1. Introduction

Cervical cancer is the fourth most prevalent cancer among women throughout the world [1]. It is often diagnosed during reproductive years, and 37% of patients with newly diagnosed cervical cancer are under the age of 45 years [2]. In recent years, detection of gynecological tumors has become easier owing to improved diagnostic techniques such as ultrasound, cytology and magnetic resonance imaging (MRI) [3, 4]. Among these, ultrasound plays a particularly important role due to its low invasiveness and excellent soft tissue contrast resolution. In general, nutrient vessels to malignant tumors are fragile and characterized by slow blood flow velocity and low vascular resistance. Therefore, evaluation of blood flow velocity and vascular resistance by the Doppler ultrasound is reported to be useful in detecting the proliferative vessels and contributing to the diagnosis of gynecological malignancies such as ovarian cancer, endometrial cancer and cervical cancer [5, 6, 7]. Notably, ultrasound is often useful in identifying early-stage, asymptomatic cervical cancer in young women [8, 9]. Currently, radical trachelectomy is regarded as the standard of care for women diagnosed with early-stage cervical cancer who desire to conserve their fertility [10, 11]. Various surgical procedures are available for radical trachelectomy, including vaginal, abdominal, laparoscopic and robotic approaches [12]. Abdominal radical trachelectomy (ART) was first performed in 1993, while laparoscopic radical trachelectomy (LRT) was introduced in 2003 [13]. ART has the several advantages such as (1) performing surgeons do not require specific training in performing complex laparoscopic surgeries, and (2) it is the preferred treatment modality in patients with larger tumors because it allows for larger parametrium resection [14]. However, ART has associated disadvantages such as higher estimated blood loss and longer hospital stays. On the other hand, LRT offers multiple advantages, including better visualization, reduced blood loss and quicker recovery [15]. Therefore, since 2011, LRT has become a more popular treatment choice than ART [16]. Despite these advantages, the safety of laparoscopic approach for cervical cancer has been questioned since the Laparoscopic Approach to Cervical Cancer (LACC) trial, published in 2018, documented a poorer survival rate associated with laparoscopic approach for radical hysterectomy [17]. Hence, an urgent need exists to compare the clinical outcomes of cervical cancer patients who undergo LRT and ART. However, owing to the rarity of this type of operation, few studies have compared the clinical outcomes of cervical cancer patients who underwent LRT and ART.

In this study, we explored the perioperative and oncological outcomes of patients with early-stage cervical cancer who underwent LRT or ART.

2. Materials and methods

2.2 Surgical procedure

We have previously reported on the ART procedure [18]. Briefly, under general anesthesia, a vertical skin incision was made between the pubis and umbilicus with the patient in the supine position. Upon entering the peritoneal cavity, pelvic lymphadenectomy was performed; any enlarged lymph nodes that were observed during the procedure were excised and sent for frozen section analysis to confirm the absence of metastasis. Thereafter, both the uterine arteries were identified and preserved. The superior vesicouterine ligament was dissected after identifying the ureteral tunnel. The ureter was separated at its entry point into the bladder. Dissection of the vesicouterine ligament was extended to the level of bladder ureter insertion into the ureter. The bladder pillar was divided, and the bladder was completely separated from the cervix and anterior vaginal wall. Following lymph node dissection around the cardinal ligament, the deep uterine vein was separated and excised. The rectovaginal septum was then separated. After cutting the inferior part of the vesicouterine ligament and sacrouterine ligaments, the bilateral paracolpium were ligated while ensuring that the hypogastric and pelvic autonomic nerves were preserved. The vagina was then cut into the vaginal tissue. After cutting the vagina into a circle, the position of the internal uterine os was verified via ultrasound, and the cut line was established. The cervix was cut into a canal length of at least 2 cm. The cut ends of the resected cervix and uterine stump were subjected to rapid intraoperative diagnosis to confirm the absence of carcinoma invasion. Double cervical cerclage was added with 1-0 ETHIBOND EXCEL polyester sutures (Ethicon, Johnson & Johnson, New Brunswick, NJ, USA), and the vaginal stump and cervix were sutured with 2-0 PDS PLUS (Ethicon, Johnson & Johnson). A Nelaton catheter (NIPRO, Osaka, Japan) was used to prevent cervical stenosis.

