1 Introduction

Soft Tissue Sarcomas (STSs) are a heterogeneous group of malignant tumors originating from various soft tissues, such as muscles, adipose tissue, nerves, and blood vessels. When localized in the groin area, they are considered a distinct subset due to their peculiar anatomical location, unique diagnostic and management challenges.¹

This region is particularly complex from an anatomical perspective, given the tumor's proximity to blood vessels, nerves, muscles, and bones (Fig. 1).

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Fig. 1 The proximal adductor area of the thigh; the close proximity to the femoral artery (A) and vein (V), the sciatic (S) and the femoral (F) nerves, the ileum and ischium-pubic rami, and the femur are factors contributing to the challenging surgical approach.

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Furthermore, the rich lymphatic drainage contributes to the high frequency of seromas and complications related to wound healing, as documented in the literature.^1,2

Understanding the specific characteristics of these tumors is essential, due to their potential aggressiveness and the diagnostic and therapeutic challenges they may pose. Early and accurate diagnosis, followed by prompt targeted treatment, are crucial to enhance survival chances and, if possible, preserve the functionality of the adductor region of the thigh.

Moreover, surgeries for these tumors often exhibit elevated postoperative complication rates (ranging from 20% to 68%) along with significant local recurrence rates (ranging from 16% to 48%) compared to their counterparts located in other limb sites.^3,4 This tendency could potentially be correlated to the latent and asymptomatic growth of STSs, resulting in substantial enlargement before diagnosis and consequently adding complexity to surgical management. The purpose of this paper is to analyze a series of 43 patients with soft tissue sarcomas of the adductor area of the thigh, elucidating the epidemiology, patients' ages, sex, diagnosis, including specific histotype, diagnostic and therapeutic approaches. We focus on the surgical treatment and related complications and on the patients’ outcomes, aiming to identify any possible prognostic factors and patients at high risk of postoperative complications.

2 Patients and methods

The series comprises all consecutive patients who underwent surgeries for primary STSs of the groin and adductor area between October 2006 and March 2022 in a tertiary research hospital. Exclusion criteria included benign tumors and patients with incomplete data.

Diagnoses were achieved through free-hand biopsies for large and palpable masses, utilizing a rongeur insert through a minimal incision⁵ or through CT-guided or ultrasound-guided trocar biopsies for smaller and deeper tumors.

The surgical team that conducted the biopsies also performed the subsequent surgeries. All histologies were evaluated by an expert pathologist, trained in musculoskeletal oncology. Histologies were succinctly classified into high-grade and low-grade based on their biological behavior.

Gadolinium-contrasted thigh MRI was performed to assess the mass and its relationship with the neurovascular bundles and bone surfaces, whereas staging for metastases was completed with a total-body CT scan or an FDG-PET scan (Fig. 2).

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Fig. 2 A pleomorphic liposarcoma in the adductor area adhering to the femur and closely associated with the sciatic nerve; the femoral neurovascular bundle is safeguarded by the adductor longus.

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The tumor volume was measured reconducting it's shape to an ellipse and evaluating the length of the three major axes. The distance from the skin was considered the minimal distance measured on the axial MRI. The Enneking staging system was used for tumor grading and to describe their extension.⁶ All cases were discussed in a multidisciplinary meeting to assess surgical indication and timing.

Antibiotic prophylaxis with cephazolin 1g was initiated upon the commencement of anesthesia and was subsequently administered every 8 h; this regimen was extended for three days postoperatively. Specific antibiotic treatment was planned if necessary.

Prophylactic administration of low molecular weight heparin was initiated a day before surgery. In cases of possible vessel compression by the tumor, heparin administration was prescribed immediately at the first observation.

Surgical procedures were performed by a consistent team of proficient oncological surgeons. When a vascular bypass was required, a vascular surgeon was also enlisted.

For conservative surgeries, patients were positioned supinely with abducted hips. Flexion was introduced when dealing with tumors located in the posterior-medial aspect of the thigh, particularly when the ischium was involved. The incision site was meticulously planned, considering the tumor's specific anatomical location, with special attention given to excising the biopsy tract. In scenarios requiring hip disarticulation or inter-ileo-abdominal amputation, patients were positioned supine or, respectively, in a “floppy lateral” posture.

Early mobilization of patients was prioritized to minimize muscular atrophy and complications stemming from prolonged immobilization. Nonetheless, weight-bearing was allowed solely after complete wound healing.

