Digital archive of theses discussed at the University of Pisa


Thesis etd-11302019-121056

Thesis type
Tesi di specializzazione (5 anni)
Thesis title
Oncologic outcomes of robotic radical hysterectomy for women with early stage cervical cancer: experience at a referral cancer center.
Course of study
relatore Prof. Gadducci, Angiolo
relatore Dott.ssa Zanagnolo, Vanna
  • survival outcome
  • robotic surgery
  • minimally invasive surgery
  • cervical cancer
  • radical hysterectomy
Graduation session start date
Release date
Cervical cancer is a major female health problem. It is the fourth most common cancer in women worldwide and the second most commonly diagnosed cancer in less developed countries.
Primary treatment of early-stage cervical cancer is radical hysterectomy with bilateral pelvic lymphadenectomy.
During last few years radical hysterectomy was performed either by laparotomy or laparoscopic approach, both considered acceptable and safety despite the lack of randomized trials.
Retrospective studies concluded that minimally invasive surgery (MIS) for cervical cancer was not associated with poorer oncologic outcomes than open approach in terms of progression-free survival (PFS) and overall survival (OS), with advantage in length of hospital stay, incidence of post-operative complication and estimated blood loss. Other retrospective studies that compared robot-assisted versus laparotomic surgery showed no difference in term of survival for cervical cancer.
Given these encouraging results, MIS has become a valid alternative to perform radical hysterectomy for early stage cervical cancer worldwide.
The phase III multicentric randomized LACC (Laparoscopic Approach to Carcinoma of the Cervix) trial was designed to confirm that minimally invasive (laparoscopic or robotic) radical hysterectomy for early stage cervical cancer was not inferior to laparotomic approach in terms of oncologic outcomes. The unexpected results showed that minimally invasive approach was associated with a lower rate of PFS and OS, and with a higher rate of death for cervical cancer and locoregional recurrence. The disadvantage for MIS was so great that the Data Safety Monitoring Committee stopped the trial prematurely after recruitment of 85.3% (631/740) of the planned patients.
The results were unexpected and shocking for the gynaecologic oncology community. Reasons why MIS might have a detrimental effect are still unclear. Although quality assessment was performed in the LACC trial, a criticism was that vast majorities of MIS procedures were conducted by conventional laparoscopy, considering that laparoscopic radical hysterectomy is one of the most challenging minimally invasive procedures in gynaecologic oncology. Other speculations were made about the use of intrauterine manipulators, the possible role of CO2 gas in cancer cells seeding, excellent oncologic outcomes of the open arm of the LACC study, the long accrual time, the distribution of recurrences in a few of the centers that participated in the study.
We have to learn from the results of the LACC trial starting by critically analyze our own data, trying to understand what could have gone wrong with the MIS, what can be modified to prevent the negative impact of such an approach and whether there is still room for another, oncologically better designed, randomized clinical trial.
We performed a retrospective analysis of patients underwent minimally invasive radical hysterectomy for early-stage cervical cancer (stage IA2, IB1 or IIA1 according to FIGO - International Federation of Gynaecology and Obstetrics - 2009) at European Institute of Oncology (IEO). The focus of the study was on long-term oncologic outcomes to critically evaluate our data compared with those available in the literature.
All patients underwent type B1, B2 or C1 robotic radical hysterectomy according to the Querleu‐Morrow classification and pelvic lymph nodes assessment. Some technical expedients were adopted to avoid malignant cells spillage. Prior to cutting the vagina, vaginal washing was performed and one Endoloop was tightened on the upper third of the vagina above the resection margin, in order the avoid the risk of unintended abdominal seeding of neoplasia. The surgical specimens were all removed through the vagina using endoscopic bags, with the lymph nodes previously packed into separate bags marked according to the side. The intrauterine manipulator was never be used and vaginal probe was employed to identify the upper vagina prior to incising the vaginal wall.
At univariate analysis, FIGO stage 2018 IB2-IB3 (p value=0.03), lymphovascular space invasion (p value=0.03), tumor size ≥ 2cm (p value=0.01), parametrial involvement (p value=0.02) and presence of residual tumor at time of radical hysterectomy (p value=0.03) were independently associated to recurrence.
At 4.5 years PFS was 93,1% (SE ± 2,1) and OS was 95,1% (SE ± 1,8).
Stratifying by tumor size, PFS in tumor < 2 cm versus tumor ≥ 2 cm was statistically different (96,8% ± 2,3 and 87,9% ± 4,1 respectively, p value 0,01), as well as OS (100% and 89,8% ± 4,0 respectively, p value 0,01).
Stratifying by evidence of tumor at time of robotic surgery, PFS was statistically different in women with no residual tumor after conization versus presence of tumor in the uterus at time of surgery (100% ± 2,5 and 90,8% ± 2,8 respectively, p value 0,04). The difference in term of OS was not significative (100% and 93,9% ± 2,4 respectively, p value 0,06). No recurrences occurred in patients who had no residual tumor after cone biopsy and no one of them died for disease.
Our study suggests that robotic approach along with some technical precautions to avoid spillage may be useful and safe as primary treatment of early-stage cervical cancer, especially for tumor < 2 cm and in case of no evidence of disease at time of radical hysterectomy in patients underwent previous conization. However, after the results of the LACC trial, further studies and a new randomized controlled trial are needed to establish the safety and the optimal indications for minimally invasive approach in cervical cancer surgery and to validate possible technical expedients to avoid cancer spillage.