Using an Olympus (VISERA ELITE II, Olympus Medical Systems Corp., Tokyo, Japan) or Striker (AIM laparoscope, Japan Striker Corp., Tokyo, Japan) endoscopic system, LRT was conducted employing a standard five-port technique [19] without intrauterine manipulation in the open-leg Trendelenburg position under general anesthesia. A LigaSure (LigaSure™ Maryland, Medtronic, Minneapolis, MN, USA) was used as the vessel-sealing device. After the ports were inserted into the peritoneal cavity, a sentinel lymph node biopsy was conducted instead of pelvic lymph node dissection. The process for sentinel lymph node biopsy was the same as described in our previous reports [20, 21]. The trachelectomy steps were the same as those for ART. However, vaginal closure was performed after the bilateral paracolpiums were ligated [19, 22]. The procedure for vaginal closure was shown in Fig. 1. Vaginal closure was conducted transvaginally, without active insufflation. Several 1-0 silk knots were tied on the cut line of vagina. The vaginal mucosa was then cut 3 mm distally from the knots. The running sutures placed on the vaginal cuff on the uterine side were fastened, and the cervical cancer was encased by vaginal mucosa to prevent the outflow of cancer cells. Circumferential colpotomy was conducted laparoscopically under active insufflation using monopolar scissors. The internal uterine os was identified by ultrasound, the cervix was cut, and a small horizontal skin incision of approximately 5 cm was made in the middle of the lower abdomen. The vaginal stump and cervix were sutured with a 2-0 STRATAFIX Spiral PDS Plus (Ethicon, Johnson & Johnson) using a laparoscope.

Fig. 1.Vaginal closure for laparoscopic radical trachelectomy. (A) Some sutures were conducted on the cut line of vagina transvaginally. (B) The vaginal mucosa was cut in a circle 3 mm outside the knots with pulling of the sutures. (C) The vaginal cuff of the uterine side was occluded with running sutures; the cervical cancer was entirely encased by the vaginal mucosa. (D) After the circumferential colpotomy was conducted laparoscopically, the cervix was removed under small laparotomy. We can confirm in this picture that vaginal closure performed by sutures fully covers the cervical cancer and prevents the leakage of cancer cells.

3. Results

Between 2010 and 2023, 407 patients with cervical cancer were scheduled for surgery at the Education Foundation of Osaka Medical and Pharmaceutical University. Among them, 379 underwent radical hysterectomy. In total, 28 patients satisfied the inclusion criteria. Of these patients, six underwent LRT with sentinel node biopsy, and 22 underwent ART with lymphadenectomy. In the ART group, procedures in two patients required conversion to radical hysterectomy due to intraoperative rapid diagnosis of cancer invasion into the uterine stump. Furthermore, one patient underwent hysterectomy one month after ART due to lymph node metastasis (Fig. 2).

Fig. 2.Schema of study participants.

Table 1 lists the characteristics of the study participants. Among the 28 patients who fulfilled the study criteria, six underwent LRT and 20 underwent ART. Two patients were excluded because of conversion to hysterectomy during surgery. The median age (34 [27–36] vs. 36 [29–43] years, p = 0.61) and body mass index (22.3 [20.5–31.2] vs. 21.3 [16.8–38.7], p = 0.23) were not significantly different between the groups. In the LRT group, no patient had a history of pregnancy. In the ART group, three (15%) patients had a history of pregnancy. In the LRT group, one (16.7%) patient had IA2 disease and five (83.3%) had IB1 disease. In the ART group, five (25%) patients had IA2 disease and 15 (75%) had IB1 disease. Histologically, three cases each of squamous cell carcinoma and adenocarcinoma were observed in the LRT group and 11 cases of squamous cell carcinoma and nine of adenocarcinoma in the ART group. The patients in the LRT group had significantly less blood loss (75 [50–500] vs. 400 [160–930] mL, p = 0.04), lower perioperative transfusion rate (0% vs. 50%, p = 0.02), longer surgical time (584 [454–658] vs. 495 [337–625] min, p = 0.02), and shorter hospital stay (13 [11–14] vs. 21 [14–51] days, p = 0.005) than the patients in the ART group.

