Neighborhood socioeconomic disadvantage is associated with worse survival in localized extremity soft tissue sarcoma

Abstract

Background

The Area Deprivation Index (ADI) is a validated measure of neighborhood-level socioeconomic disadvantage. This study aimed to assess the association between ADI and long-term (1) disease-specific survival (DSS), (2) metastasis-free survival (MFS), and (3) local recurrence-free survival (RFS) in patients with localized extremity soft tissue sarcoma (STS).

Methods

This was a retrospective study of 238 patients who underwent resection of a localized extremity or pelvis STS from January 2010 to December 2021. Patients with American Joint Committee on Cancer (AJCC) stage 4 were excluded. The ADI is a range with higher values indicating greater deprivation. We categorized ADI into three groups (ADI 1 = 0 to 33, ADI 2 = 34 to 66, ADI 3 = 67 to 100). A Kaplan-Meier analysis was used to estimate the five- and ten-year DSS, MFS, and RFS, with log-rank test and Cox proportional hazards models used to assess significance.

Results

Five-year DSS was worse for patients in ADI 3 and ADI 2 compared to ADI 1 (68.4% vs. 74.2% vs. 91.4%, p = 0.04), with similar patterns at ten-years (42.0% vs. 52.1% vs. 91.4%, p = 0.04). When controlling for age, race, histologic grade, and AJCC stage, ADI 3 was associated with increased five-year risk of disease-specific death compared to ADI 1 [HR 3.47 (1.03–11.66), p = 0.04], while at ten years both ADI group 2 [HR 3.8 (1.13–12.81), p = 0.03] and ADI group 3 [HR 4.88 (1.47–16.18), p = 0.01] demonstrated significantly increased risk of disease-specific death. Five and ten-year risk of metastasis showed similar, but insignificant, trends in unadjusted models but significant differences in adjusted models. Signficant differences in risk of local recurrence for ADI Group 2 and 3 were observed at ten-years in adjusted models.

Conclusion

Patients with soft-tissue sarcoma are significalty impacted by social determinants of health. Efforts to identify the causes of these differences are needed to ensure equity in sarcoma care. Possible explanations include delayed diagnosis, infrequent visits, and physician bias.

Level of Evidence: III

Introduction

Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignancies derived from mesenchymal tissues, collectively representing less than 1% of adult cancers [1–3]. Despite advances in management, oncological outomes have remained relatively poor, with long-term disease-specific survival ranging widely depending on histologic subtype, grade, and stage [4, 5]. The rarity and complexity of these tumors necessitates treatment in high-volume, multidisciplinary centers, where specialized expertise in surgery, radiation, and systemic therapy is concentrated. Yet even when care is centralized, outcomes are not uniformly distributed across patient populations. Increasing evidence suggests that social determinants of health, in addition to tumor biology, play a critical role in impacting cancer outcomes [6–8].

Socioeconomic disparities in cancer outcomes have been well-documented across multiple disease sites, including breast, colorectal, and lung cancers [9–12]. Patients of lower socioeconomic status are more likely to experience delayed diagnosis, less frequent guideline-concordant therapy, and inferior survival. The mechanisms underlying these disparities are multifactorial and include barriers to access, differences in health literacy, financial hardship, and systemic inequities in healthcare delivery [10–14]. Within sarcoma specifically, relatively little is known about how socioeconomic disadvantage influences survival.

The Area Deprivation Index (ADI) is a validated composite measure of neighborhood-level socioeconomic disadvantage [15]. Derived from United States Census data, ADI incorporates variables related to income, education, employment, and housing quality, producing a score from zero to one hundred. Higher scores correspond to greater deprivation. ADI has emerged as a powerful proxy for socioeconomic status across specialties, with prior studies demonstrating its association with prolonged hospitalization, increased readmission, and reduced achievement of patient-reported outcome thresholds in orthopedic surgery [16].

