LACC trial: not the end of minimally invasive radical hysterectomy, but a new beginning

Historical evolution of RH

Compared with abdominal RH, the development of MIS has been relatively recent. RH for cervical cancer was first described by Wertheim over 100 years ago but was then superseded by radiotherapy due to high complication rates and suboptimal tumour survival outcomes. Efforts by Meigs and other pioneers improved both safety and oncological outcomes, establishing abdominal RH as the standard treatment for early-stage cervical cancer. However, despite a history spanning over a century, abdominal RH still requires refinement, and there is ongoing debate regarding the standardisation of the procedure.8 9 It has been reported that the 5-year disease-free survival (DFS) rate for stage I cervical cancer following abdominal RH ranges from 80% to 95%, with significant variations between institutions and surgeons.10 Recently, the 5-year DFS rate for cervical cancer has shown improvement. The LACC trial, for instance, reported a 96% 4.5-year DFS for open RH.6 Additionally, total mesometrial resection (TMMR) performed by Dr Höckel demonstrated an impressive 5-year DFS without requiring adjuvant radiotherapy.11 However, the LACC trial reported a 4.5-year DFS rate of approximately 85% in the MIS group, which is significantly lower than that observed in the open surgery group.4 6 It is important to note that at the time of the LACC trial’s launch in 2008, MIS had only undergone just over a decade of development, starting with the first laparoscopic RH reported in 1992. The trial included over 30 clinical centres worldwide. This relatively short timeframe was insufficient to develop widespread expertise in such a complex procedure across diverse global surgical centres. Moreover, the LACC trial lacked strict criteria for the performance of MIS procedures, and no standardised protocols for MIS were available at the time, as it was still an emerging surgical approach. Therefore, the inferior oncological outcomes of MIS compared with open surgery observed in the LACC trial are not unexpected, considering the century-long history of open RH. Given this context, dismissing the role of MIS in radical cervical cancer surgery seems premature and somewhat arbitrary.

Standardisation of surgical techniques

The success of cancer surgery largely depends on achieving appropriate resection margins and adhering to tumour-free surgical principles during the procedure, that is, standardised surgery. In cervical cancer surgery, the central challenge lies in achieving optimal radical resection. Both MIS RH and open RH require adequate dissection of the sub-peritoneal avascular spaces in the pelvis. Our experience emphasises that standardising avascular spaces is key to ensuring surgical homogeneity.9 Dissecting well-defined spaces facilitates uniform tissue removal, which enhances the homogeneity of surgeries. However, these spaces are traditionally believed not to exist naturally but to be surgically created. If these spaces are artificially formed, their standardisation becomes challenging, potentially introducing biases during procedures and leading to variations in resection margins and surgical scope. Additionally, we have clinically observed that MIS practitioners frequently used energy devices to dissect and expose blood vessels. Unlike abdominal RH, which employs en bloc tissue clamping and excision, we are concerned that this approach may leave perivascular adipose tissue unremoved, potentially harbouring occult metastatic tumours and compromising the radicality of the surgery. Therefore, we propose that the extensive use of energy devices and sharp dissection in MIS RH may further amplify inconsistencies in opening these spaces, potentially introducing biases in surgical quality. From an ontogenetic perspective, primordia are defined as clusters of primitive cells that develop into compartments with boundaries where cell mixing does not occur—an ideal concept for cancer resection.12 This implies the existence of natural spaces between organ boundaries. Embryologically based anatomical surgery, such as total mesorectal excision and TMMR, has excellent oncological outcomes.11 13 However, during the development of these techniques, the natural spaces and resection boundary landmarks were not clearly defined, making the identification of surgical landmarks ambiguous.14 The spaces surrounding the Müllerian duct, which are critical to dissect during RH, are particularly complex. Although Höckel and his team studied uterovaginal development using serial sections of female human embryos and fetuses, defining the distal Müllerian morphogenetic unit from the Müllerian mesenchyme, they did not clearly outline the relevant anatomical spaces or surgical landmarks.15 Their modified surgery for stage IB-IIB cervical carcinoma, TMMR, aims to remove the uterus, proximal vagina and extra-cervical mesenchyme within the borders of the distal Müllerian morphogenetic unit. However, the lack of clear anatomical markers and standardised dissection methods for TMMR limits its widespread adoption and makes Höckel’s surgical outcomes difficult to replicate. Therefore, TMMR is considered merely a meticulous RH; while the concept remains compelling, it is still largely hypothetical and requires further refinement to become a practical surgical approach.14