Table 2 presents a comparison of short-term postoperative complications between the two groups. No intra-operative complications were observed in either group. The rate of postoperative complications was significantly lower in the LRT group than in the ART group (33% vs. 80%, p = 0.03). One patient experienced urinary tract infection and two experienced voiding dysfunctions in the LRT group, while in the ART group, two patients experienced intestinal ileus, two experienced uterine infections, two experienced urinary tract infections, and 14 experienced voiding dysfunctions in the ART group.

Table 3 lists the oncologic outcomes of the six patients who underwent LRT and 19 who underwent ART. None of the patients in either group had lymph node metastases. The rate of lymphovascular space invasion was 0% in the LRT group and 37% in the ART group (p = 0.08). In the LRT group, no patients underwent adjuvant chemotherapy. Six patients (32%) who underwent ART also received adjuvant chemotherapy. The median follow-up duration was 19 (4–37) months for LRT and 116 (46–160) months for ART. No recurrence was noted in the LRT group. In contrast, two patients encountered recurrences after ART. No deaths due to the disease occurred in either group.

Table 4 depicts a comparison of long-term postoperative complications between the two groups. The rate of postoperative cervical stenosis was significantly lower in the LRT group than in the ART group (0% vs. 47%, p = 0.03). Although postoperative molimina and lymphedema were not observed in LRT, they were observed in one (5%) and three (16%) patients, respectively, undergoing ART. No lymphocysts were observed in either group.

Table 5 indicates fertility treatment and obstetric outcome of 26 patients underwent radical trachelectomy. In the LRT group, among the 2 patients who wish prompt pregnancy, 1 received in vitro fertilization and embryo transfer (IVF-ET), and 1 spontaneous pregnancy was confirmed, which resulted in a live birth. In the ART group, among the 14 patients who wish prompt pregnancy, 11 received IVF-ET, and 8 pregnancies were observed in 6 patients. Two of these cases showed spontaneous abortion in the first trimester, and six resulted in births in 5 patients. There were no differences in the pregnancy rate in two groups (LRT: 50% vs. ART: 43%, p = 0.84). All deliveries were performed by cesarean section before 37 weeks of gestation. The median gestational weeks at the delivery was 36 weeks in the LRT group and 34 weeks (26–36 weeks) in the ART group. Regarding the prognosis of the children, cerebral palsy was seen in case 19. The others had normal development.

4. Discussion

In the current study, LRT resulted in less blood loss, a shorter hospital stay, and fewer postoperative complications than did ART, without any worsening of the oncological prognosis.