Pathology specimens were analyzed by the same pathologist who examined the biopsies. Surgical margins were categorized as wide, marginal, or intralesional.

Complications were classified as “early” or “late” based on whether they manifested within or after 30 days following surgery, respectively. Wound dehiscence was defined as a partial or complete separation of wound edges, often attributable to ischemic or infectious issues.

Blood loss was categorized as “hemorrhage” when surgical intervention was imperative for its resolution, and as “anemia” when it only required blood transfusion support.

Respiratory complications encompassed pulmonary lacerations, pneumonia, and pulmonary embolism. Urological issues included urethral damage.

The Clavien-Dindo classification was used to grade the severity of complications.⁷

Follow-up appointments were scheduled at three-month intervals for the initial two years, every four months in the third year, and semiannually during the fourth and fifth years for high-grade histologies. Subsequently, annual appointments were arranged for an additional five years. For low-grade tumors, follow-up appointments were set at four-month intervals during the first year, subsequently every six months until the fifth year and then annually for the following five years. Nevertheless, deviations in the follow-up schedule were conceivable based on distinct histologies and individual considerations.

The functional results were assessed using the Musculoskeletal Tumor Society (MSTS) Score and the Toronto Extremity Salvage Score (TESS) for the lower limb.^8,9

3 Results

3.2

3.2 Site and involvements

The predominant tumor location was the anterior-medial region of the adductor area in 40 patients, while three cases exhibited involvement of the posterior-medial segment. Tumors were located in the proximal third of the thigh in 10 patients, in the middle third in 11 cases, in the proximal and middle third in 6 cases whereas in the middle and distal third in 7 cases. The entire medial compartment was compromised in 9 cases. The average tumor volume was 959.05 cm³ (range: 31–4337 cm³, median: 550.00 cm³).

Sarcomas adhered to the femur in 13 cases, three of them had also invaded the ileum and ischium-pubic rami. In one case, the tumor only adhered to the ileum and ischium-pubic rami. The femoral vascular bundles were involved in 22 cases, with varying degrees. The femoral nerve was compromised in 14 cases (Fig. 3), and in three of these cases, the sciatic nerve also adhered. The sciatic nerve alone was involved in six cases.

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Fig. 3 An intraoperative image depicting the compromise of the femoral nerve (F); the soft tissue sarcoma (STS) was in contact with the femoral artery (A) and vein (V), both of which were easily dissected by the tumor.

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In the case with the second most bulky tumor of the series, both the sciatic and the femoral nerves, as well as the femur and pelvic bones and the vascular bundles were involved. The minimal distance from the skin surface was available for 24 patients, with an average value of 13 mm (range: 0–47, median: 8).

3.13

3.13 Recurrences

Four local recurrences were reported at 3, 10, 11, and 20 months from index surgeries, all in cases with high-grade tumors. They were located in the proximal third of the thigh, the whole medial compartment of the thigh, and two in the medial third of the thigh. Both the specific site and adherence to the femur were not statistically associated with the recurrence rate (p: 0.999 and 0.572, respectively). The 5-year local recurrence-free survival was 89.0%; the related Kaplan-Meier curve is shown in Fig. 4.

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Fig. 4 The Kaplan-Meier curves related to the LRFS, DMFS, OS and DRS.

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4 Discussion

Soft tissue sarcomas are quite rare, comprising only 1% of the spectrum of adult malignant tumors. In Europe, the annual occurrence of STSs stands at a rate of 4.5 fresh occurrences per 100,000 inhabitants.¹⁰ The concern of STS arises in patients who manifest a soft tissue mass exceeding 5 cm, characterized by either progressive enlargement or a subfascial location, irrespective of the presence of pain.

The treatment is centered on the diagnosis, which must be histologically based to perform possible neoadjuvant treatment such as chemotherapy and, most recently, radiotherapy. Biopsy is a mandatory step and must be carried out considering the surgical incision; in this series, biopsy demonstrated to be effective in choosing the right surgical approach. Indeed, if the determination of the specific histology was verified in 78.7% of cases, the right grade was detected in 93.1% of cases, allowing for a correct multimodal approach.

While low-grade sarcomas can often be managed through direct surgical excision with a wide margin, high-grade tumors may necessitate neoadjuvant interventions such as radiotherapy, chemotherapy, or a combination of both.

The decision regarding the implementation of preoperative treatment is contingent upon various patient-specific factors, including age, performance status, and disease attributes such as location in relation to the fascia, diameter (whether greater or less than 5 cm), and the availability of effective treatments or experimental protocols.

