Difference (%)10%25%50%10%25%50%
      DistributionAsymptotic normalAsymptotic normalAsymptotic normalAsymptotic normalAsymptotic normalAsymptotic normal
      MethodNormal approximationNormal approximationNormal approximationNormal approximationNormal approximationNormal approximation
      Laparotomy 4-year mortality risk0.07700.07700.07700.07700.07700.0770
      MIS 4-year mortality risk0.08470.09630.11550.06930.057750.0385
      Laparotomy weight (1:1 allocation)111111
      MIS weight (1:1 allocation)111111
      Nominal power0.80.80.80.80.80.8
      Number of sides222222
      Null proportion difference000000
      Alpha (2-sided)0.050.050.050.050.050.05
      Actual power0.800.800.800.800.800.80
      Total sample size39,3506670184235,90053221152
      Pearson χ2 test for proportion difference. Observed 4-year survival rates were used for sample size estimation. Laparotomy group served as the control.
      MIS, minimally invasive surgery.
      Matsuo et al. Trachelectomy for reproductive-aged women with early-stage cervical cancer: minimally invasive surgery versus laparotomy. Am J Obstet Gynecol 2019.
      If the association of surgical approach for radical trachelectomy and survival is to be examined in women with early-stage cervical cancer, an ideal approach would be a randomized controlled trial. In such case, (1) surgical approaches (laparoscopy, robotic-assisted, vaginal, and laparotomy), (2) surgical technique (intra-uterine manipulator and colpotomy), and (3) tumor factors (size and tumor location) would be all controlled. However, given the limited number of subjects, prospective trials comparing minimally invasive and abdominal trachelectomy will likely not be feasible.
      In conclusion, these data demonstrate that the use of MIS for trachelectomy for early-stage cervical cancer has increased significantly in recent years. Given the concerns surrounding the influence of MIS for women who undergo radical hysterectomy, further study to monitor outcomes in these women who undergo minimally invasive trachelectomy is a necessity.

      Appendix

      Supplemental Table 1Prognostic factors for overall survival (n = 206)
      CharacteristicHR (95% CI)P value
      Age (continuous)0.95 (0.85–1.05).28
      Race/ethnicity
       White1
       Black2.89 (0.60–13.91).19
       Hispanic1.17 (0.14–9.53).88
       Other1.04 (0.13–8.50).97
       Unknown
      Year of diagnosis
       20101
       20110.37 (0.07–1.90).23
       20120.38 (0.07–1.96).25
       20130.28 (0.03–2.43).25
       20140.37 (0.04–3.37).38
       2015
      Insurance
       Private1
       Medicaid1.66 (0.35–7.82).52
       Medicare
      Nonestimable
      .99
       Uninsured1.80 (0.23–14.41).58
       Other government/unknown
      Nonestimable
      .99
      Income
       <$38,0001
       $38,000–$47,9990.47 (0.09–2.58).39
       $48,000–$62,9990.23 (0.04–1.23).09
       ≥$63,0000.29 (0.06–1.28).10
      Education
       ≥21%1
       13-20%3.03 (0.34–27.16).32
       7.0-12.9%2.27 (0.25–20.30).46
       <7%1.17 (0.11–12.96).90
      Urban rural
       Metropolitan1
       Rural
      Nonestimable
      .99
       Unknown
      Nonestimable
      .99
       Urban1.27 (0.16–9.89).82
      Comorbidity
       01
       1
      Nonestimable
      .99
       ≥2
      Nonestimable
      .99
      Facility type
       Academic/research1
       Community cancer
      Nonestimable
      .99
       Comprehensive community cancer2.66 (0.77–9.21).12
       Integrated network cancer1.22 (0.14–10.41).86
      Facility location
       Northeast1
       Midwest1.35 (0.27–6.70).71
       South1.59 (0.36–7.11).54
       West0.44 (0.05–4.19).47
      Stage
       1A2
      Nonestimable
      .99
       1B11
       1B2
      Nonestimable
      .99
       1B NOS1.02 (0.22–4.74).98
      Histology
       Squamous cell1
       Adenocarcinoma0.27 (0.06–1.35).11
       Adenosquamous1.98 (0.49–7.91).34
      Grade
       Well differentiated1
       Moderately differentiated
      Nonestimable
      .99
       Poorly differentiated
      Nonestimable
      .99
       Unknown
      Nonestimable
      .99
      Tumor size, cm
       <11
       1-21.07 (0.10–11.81).96
       >23.67 (0.45–29.85).22
       Unknown0.79 (0.05–12.71).87
      Tumor size, cm
       <21
       2-43.18 (0.82–12.29).09
       >4
      Nonestimable
      .99
       Unknown0.69 (0.07–6.61).75
      LVSI
       Absent1
       Present2.44 (0.69–8.66).17
       Unknown0.89 (0.10–7.94).91
      Regional nodes
       Not examined1
       Examined0.63 (0.08–4.96).66
       Unknown
      Nonestimable
      .99
      Regional nodal metastasis
      Nodes positive/negative were compared restricting to patients with nodes examined.