Different surgical approaches for the treatment of cervical cancer may produce different oncological outcomes, as demonstrated by the multicenter randomized LACC trial (LACC ClinicalTrials.gov number, NCT00614211) [23], which is the biggest prospective research to compare minimally invasive radical hysterectomy with abdominal radical hysterectomy. The LACC trial indicated that minimally invasive radical hysterectomy resulted in poorer oncological outcomes than did abdominal radical hysterectomy. Although the LACC trial examined radical hysterectomy, these data shed light on the surgical approaches to radical trachelectomy for early cervical cancer. In this study, the oncological results of LRT were similar to those of ART. We previously reported that surgical techniques and steps to avoid tumor cell spillover could be crucial for a favorable prognosis in laparoscopic radical hysterectomy [19]. Similarly, in this study, we performed LRT with rigorous uterine manipulator avoidance and used a vaginal cuff encapsulating the tumor to avoid the spillage of tumor cells. Recently, Han et al. [15], in their meta-analysis, analyzed 1079 patients who underwent minimally invasive radical trachelectomy (MIRT) or ART. They reported recurrence rates of 5.5% and 4.4% for MIRT and ART, respectively, and death rates of 1.4% and 2.3% for MIRT and ART, respectively, with no significant differences in overall survival (hazard ratio (HR), 0.51; 95% confidence interval (CI), 0.16–1.65; I² = 0.0%; p = 0.881), recurrence rate (RR, 1.26; 95% CI, 0.68–2.33; I² = 0.0%; p = 0.815) and death rates (RR, 0.54; 95% CI, 0.23–1.31; I² = 0.0%; p = 0.680) between MIRT and ART [15]. In previous reports, the use of a uterine manipulator and vaginal cuff varied. Vieira et al. [24] compared postoperative recurrence and death rates in cervical cancer patients who underwent LRT and ART. In their study, LRT was performed using a uterine manipulator and vaginal cuff. The results revealed that the recurrence and death rates of ART were 1.7% in a median follow-up period of 66 months; they reported no recurrence or death from LRT in a median follow-up period of 25 months. Miaochun et al. [25] reported no recurrence in patients who underwent LRT without the use of a uterine manipulator or vaginal cuff, with a median follow-up of 13.5 months. Our study also observed no LRT recurrence, consistent with the findings of the previous studies. Because LRT was introduced later than ART, the follow-up period tended to be shorter in the LRT group than in the ART group. Additionally, the recurrence rate was lower in patients undergoing radical trachelectomy. Therefore, comparison of the oncological prognosis between LRT and ART is difficult. However, considering the outcomes of the LACC trial, surgical techniques that avoid tumor spillage, such as uterine manipulator avoidance or vaginal closure as an oncological hygiene strategy, may have contributed to the lower recurrence rates of LRT. We suggest that a surgeon with laparoscopic experience and training in improved laparoscopic techniques that avoid tumor leakage can recommend LRT for early-stage cervical cancer patients. More prospective studies with larger sample sizes are needed to ascertain the oncological outcomes.

In previous studies, the mean operative times were 320 (210–410) min for MIRT and 192.5 (105–270) min for ART (p < 0.001) [26]. The mean blood loss was 50 (10–225) mL for MIRT and 300 (50–1100) mL for ART (p < 0.01) [24]. The mean length of hospital stay was 4 (2–6) days for MIRT and 7 (5–18) days for ART (p < 0.05) [26]. The significant differences in operative time, blood loss, and length of hospital stay between MIRT and ART reported in previous studies are consistent with our findings. It has been proven that LRT offers several advantages, such as good visualization, less blood loss and shorter hospital stays, although the surgical time of LRT is longer than that of ART. As LRT calls for sophisticated techniques, the laparoscopic approach may add to surgical difficulty and operation time if the surgeon is not skilled.

The rates of urinary tract complications were reported to be 13% for MIRT and 25% for ART (p = 0.81) [27]. In the present study, the voiding dysfunction rate was significantly lower in the LRT group (33.3%) than in the ART group (70%). The reasons for this are unknown; however, reliable preservation of the hypogastric and pelvic autonomic nerves through laparoscopic magnification may contribute to the low rate of voiding dysfunction in LRT. The rate of cervical stenosis has been reported to be 0% for MIRT and 13% for ART (p = 0.42) [26]. In the present study, the rate of cervical stenosis in the LRT group was 0%; however, it was 47% in the ART group. The method used to assess cervical stenosis differed between various studies. We considered cases with cervical stenosis as cases in which gynaecologists at our institution could not visually identify the cervical canal. This discrepancy may be attributed to several reasons. The incidence of cervical stenosis increases as the period after surgery increases in ART. In the present research, the observation period was significantly shorter in the LRT group, which may be related to the lower rate of cervical stenosis in the LRT group than in the ART group; hence, studies with longer observation periods are required.