Given the specialized and resource-intensive nature of sarcoma care, patients from socioeconomically disadvantaged neighborhoods may face unique challenges that may impact outcomes. Travel to referral centers, adherence to complex treatment regimens, and access to adjuvant therapies all require stability in housing, employment, transportation, and financial resources—factors that may be lacking in high-ADI communities. Understanding whether ADI is associated with survival in localized STS is critical for designing interventions to mitigate inequities and for guiding the allocation of resources to vulnerable populations.

This investigation aimed to assess the association between Area Deprivation Index, a surrogate for neighborhood socioeconomic disadvantage, and five and ten-year oncologic outcomes in patients with localized soft tissue sarcoma, specifically: (1) disease-specific survival, (2) metastasis-free survival, and (3) local recurrence-free survival.

Methods

This study is a retrospective cohort of 238 patients 18 years and older who underwent surgical resection for localized soft tissue sarcoma of the extremities and pelvis between January 2010 and December 2021 at a single tertiary referral sarcoma center. Eligible patients were identified from a prospectively maintained institutional database and confirmed through review of electronic medical records. Patients who presented with metastatic disease at diagnosis, corresponding to American Joint Committee on Cancer (AJCC) stage IV, were excluded to ensure the analysis was limited to those with localized sarcoma. Patients with atypical lipomatous tumor/well-differentiated liposarcma (ALT/WDLS) were excluded due to their low malignant potential.

Neighborhood socioeconomic status was assessed using the national Area Deprivation Index (ADI), a validated composite metric derived from U.S. Census data that incorporates education, employment, income, and housing quality indicators. Each patient’s residential address at the time of diagnosis was obtained and matched to the national ADI database, yielding a score between zero and 100, with higher values reflecting greater socioeconomic disadvantage. For analysis, patients were stratified into three groups: ADI group 1 (scores 0 to 33), ADI group 2 (scores 34 to 66), and ADI group 3 (scores 67 to 100).

The primary outcome of interest was five- and ten-year disease-specific survival, defined as the interval between surgery and death attributable to sarcoma, with deaths from other causes censored at the time of occurrence. Secondary outcomes included metastasis-free survival, defined as time to development of distant metastasis or last follow-up without evidence of metastasis, and local recurrence-free survival, defined as time to local recurrence or last follow-up without evidence of local recurrence. Survival status and recurrence data were obtained from patients’ electronic medical records. Mortality was further verified through review of publically available obituary records.

Baseline characteristics, including AJCC stage and histologic grade, were compared across ADI group using chi-square tests. Post-hoc pairwise comparisons with multiple testing correction were performed when appropriate. Kaplan-Meier survival curves were used to estimate survival functions for disease-specific survival, metastasis-free survival, and local recurrence-free survival within each ADI group. Differences between groups were evaluated using the log-rank test. To assess the independent association between ADI and outcomes, Cox proportional hazards models were performed with adjustment for prespecified covariates, including age, race, AJCC stage, and histologic grade. For the local recurrence model, histologic grade was excluded due to structural collinearity with AJCC stage, as grade is embedded within the stage definition for soft tissue sarcoma. Hazard ratios with corresponding 95% confidence intervals were reported. Kaplan-Meier and Cox-proportional hazards models were also performed on a subgroup of patients that included only AJCC stage 2 and stage 3. Statistical significance was defined by a two-sided alpha of less than 0.05. All data management and statistical analyses were conducted using R statistical software (version 4.2; R Foundation for Statistical Computing, Vienna, Austria).

Results

Patient characteristics

The median age in each group was 63.5 years (ADI 1), 63.0 years (ADI 2), and 63.0 (ADI 3) (Table 1). The majority of patients in ADI 1, ADI 2, and ADI 3 were White (86.1%, 89.7%, and 69.9%, respectively). There were considerably more black patients in ADI 3 (30.1%) compared to ADI 1 (5.3%) and ADI 2 (10.3%) (Table 1). ADI 1 had the highest proportion of grade 1 (42.1%) and stage 1 (50%) patients when compared to to ADI 2 (grade 1 = 24.3%; stage 1 = 37.1%) and ADI 3 (grade 1 = 16.1%; stage 1 = 37.6%). The greatest proportion of high grade (grade 3) sarcoma was in ADI 3 (45.2%) when compared to ADI 1 (36.8%) and ADI 3 (44.9%). ADI 1 had the largest proportion of stage 3 patients (27.8%), compared with 20.0% in ADI 2 and 25.8% in ADI 3. The most common histologic subtype amongst all ADI groups was liposarcoma (ADI 1 = 21.1%, ADI 2 = 23.5%, and ADI 3 = 2.

