LACC Trial Research Articles

Achieving Type C2 (Type III) Laparoscopic Radical Hysterectomy with Preservation of Nerves: A Possibility

Video Objective This video is a demonstration of nerve sparing radical hysterectomy done laparoscopically but what makes it unique is that we could achieve complete parametrectomy which is the most vital step to prevent pelvic recurrences. As we know, the lymphatics follow the veins, removal of parametrium and paracervix on both the sides becomes crucial in achieving complete tumor clearance. Preservation of the nerves helps in the maintenance of bladder, anorectal and sexual functions making the postoperative period better, less morbid & uneventful. In contrast to open surgery, where you have to palpate the tissues to know the extent of dissection of the parametrium, laparoscopy helps us to have an extra edge with pelvic anatomy and magnification of the same. Setting A 70 year old post-menopausal lady had presented to us with white P/V discharge and post-menopausal spotting. Cervical biopsy reported well differentiated squamous cell carcinoma and imaging revealed that there was no extension into the parametrium. Interventions This video highlights the efforts made for hemostasis during the procedure and the relationship of ureters with the uterine vessels on either side. Following the dictum, “fat belongs to the bladder” and “fat belongs to the rectum” that we have always followed, we achieve a bloodless field with preservation of the innervation to bladder and rectum on both the sides. Post-operative course of the patient was unremarkable and she didn't have any bowel and bladder complaints. Conclusion With proficient surgeons, we can achieve complete parametrectomy, equal survival rates and less pelvic recurrences in comparison to open surgery in a rebut to the LACC trial which has taken the world by a storm. It is all about the anatomy and the anatomy of parametrium is the key to achieve a laparoscopic nerve sparing radical hysterectomy with no local recurrences and no lifestyle changes postoperatively.

Efficacy of different surgical approaches in the clinical and survival outcomes of patients with early-stage cervical cancer: protocol of a phase III multicentre randomised controlled trial in China

IntroductionIn the last three decades, minimally invasive surgery (MIS) for radical hysterectomy (RH) has become a popular treatment option for early-stage cervical cancer. However, a recently published randomised controlled trial...

Laparoscopic radical hysterectomy with transvaginal closure of vaginal cuff - a multicenter analysis.

Laparoscopic/robotic radical hysterectomy has been historically considered oncologically equivalent to open radical hysterectomy for patients with early cervical cancer. However, a recent prospective randomized trial (Laparoscopic Approach to Cervical Cancer, LACC) has demonstrated significant inferiority of the minimally invasive approach. The aim of this study is to evaluate the oncologic outcomes of combined laparoscopic-vaginal radical hysterectomy. Between August 1994 and December 2018, patients with invasive cervical cancer were treated using minimally-invasive surgery at the Universities of Jena, Charité Berlin (Campus CCM and CBF) and Cologne and Asklepios Clinic Hamburg. 389 patients with inclusion criteria identical to the LACC trial were identified. In contrast to the laparoscopic/robotic technique used in the LACC trial, all patients in our cohort underwent a combined transvaginal-laparoscopic approach without the use of any uterine manipulator. A total of 1952 consecutive patients with cervical cancer were included in the analysis. Initial International Federation of Gynecology and Obstetrics (FIGO) stage was IA1 lymphovascular space invasion (LVSI+), IA2 and IB1/IIA1 in 32 (8%), 43 (11%), and 314 (81%) patients, respectively, and histology was squamous cell in 263 (68%), adenocarcinoma in 117 (30%), and adenosquamous in 9 (2%) patients. Lymphovascular invasion was confirmed in 106 (27%) patients. The median number of lymph nodes was 24 (range 2-86). Lymph nodes were tumor-free in 379 (97%) patients. Following radical hysterectomy, 71 (18%) patients underwent adjuvant chemoradiation or radiation. After a median follow-up of 99 (range 1-288) months, the 3-, 4.5-, and 10-year disease-free survival rates were 96.8%, 95.8%, and 93.1 %, and the 3-, 4.5-, and 10-year overall survival rates were 98.5%, 97.8%, and 95.8%, respectively. Recurrence location was loco-regional in 50% of cases with recurrence (n=10). Interestingly, 9/20 recurrences occurred more than 39 months after surgery. The combined laparoscopic-vaginal technique for radical hysterectomy with avoidance of spillage and manipulation of tumor cells provides excellent oncologic outcome for patients with early cervical cancer. Our retrospective data suggest that laparoscopic-vaginal surgery may be oncologically safe and should be validated in further randomized trials.

