Simple hysterectomy in early-stage cervical cancer: is it the way forward?

Despite global efforts in HPV vaccination campaigns, cervical cancer remains a significant public health problem and ranks as the fourth most frequent malignancy in women.1 2 However, with improvements in cancer screening programmes worldwide, more women are being diagnosed in the early stages of the disease, which has a significantly high overall survival rate.

While radical hysterectomy (RH) is an established management approach, a higher blood loss, risk of urinary injury and bladder atony make it a more morbid surgery compared to simple hysterectomy (SH). In its primitive form, RH was first described by Clark and Reis in 1895.3 Since then, multiple modifications have been described by Wertheim, Meigs4 and others over the last century in an attempt to improve oncological outcomes and reduce surgical morbidity. Additionally, with the advancements in laparoscopy and robotics, the minimally invasive approach has gained popularity and is widely used.

Current European guidelines recommend SH with sentinel lymph nodes for IA2 disease and RH with pelvic lymphadenectomy as standard treatment for stages IB1-IB2-IIA1 respectively. They also suggest tailoring the surgery based on tumour size, stromal invasion and lymph-vascular space invasion (LVSI).5

Previously, it was advised to remove the entire parametria due to the risk of metastasis. However, this was associated with significant bowel and bladder complications and sexual dysfunction due to injury to the autonomous nerve fibres. Additionally, several retrospective studies have reported very low rates of parametrial involvement in patients with early cervical cancer, thus questioning the need for radical approaches in tumours with a good prognosis.6–9 Attempts to reduce the surgical morbidity of RH while preserving oncological success led to the formulation of the ConCerv and LESSER Trials, which recruited 100 and 40 participants, respectively.10 11 Both reported SH to be a reasonable alternative in early-stage, low-risk cervical carcinomas.

An international randomised control trial comparing RH to SH in low-risk patients with early-stage cervical cancer was recently published.12 This study presents the results of the Canadian Cancer Trials Group (CCTG) CX.5-SHAPE trial, launched in 2012 by the CCTG. It included 700 patients from 13 centres in 12 countries with low-risk cervical squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma. The primary endpoint of the study aimed to compare pelvic recurrence-free survival. The results demonstrate SH to be non-inferior to RH in early-stage, low-grade cervical cancer. This has generated enthusiasm among gynaecological oncologists, as preventing radical surgeries would improve the quality of life and reduce morbidities associated with radical surgery.

In addition to the non-inferiority of the 3 year pelvic recurrence rate, 3 year extra-pelvic recurrence-free survival (98.1% vs 99.7%) and overall survival (99.1% vs 99.4%) were also similar between the two surgical approaches. The rate of adjuvant chemo - or radiotherapy was identical between patients undergoing SH (9.2%) and RH (8.4%), respectively. Additionally, there was no significant difference in intraoperative complications (7.1% vs 6.4%). However, patients with RH had a threefold higher incidence of bladder injury (9 vs 3) and almost twice the rate of ureteral injuries (five vs three) compared with SH. Furthermore, fewer urological surgical complications were noted in the SH arm with far lesser incidences of acute urinary retention (0.6% vs 11.0%), urinary incontinence (2.4% vs 5.5) and late urinary retention (0.6% vs 9.9%)

The fact that the SHAPE trial demonstrated the non-inferiority of SH is a major achievement as studies of this magnitude are difficult to plan and implement.13 The local recurrence rates were also similar between the two approaches, with no significant increase in the rate of adjuvant radiation therapy postoperatively. Patients also reported better sexual health outcomes following SH compared to RH. The findings of the SHAPE trial have also been validated in two recent meta-analyses.14 15 However, we had concerns and criticisms regarding certain areas of the methodology.

The SHAPE researchers employed a laparoscopic approach in both groups, with the majority of surgeries (79.9 % SH and 69.5% RH) being performed laparoscopically. Within the abdominal group, the rate of positive vaginal margins was 2.7%, and the local recurrence rate was 3.0%. These rates surpassed those in the LACC trial, which recorded 2.13% for positive margins and 1.28% for local recurrence, despite the LACC trial involving a higher-risk group.16 The study, ideally, should have compared the outcomes using an abdominal approach to reduce confounding factors, maintain a homogenous population of patients and yield more definitive results.

The authors also mention that around 10% of the patients in the SH group and 12.9% in the RH group violated the study protocol. Furthermore, 9.1% of the SH group and 8.9% of the RH group received adjuvant treatment. However, in routine clinical practice, patients undergoing SH seldom receive adjuvant therapy. Additionally, 84% of the patients in the SH arm and 76% in the RH arm had LEEP/conisation preoperatively. This would also act as a confounding factor as the SUCCOR study noted that patients with preoperative LEEP and conisation had improved survival rates.17 Further, this difference might have contributed to a positive impact on survival analyses of the SH group.18

In the study, all patients underwent systematic pelvic lymphadenectomy, even if their sentinel lymph node biopsy (SNB) was negative. Patients with negative SNB but positive lymph nodes were subsequently excluded from the study. Currently, there is no uniform consensus regarding the use of SNB. ESGO 2023 recommends SNB in T1a1 LVSI-positive stages and affirms it to be provided in evaluations with a frozen section for T1b1, T1b2 and T2a1. NCCN 2024 guidelines, however, consider it an alternative to pelvic lymphadenectomy in stages IA2–IB1 and LVSI-negative.5 19 20

The study initially was a superiority trial aimed to evaluate recurrences and survival rates at 7 years. However, as the number of pelvic recurrences was significantly lower than anticipated, the authors compared the non-inferiority of 3-year pelvic recurrence. The median follow-up time was also just 4.5 years. It is unlikely that one can assert the superiority of a certain surgical approach in terms of survival and recurrence with such a limited follow-up time. In the absence of long-term survival data, many gynaecological oncologists may not be willing to switch to SH and sacrifice the greater oncological safety proven by RH.

The SHAPE researchers recently published a post-hoc analysis comparing the performance of minimally invasive and open approaches. With a median follow-up of 4.5 years, there were 12 recurrences (4.3%) among 281 patients who underwent minimally invasive surgery, compared to three recurrences (5.3%) among 57 patients who had open surgery. The authors found no statistically significant difference in outcomes between the two approaches.21 However, several key issues must be considered before minimally invasive simple hysterectomy can be deemed an acceptable method in low-risk populations. Post-hoc analyses are susceptible to misleading results and require further validation. Additionally, the small number of recurrence events does not permit an adequate assessment of the intervention’s risk based on the sample size.22

The Greek philosopher Heraclitus famously said that the only constant in life is change. Although it may be difficult to depart from a well-established standard of treatment that has demonstrated good results throughout, the results of this trial demonstrate that some patients with low volume and small tumours might benefit from reducing surgical radicality. The study has its limitations with confounding factors and limited follow-up duration. However, it highlights the need to develop new guidelines and recommendations for managing patients with early-stage cervical malignancies.

As physicians striving to achieve the best for our patients, we must come to terms with our aversion to the unknown and should continue to pursue the desire for cognitive closure. The ongoing LASH study is an ambitious attempt to assess the safety of minimally invasive SH in patients with low-risk cervical cancer after conisation with negative margins.23 The oncological safety of employing a minimally invasive approach is also being studied by the G-LACC trial.24 The interim results of another major trial demonstrated that robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer postoperative complications and superior patient-reported outcomes.25 Till we await the final results of these ambitious studies and the subsequent changes in recommendations and protocols, it is pertinent to discuss current management guidelines with patients to support informed decision-making and ensure optimal treatment outcomes.