Unplanned Excision of Soft Tissue Sarcoma - The Impact of Residual Disease in Re-Excision Specimen

Background: This study aims to assess the oncologic outcomes of unplanned versus planned excision in patients with high-grade soft tissue sarcoma.

Methods: A retrospective review was conducted, including 147 patients surgically treated for non-metastatic high-grade soft tissue sarcoma at a single institution between 2010 and 2021. Perioperative, clinical, and surveillance data were collected. Outcomes were compared between patients with unplanned (n = 53) and planned (n = 94) excisions. Multivariate analyses controlled for tumor characteristics and adjuvant therapies.

Results: The cohort included 53 patients treated with unplanned excision and 94 patients with planned excision, with a mean follow-up of 65.3 months postoperatively. Demographic variables, tumor size, type, histological grade, and margin status were statistically comparable between the planned and unplanned excision groups based on univariate analysis. Unplanned excisions were associated with significantly higher rates of local recurrence (39.6% vs 7.4%, p < 0.001) and metastasis (18.9% vs 5.3%, p = 0.009) compared to planned excisions. On multivariate analysis, planned excision conferred a decreased risk for local recurrence (HR 0.12, 95% CI 0.05-0.31, p < 0.001) and metastasis (OR 0.22, 95% CI 0.05-1.02, p = 0.05). Final positive margins were strongly associated with local recurrence (HR 18.26, 95% CI 6.80-48.99, p < 0.001). Over 90% of re-excision specimens after unplanned excision contained residual disease. Patients with microscopic or macroscopic disease identified in the re-excision specimen had a 42% and 44% risk of local recurrence, respectively, in comparison to those patients with no residual disease identified as having no incidence of local recurrence.

Conclusion: This study highlights the importance of a proper primary excision by an orthopedic oncologist for patients with high-grade soft tissue sarcoma. Unplanned excisions often result in tumor beds with either gross or residual microscopic disease and have a significantly increased risk of local recurrence, distant metastasis, and shortened survival.

Soft tissue sarcomas are rare tumors that are associated with significant morbidity and mortality. Despite being rare, in 2021 alone, 13,400 people in the United States were newly diagnosed [1]. At ten years, 25% of patients develop metastases with an overall survival of 70% following treatment consisting of surgery and radiotherapy with or without chemotherapy [2]. Tumor grade and stage impact patient survival [3-6], whereas radiation therapy and surgical margin status affect local recurrence [7-9]. Local recurrence increases disease morbidity, often requiring re-excision, additional radiotherapy, soft tissue reconstructive procedures and sometimes amputation; however, the relationship between local recurrence and overall survival is unclear.

Unplanned excision of soft tissue sarcomas occurs in 18-49% of patients [10-12]. When patients with soft tissue sarcomas undergo excision without adequate pre-operative clinical and radiologic evaluation and discussion in a Multidisciplinary Tumor Board (MTB), inadequate excision margins, wound complications, and contamination of normal adequate tissue are potential consequences. Potter, et al. [13] retrospectively assessed the outcomes of patients with high-grade soft tissue sarcoma and demonstrated that unplanned excisions resulted in increased rates of local recurrence but had no significant effect on disease-specific survival. Liang Y, et al. [14] demonstrated similar results even when controlling for various baseline covariates (including size, depth, and grade). Other studies have demonstrated worse oncologic outcomes in unplanned excision despite subsequent tumor bed excision [9,11,15,16]. Zaidi, et al. [17] in a multi-institutional study of patients with high-grade soft tissue sarcomas, concluded that unplanned excision resulted in higher rates of local recurrence but did not appear to affect overall survival compared to a cohort who had planned excision. Most studies suggest a higher rate of local recurrence in the setting of unplanned excision but do not uniformly control for tumor size, grade, stage, and the effect of adjuvant therapies.

The purpose of this study is to assess the oncologic outcomes of unplanned versus planned excision in patients with high-grade soft tissue sarcomas utilizing a multivariant analysis to control for tumor characteristics and the presence or absence of gross or microscopic residual disease after unplanned excision.