Recurrence and survival after robotic-assisted radical hysterectomy (RRH) for early-stage cervical cancer (CC): Experience may matter.

5535 Background: The phase III LACC Trial found that minimally invasive surgery (MIS) / radical hysterectomy was inferior to open radical hysterectomy (ORH) with reduced disease-free survival (86% v 96.5%) and a higher disease-specific death rate (DSDR) (4.4% v 0.6%). We evaluated our experience with attention to the learning curve. Methods: Patients (pts) with early-stage CC (4/2007-12/2017) who underwent RRH with a uterine manipulator were evaluated in a contemporaneously maintained database. First 10 learning curve cases per surgeon (Group A) were compared to all subsequent cases (Group B). Inclusion criteria mirrored the LACC trial: > one-year follow-up, adenocarcinoma, adenosquamous, or squamous carcinoma, stage IA2 or IB1 using FIGO 2014 guidelines, and pathologic tumor size (TS) of 4 cm or less. Atypical histologies and lesions > 4 cm were excluded. Study parameters assessed included recurrence free survival (RFS), DSDR, and pattern of recurrence. Results: 144 RRH pts were identified and 90 met inclusion criteria with mean age of 45.6±14.3 years. Exclusions included stage 1A1 without LVSI (n = 13), atypical histology (n = 10), lost to follow-up (n = 13), and occult stage 1B2 (n = 18). 40 pts met Group A and 50 met Group B criteria. Median follow-up was 61±34.3 months (A = 71.5, B = 52.5). The 5-year RFS was 92% (95 CI ±4%) and the DSDR 5.5% (n = 5). There were 7 (7.8%) recurrences with median time to recurrence of 12±8.3 mos. Recurrence in Group A (n = 6, 15%) exceeded Group B (n = 1, 2%), p= 0.025. DSDR was 10% Group A v 2% B ( p= 0.184). The 4.5 yr RFS was 84.8% (95 CI ±7%) in Group A v 98% (95 CI ±3%) in Group B. There were no differences in risk factors for recurrence between A & B (TS > 2 cm, LN (+), adjuvant therapy (AT), and LVSI p> 0.05), except (+) vaginal margin status (A = 10% v B = 0%, p= 0.034). Three recurrences involved carcinomatosis, which may be insufflation related. All recurrent cases had TS > 2 cm and 5 received AT. Conclusions: In this study, recurrence of disease in early-stage CC clustered in the first 10 cases per surgeon and occurred in TS > 2 cm. This data suggests a possible learning curve effect and argues against a uterine manipulator cause. Carcinomatosis may be insufflation related, unique to MIS, and deserves further study.

Rubbing salt on the wound.