Recently, based on long-term laparoscopic anatomical observations, we have identified three crucial characteristics of natural space: smooth membranous planes on both sides, visible vascular networks underneath the membrane and the feasibility of blunt expansion of the space.16 Building on these features, we systematically explored the spaces within the pelvis. Specifically, the borders of the Müllerian unit are divided into ventral and dorsal sections by the uterine vasculature laterally limited by the medial aspect of the internal iliac vessels (figure 1). The ventral space is divided into the median and lateral spaces by the uterine artery’s vesical branch(es) with accompanying superficial vesical veins (figure 1). The bilateral uterosacral ligaments divide the dorsal space into the median and lateral spaces (figure 1).16 In clinical practice, we have repeatedly observed that dissecting along these characteristic spaces surrounding the Müllerian compartment often reveals six main vascular ‘outlets’ supplying the Müllerian compartment (ie,(1) the uterine artery and the superficial uterine vein; (2) the vesical branch of the uterine artery with the superficial vesical vein; (3) the ureteral branch of the uterine artery; (4) the deep uterine vein; (5) the middle and inferior vesical veins; (6) the vaginal branches of the uterine artery and their accompanying veins), while the inferior hypogastric plexus plane naturally emerges (figure 1).16 This represents a critical insight, as it suggests the potential for standardising RH. That is, this anatomical system provides reproducible anatomical markers for embryologically based organ resection, making it possible to standardise surgical procedures. By ligating and dividing these outlets, transecting the uterosacral ligaments near its sacral attachment, and detaching the vagina, preserving the nerve plane, the Müllerian unit can be removed intact. Based on this system,16 the Müllerian unit’s natural spaces and anatomical landmarks can be identified, achieving reproducible and standardised TMMR. We believe this anatomical system is applicable to both open and MIS procedures, and high-definition laparoscopy may be more suitable for implementation.

Finally, the standardisation and success of cancer surgery relies heavily on strict adherence to tumour-free surgical principles. During the early development of MIS for cervical cancer, breaches of these principles were likely to have occurred. The use of transcervical uterine manipulators and unprotected vaginal openings was widely practised during the LACC trial and earlier, and these practices were considered violations of tumour-free surgical principles. Currently, uterine manipulator-free surgery has been widely adopted. Techniques such as vaginal incision through the vaginal route, transvaginal ligation and closure of the upper vagina and cervix prior to incision, or laparoscopic ligation of the upper-mid vagina followed by incision distal to the ligature have proven effective in preventing tumour cell contamination.17 Evidence from systematic reviews suggests that laparoscopic-assisted vaginal hysterectomy demonstrates no significant impact on DFS or overall survival in patients with early-stage cervical cancer, which is comparable with the open approach group of the LACC trial.18 It is important to recognise that MIS for cervical cancer surgery is continuously evolving and improving toward greater refinement.

Conclusions

The results of the LACC trial have had far-reaching impacts, raising concerns and scepticism not only about MIS for cervical cancer but also for MIS in nearly all malignancies. The inferior outcomes of MIS for cervical cancer surgery reported in the LACC trial must be acknowledged and addressed seriously. However, MIS is just a surgical approach, and surgical outcomes should be determined by the quality of the surgery performed, not only by the approach itself. Minimisation of the invasiveness of surgical procedures is an advance that is arguably as significant as the discovery of anaesthesia. Laparoscopy and robotic laparoscopy offer enhanced precision, reduced pain, faster recovery and improved visualisation, making them superior to traditional methods. This presents an inherent advantage for the future treatment of gynaecological tumours, particularly in nerve-sparing RH. It is promising that future minimally invasive RH will achieve better oncological outcomes, reduced bleeding, fewer injuries to surrounding organs, improved nerve sparing and functional protection, thereby realising the true potential of MIS. To validate this hypothesis, two critical steps should be emphasised: (1) establishing structured educational programmes to ensure surgical proficiency in anatomically standardised MIS techniques, and (2) conducting prospective multicentre trials comparing improved MIS (which achieves appropriate resection margins and adheres to tumour-free surgical principles) with laparotomy. The LACC trial should not mark the end of MIS for cervical cancer but rather a new phase of reflection and innovation.