       Negative1
       Positive1.04 (0.13–8.25).97
       Unknown
      Surgical approach
       Open1
       MIS0.50 (0.15–1.70).27
      Univariable analysis with Cox proportional hazard regression model for analysis. In total, 2015 patients were excluded because of missing survival data.
      CI, confidence interval; HR, hazard ratio; LVSI, lymphovascular space invasion; MIS, minimally invasive surgery; NOS, not otherwise specified.
      Matsuo et al. Trachelectomy for reproductive-aged women with early-stage cervical cancer: minimally invasive surgery versus laparotomy. Am J Obstet Gynecol 2019.
      a Nonestimable
      b Nodes positive/negative were compared restricting to patients with nodes examined.

      References

        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2018.
        CA Cancer J Clin. 2018; 68: 7-30
        • Birth: Final data for 2015
        National vital statistics reports.
        (Available at:)
      1. CDC National Vital Statistics Data Brief 152.
        (Available at:)
        • National Comprehensive Cancer Network Clinical Practice Guideline in Oncology
        Cervical Cancer.
        (Available at:)
        • Cui R.R.
        • Chen L.
        • Tergas A.I.
        • et al.
        Trends in use and survival associated with fertility-sparing trachelectomy for young women with early-stage cervical cancer.
        Obstet Gynecol. 2018; 131: 1085-1094
        • Ebisawa K.
        • Takano M.
        • Fukuda M.
        • et al.
        Obstetric outcomes of patients undergoing total laparoscopic radical trachelectomy for early stage cervical cancer.
        Gynecol Oncol. 2013; 131: 83-86
        • Kasuga Y.
        • Nishio H.
        • Miyakoshi K.
        • et al.
        Pregnancy outcomes after abdominal radical trachelectomy for early-stage cervical cancer: a 13-year experience in a single tertiary-care center.
        Int J Gynecol Cancer. 2016; 26: 163-168
        • Machida H.
        • Mandelbaum R.S.
        • Mikami M.
        • et al.
        Characteristics and outcomes of reproductive-aged women with early-stage cervical cancer: trachelectomy versus hysterectomy.
        Am J Obstet Gynecol. 2018; 219: 461.e1-461.e18
        • Nishio H.
        • Fujii T.
        • Kameyama K.
        • et al.
        Abdominal radical trachelectomy as a fertility-sparing procedure in women with early-stage cervical cancer in a series of 61 women.
        Gynecol Oncol. 2009; 115: 51-55
        • Pareja R.
        • Rendon G.J.
        • Sanz-Lomana C.M.
        • Monzon O.
        • Ramirez P.T.
        Surgical, oncological, and obstetrical outcomes after abdominal radical trachelectomy—a systematic literature review.
        Gynecol Oncol. 2013; 131: 77-82
        • Sonoda Y.
        • Abu-Rustum N.R.
        • Gemignani M.L.
        • et al.