This is a retrospective cohort study of 147 consecutive patients treated surgically for non-metastatic high-grade soft tissue sarcoma of the extremities at the same institution from 2010 to 2021. High-grade was defined as grade 2 or 3 (based on mitotic activity, necrosis and tumor differentiation). Tumors in the pelvis, retroperitoneum, head, and neck were excluded. Patients with metastatic disease at presentation, low-grade sarcoma, and patients managed nonoperatively were also excluded from this study. The study was approved by the institutional review board. Unplanned excision was defined as excision of a soft tissue mass with or without appropriate imaging studies but without prior biopsy or review by a multidisciplinary panel. Planned excision was defined as surgical excision following appropriate staging, biopsy, and multidisciplinary review.

Demographic and clinical data were collected for each patient, including age, gender, race, ethnicity, Body Mass Index (BMI), presence of diabetes, smoking status, treatment with preoperative or postoperative chemotherapy, and radiotherapy in the form of external beam radiation or brachytherapy. Additionally, tumor characteristics were recorded for each patient as documented by a trained and experienced musculoskeletal pathologist, including tumor type, size, grade, location viability, tumor size, excision margins, and the presence of gross or microscopic tumor in the final specimen in the context of a previously unplanned excision. Patients with synovial sarcoma, clear-cell sarcoma, angiosarcoma, rhabdomyosarcoma, and epithelioid sarcoma (SCARE) were identified and specifically assessed, as these subtypes are most likely to metastasize to locoregional lymph nodes [18]. For patients with these subtypes, treatment involved sentinel node biopsy for any lymph node that was clinically or radiographically suspicious. Patients with Myxofibrosarcoma (MFS) were also assessed with subgroup analysis due to the high risk of local recurrence in these patients [19]. Percent viability of the excised tumor was grouped by < 5%, 5-50%, and > 50% as previously described by Lucas DR, et al. [20]. The need for complex soft tissue reconstructive procedures, including locoregional or free flaps, was documented in the case of large soft tissue defects after the excision. Any postoperative complications, including wound dehiscence, deep infection, deep vein thrombosis, or pulmonary embolism, were documented. Clinical outcomes were surveyed and documented by the primary musculoskeletal oncology attending surgeon including local recurrence, distant metastasis, treatment-related complications and mortality.

Descriptive statistics were utilized to compare planned and unplanned excision of soft tissue sarcomas and provide a comprehensive overview of patient demographics, tumor characteristics, and treatment modalities. Quantitative variables were expressed as mean and standard deviations or median and interquartile ranges depending on their distribution. Categorical variables were expressed as absolute values or percentages. Comparative analyses, including chi-square or Fisher's exact tests and t-tests or Mann-Whitney U tests, were applied to explore associations and differences in categorical and continuous variables, respectively. Subgroup analyses further stratified the data based on tumor subtype, grade, and patient demographics to investigate potential variations on the impact of unplanned excision. Multivariate regression, using Cox models and logistic regression, were utilized to identify independent predictors of overall survival and assess factors associated with specific outcomes. Survival analysis techniques, such as Kaplan-Meier curves, log-rank tests, and Cox Proportional-Hazards models, were employed to estimate overall survival rates and assess differences between patients with and without unplanned excision, while adjusting for relevant covariates. Data were analyzed using STATA version 18.0 (STATA Corp, USA) and R version 3.5.1 (R Foundation for Statistical Computing). Statistical significance was defined as a p value less than 0.05.

The study comprised 147 participants: 53 individuals (36%) undergoing re-excision for unplanned surgeries and 94 (64%) undergoing planned wide excision. The mean age at the time of surgery was comparable between the unplanned and planned groups; 54.60 (SD = 15.69) and 54.49 (SD = 17.79) years, respectively (p = 0.94). Gender distribution also showed no significant difference, with 58.5% males and 41.5% females in the unplanned group, and 55.3% males and 44.7% females in the planned group (p = 0.71). Body Mass Index (BMI) was not significantly different between the two groups, with mean values of 28.24 (SD = 6.162) for the unplanned group and 28.62 (SD = 7.200) for the planned group (p = 0.74). Similarly, the prevalence of diabetes was not significantly different, with rates of 30.2% in the unplanned group and 20.2% in the planned group (p = 0.17) (Table 1).

