Morcellation worsens survival outcomes in patients with undiagnosed uterine leiomyosarcomas: A retrospective MITO group study

doi:10.1016/j.ygyno.2016.11.002

Gynecologic Oncology

Volume 144, Issue 1, January 2017, Pages 90-95

https://doi.org/10.1016/j.ygyno.2016.11.002 Get rights and content

Highlights

•
Morcellation worsens survival of patients affected by uterine leiomyosarcomas.
•
Effects of morcellation on STUMP and ESS need to be further evaluated.
•
The role of morcellation of apparent benign fibroids deserves further investigations.

Abstract

Objective

To investigate the impact of morcellation on survival outcomes of patients affected by undiagnosed uterine sarcoma.

Methods

This is a retrospective study performed in 8 referral centers of MITO group. Data of women undergoing morcellation for apparent benign uterine myomas who were ultimately diagnosed with stage I uterine sarcoma on final pathology were compared with data of women who did not undergo morcellation. Uterine sarcoma included: leiomyosarcomas (LMS), smooth muscle tumors of uncertain malignant potential (STUMP), low-grade endometrial stromal sarcomas (LG-ESS) and undifferentiated uterine sarcomas (UUS). Two-year survival outcomes were evaluated using Kaplan-Meir and Cox models.

Results

Overall 125 patients were identified: 31(24.8%), 21(16.8%) and 73(58.4%) patients had power morcellation during laparoscopy, non power morcellation during open surgery and non morcellation during open procedures, respectively. Considering patients affected by LMS, morcellation did not correlated with disease-free survival. However, patients undergoing either morcellation or power morcellation experienced a 3-fold increase risk of death in comparison to patients who had not morcellation (p = 0.02). A trend towards an increase of recurrence was observed for patients undergoing morcellation for STUMP (HR 7.7, p = 0.09); while no differences in survival outcomes were observed for patients with LG-ESS and UUS.

Conclusions

Our data suggest that morcellation increase the risk of death in patients affected by undiagnosed LMS. Further prospective studies are warranted in order to assess the risk to benefit ratio of power morcellator utilization in patients with apparent benign uterine myomas.

Introduction

Uterine leiomyosarcoma represents a rare entity, constituting about 1.5% of all uterine malignancies, with an estimated annual incidence of 0.64/100,000 women [1]. Excluding carcinosarcomas which are actually classified as undifferentiated carcinomas, leiomyosarcomas (LMSs) and stromal sarcomas account for about 70% and 30% of all uterine sarcomas, respectively [2].

The survival of patients with LMS is strongly associated with the FIGO stage of disease at diagnosis: Stage I tumors have a 5-year survival rate of 84.3%, that decreases dramatically in stage II (43.6%), III (38.8%), and IV (19.8%) respectively [2]. Unfortunately, preoperatively it may be difficult to discriminate between benign uterine fibroids and uterine sarcomas. The true prevalence of uterine sarcomas in presumed fibroids is not exactly known, given the wide range (0.45–0.014%) reported in meta-analyses mainly based on retrospective data [3], [4]. Moreover, although some patients' characteristics (including older age and the presence of symptoms) and morphological features of the uterine lesions at imaging may be suggestive for the presence of uterine sarcoma, a reliable differential diagnosis is still difficult [5].

In November 2014, the U.S. Food and Drug Administration (FDA) issued a safety communication against power morcellation; morcellation was “discouraged” due to its detrimental potential effects in patients with undiagnosed uterine sarcoma [6]. In fact, if a presumed fibroid reveals to be a sarcoma (or other malignancy), any method of morcellation disrupts the integrity of the tumor, thus possibly upstaging the disease and affecting survival. In case of power morcellation, the centripetal forces of the cylindrical knife may add to the phenomenon of ‘seeding’ of tumor cells on the peritoneum [7].

Thereafter, representatives of many scientific societies published their opinions on this issue concluding about the lack of solid scientific evidence to reach strong recommendations on the use of power morcellation [8]. In this retrospective study we sought to determine the oncologic outcome of undiagnosed uterine sarcoma in a large group of women who underwent morcellation in comparison to a group of patients treated without morcellation at 8 referral institutions of MITO (Multicentre Italian Trialists in Ovarian Cancer and Gynecologic Malignancies) group.