Currently, the standard treatment for localized soft tissue sarcomas is surgery, as stated by the guidelines of the National Comprehensive Cancer Network.¹¹

Additionally, the guidelines suggest contemplating neoadjuvant or postoperative adjuvant chemotherapy as potential choices for addressing high-grade and sizable tumors. Given the conflicting outcomes documented in clinical trials examining perioperative chemotherapy for localized STSs, the guideline acknowledges the existing evidence and consensus as falling under category 2B classification. A combination of anthracycline and ifosfamide is recommended.¹²

The guidelines of The European Society of Medical Oncology do not consider perioperative chemotherapy as a routine treatment but as a potential option for high-risk patients.¹³

Neoadjuvant chemotherapy presents the possible advantage of decreasing the tumor size, allowing for a safer, easier, and less invasive surgery. This concept is particularly crucial for STSs of the groin and adductor area, where a significant effect on tumor size could mean sparing neurovascular bundles. Nevertheless, it is crucial that the patient's overall health status and age permit the administration of neoadjuvant treatment at a full dose to be effective. Otherwise, such an approach could merely result in postponing surgeries and potentially exacerbating the patient's frailty.

In the present series, among the 32 patients affected by high-grade histologies, chemotherapy was performed in 16 cases, including neoadjuvant in nine cases, both neoadjuvant and adjuvant in two cases, and only adjuvant in five cases.

Advanced age is the primary reason for not performing chemotherapy; 11 out of 32 patients did not undergo chemotherapy due to age limitations, one patient had a chemo-resistant histology (extra-skeletal myxoid chondrosarcoma), two patients died from complications in the immediate postoperative months, and 2 patients were in poor clinical conditions.

Radiotherapy has emerged as a cornerstone in achieving effective local control in STSs of the groin. The anatomical constraints and proximity to vital structures often make achieving clean surgical margins challenging. The adjunctive use of radiotherapy allows for dose escalation to the tumor while sparing surrounding healthy tissues. This approach enhances the chances of achieving complete local control and minimizes the risk of local recurrence.

Radiotherapy is typically recommended for cases involving high-grade radiosensitive tumors exceeding 5 cm in size and situated deep to the muscular fasciae. Currently, despite the availability of numerous schedules in the literature, definitive treatment protocols remain somewhat ambiguous. While chemotherapy is typically reserved for high-grade tumors, radiotherapy is deemed appropriate for both low-grade and high-grade histologies. In the current series, radiotherapy was administered for low-grade tumors intraoperatively and postoperatively in one and three cases, respectively.

Recent studies emphasize the significance of neoadjuvant radiotherapy in minimizing the extent of irradiated tissue and facilitating a reduction in tumor size, thereby enabling the preservation of adjacent structures.¹⁴ However, it is important to acknowledge the potential increment in postoperative complications, particularly wound dehiscence, edema, and lymphedema, which are among the challenges associated with irradiation of the groin area.

Furthermore, the optimal timing for surgery after neoadjuvant treatment remains uncertain. The chronology of radiation, chemotherapy, and surgical resection appears to have no influence on the success of reconstructive procedures, such as microsurgical tissue transfers. Most surgeons prefer postoperative radiation because it may have decreased risks of wound complications. In cases of neoadjuvant radiation, free flaps may be performed for soft-tissue reconstruction. Several studies have shown superior functional outcomes with preoperative, rather than postoperative radiotherapy. Pre- and postoperative irradiation mainly affects plastic surgery procedures in terms of impaired wound healing and fibrosis.^15,16

Obviously, postoperative radiotherapy does not interfere with surgery; however, its administration should ideally follow complete wound closure to mitigate any associated complications that might hinder its implementation. Additionally, it is crucial to extend the radiation field to encompass the entire operative site rather than focusing solely on the area of the mass.

Intraoperative and postoperative radiotherapy is advisable, especially when the quality of the margin was judged at risk of local relapse. Surgery results are fundamental, and the obtained margin can be considered the main prognostic factor.

Kikuta et al. retrospectively analyzed 30 patients with recurrent MFS. They described a 5-year recurrence-free survival rate of 9.8% and 62.3% for those with a positive histological margin and those with a negative margin, respectively. These data indicate that a positive margin is a significant predictor of a poor prognosis.¹⁷

This series demonstrates that STSs of the groin area are correctly approached when all professional figures are present, and surgeries are programmed. An oncologically adequate margin was obtained in all our cases, thanks to the possibility to perform vascular bypass or resect the bone when necessary. The thigh is the most common site for STSs, particularly the adductor area.¹⁸

The present series confirms this data, considering that more than 90% of tumors are located in the medial aspect. Tumors located in this area can consistently increase their size before becoming symptomatic; indeed, the main symptom is sensing the mass, followed by local pain in the late stages.