        A fertility-sparing alternative to radical hysterectomy: how many patients may be eligible?.
        Gynecol Oncol. 2004; 95: 534-538
        • Matsuo K.
        • Machida H.
        • Mandelbaum R.S.
        • et al.
        Trachelectomy for stage IB1 cervical cancer with tumor size >2 cm: trends and characteristics in the United States.
        J Gynecol Oncol. 2018; 29: e85
        • Melamed A.
        • Margul D.J.
        • Chen L.
        • et al.
        Survival after minimally invasive radical hysterectomy for early-stage cervical cancer.
        N Engl J Med. 2018; 379: 1905-1914
        • Ramirez P.T.
        • Frumovitz M.
        • Pareja R.
        • et al.
        Minimally invasive versus abdominal radical hysterectomy for cervical cancer.
        N Engl J Med. 2018; 379: 1895-1904
        • Bilimoria K.Y.
        • Stewart A.K.
        • Winchester D.P.
        • Ko C.Y.
        The National Cancer Data Base: a powerful initiative to improve cancer care in the United States.
        Ann Surg Oncol. 2008; 15: 683-690
      2. Infertility definitions and terminology.
        (Available at:)
        • Churchill S.J.
        • Armbruster S.
        • Schmeler K.M.
        • et al.
        Radical trachelectomy for early-stage cervical cancer: a survey of the society of gynecologic oncology and gynecologic oncology fellows-in-training.
        Int J Gynecol Cancer. 2015; 25: 681-687
        • Wright J.D.
        • Herzog T.J.
        • Neugut A.I.
        • et al.
        Comparative effectiveness of minimally invasive and abdominal radical hysterectomy for cervical cancer.
        Gynecol Oncol. 2012; 127: 11-17
        • Janda M.
        • Gebski V.
        • Davies L.C.
        • et al.
        Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage i endometrial cancer: a randomized clinical trial.
        JAMA. 2017; 317: 1224-1233
        • Walker J.L.
        • Piedmonte M.R.
        • Spirtos N.M.
        • et al.
        Laparoscopy compared with laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group Study LAP2.
        J Clin Oncol. 2009; 27: 5331-5336
        • Veldkamp R.
        • Kuhry E.
        • Hop W.C.
        • et al.
        Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial.
        Lancet Oncol. 2005; 6: 477-484
        • Leung K.L.
        • Kwok S.P.
        • Lam S.C.
        • et al.
        Laparoscopic resection of rectosigmoid carcinoma: prospective randomised trial.
        Lancet. 2004; 363: 1187-1192
        • Huscher C.G.
        • Mingoli A.
        • Sgarzini G.
        • et al.
        Laparoscopic versus open subtotal gastrectomy for distal gastric cancer: five-year results of a randomized prospective trial.
        Ann Surg. 2005; 241: 232-237
        • Vinuela E.F.
        • Gonen M.
        • Brennan M.F.
        • Coit D.G.
        • Strong V.E.
        Laparoscopic versus open distal gastrectomy for gastric cancer: a meta-analysis of randomized controlled trials and high-quality nonrandomized studies.
        Ann Surg. 2012; 255: 446-456
        • Obermair A.
        • Gebski V.
        • Frumovitz M.
        • et al.
        A phase III randomized clinical trial comparing laparoscopic or robotic radical hysterectomy with abdominal radical hysterectomy in patients with early stage cervical cancer.
        J Minim Invasive Gynecol. 2008; 15: 584-588
        • Nam J.H.
        • Park J.Y.
        • Kim D.Y.
        • Kim J.H.
        • Kim Y.M.
        • Kim Y.T.
        Laparoscopic versus open radical hysterectomy in early-stage cervical cancer: long-term survival outcomes in a matched cohort study.
        Ann Oncol. 2011; 23: 903-911
        • Sert B.M.
        • Boggess J.F.
        • Ahmad S.
        • et al.
        Robot-assisted versus open radical hysterectomy: a multi-institutional experience for early-stage cervical cancer.
