By Alexandra Morell, MD
Synopsis: In this retrospective cohort study including 276 patients with early-stage cervical cancer, modified tumor-free techniques during laparoscopic radical hysterectomy, including avoidance of a uterine manipulator and vaginal closure prior to colpotomy, demonstrated a lower recurrence rate (1.3% vs. 12.8%) and significantly better two-year disease-free survival (99.3% vs. 91.9%, P = 0.002) compared with traditional laparoscopic radical hysterectomy.
Source: Li Y, Zhao J, Ding X, et al. Oncologic outcomes of laparoscopic radical hysterectomy incorporating modified tumor-free techniques. Obstet Gynecol. 2025;145(2):134-143.
In the United States, there were 13,820 new cervical cancer cases in 2024.1 Cervical cancer incidence has declined over the last five decades largely because of robust screening programs and, more recently, the development of the human papillomavirus (HPV) vaccine. Risk factors for the development of cervical cancer include young age of coitarche, multiple sexual partners, poor access to screening, and a history of sexually transmitted infections.2 HPV, a double-stranded deoxyribonucleic acid (DNA) virus, is the causative agent of precursor lesions to cervical cancer and progression in cervical cancer in most cases.
The management of cervical cancer is dependent on the stage at diagnosis. Early-stage disease often is treated with cervical conization or hysterectomy, while later-stage disease often is treated with chemoradiation or systemic chemotherapy, depending on the extent of disease.2 For patients with stage IA2, IB1, IB2, and IIA1 cervical cancers, radical hysterectomy is the preferred surgical management.3 Radical hysterectomy differs from a simple hysterectomy in that it involves removal of parametrial and upper vaginal tissue.2 Because of lower disease-free survival (DFS) with minimally invasive techniques, radical hysterectomy often is performed with an open approach.3
The objective of this study was to evaluate oncologic outcomes for patients with early-stage cervical cancer undergoing minimally invasive radical hysterectomy with modified surgical techniques. This was a retrospective cohort study at a single tertiary care center in China performed between January 2017 and January 2023. Inclusion criteria included undergoing laparoscopic radical hysterectomy with a gynecologic oncologist with suspected stage IB1, IB2, or IIA1 squamous cell carcinoma (SCC); adenosquamous carcinoma (AS); or adenocarcinoma (AC) of the cervix.
Prior to 2019, patients in this cohort underwent a conventional laparoscopic radical hysterectomy, which involved the use of a uterine manipulator and unprotected intracorporeal colpotomy. After 2019, laparoscopic radical hysterectomies at this institution were performed with a modified tumor-free technique (MTF). The study aimed to compare oncologic outcomes between the conventional approach (non-MTF) performed prior to 2019 and the MTF approach performed after 2019.
The MTF approach involved suspension of the uterine fundus with a suture and using a suprapubic laparoscopic port site to facilitate uterine position during surgery as opposed to a uterine manipulator. In addition, the MTF approach used a sterilized cable tie or vaginal cerclage to close the upper vagina prior to performing a colpotomy. Other surgical adjustments included avoidance of lymph node fragmentation and immediate placement of any lymph node tissues into sealed bags, copious irrigation of the pelvis with sterilized water, and coagulation of the fallopian tubes at the start of the procedure to limit possible spilling of contents from the uterine cavity into the peritoneal cavity.
Patient charts were reviewed for demographic, clinicopathologic, and perioperative outcomes and postoperative complications. The primary outcome of the study was DFS. Secondary outcomes included perioperative variables (operative time, hemoglobin decrease, length of hospital stay) and postoperative complications. For statistical analyses, a t-test or Mann-Whitney U test was used for continuous variables and a chi-squared or Fisher exact test was used for categorical variables. Kaplan-Meier methods were used to demonstrate DFS and overall survival. In addition, multivariable regression was performed to assess variables associated with DFS.
Subgroup analyses were performed based on tumor size. An inverse probability treatment weighting (IPTW) was used when making comparisons between groups, which adjusted for factors that affect survival, including age, body mass index, diagnostic procedure, pathology, grade, lymph node metastasis, parametrial invasion, lymphovascular space invasion, depth of stromal invasion, tumor size, and adjuvant radiation. Each patient was weighted using the IPTW to balance characteristics between the MTF and non-MTF groups.
A total of 276 patients were included, with 151 patients (54.7%) in the MTF group and 125 patients (45.3%) in the non-MTF group. Prior to IPTW, the two groups were significantly different regarding age (44.1 vs. 47.0 years, P = 0.13), stage II disease (3.3% vs. 10.4%, P = 0.033), and lymph node metastasis (8.6% vs. 20.0%, P = 0.011). There was no significant difference in operative time, hemoglobin difference, or postoperative complications between the MTF and non-MTF groups. The MTF group had a median hospital stay of six days (range 5-7) vs. seven days (range 6-9) in the non-MTF group (P < 0.001). The cervical cancer recurrence rate was 1.3% (n = 2) in the MTF group (with a median follow-up of 36 months) compared with 12.8% (n = 16) in the non-MTF group (with a median follow-up of 66.8 months).