Tumor size, categorized as less than 5 cm, 5-10 cm, and more than 10 cm, did not show significant differences between unplanned and planned surgeries (p = 0.41). Depth of tumor location, however, demonstrated a significant distinction (p < 0.001), with only 9.4% of the unplanned group having deep seated tumors compared to 42.6% in the planned group. 90.6% of unplanned excisions were performed for superficial tumors. The distribution of special tumor types (SCARE and MFS) and tumor grade (2 and 3) did not reveal significant differences between the unplanned and planned groups (p = 0.23 and p = 0.41, respectively). Viability, categorized as < 5%, 5-50%, and > 50%, also did not differ significantly between the groups (p = 0.23). Fungating tumors were observed in 9.6% of the unplanned group and 7.4% of the planned group, with no significant difference (p = 0.75). Margins status showed no significant difference between groups (p = 0.28), with 9.4% positive margins in the unplanned group at the time of re-excision and 4.3% in the planned group. Residual disease in re-excision specimens of unplanned surgeries was microscopic in 22.6% of cases, and macroscopic in 67.9%. The presence of residual disease after unplanned excision significantly increases the risk of local recurrence. Patients with microscopically involved margins in the re-excision specimen had a 42% LR, and the same risk was 44% when the macroscopic disease was identified in the re-excised specimen. In comparison, of the patients without residual disease in tumor bed at the time of the re-excision, none had a local recurrence. All patients with unplanned excision of myxofibrosarcoma had residual disease in the re-excised specimen. The incidence of local recurrence for that group was 55% (n = 6).

Regarding adjuvant therapies, there was no significant difference in treatment with External Beam Radiation Therapy (EBRT) between the two groups (p = 0.15), with 67.9% in the unplanned group and 78.7% in the planned group receiving this treatment, though the timing of radiotherapy as well as the choice of total radiation dose and field of therapy were different in those treated with prior unplanned excision. Treatment with brachytherapy did not show a significant difference when comparing patients treated with unplanned excision to planned (p = 0.21). Treatment with neoadjuvant chemotherapy also was not significantly different between groups (p = 0.36), with 35.8% in the unplanned group and 43.6% in the planned group receiving neoadjuvant chemotherapy.

In the unplanned group, 24.5% of cases required complex soft tissue closure and/or reconstruction compared to 7.4% in the planned group (p = 0.004). 37.6% of the unplanned surgery re-excision group experienced a wound complication, while the planned surgery group had a slightly higher rate of 40.4%, with no statistically significant difference observed (p = 0.75). More specifically, 13.2% of the unplanned group and 14.9% of the planned group experienced surgical site infection (SSI) (p = 0.78).

Recurrence patterns, including Local Recurrence (LR) and metastasis, demonstrated significant differences (LR; p < 0.001, Mets; p = 0.009) between the unplanned and planned groups, with higher rates in the unplanned group (LR: 39.6%, Mets: 18.9%) compared to the planned group (LR: 7.4%, Mets: 5.3%). The overall status of participants at the last follow-up demonstrated significant differences (p < 0.001) in the distribution of participants categorized as No Evidence of Disease (NED), Alive With Disease (AWD), Dead Of Disease (DOD), or Dead of Other Causes (DOC) between the unplanned and planned groups. The average follow-up duration in months did not significantly differ between the two groups, with 66.27 months (SD = 30.86) for the unplanned group, 64.73 months (SD = 32.54) for the planned group, p-(p = 0.78.)

