Long-term outcomes of pelvic exenterations for gynecological malignancies: a single-center retrospective cohort study

Pelvic exenteration (PE) is a radical surgical procedure involving the resection of multiple endopelvic and extra-pelvic organs, originally introduced by Alexander Brunschwig in 1948 as a palliative treatment for cervical cancer patients with residual or recurrent disease post-radiotherapy [1, 2]. PE used to have a high perioperative mortality rate but failed to achieve satisfactory survival [3, 4].

In the past decades, with the optimization of candidate selecting and the advancement of medical technology, the mortality of PE has descended to less than 5%, and the 5-year survival rate could reach 20%-72.6% [5‐8]. This remarkable progress has repositioned PE from a palliative intervention to a radical treatment approach for certain cases of recurrent or locally advanced gynecological malignancies, particularly in scenarios where no other equally effective treatment alternative is available. The rationale behind this transition lies in the more rigorous patient selection process, which meticulously assesses the extent of disease involvement, patients' overall health status, and potential postoperative recovery. Advancements in surgical techniques, particularly the introduction of minimally invasive approaches, have further revolutionized PE. Traditional laparoscopic and robot-assisted laparoscopic surgery have become viable surgical options for PE. These approaches aim to reduce morbidity, enhance postoperative quality of life, and improve overall outcomes [9‐12].

Despite significant strides in enhancing the surgical outcomes of PE, it remains a complex and demanding procedure necessitating a high degree of technical skill and extensive experience from the surgical team. Consequently, its application has been more limited in developing countries.

Here, we retrospectively investigated the safety and long-term survival outcome of PE as well as the feasibility of minimal invasive PE for gynecologic malignancies in a single medical center in China, aiming to provide more evidence for the clinical application of PE.

Despite its high morbidity and mortality, pelvic exenteration remains a critical treatment option for patients with locally advanced gynecological tumors. Given the complexity and systemic nature of PE, involving multi-organ resection, the careful selection of candidates and the expertise of the surgical team are crucial in reducing the incidence of associated complications. Additionally, the advancement of surgical techniques contributes to improving the quality of the operation. Our current study suggested that PE was safe for patients evaluated through a multi-disciplinary treatment approach, with some achieving long-term survival post-procedure. We also observed that umbilical single-port laparoscopy may be a technically feasible option for APE, meriting further investigation.

The primary indication of PE is locally advanced or recurrent cervical cancer [14]. Cervical cancer was also the major disease in the current study, accounting for 87.8%. Consistent with this, cervical cancer constituted 87.8% of cases in our study, with most patients having a history of previous treatment, including 90.2% who received radiotherapy. This underscores that PE’s main role remains as palliative treatment for cervical cancer patients unresponsive to radiotherapy.

Previous studies [5, 15] have reported that about 7.7%-18% of patients found extra-pelvic metastases during the procedure and then finally gave up the operation. In the current study, only 2 cases (4.9%) of extra-pelvic metastases were found during the operation, suggesting that the preoperative screening and selection was strict. And multi-disciplinary team (MDT) assessment before the procedure is highly recommended.

Pelvic wall involvement was once considered a contraindication for PE due to the difficulty in achieving radical resection. However, assessing pelvic wall involvement based solely on gynecological examination can be subjective. Post-radiotherapy fibrosis of the pelvic wall tissues may affect preoperative evaluations. Several studies have indicated that patients with pelvic wall recurrence can still benefit from PE [8, 16, 17]. Jurado et al. [5] found that R0 resection was achieved in 28.6% of the patients with lateral recurrences and the 10-year disease-specific survival rate of those patients was 33.3%, which was not significantly different from that of patients with central recurrence. In a retrospective study of Höckel et al. [18], 67 cases in 91 patients with locally advanced or recurrent cervical cancer or vaginal cancer underwent laterally extended endopelvic resection (LEER) were found tumor fixed to the pelvic wall. And all the procedures were performed successfully, with a mortality and morbidity of 2% and 70% respectively, and the locoregional tumor control rate reached 92%. Their R0 resections involved extended pelvic wall muscle resection, aligning with the surgical principle in our study, which advocates for as extensive as possible removal of involved pelvic wall muscle to ensure negative margins, based on pelvic devascularization resection.

In our study, two patients with FIGO stage IV A cervical cancer underwent APE. These patients presented with vesicovaginal fistula and bilateral renal dysfunction, respectively. While surgery was not the first-line treatment option, after extensive discussions, both patients and their families opted for surgical intervention, seeking symptom relief. Postoperatively, they received adjuvant radiotherapy and chemoradiation, respectively. Up to the last follow-up, no recurrence was observed in these cases. The decision to perform PE in stage IV A cervical cancer patients remains a topic of debate [19‐21]. A study by Marnitz et al. [20] showed that 43% of German surgeons would opt for PE in such cases. This percentage increases to 61% if pre-surgery tumor-related fistulas and severe local symptoms are present, with a 5-year overall survival rate of 52.5% when PE is utilized as the initial treatment modality [21]. Currently, platinum-based concurrent radiotherapy and chemotherapy remain the standard care for stage IV A cervical cancer. However, for certain patients suffering from fistulas and severe locoregional symptoms, PE, following thorough evaluation and detailed communication, stands as a viable and safe alternative.