When analyzed by tumor size, the recurrence rate for tumors less than 2 cm was 1.1% vs. 4.1% for the MTF and non-MTF groups, respectively. For tumors greater than 2 cm, the recurrence rate was 0% vs. 13.5% for the MTF and non-MTF groups, respectively. The unadjusted DFS at two years was 99.3% vs. 91.9% for the MTF and non-MTF groups, respectively (P = 0.002). After IPTW, this remained statistically significant (P = 0.031). The unadjusted two-year overall survival was 100.0% vs. 96.0% for the MTF and non-MTF groups, respectively (P = 0.016). After IPTW adjustments, overall survival differences were not statistically significant (P = 0.100). On multivariate analysis, only surgical technique (MTF) was predictive of improved DFS (hazard ratio [HR], 0.10; 95% confidence interval [CI], 0.01-0.77; P = 0.027).
Commentary
The Laparoscopic Approach to Cervical Cancer (LACC) Trial investigated the use of minimally invasive techniques for surgical management of early-stage cervical cancer.4 This Phase III randomized controlled trial of patients with stage IA1, IA2, and IB1 SCC, AS, or AC of the cervix demonstrated a lower three-year DFS of 91.2% vs. 97.1% (HR, 3.74; 95% CI, 1.63-8.58) and lower three-year overall survival of 93.8% vs. 99.0% (HR, 6.00; 95% CI, 1.77-20.30) for patients undergoing minimally invasive surgery compared with open surgery, respectively.
Following this publication, Melamed et al published an epidemiologic cohort study using Surveillance, Epidemiology, and End Results (SEER) data of outcomes for patients with IA2 or IB1 SCC, AS, or AC who underwent radical hysterectomy between 2010 and 2013.5 Of the 2,461 included patients, 1,225 underwent minimally invasive procedures (49.8%) and the four-year mortality was 9.1% vs. 5.3% (HR, 1.65; 95% CI, 1.22-2.22) for minimally invasive vs. open surgery, respectively.
A second epidemiologic study looking at five-year survival of patients with stage IB1 SCC or AC of the cervix after radical hysterectomy using the National Cancer Database demonstrated a worse survival for patients undergoing minimally invasive hysterectomy compared to open radical hysterectomy (81.3% vs. 90.8%, P < 0.001).6 It is important to note that this study only included patients with tumor size greater than or equal to 2 cm, since it was limited to stage IB1 disease. In 2020, the International Federation of Gynecologic Oncology released a statement that open surgery should be deemed the “gold standard” for early-stage radical hysterectomy, citing the findings of the LACC trial but also noting that women should be counseled about available surgical routes and implications of minimally invasive vs. open surgery to decide the approach.7
Several theories have been posited for worse outcomes associated with minimally invasive surgery in early cervical cancer. These include tumor spillage secondary to the use of a uterine manipulator and increased spread of the disease with pneumoperitoneum.4 The current study adjusted the laparoscopic technique to account for posited reasons for differences seen between minimally invasive and open techniques by avoiding the use of a uterine manipulator, using protected colpotomy, and blocking the fallopian tubes to limit contamination between the uterus and peritoneal cavity. Although this study is retrospective and uses an historical cohort, it is interesting to note the low recurrence rate at a median follow-up of 36 months and increased DFS in the patients undergoing surgery with modified techniques as opposed to conventional minimally invasive techniques. This study also demonstrated that surgery with an MTF technique did not significantly increase operative time compared to traditional approaches.
Further studies are warranted to understand how laparoscopic radical hysterectomy with modified tumor techniques would compare to open radical hysterectomy and if the adjustments noted in this study could lead to comparable survival outcomes between the two routes. Of interest, the Trial of Robotic versus Open Hysterectomy Surgery in Cervix Cancer (ROCC) clinical trial currently is ongoing to assess robotic radical hysterectomy.8 It requires lack of a uterine manipulator and closure of the vagina prior to colpotomy, similar adjustments to minimally invasive surgery as described in this study. The results of the ROCC trial will provide better insight into how and if modified tumor techniques can be implemented on a broader scale in early-stage cervical cancer.
Alexandra Morell, MD, is Adjunct Instructor, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY.
References
1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49.
2. Tewari KS. Cervical cancer. N Engl J Med. 2025;392(1):56-71.
3. Abu-Rustum NR, Yashar CM, Arend R, et al. NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024. J Natl Compr Canc Netw. 2023;21(12):1224-1233.
4. Ramirez PT, Frumovitz M, Pareja R, et al. Minimally invasive versus abdominal radical hysterectomy for cervical cancer. N Engl J Med. 2018;379(20):1895-1904.
5. Melamed A, Margul DJ, Chen L, et al. Survival after minimally invasive radical hysterectomy for early-stage cervical cancer. N Engl J Med. 2018;379(20):1905-1914.
6. Margul DJ, Yang J, Seagle BL, et al. Outcomes and costs of open, robotic, and laparoscopic radical hysterectomy for stage IB1 cervical cancer. J Clin Oncol. 2018;36(15_suppl):5502.
7. FIGO Gynecologic Oncology Committee. FIGO statement on minimally invasive surgery in cervical cancer. Int J Gynaecol Obstet. 2020;149(3):264.
8. ClinicalTrials.gov. A Trial of Robotic Versus Open Hysterectomy Surgery in Cervix Cancer. https://clinicaltrials.gov/study/NCT04831580
In this retrospective cohort study including 276 patients with early-stage cervical cancer, modified tumor-free techniques during laparoscopic radical hysterectomy, including avoidance of a uterine manipulator and vaginal closure prior to colpotomy, demonstrated a lower recurrence rate (1.3% vs. 12.8%) and significantly better two-year disease-free survival (99.3% vs. 91.9%, P = 0.002) compared with traditional laparoscopic radical hysterectomy.
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