Section snippets

Materials and methods

This is a retrospective study performed in eight high volume centers hospitals of MITO group. The medical records of consecutive women who underwent surgical treatment for apparent benign uterine myomas that revealed to be sarcomas at final diagnosis from January 1, 2004, to December 31, 2014 were reviewed and Institutional review board (IRB) was obtained for the study. All patients included in the study gave written consent to data collection and to the use of personal records for health

Results

Overall, 4.000 surgical interventions for benign fibroids were performed in 10 years in the 8 centers participating the study. Among those, 125 patients (3.1%) affected by unexpected FIGO stage I uterine sarcomas were identified: 52 (41.6%) patients had morcellation and 73 (58.4%) had not. Patients characteristics are reported in Table 1.

Median age was 55 years and the majority (72.8%) of women had uterine LMS. In most part of patients undergoing morcellation (n = 31; 59.6%) surgery was performed

Discussion

This retrospective, multi-institutional study confirms the detrimental impact of morcellation on oncologic outcomes of patients diagnosed with unexpected uterine leiomyosarcoma. Our data report a 3 times higher risk of death in patients who had morcellation of undiagnosed LMS in comparison to patients who had no morcellation.

Recently, the FDA claimed on the prognostic impact of morcellation of unexpected sarcomas. FDA warning was based on a pooled analysis of retrospective studies suggesting

Disclosure

The Authors declare no conflicts of interest. No funding sources supported this investigation.

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FDA Discourages Use of Laparoscopic Power Morcellation for Removal of Uterus or Uterine Fibroids