Table 1.

Patient characteristics

Variable	Level	ADI 1 (n = 38)	ADI 2 (n = 107)	ADI 3 (n = 93)
Age*		63.5 (50.0-73.0)	63.0 (46.5-76.0)	63.0 (55.0-72.0)
Sex	Female	20 (52.6%)	42 (39.3%)	39 (41.9%)
	Male	18 (47.4%)	65 (60.7%)	54 (58.1%)
Race	White	33 (86.8%)	96 (89.7%)	65 (69.9%)
	Black	2 (5.3%)	11 (10.3%)	28 (30.1%)
	Other	3 (9.1%)	7 (6.5%)	2 (2.2%)
Histologic Grade	1	16 (42.1%)	26 (24.3%)	15 (16.1%)
	2	5 (13.2%)	29 (27.1%)	33 (35.5%)
	3	14 (36.8%)	48 (44.9%)	42 (45.2%)
	X	3 (7.9%)	4 (3.7%)	3 (3.2%)
AJCC Stage	1	18 (50.0%)	39 (37.1%)	35 (37.6%)
	2	8 (22.2%)	45 (42.9%)	34 (36.6%)
	3	10 (27.8%)	21 (20.0%)	24 (25.8%)
Sarcoma Type	Liposarcoma	8 (21.1%)	25 (23.5%)	23 (24.7%)
	Myxofibrosarcoma	6 (15.8%)	15 (14.0%)	15 (16.1%)
	Undifferentiated Pleomorphic Sarcoma	4 (10.5%)	17 (15.9%)	13 (14.0%)
	Leiomyosarcoma	2 (5.3%)	10 (9.4%)	7 (7.5%)
	Other	18 (47.4%)	40 (37.4%)	35 (37.6%)

*Median (Interquartile Range); ADI Area Deprivation Index, AJCC American Joint Committee on Cancer, X Grade cannot be assessed, ADI Groups defined as: ADI 1 = 0–33, ADI 2 = 34–66, ADI 3 = 67–100

Disease-specific survival (DSS)

Overall DSS was 74.4% at five-years and 53.0% at ten-years. Five-year DSS was 91.4% for ADI group 1, 74.2% for ADI group 2, and 68.4% for ADI group 3 (p = 0.04) (Fig. 1). Ten-year DSS was 91.4% for ADI group 1, 52.1% for ADI group 2, and 42.0% for ADI group 3 (p = 0.04) (Fig. 1). When controlling for age, race, AJCC stage, and histologic grade, ADI group 3 was associated with increased risk of disease-specific death compared to ADI group 1 at five-years (HR 3.47, 95% CI 1.03–11.66; p = 0.04) (Table 2). At ten-years, both ADI group 2 and ADI group 3 were associated with increased risk of disease-specific death (ADI group 2: HR 3.8, 95% CI 1.13–12.81, p = 0.03; ADI group 3: HR 4.88, 95% CI 1.47–16.2; p = 0.01) (Table 2). When limiting the analysis to patients with AJCC stage 2 and stage 3 only, the same trends were observed with both five-year and ten-year risk of disease-specific death for ADI group 2 and ADI group 3 being signficiantly associated with worse outcomes in adjusted models (Fig. 2; Table 3).

Fig. 1.

Five-year and ten-year disease-specific survival (DSS) Plots; ADI = Area Deprivation Index; ADI Tertile 1 ranges from (0–33); ADI tertiles defined as: ADI Tertile 1 = 0–33, ADI Tertile 2 = 34–66, ADI Tertile 3 = 67–100

Table 2.

