Survival after Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer

104

BackgroundRadical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival.Primary ObjectiveTo investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy.Study HypothesisRobot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes.Trial DesignProspective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden.Major Inclusion/Exclusion CriteriaWomen over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years.Primary EndpointRecurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer.Sample SizeThe clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (α) of 5% and a power (1−β) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients.Estimated Dates for Completing Accrual and Presenting ResultsTrial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.Trial RegistrationThe trial is registered at ClinicalTrials.gov (NCT03719547).

Section: Introductionmentioning

confidence: 90%

Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial

Falconer

Pálsdóttir

Stålberg

et al. 2019

104

“…In another, study evaluating open versus minimally invasive radical hysterectomy through an analysis of a national registry database,29 the investigators found that for women who underwent minimally invasive surgery the 4-year mortality was 9.1% and 5.3% among those who underwent open surgery (HR=1.65; 95% CI 1.22 to 2.22; p=0.002), with median follow-up of 45 months. The adoption of minimally invasive surgery in 2006 coincided with a decline in the 4-year relative survival rate of 0.8% (95% CI 0.3% to 1.4%) per year (p=0.01 for change of trend).…”

Section: Discussionmentioning

confidence: 99%

International radical trachelectomy assessment: IRTA study

Salvo

Ramírez

Leitao

et al. 2019

BackgroundRadical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy.Primary ObjectiveTo compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy.Study HypothesisWe hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach.Study DesignThis is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data.Inclusion CriteriaPatients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both).Exclusion CriteriaPrior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach.Primary EndpointThe primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy.Sample SizeAn estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group.

“…In addition, the epidemiologic study conducted by Melamed et al8 reported that over a median follow-up of 45 months, the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery, and a decline in survival coinciding with the incorporation of the minimally invasive approach. The results of these studies challenged the previously published retrospective literature as it pertained to oncologic outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Minimally invasive surgery was associated with lower rates of disease-free survival in comparison with the open approach (3-year rate, 91.2% vs 97.1%; HR for disease recurrence or death from cervical cancer, 3.74; 95% CI 1.63 to 8.58) 7. In a cohort study involving women who underwent radical hysterectomy for stage IA2 or IB1 cervical cancer, published in the same edition of the New England Journal of Medicine , Melamed et al showed that minimally invasive radical hysterectomy was associated with a shorter overall survival than open surgery among women with 2009 FIGO stage IA2 or IB1 cervical carcinoma 8. In this same study, the authors showed hat the 4-year mortality was 9.1% among women who underwent minimally invasive surgery and 5.3% among those who underwent open surgery and that the adoption of minimally invasive surgery coincided with a decline in the 4-year relative survival rate of 0.8%.…”

Section: Introductionmentioning

confidence: 99%

Minimally invasive radical hysterectomy: an analysis of oncologic outcomes from Hospital Italiano (Argentina)

Odetto

Puga

Saadi

et al. 2019

BackgroundThe Laparoscopic Approach to Cervical Cancer (LACC) trial demonstrated a higher rate of disease recurrence and worse disease-free survival in patients who underwent minimally invasive radical hysterectomy.ObjectivesTo evaluate surgical and oncological outcome of laparoscopic radical hysterectomy performed at Hospital Italiano in Buenos Aires, Argentina.MethodsThis retrospective study included all patients with cervical cancer, 2009 FIGO stage IA1, with lymphovascular invasion to IB1 (<4 cm) who underwent a laparoscopic radical hysterectomy between June 2010 and June 2015. Patients were eligible if they had squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, and no lymph node involvement by imaging. Patients must have undergone a type C1 radical hysterectomy. Only patients who were treated by a laparoscopic approach were included. Patients were excluded if histopathology showed a component of neuroendocrine carcinoma before or after surgery; if they had synchronous primary tumors, history of abdominal or pelvic radiotherapy, or were operated on at an outside institution; and if they had only surgery and no follow-up in our institution. Relapse rate and disease-free survival were evaluated using the Kaplan-Meier method.ResultsA total of 108 patients were evaluated. The median age was 41 years (range 27–70). Distribution of histologic sub-types was squamous carcinoma in 77 patients (71%), adenocarcinoma in 27 patients (25%), and adenosquamous carcinoma in four patients (4%). Ninety-nine patients (92%) had stage IB1 tumors and 58 (54%) patients had tumors ≤2 cm. The median surgical time was 240 min (range 190–290), the median estimated blood loss was 140 mL (range 50–500) and the transfusion rate was 3.7%. The median length of hospital stay was 2 days (range 1–11). The median follow-up time was 39 months (range 11–83). The global recurrence rate after laparoscopic radical hysterectomy was 15% (16/108). According to tumor size, the recurrence rate was 12% in patients with tumors ≤2 cm (7/58) and 18% in patients with tumors >2 cm (9/50) (OR=0.76; 95% CI 0.26 to 2.22; p=0.62) The 3- and 5-year relapse rate was 17% (95% CI 11% to 27%). The 3- and 5-year disease-free survival was 81% (95% CI 71% to 88%) and 70% (95% CI 43% to 86%), respectively. Overall survival at 3 years was 87% (95% CI 76% to 93%).ConclusionThe recurrence rate after laparoscopic radical hysterectomy was 15%, and in tumors ≤2 cm it was 12%. The 3-year disease-free survival was 81%. Given these results our hospital has changed the approach to open radical hysterectomy.