        Eur J Surg Oncol. 2016; 42: 513-522
        • Shazly S.A.
        • Murad M.H.
        • Dowdy S.C.
        • Gostout B.S.
        • Famuyide A.O.
        Robotic radical hysterectomy in early stage cervical cancer: a systematic review and meta-analysis.
        Gynecol Oncol. 2015; 138: 457-471
        • Wang Y.Z.
        • Deng L.
        • Xu H.C.
        • Zhang Y.
        • Liang Z.Q.
        Laparoscopy versus laparotomy for the management of early stage cervical cancer.
        BMC Cancer. 2015; 15: 928
        • Leitao Jr., M.M.
        The LACC trial: has minimally invasive surgery for early-stage cervical cancer been dealt a knockout punch?.
        Int J Gynecol Cancer. 2018; 28: 1248-1250
        • Api M.
        • Boza A.
        • Ceyhan M.
        Robotic versus laparoscopic radical trachelectomy for early-stage cervical cancer: case report and review of literature.
        J Minim Invasive Gynecol. 2016; 23: 677-683
        • Johansen G.
        • Lonnerfors C.
        • Falconer H.
        • Persson J.
        Reproductive and oncologic outcome following robot-assisted laparoscopic radical trachelectomy for early stage cervical cancer.
        Gynecol Oncol. 2016; 141: 160-165
        • Park J.Y.
        • Joo W.D.
        • Chang S.J.
        • et al.
        Long-term outcomes after fertility-sparing laparoscopic radical trachelectomy in young women with early-stage cervical cancer: an Asan Gynecologic Cancer Group (AGCG) study.
        J Surg Oncol. 2014; 110: 252-257
        • Vieira M.A.
        • Rendon G.J.
        • Munsell M.
        • et al.
        Radical trachelectomy in early-stage cervical cancer: a comparison of laparotomy and minimally invasive surgery.
        Gynecol Oncol. 2015; 138: 585-589
        • Yoo S.E.
        • So K.A.
        • Kim S.A.
        • et al.
        Surgical and obstetrical outcomes after laparoscopic radical trachelectomy and pelvic lymphadenectomy for early cervical cancer.
        Obstet Gynecol Sci. 2016; 59: 373-378
        • Kong T.W.
        • Chang S.J.
        • Piao X.
        • et al.
        Patterns of recurrence and survival after abdominal versus laparoscopic/robotic radical hysterectomy in patients with early cervical cancer.
        J Obstet Gynaecol Res. 2016; 42: 77-86
        • Rakowski J.A.
        • Tran T.A.
        • Ahmad S.
        • et al.
        Does a uterine manipulator affect cervical cancer pathology or identification of lymphovascular space involvement?.
        Gynecol Oncol. 2012; 127: 98-101
        • Dursun P.
        • LeBlanc E.
        • Nogueira M.C.
        Radical vaginal trachelectomy (Dargent's operation): a critical review of the literature.
        Eur J Surg Oncol. 2007; 33: 933-941
        • Pareja R.
        • Rendon G.J.
        • Vasquez M.
        • Echeverri L.
        • Sanz-Lomana C.M.
        • Ramirez P.T.
        Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: a literature review and analysis of oncological and obstetrical outcomes.
        Gynecol Oncol. 2015; 137: 574-580
        • Plante M.
        Bulky early-stage cervical cancer (2-4 cm lesions): upfront radical trachelectomy or neoadjuvant chemotherapy followed by fertility-preserving surgery: which is the best option?.
        Int J Gynecol Cancer. 2015; 25: 722-728
        • Ramirez P.T.
        • Schmeler K.M.
        • Soliman P.T.
        • Frumovitz M.
        Fertility preservation in patients with early cervical cancer: radical trachelectomy.
        Gynecol Oncol. 2008; 110: S25-S28
        • Sideri M.
        Surgery for cervical neoplasia.
        in: Morrow C.P. Morrow’s gynecologic cancer surgery. 2nd ed. South Coast Medical Publishing, Encinitas, CA2013: 513-698