According to a past report, the success rate of fertility was 28.6–33.3% with MIRT and 50.0–51.9% with ART. Term (RR, 0.44; 95% CI, 0.06–3.33; I² = 0.0%; p = 0.312) and preterm delivery rates (RR, 1.55; 95% CI, 0.19–13.04; I² = 0.0%; p = 0.172) did not differ significantly between MIRT and ART procedures [15]. He et al. [28] reported that all patients undergoing MIRT became pregnant through natural conception, and 50% of patients undergoing ART became pregnant through natural conception and 50% via IVF-ET. In the present study, the pregnancy rates did not differ significantly between the LRT and ART groups (50% vs. 43%, p = 0.84). One patient who underwent LRT became pregnant spontaneously and delivered preterm. In the ART group, six patients became pregnant and five patients underwent live births. All six patients who became pregnant required infertility treatment. All five patients had premature live births. In our facility, we allow patients to attempt to become pregnant starting at 6 months after surgery and carry out an infertility investigation if they do not become pregnant even after 1 year, or when the patient desires to receive such an investigation. However, considering the risk of recurrence, implementing infertility examinations early after surgery may be more beneficial. Moreover, the incidence of cervical stenosis, which can increase the use of assisted reproductive technology, increases as the period after surgery increases, allowing early pregnancy after surgery, which may lead to an increase in spontaneous pregnancies. All deliveries were performed before 37 weeks of gestation. This is because, to avoid emergency cesarean section, which increases surgical risks even in cases without obstetric complications, elective cesarean section was performed between 34 and 36 weeks of pregnancy, depending on the maturity of the fetus. All late preterm infants born via elective cesarean section presented normal development. Given the surgical risks, such as adhesions and anatomical complexity, cesarean sections should preferably be performed by doctors experienced in gynecologic oncologic surgery; therefore, we believe that elective cesarean sections against post-trachelectomy pregnancy in the late preterm are compromised.

Notably, almost 90% of cervical cancer cases and deaths happen in low-and middle-income countries (LMICs) [29] and this is attributable to the current inadequate infrastructure and human resources to perform standard treatments such as surgery, radiotherapy, chemotherapy and palliative care to meet population needs [30]. Moreover, there is a dearth of specialty trained gynecologic oncologists who can perform radical hysterectomy [31]. Under the circumstances, ART is expected to become the main approach of radical trachelectomy, but no reports on it have been published yet. Although many challenges, such as recruiting specialists, continuing long-term follow-up of patients, and ensuring early treatment in case of recurrence, remain unaddressed, popularizing this well-established procedure in LMICs would be highly desirable.

This research had some limitations. First, the sample size was small. Second, the follow-up duration in the LRT group was significantly shorter than that in the ART group. Third, allocation of patients to the LRT or ART groups involved potential bias. Finally, in LRT, sentinel lymph node biopsy was performed instead of pelvic lymph node dissection, which was conducted using ART. Therefore, the results are not definitive, and more prospective studies are needed to evaluate the effectiveness and safety of LRT for cervical cancer.

5. Conclusions

In conclusion, our outcomes indicate that LRT and ART have similar oncologic outcomes in treating patients with early-stage cervical cancer. Furthermore, LRT showed the advantages of minimally invasive surgery such as less blood loss, shorter hospital stay, and fewer postoperative complications. These findings imply that LRT is a useful approach as an alternative to ART. However, due to the small number of cases in this research, more investigations are needed.

Availability of data and materials

The data presented in this study are available on request from the corresponding author.

Author contributions

HM and TT—designed the research study. RN, HT, AT and SH—performed formal analysis. ST, HM, SF and YT—performed data curation. HM—wrote original draft. ST and TT—reviewed and edited the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

The study was conducted in accordance with the guidelines of the Declaration of Helsinki and approved by the Educational Foundation of Osaka Medical and Pharmaceutical University Clinical Research Review Board (IRB protocol ID: 2014-018, 2020-087 and 2023-220). All the patients provided documented informed consent for both ART and the use of their clinical data in this study.

Acknowledgment

We thank Junko Hayashi and Kumiko Satoh for their valuable secretarial assistance.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.