Cox Proportional hazard model for risk of disease-specific death

Variable	Level	5-Year Risk: HR	5-Year Risk: 95% CI	5-Year Risk: P-value	10-Year Risk: HR	10-Year Risk: 95% CI	10-Year Risk: P-value
Age		1.0	0.98–1.02	0.90	1.0	0.99–1.02	0.82
ADI	Group 1
	Group 2	3.03	0.89–10.34	0.08	3.8	1.13–12.81	0.03
	Group 3	3.47	1.03–11.66	0.04	4.88	1.47–16.18	0.01
Race	Black
	Non-Black	1.65	0.73–3.74	0.23	1.37	0.68–2.74	0.38
Histologic Grade	Grade 1
	Grade 2	6.14	0.71–52.96	0.10	2.37	0.61–9.24	0.22
	Grade 3	14.99	1.51–148.71	0.02	4.99	1.07–23.25	0.04
	Grade X	12.14	0.75–195.52	0.08	5.26	0.53–51.71	0.15
AJCC Stage	Stage 1
	Stage 2	1.0	0.3–3.38	0.99	1.54	0.53–4.52	0.43
	Stage 3	2.1	0.67–6.52	0.20	2.81	1.0–7.93	0.05

ADI Area Deprivation Index, HR Hazard Ratio, CI Confidence interval, AJCC American Joint Committee on Cancer; bold indicates statistically significant results (alpha < 0.05); ADI groups defined as: ADI Group 1 = 0–33, ADI Group 2 = 34–66, ADI Group 3 = 67–100

Fig. 2.

Five-year and ten-year disease-specific survival (DSS) Plots for AJCC 2 and 3 only; ADI = Area Deprivation Index; AJCC = American Joint Committee on Cancer; ADI tertiles defined as: ADI Tertile 1 = 0–33, ADI Tertile 2 = 34–66, ADI Tertile 3 = 67–100

Table 3.

Cox proportional hazard model for risk of disease-specific death for AJCC 2 and 3 only

Variable	Level	5-Year Risk: HR	5-Year Risk: 95% CI	5-Year Risk: P-value	10-Year Risk: HR	10-Year Risk: 95% CI	10-Year Risk: P-value
Age		1.0	0.98–1.02	0.80	1.0	0.98–1.02	0.88
ADI	Group 1
	Group 2	4.39	1.01–19.11	0.048	5.19	1.2–22.4	0.03
	Group 3	4.62	1.07–19.91	0.04	6.07	1.42–25.89	0.01
Race	Black
	Non-Black	1.51	0.66–3.44	0.33	1.52	0.7–3.27	0.29
Histologic Grade	Grade 2
	Grade 3	2.5	1.13–5.53	0.02	2.23	1.08–4.6	0.03
AJCC Stage	Stage 2
	Stage 3	2.03	1.08–3.81	0.03	1.76	0.97–3.19	0.06

ADI Area Deprivation Index, HR Hazard Ratio, CI Confidence interval, AJCC American Joint Committee on Cancer; bold indicates statistically significant results (alpha < 0.05); ADI groups defined as: ADI Group 1 = 0–33, ADI Group 2 = 34–66, ADI Group 3 = 67–100

Metastasis-free survival (MFS)

Overall MFS was 62.9% at five-years and 42.8% at ten-years. Five-year MFS was 82.1% for ADI group 1, 63.8% for ADI group 2, and 55.0% for ADI group 3 (p = 0.14) (Fig. 3). Ten-year MFS was 48.6% for ADI group 1, 50.6% for ADI group 2, and 36.3% for ADI group 3 (p = 0.14) (Fig. 3). In adjusted Cox models, ADI group 3 was associated with increased risk of metastasis compared to ADI group 1 at five- (HR 2.49, 95% CI 1.02–6.07; p = 0.04) and ten-years (HR 2.24, 95% CI 1.02–4.9; p = 0.04) (Table 4). In subgroup analyses with AJCC stage 2 and stage 3 only, similar trends were observed in unadjusted models but were not found to be significant (Fig. 4). In adjusted models, both ADI group 2 and ADI group 3 were significantly associated with increased risk of metastasis compared to ADI group 1 at five- and ten-years (Table 5).