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A human-interpretable machine learning pipeline based on ultrasound to support leiomyosarcoma diagnosis
2023, Artificial Intelligence in Medicine
The preoperative evaluation of myometrial tumors is essential to avoid delayed treatment and to establish the appropriate surgical approach. Specifically, the differential diagnosis of leiomyosarcoma (LMS) is particularly challenging due to the overlapping of clinical, laboratory and ultrasound features between fibroids and LMS. In this work, we present a human-interpretable machine learning (ML) pipeline to support the preoperative differential diagnosis of LMS from leiomyomas, based on both clinical data and gynecological ultrasound assessment of 68 patients (8 with LMS diagnosis). The pipeline provides the following novel contributions: (i) end-users have been involved both in the definition of the ML tasks and in the evaluation of the overall approach; (ii) clinical specialists get a full understanding of both the decision-making mechanisms of the ML algorithms and the impact of the features on each automatic decision. Moreover, the proposed pipeline addresses some of the problems concerning both the imbalance of the two classes by analyzing and selecting the best combination of the synthetic oversampling strategy of the minority class and the classification algorithm among different choices, and the explainability of the features at global and local levels. The results show very high performance of the best strategy (AUC = 0.99, F1 = 0.87) and the strong and stable impact of two ultrasound-based features (i.e., tumor borders and consistency of the lesions). Furthermore, the SHAP algorithm was exploited to quantify the impact of the features at the local level and a specific module was developed to provide a template-based natural language (NL) translation of the explanations for enhancing their interpretability and fostering the use of ML in the clinical setting.
Uterine sarcomas: A critical review of the literature
2023, European Journal of Obstetrics and Gynecology and Reproductive Biology
This review aims to provide a comprehensive description of surgical approaches for the management of uterine sarcomas. Uterine sarcomas are rare uterine neoplasms. Frequently, diagnosis is made after hysterectomy or myomectomy scheduled for presumed benign leiomyomas. The gold standard for surgical treatment of uterine sarcomas is hysterectomy with bilateral salpingo-oophorectomy. It is possible to adopt a fertility-sparing approach for those patients who wish to maintain their fertility. The role of pelvic lymphadenectomy is controversial; in fact, removal of lymph nodes is only recommended in the case of radiological suspicion of nodal involvement. Use of a morcellator is associated with increased risk of total recurrence, intra-abdominal recurrence and death. Advanced disease management should be customized based on the patient’s performance status given the uncertain role of adjuvant chemotherapy. Treatment of advanced or recurrent disease remains a subject of debate, but surgery is the best approach in terms of morbidity and mortality. There are few options for management of these uterine tumours, and further studies are needed to clarify the diagnostic and therapeutic pathways of patients with a first diagnosis of uterine sarcoma and patients with relapse of uterine sarcoma. No specific evidence supports the adoption of adjuvant therapy in uterine-confined disease, and molecular/genomic profiling may be useful to identify patients at risk of recurrence.
Uterine leiomyosarcoma – French guidelines from the GSF/NETSARC and TMRG groups
2023, Bulletin du Cancer
Les léiomyosarcomes utérins sont les sarcomes utérins les plus fréquents. Ils touchent surtout la femme ménopausée. Le pronostic est médiocre avec une récidive métastatique dans plus de la moitié des cas. L’objet de cette revue est d’effectuer des recommandations françaises communes de prise en charge des léiomyosarcomes utérins dans le cadre des réseaux Groupe Sarcome Français - Groupe d’Étude des Tumeurs Osseuse (GSF-GETO)/NETSARC+ et Tumeurs Malignes Rares Gynécologiques (TMRG) afin d’unifier leur prise en charge thérapeutique. Le bilan initial comprend une IRM avec séquence de diffusion et de perfusion en plus d’une échographie. Le diagnostic est histologique avec une relecture en centre expert des sarcomes (Réseau de Référence en Pathologie des Sarcomes (RRePS)). L’hystérectomie totale avec salpingectomie bilatérale, en bloc c’est-à-dire sans morcellement, est réalisée dès lors que la résection complète est possible, quel que soit le stade. Le curage ganglionnaire est indiqué uniquement en cas d’adénopathie macroscopiquement visible. L’ovariectomie bilatérale est indiquée chez les femmes en péri-ménopause ou ménopausées. La radiothérapie externe adjuvante n’est pas un traitement standard. Elle peut être indiquée de façon individualisée après discussion en réunion de concertation pluridisciplinaire en cas d’exérèse incomplète. La chimiothérapie adjuvante n’est pas un traitement standard. Elle peut représenter une option à partir des stades III et repose sur des protocoles à base de doxorubucine. En cas de récidive locale, les options thérapeutiques reposent sur une reprise chirurgicale, et/ou une radiothérapie en l’absence d’irradiation antérieure. Un traitement systémique par chimiothérapie est le plus souvent indiqué. En cas de maladie métastatique, le traitement chirurgical se discute systématiquement lorsque la maladie est résécable. En cas de maladie oligo-métastatique, le traitement focal des métastases doit être envisagé. En cas de stade IV, après diagnostic histologique confirmé par pathologiste de référence, une chimiothérapie est indiquée, et repose sur des protocoles à base de doxorubicine en première ligne. La doxorubicine, la dacarbazine, la trabectédine, la gemcitabine seule ou en association avec le docétaxel ou le DTIC et le pazopanib sont des médicaments actifs qui peuvent être utilisés en première ligne et au-delà. En cas d’altération de l’état général trop importante, une prise en charge par soins de support exclusifs est recommandée. Une radiothérapie palliative externe peut être proposée à visée symptomatique.