Univariate analysis demonstrated that unplanned excisions are associated with a significantly higher risk of local recurrence compared to planned excisions. (Hazard Ratio HR= 0.15, 95% [0.06, 0.36], p < 0.001) Tumor size did not demonstrate a significant association with local recurrence (p = 0.32) Deep-seated tumors had a significant association with lower local recurrence risk compared to superficial tumors (HR = 6.45, 95% C.I. [1.53, 27.21], p = 0.01). The type of STS showed no significant association with local recurrence (p = 0.17). Tumor grade (grade II or III) did not significantly correlate with local recurrence (p = 0.69). Tumor viability, stratified into the following groups: 5%, 5-50%, and more than 50%, did not exhibit a significant association with local recurrence (p = 0.12). Fungating tumors were associated with a higher risk of local recurrence (HR = 3.91, 95% C.I. [1.58, 9.69], p = 0.003).

Positive margins significantly increased the risk of local recurrence. (HR = 17.3, 95% C.I. [7.7, 39.0], p < 0.001). The use of External Beam Radiation Therapy (EBRT) compared to no radiation approached significance in demonstrating a protective effect of adjuvant radiation on local recurrence (HR = 0.50, 95% C.I. [0.23, 1.06], p = 0.07). There was no significant difference between brachytherapy and EBRT in local recurrence rates in the cohort of 46 patients treated with brachytherapy and 110 treated with EBRT. Neoadjuvant chemotherapy did not have a significant effect on local recurrence (p = 0.24). The presence of Surgical Site Infections (SSI), wound complications, and the need for complex initial reconstructive strategies did not show significant associations with local recurrence (Respectively: p = 0.58, p = 0.36, p = 0.25) (Table 2).

In the multivariable Cox regression analysis, we explored the independent associations of several key variables with the hazard of local recurrence in this context. When controlling for grade, size and utilization of radiation therapy, or chemotherapy, the status of surgical margins was a robust predictor of the event, with a substantial hazard ratio of 18.26 (95% CI: 6.80; 48.99) for cases with positive margins compared to those with negative margins (p < 0.001). The type of excision, whether unplanned or planned, also demonstrated a significant impact on the hazard. Planned excisions had a HR of 0.12 (95% CI: 0.05; 0.31) compared to unplanned excisions (p < 0.001), indicating a substantially lower risk of LR in cases where excisions were planned when controlling for all other variables (Table 3).

In the multivariable Cox regression analysis for metastasis occurrence, the type of excision, whether unplanned or planned, emerged as a significant predictor. Planned excisions had an odds ratio (OR) of 0.22 (95% CI: 0.05; 1.02) compared to unplanned excisions (p = 0.05), suggesting a substantially lower likelihood of metastasis in cases where excisions were planned. The status of surgical margins was also a robust predictor of metastasis, with cases having positive margins exhibiting a strikingly high odds ratio of 65.56 (95% CI: 8.27; 519.89) compared to cases with negative margins (p < 0.001) (Table 4) (Figure 1(A-C)).

Figure 1: Local recurrence survival curves. A). Planned versus unplanned excision. B). Positive versus negative margins. C). Radiation versus no radiation.

The surgical setting emerged as a significant predictor of disease-specific survival. Patients who underwent planned excisions had an HR of 0.24 (95% CI: 0.06; 0.93) compared to those in unplanned settings (p = 0.04). Larger tumor sizes were associated with higher hazards of disease-specific mortality. Specifically, tumors larger than 10 cm had 7 mortality events and tumors larger then 5 cm had 3 events. With a HR of 1.1 (95% CI: 1.00; 1.20), indicating a trend toward increased mortality risk compared to smaller tumors p = 0.04). The type of STS did not show a statistically significant association with disease-specific survival. Tumor grade did not exhibit a significant association with disease-specific survival. Tumor viability at the time of excision did not significantly impact disease-specific survival (p = 0.62). The presence of fungating tumors however significantly influenced disease-specific survival (p < 0.001). Fungating tumors had a substantially higher HR of 8.66 (95% CI: 2.42; 30.92) compared to non-fungating tumors. The status of surgical margins significantly impacted disease-specific survival (p < 0.001). Tumors with positive margins had a substantially higher HR of 24.13 (95% CI: 6.77; 86.06) compared to those with negative margins. Neither External Beam Radiation (EBRT) nor chemotherapy, whether neoadjuvant or combined, showed statistically significant associations with disease-specific survival (p > 0.05) (Table 5) (Figure 2).