The quotation ‘People who peek through key-holes have to expect an occasional poke in the eye’ comes to mind in view of the recently published LACC Trial in the New England Journal of Medicine showing significantly worse survival following ‘keyhole’ surgery (laparoscopic or robotic) in early stage cervical cancer (Ramirez et al. N Engl J Med 2018;379:1895–904). A second study in the same edition reinforced the results by also showing a worse survival with ‘keyhole’ surgery (Melamed et al. N Engl J Med 2018;379:1905–14). This must be considered to be as unfortunate as having ‘both eyes poked at the same time via the same keyhole’. Before gynaecological oncologists have regained full sight, comes this third publication focusing on fertility-sparing surgery in early stage cervical cancer which ‘rubs salt on the wound’ by also showing excellent survival with an abdominal approach. The study by Li et al. (BJOG 2019; 126:1169–74) the largest published series on abdominal radical trachelectomy (ART) demonstrating a 98.6% 5-year survival, agrees well with the abdominal arm in the LACC trial of 99% 3-year survival and contrasts significantly with the laparoscopic arm of 93.8% 3-year survival. In addition, the results are comparable to previous publications on ART and add substantially to the literature (previously, 866 cases with a cumulative mortality rate of 1.4%). Of interest are the results on tumours larger than 2 cm with a recurrence rate of 5.3% compared with 2.0% in tumours <2 cm (nonsignificant P value). Analysis of the New England Journal of Medicine publications identified that it was in this sub-group specifically there were the greatest differences in recurrences. It is also in this sub-group that survival differences are the greatest compared with vaginal radical trachelectomy (cumulative recurrence rate of 23.9%), which also utilises a laparoscopic approach (BJOG 2019;126:1169–74). Data following total laparoscopic radical trachelectomy are limited. Consistent with this, is the FIGO 2018 re-classification of cervix cancer reducing the cut-off between IB1 and IB2 tumours from 4 to 2 cm (Bhatla et al. Int J Gynaecol Obstet 2018;143 (Suppl 2):22–36). Where does all this leave us? Is the problem the surgeon or the tools or the procedure? Many are questioning the surgical techniques in order to retain a minimally invasive approach including the use of manipulators, the CO2 pneumoperitoneum, tumour exposure to the peritoneum and the surgical radicality. It's also time to reflect. Fertility-sparing or not, why have different surgeons/centres been advocating different surgical procedures/approaches? One explanation is the Collingridge dilemma stating that technological advances contain two components; (1) information: where the effects of technological advances cannot be predicted until they are extensively developed and widely used in clinical practice, and (2) power: where control (by the use of robust clinical evaluations) is difficult when the technology has become entrenched (Collingridge. The Social Control of Technology. London, UK: Palgrave Macmillan, 1981). This is highlighted by the Pacing problem, where innovations develop exponentially while control mechanisms develop incrementally. The solution would be the Precautionary principle, where innovations should not be embraced until developers can prove they will not cause harm. Critics argue this will not eliminate innovations developing in the wrong direction but result in no innovations developing at all. Although it is painful to have to revert back to an abdominal route, the solace is that ‘rubbing salt on the wound’, regardless of the additional pain, will help the wound recover faster. And so, for women with a stage IB2 cervical tumour (FIGO 2018) who wish to preserve fertility, the recommended operation should be an ‘abdominal’ radical trachelectomy. None declared. A completed disclosure of interests form is available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Interpretation and Implications of LACC Trial

LACC trial is a multicentre randomized controlled noninferiority trial. It evaluated the oncological outcomes after minimally invasive surgery and open abdominal radical hysterectomy among women with early-stage cervical cancer. The results showed lower disease-free survival (DFS) and overall survival (OS) in the minimally invasive surgery (MIS) arm. The results of the LACC trial were surprising and contrary to the outcomes in various other retrospective studies which compared outcomes in MIS and open arms for carcinoma cervix. We write this review article to rebut the LACC trial and point out few shortcomings of the trial. These may explain the outcomes. The surgeon proficiency criteria for MIS RH in the trial are inadequate. Surgeons were required to submit two unedited operative videos of MIS radical hysterectomy and outcomes of at least ten cases. The routine use of a uterine manipulator causes tumour fragmentation and is against the norms of oncosurgery. Missing histopathological data in almost a third of cases and inadequate follow-up data add to the lacunae. We think the inferior oncological outcomes in MIS arm are not due to MIS per se but due to these factors. Great caution is required in interpreting the results of the LACC trial. The authors of LACC trial mention that the results cannot be generalized to low-risk patients who still can undergo laparoscopic surgery. We recommend further trials to address the issue of safety of minimal access surgery in the treatment of early-stage carcinoma cervix. MIS radical hysterectomy can still be considered an oncologically safe treatment option in trained hands.

Phase III randomized trial of laparoscopic or robotic versus abdominal radical hysterectomy in patients with early-stage cervical cancer: LACC Trial

Phase III randomized trial of laparoscopic or robotic versus abdominal radical hysterectomy in patients with early-stage cervical cancer: LACC Trial

A phase III randomized clinical trial of laparoscopic (TLRH) or robotic radical hysterectomy (RRH) versus abdominal radical hysterectomy (ARH) in patients with early-stage cervical cancer: Preliminary quality-of-life outcomes

Objectives: No randomized controlled trials have compared open to minimally invasive surgery for early-stage cervical cancer. The LACC trial is a prospective multi-institutional trial comparing radical hysterectomy performed by an open approach with a minimally invasive approach. The objective of this report is to provide preliminary results on quality-of-life (QOL) outcomes.