Uterine leiomyosarcomas represent the most common uterine sarcomas. The prognosis is poor with metastatic recurrence in more than half of the cases. The purpose of this review is to make French recommendations for the management of uterine leiomyosarcomas within the framework of the French Sarcoma Group - Bone Tumor Study Group (GSF-GETO)/NETSARC+ and Malignant Rare Gynecological Tumors (TMRG) networks in order to optimize their therapeutic management. The initial assessment includes a MRI with diffusion perfusion sequence. The diagnosis is histological with a review in an expert center (Reference Network in Sarcoma Pathology (RRePS)). Total hysterectomy with bilateral salpingectomy, en bloc without morcellation, is performed when complete resection is possible, whatever the stage. There is no indication of systematic lymph node dissection. Bilateral oophorectomy is indicated in peri-menopausal or menopausal women. Adjuvant external radiotherapy is not a standard. Adjuvant chemotherapy is not a standard. It can be an option and consists in doxorobucin based protocols. In the event of local recurrence, the therapeutic options are based on revision surgery and/or radiotherapy. Systemic treatment with chemotherapy is most often indicated. In case of metastatic disease, surgical treatment remains indicated when resecable. In cases of oligo-metastatic disease, focal treatment of metastases should be considered. In the case of stage IV, chemotherapy is indicated, and is based on first-line doxorubicin-based protocols. In the event of excessive deterioration in general condition, management by exclusive supportive care is recommended. External palliative radiotherapy can be proposed for symptomatic purposes.
Other rare uterine sarcomas: Adenosarcoma, endometrial stromal sarcoma, STUMP
2023, Diagnosis and Treatment of Rare Gynecologic Cancers
Uterine sarcomas are rare entities, representing only 1% of all gynecologic malignancies, and 3% of all uterine cancers. Uterine sarcomas are comprised of different subtypes, the most common being uterine leiomyosarcoma (25%–60% cases), endometrial stromal sarcoma (10–20% cases), high-grade undifferentiated sarcoma (3%–5% cases), and uterine adenosarcoma (5–9% cases). The mortality rate associated with uterine sarcomas is much higher than their endometrial cancer counterparts, which has been mostly driven by high-risk uterine leiomyosarcoma. Five-year overall survival rates have been reported between 25% and 80%, depending on sarcoma histologic subtype and stage. There have been no significant differences in incidences of these rare uterine sarcomas by ethnicity. Given the limited numbers of patients that incur this diagnosis annually, challenges exist in preoperative diagnosis, workup, and treatment of these rare tumors. Universal adoption of adjuvant treatment strategies following surgical management has also been limited given lack of prospective clinical trials in these tumors. Thus, majority of treatment recommendations have been based on review of available data and consensus agreements. In this chapter, we will focus specifically on the rare uterine sarcoma subtypes of adenosarcoma, endometrial stromal sarcoma, and smooth muscle tumors of uncertain malignant potential (STUMP).
SELNET clinical practice guidelines for soft tissue sarcoma and GIST
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Endometrial Sampling for Preoperative Diagnosis of Uterine Leiomyosarcoma
2022, Journal of Minimally Invasive Gynecology
To examine the effectiveness of endometrial sampling for preoperative detection of uterine leiomyosarcoma in women undergoing hysterectomy, identify factors associated with missed diagnosis, and compare the outcomes of patients who had a preoperative diagnosis with those of patients who had a missed diagnosis.
Retrospective cohort study using linked data from the New York Statewide Planning and Research Cooperative System and New York State Cancer Registry from 2003 to 2015.
Inpatient and outpatient encounters at civilian hospitals and ambulatory surgery centers in New York State.
Women with uterine leiomyosarcoma who underwent a hysterectomy and a preoperative endometrial sampling within 90 days before the hysterectomy.
Endometrial sampling.
A total of 79 patients with uterine leiomyosarcoma met the sample eligibility criteria. Of these patients, 46 (58.2%) were diagnosed preoperatively, and 33 (41.8%) were diagnosed postoperatively. Patients in the 2 groups did not differ significantly in age, race/ethnicity, bleeding symptoms, or comorbidities assessed. In multivariable regression analysis, women who had endometrial sampling performed with hysteroscopy (compared with women who had endeometrial sampling performed without hysteroscopy) had a higher likelihood of preoperative diagnosis (adjusted risk ratio [aRR] 3.03; 95% confidence interval [CI], 1.43–6.42). Patients with localized stage (vs distant stage) or tumor size >11 cm (vs <8 cm) were less likely to be diagnosed preoperatively (aRR 0.50; 95% CI, 0.28–0.89, and aRR 0.54; 95% CI, 0.30–0.99, respectively). Supracervical hysterectomy was not performed in any of the patients whose leiomyosarcoma was diagnosed preoperatively compared with 21.2% of the patients who were diagnosed postoperatively (p = .002).
Endometrial sampling detected leiomyosarcoma preoperatively in 58.2% of the patients. The use of hysteroscopy with endometrial sampling improved preoperative detection of leiomyosarcoma by threefold. Patients with a missed diagnosis had a higher risk of undergoing suboptimal surgical management at the time of their index surgery.

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Morcellation worsens survival outcomes in patients with undiagnosed uterine leiomyosarcomas: A retrospective MITO group study

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Materials and methods

Results

Discussion

Disclosure

Gynecol. Oncol.

Int. J. Gynaecol. Obstet.

Am. J. Obstet. Gynecol.

Am. J. Obstet. Gynecol.

Gynecol. Oncol.

Lancet Oncol

Am. J. Obstet. Gynecol.

J. Minim. Invasive Gynecol.

Gynecol. Oncol.

J. Minim. Invasive Gynecol.

The epidemiology of sarcomas of the uterus

J. Natl. Cancer Inst.

Uterine sarcomas: clinical features and management

Malignancy rate of 10,731 uteri morcellated during laparoscopic supracervical hysterectomy in 2013

Arch. Gynecol. Obstet.

Leiomyosarcoma in a series of hysterectomies performed for presumed uterine leiomyomas

Am. J. Obstet. Gynecol.

FDA Discourages Use of Laparoscopic Power Morcellation for Removal of Uterus or Uterine Fibroids