Figure 2: Impact of residual disease on LR in unplanned excision and re-excision.

The impact of a previous unplanned excision on the local recurrence, distant metastasis, and overall survival following re-excision is a subject of great interest in musculoskeletal oncology. This study assessed the impact of various tumor and treatment characteristics using a multivariate analysis on these outcome measures in patients with high-grade soft tissue sarcomas.

The literature is equivocal regarding the impact of unplanned excision on the risk of local recurrence. Studies by Qureshi YA, et al. [11] and Potter BK, et al. [13] demonstrate in their respective cohorts that patients treated with unplanned excision of a soft tissue sarcoma are at an increased risk of local recurrence, while Sacchetti F, et al. [21], showed that treatment following unplanned excision does not independently impact the risk of local recurrence. This meta-analysis included soft tissue sarcomas of various grades and did not explicitly control for tumor size and depth in its primary analyses, though the authors did acknowledge these factors as potential sources of bias in their discussion. In the current study cohort, 53 cases had unplanned excision, and they had a significantly increased risk of local recurrence when controlling for tumor grade, size, margins at the time of re-excision, and utilization of radiation therapy. The variability present in the literature may be due to several factors. The geographic and institutional rates of unplanned excision vary widely. Relatively low rates of unplanned excision in some series may influence the analysis of differences in outcomes between planned and unplanned patient cohorts. Tumor and patient variability and failure to control covariates may conspire to mask real differences between these patient groups. In this study cohort, there were significantly more superficial tumors in the unplanned group than in the planned excision cohort. This observation is not surprising and has been attributed to the surgeon performing the initial procedure more often mistaking these more superficial tumors to be benign and performing, in hindsight, an unsatisfactory excision [9,10,22,23]. This is notable as these more superficial tumors excised by non-orthopedic oncology surgeons were associated in this study with an increased risk of recurrence (p = 0.01). In this cohort, the increased risk of recurrence in patients with unplanned excisions is also related to the extent of the previous excision and residual tumor cells in the tumor bed. Also, 67.9% of patients treated with unplanned excision had residual macroscopic disease, and 22.6% had residual microscopic disease in the tumor bed, amounting to over 90% of patients with evidence of residual disease at the time of re-excision. This can be considered in the context of other studies that demonstrate 47 to 70% of patients with residual disease at the time of re-excision in the tumor bed of a patient that underwent previously unplanned excision [13, 24-27]. Patients with microscopic residual disease at the time of re-excision have an almost 50% risk of local recurrence. The current study demonstrated that the risk of local recurrence is increased by previously unplanned excision, particularly when controlling for tumor grade, size, and utilization of radiation therapy. In this cohort, having postoperative SSI, wound complications, or the need for complex reconstructive strategies did not pose an increased risk of local recurrence. This is in contrast to other investigations where patients with wound-related complications have increased tumor-related events [28,29]. These studies, however, do not control for variables such as tumor size, depth, grade, and the utilization of radiotherapy that may confound this association. Additionally, in this study cohort, patients treated previously with unplanned excision for MFS demonstrated a 55% risk of local recurrence despite a wide margin re-excision. Special considerations must be made for these patients when considering re-excision and radiotherapy regimens to address the increased risk of local recurrence.