Vessel compromise is quite common, given that there is contact with the main vascular bundle in more than 50% of tumors; nevertheless, in most cases, they are cleavable, and vascular bypass is rarely necessary (three out of 42 patients). The choice to perform it is not yet codified in the literature; it depends on the extent of tumor contact and specific histologies; a low-grade tumor allows for vessel sparing in most cases, considering that local recurrences only occur in high-grade tumors. Moreover, performing neoadjuvant treatment could allow tumor excision with a thinner safety margin.

Nonetheless, the potential for significant complications must be weighed meticulously during surgical planning. The prospect of potential wound dehiscence warrants careful consideration due to its potentially life-threatening implications for both limb viability and patient survival.

In situations where the femoral vessels are compromised, and reconstructive surgery is deemed unsuitable due to the patient's general health status or concurrent functional impairment arising from femoral and sciatic involvement, conservative treatment becomes untenable. In such cases, hip disarticulation or inter-ileo-abdominal procedures emerge as the only viable solutions.

Groin tumors can also adhere to bone surfaces such as the ileo-pubic and ischio-pubic rami, the ischiatic tuberosity and the femur.

While detaching the mass from the bone through a subperiosteal dissection could be considered for low-grade histologies, bone resection is mandatory for high-grade sarcomas. Bone involvement has to be considered, and a correct surgical approach planned; while the ischium and the ileo-pubic rami can be easily sacrificed, femoral adherence has to be accurately evaluated.

When the tumor adheres to less than 50% of the femur's circumference, a hemidiaphysis resection en-bloc with the tumor must be considered, after inserting an intramedullary nail into the femur before the tumor extirpation surgery. Currently, carbon-fiber nails are advisable because they do not interfere with eventual postoperative radiotherapy.¹⁹

When the tumor adheres to more than half of the circumference of the femur, partial resection can pose too high a risk, and a complete diaphyseal or proximal femur en-bloc resection and related reconstruction with massive homograft or megaprosthesis is recommended.

Surgery for metastatic patients is indicated to control symptoms or bridge to chemotherapy. In these patients, obviously, surgery only has a palliative purpose.

5 Conclusions

Surgery for the excision of soft tissue sarcoma in the groin area is associated with potential complications, including wound-related issues, infection, nerve and vascular injuries, lymphedema, functional impairments, and recurrence. A comprehensive understanding of these complications, their contributing factors, and preventive strategies is indispensable for optimizing patient outcomes and guiding future research endeavors in this field. Gathering patients with soft tissue sarcoma at specialized reference centers, where a comprehensive team of specialists is available, is essential today to ensure a multidisciplinary approach, thus guaranteeing improved oncological and functional outcomes.

Ethical statement

This study received clearance from the institutional review board. It was designed in compliance with the Declaration of Helsinki's guiding principles and the ethical guidelines of the relevant Committee on Human Experimentation.

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Patient's consent

All patients gave their consent to be included in the study and for its publication.

CRediT authorship contribution statement

Chiara Pagnoni: Conceptualization, Methodology, Validation, Investigation, Resources, Writing – original draft. Giovanni Zoccali: Investigation, Data curation, Writing – review & editing. Alessandra Scotto di Uccio: Conceptualization, Data curation, Writing – review & editing, Visualization. Francesca Sperati: Conceptualization, Formal analysis, Writing – review & editing. Leonardo Favale: Validation, Investigation, Resources, Data curation, Writing – review & editing. Sergio Valeri: Validation, Investigation, Resources, Data curation, Writing – review & editing. Alessio Annovazzi: Validation, Investigation, Resources, Data curation, Writing – review & editing. Maria Grazia Petrongari: Validation, Investigation, Resources, Data curation, Writing – review & editing. Vincenzo Anelli: Validation, Investigation, Resources, Data curation, Writing – review & editing. Virginia Ferraresi: Validation, Investigation, Resources, Data curation, Writing – review & editing. Carmine Zoccali: Conceptualization, Methodology, Validation, Investigation, Resources, Writing – original draft, Writing – review & editing, Supervision, Project administration.