Ovarian cancer, endometrial cancer and carcinosarcoma often have a tendency of distant metastasis. Whether PE should be performed for those patients remains controversial. In the current study, 1 patient underwent PPE due to recurrent endometrial adenocarcinoma, and 1 patient underwent APE due to recurrent endometrial stromal sarcoma. No preoperative distant metastasis or positive lymph node was found by physical examination and imaging examination, and both of them received radiotherapy after the surgery. No recurrence was found by the time of the last follow-up. Khoury-Collado et al. [22] suggested that PE was a feasible treatment for patients with endometrioid adenocarcinoma and low-grade sarcoma. Seagle et al. [23] showed that for patients of uterine malignancies undergoing PE, if the lymph nodes confirmed positive, the OS was significantly shorter than that of patients with negative lymph node. Similarly, the OS of patients with distant metastases was also significantly shorter than that of patients without distant metastases. In view of these evidences, positive lymph nodes and distant metastasis should be a contraindication for PE in such patients.

In the current study, the median operation time was similar to previous studies, while the median blood loss and length of postoperative hospital stay were comparatively lower [5, 20, 24, 25]. Notably, we found that the years of the operation was significantly related to the operation time, suggesting a learning curve for PE and emphasizing the importance of the surgical team’s experience. Previous studies have demonstrated that increased surgical team experience leads to reduced morbidity, shorter ICU stays, decreased costs, and lower perioperative mortality rates in medical centers with extensive PE experience [26, 27]. Such hospitals had more experience in complicated and major surgeries and most of them were teaching hospitals, which were armed with rich medical resources, so that they were more capable to deal with severe complications.

With the improvement of the medical care, the morbidity of PE and the perioperative mortality have gradually descended [3, 24, 28]. The morbidity of PE was 30% to 82% according to literature [7, 14, 16, 29, 30]. And the mortality has dropped to 2%-4% [31, 32]. In our study, the overall morbidity was 52.4%, with grade III and higher complications occurring in 24% of cases. The incidence of pelvic and abdominal infection was the highest in both short-term and long-term complications. One patient died 38 days after the procedure due to sepsis and MODS. Part of the patients (21.4%) had infections and fistulas before the surgeries, and the long operation time and large surgical wounds of PE may lead to the spread of infections. In addition, urinary tract or/and digestive tract reconstruction, drainage in the pelvic and abdominal for a long time, and the worsened nutritional status due to delayed post-surgery gastrointestinal recovery, are possibly related to the high incidence of infection after PE. Our findings indicate a significant association between the year of surgery and the occurrence of major complications, further highlighting the critical role of the surgical team's experience. With the improvement of surgical techniques, the increasingly strict selection of patients and more reasonable application of antibiotics, the incidence of perioperative infection has gradually decreased [33]. There was no perioperative death, which preliminarily showed that PE was safe and feasible for strictly selected patients.

Recently, laparoscopic PE has been performing with the intention to reduce the morbidity and laparoscopic and robotic surgeries have become one of the alternative methods for PE [9, 12, 34]. As Martínez et al. [11] reported, there was no significant difference between patients received laparoscopic and open PE in perioperative morbidity, operation time, the length of hospital stays, and OS, but patients received laparoscopic PE had less intraoperative blood loss and lower blood transfusion rate. The study of Bizzarri et al. [35] suggested that the perioperative morbidity of minimally invasive PE was lower than that of open PE and intraoperative blood loss was less. In addition, laparoendoscopic single site surgery has been widely used in gynecology. Besides the advantages of traditional laparoscopy, LESS has the advantages of better cosmetic effects, less puncture-related complications and postoperative pain. The incisions required for open PE are typically extensive, increasing the likelihood of wound complications. In contrast, trans-umbilical laparoendoscopic single-site (LESS) surgery involves a solitary incision at the umbilicus, potentially reducing the risk of such issues. In our current study, we successfully performed three trans-umbilical LESS anterior pelvic exenterations (APE) without any intraoperative complications. Notably, the intraoperative blood loss in these cases was significantly lower than in open APE. Furthermore, no recurrence was observed up to the last follow-up. To the best of our knowledge, this represented the first report of trans-umbilical LESS PE and further evidence is warranted to verify the feasibility. However, it becomes difficult to identify tumor and normal tissue owing to the lack of feedbacks in laparoscope, and thus sometimes it is hard to determine the range of resection. Therefore, the assessment of the relationship between the tumor and the pelvic wall is important. It is not suitable for tumors which is tightly fixed to the pelvic wall to receive laparoscopic PE. Patients with large residual lesions and severe pelvic-abdominal adhesions, as discovered during exploration, were not suitable candidates for LESS. For such patients, conversion to open surgery should be considered. Moreover, studies [36, 37] have pointed out that for patients with early-staged cervical cancer, the prognosis of receiving minimally invasive surgeries is worse than that of open surgeries. The effect of laparoscopic PE remains to be further observed and studied.

There were several limitations to our study. First, this study was a retrospective single-center study, which has inherent biases. Second, the sample size of the study was relatively small, limiting the generalizability of the findings. Lastly, this study included multiple cancer types, and further analysis specifically focusing on cervical cancer is needed.

In this study, we conducted a retrospective analysis on the safety and long-term survival outcomes of pelvic exenteration (PE), as well as the feasibility of minimally invasive PE, in treating gynecologic malignancies at a single medical center in China. Our results suggested that PE was safe for patients assessed by the multi-disciplinary treatment. Some patients could achieve long-term survival after the procedure. In addition, our study provided preliminary evidence that umbilical single-port laparoscopy was a technically feasible approach for APE and further investigation was warranted.