In the current cohort, 10.2% of all patients developed metastatic disease, consistent with the literature demonstrating the risk of metastatic disease after oncologic excision for soft tissue sarcoma ranging from 15% to 24% in cohorts of patients not restricted by tumor grade [11,23,24,30,31]. What is surprising is that in patients with previously unplanned excision, there was a significantly increased incidence of metastatic disease (18.9%) compared to planned excision (5.3%). The effect of a previous unplanned excision on metastasis is controversial, with some studies interestingly demonstrating a decreased risk of metastasis when these tumors are initially excised in an unplanned procedure [14,32]. This protective effect of an unplanned excision demonstrated must be understood in consideration of the characteristics of the patients making up each study group. Studies such as those by Fiore M, et al. [33] and Lewis JJ, et al. [34] demonstrated protective effects of a previous unplanned excision. However, in the study by Fiore M, et al. [33] the groups of patients treated with a primary planned excision had higher grade tumors and deeper tumors, both well-documented significant predictors of distant metastasis [35-37]. Similarly, in the study by Lewis JJ, et al. [34], significantly more patients had negative margins and smaller tumors when treated with a re-excision procedure than when treated with one planned procedure. Negative margins and smaller size tumors have also been identified as predictors of a reduced risk of distant metastasis [5,37,38]. In this study cohort, there was no significant difference in size, grade, or surgical margins between patients treated with re-excision versus those treated with a planned primary excision. Additionally, size, grade, surgical margins, and depth were controlled for in multivariate analysis. Thus, even when controlling for these tumor characteristics, prior unplanned excision of soft tissue sarcoma is associated with an increased risk of metastasis. Notably, in this cohort of patients treated with re-excision, over 90% of patients had evidence of residual disease at the time of the re-excision procedure. Evidence of residual disease has been demonstrated to increase the risk of distant metastasis in various studies [23,39]. Thus, the increased risk of distant metastasis in patients with a prior unplanned excision may be attributable to the significant proportion of patients with active residual disease in the tumor bed. To understand the true cause and effect relationship that an unplanned excision has on distant metastasis, large prospective studies should be performed. When patients present with a high likelihood of residual disease following an unplanned excision, the increased risk of metastasis must be considered.

The effect of a previously unplanned excision on overall survival also remains controversial [9,13,34]. In this study, the disease-specific mortality at 5 years is 3.2% after planned excision compared to 13.2% after excision for an unplanned excision. The significant detriment of a previously unplanned excision on disease-specific survival demonstrated in this study, just as in the increased risk of metastasis in this study, may be explained by the large proportion of patients with residual disease at the time of re-excision. Various retrospective studies have demonstrated residual disease to be associated with worse overall survival [13,39,40]. Fortunately, recent treatment regimens have improved disease and disease-free survival, therefore limiting the ability to have statistical analysis based on large numbers of deaths. Additional large studies are warranted to more accurately assess the impact of unplanned excision on disease-specific survival, including multivariate analyses to control for disease characteristics as confounding variables.

In tandem with surgical treatment, adjuvant radiotherapy remains standard practice in treating high-grade soft tissue sarcoma. Various studies demonstrated that adjuvant radiation decreases local recurrence in patients with high-grade sarcoma without a significant effect on overall survival [8,41]. Some retrospective analyses, as well as early randomized trials, suggest that when the primary surgery results in negative margins, radiotherapy does not confer a reduction in the risk of recurrence [42-45]. Thus, in the current cohort of patients treated both with unplanned and planned excisions, with nearly 96% treated with negative surgical margins, the effect of adjuvant radiation in reducing local recurrence approached but did not achieve significance (p = .07). This study additionally assessed postoperative brachytherapy as an adjuvant treatment modality. The cohort demonstrated that brachytherapy compared to external beam therapy was no different when considering the risk of local recurrence (p = .74), similar to various retrospective and prospective trials that have validated it in reducing local recurrence [46,47]. Brachytherapy offers a shorter, lower cost radiotherapy treatment that reduces local recurrence similarly to external beam radiotherapy [46,48]. With a rapid dose drop from the site of treatment, brachytherapy should be considered to spare normal tissue, while external beam therapy can cover a larger volume with increased homogeneity. Various studies have assessed the impact of brachytherapy on postoperative complications [47,49]. The effect of brachytherapy on these postoperative complications still requires further research, while controlling for various confounding factors that may contribute to each complication. Additionally, in MFS, radiotherapy requires larger fields due to the proximal and distal tumor extension commonly seen in this disease [50,51]. For this reason, our group does not recommend utilization of brachytherapy in patients with this sarcoma subtype. Though the efficacy of brachytherapy was assessed as a secondary objective in this study, it should be assessed in a larger cohort study with more detailed statistical analysis targeted at this specific technique.

The use of chemotherapy in the treatment of soft tissue sarcoma has been limited to patients presenting with large high-grade tumors or in the context of metastatic disease. The efficacy of systemic chemotherapy in reducing local recurrence, distant metastasis, and improving survival, is still debated [52-55]. This study indicates no significant benefit of chemotherapy administration and local disease recurrence risk (p = .75) or overall survival (p = 0.40). Randomized prospective trials including large patient cohorts are warranted to evaluate the utility of modern chemotherapy regimens for various types of soft tissue sarcoma.

The effect of a previously unplanned excision on wound-related complications is an important consideration. In a retrospective series of 67 patients treated with re-excision for unplanned excision of soft tissue sarcoma by Traweek RS, et al. [56], 45% of patients experienced wound complications, 15% of which being considered major wound complications. In this study, the cohort of patients with previous unplanned excision more often required a complex soft tissue reconstruction including skin grafts and tissue flaps, however, there was no significant effect on wound-related complications or surgical site infections. This is likely influenced by the cohort of patients treated with re-excision having more superficial tumors, likely increasing the need for locoregional flaps. Additionally, having more superficial and smaller tumors in the unplanned cohort may reduce any added risk of seroma or deep wound related complications. Further studies are warranted to more closely evaluate the effect of unplanned excision on soft tissue complications and assess any added risk that postoperative external beam radiotherapy versus brachytherapy may introduce for wound related complications in various regimens.

There are several limitations in this study that must be considered. The study cohort includes only patients from a single sarcoma center, therein limiting the generalizability to all institutions. Additionally, during the study period, some variables in hospital practice and treatment protocols could have changed. Finally, the cohort assessed in this study is small in number, and a larger cohort would be beneficial, specifically when assessing the influence of more rare events such as mortality, brachytherapy treatment and certain sarcoma subtypes of interest like myxofibrosarcoma.

The study cohort of patients with unplanned excision truly highlights the significance of residual disease at the time of re-excision when considering any additional risk associated with unplanned excision. Identification of patients with residual disease is crucial, as these patients in our study, are at an increased risk of local recurrence, distant metastasis, and worse overall survival. Thus, treatment should be individualized and optimized for these patients. Patients with an unplanned excision with either microscopic or macroscopic residual disease had greater than a 40% incidence of local recurrence compared to patients with no residual disease at the time of re-excision who had no cases of local recurrence. The findings of this study underscore the critical need for continued education and improved clinical practices regarding soft tissue sarcomas. Future efforts should focus on developing comprehensive educational initiatives for non-oncology surgeons. These programs should emphasize the recognition of suspicious soft tissue masses, and the risks associated with unplanned excisions. Concurrently, optimizing referral pathways from primary care and non-oncology specialties to sarcoma centers is crucial. This could involve implementing alerts and establishing electronic platforms for immediate consultation and rapid access clinics for urgent evaluations of patients with uncertain soft tissue tumors. Enhancing multidisciplinary collaboration through regular tumor boards that include community surgeons can foster better communication and awareness. Finally, developing and widely disseminating updated best practice guidelines and protocols for managing soft tissue masses, with an emphasis on pre-excisional biopsy and imaging, can be helpful in reducing the incidence of unplanned excisions and improving patient outcomes.

This study highlights the importance of a proper primary excision by an orthopedic oncologist for patients with high-grade soft tissue sarcoma. Unplanned excisions often result in tumor beds with either gross or residual microscopic disease and have a significantly higher risk of local recurrence and poorer overall clinical outcomes.

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