Fig. 3.

Five-year and ten-year metastasis-free survival (MFS) Plots; ADI = Area Deprivation Index; ADI tertiles defined as: ADI Tertile 1 = 0–33, ADI Tertile 2 = 34–66, ADI Tertile 3 = 67–100

Table 4.

Cox proportional hazard model for risk of metastasis

Variable	Level	5-Year Risk: HR	5-Year Risk: 95% CI	5-Year Risk: P-value	10-Year Risk: HR	10-Year Risk: 95% CI	10-Year Risk: P-value
Age		1.0	0.98–1.01	0.88	0.99	0.98–1.01	0.24
ADI	Group 1
	Group 2	2.24	0.92–5.46	0.08	1.87	0.85–4.11	0.12
	Group 3	2.49	1.02–6.07	0.04	2.24	1.02–4.9	0.04
Race	Black
	Non-Black	1.44	0.76–2.72	0.26	1.43	0.78–2.64	0.25
Histologic Grade	Grade 1
	Grade 2	1.7	0.51–5.62	0.39	1.06	0.4–2.8	0.91
	Grade 3	2.2	0.58–8.37	0.25	1.55	0.5–4.79	0.45
	Grade X	2.15	0.25–18.47	0.49	1.29	0.16–10.25	0.81
AJCC Stage	Stage 1
	Stage 2	1.89	0.69–5.21	0.22	1.86	0.73–4.71	0.19
	Stage 3	4.01	1.54–10.47	0.001	3.78	1.55–9.24	0.01

ADI Area Deprivation Index, HR Hazard Ratio, CI Confidence interval, AJCC American Joint Committee on Cancer; bold indicates statistically significant results (alpha < 0.05); ADI groups defined as: ADI Group 1 = 0–33, ADI Group 2 = 34–66, ADI Group 3 = 67–100

Fig. 4.

Five-year and ten-year metastasis-free survival (MFS) Plots for AJCC 2 and 3 only; ADI = Area Deprivation Index; AJCC = American Joint Committee on Cancer; ADI tertiles defined as: ADI Tertile 1 = 0–33, ADI Tertile 2 = 34–66, ADI Tertile 3 = 67–100

Table 5.

Cox proportional hazard model for risk of metastasis for AJCC 2 and 3 only

Variable	Level	5-Year Risk: HR	5-Year Risk: 95% CI	5-Year Risk: P-value	10-Year Risk: HR	10-Year Risk: 95% CI	10-Year Risk: P-value
Age		0.99	0.97–1.01	0.17	0.99	0.98–1.01	0.20
ADI	Group 1
	Group 2	3.08	1.06–8.93	0.04	3.25	1.13–9.36	0.03
	Group 3	3.14	1.08–9.1	0.04	3.3	1.14–9.52	0.03
Race	Black
	Non-Black	1.77	0.86–3.65	0.12	1.87	0.91–3.85	0.09
Histologic Grade	Grade 2
	Grade 3	1.33	0.73–2.42	0.36	1.47	0.81–2.68	0.20
AJCC Stage	Stage 2
	Stage 3	2.19	1.27–3.77	0.001	2.09	1.22–3.57	0.01

ADI Area Deprivation Index, HR Hazard Ratio, CI Confidence interval, AJCC American Joint Committee on Cancer; bold indicates statistically significant results (alpha < 0.05); ADI groups defined as: ADI Group 1 = 0–33, ADI Group 2 = 34–66, ADI Group 3 = 67–100

Local recurrence-free survival (LRFS)

Overall LRFS was 81.7% at five-years and 67.1% at ten-years. Five-year LRFS was 89.8% for ADI group 1, 83.5% for ADI group 2, and 76.9% for ADI group 3 (p = 0.33) (Fig. 5). At ten-years, LRFS was 89.8% for ADI group 1, 53.3% for ADI group 2, and 71.8% for ADI group 3 (p = 0.33) (Fig. 5). In adjusted Cox models, ADI group 2 and ADI group 3 were significantly associated with increased risk of local recurrence compared to ADI group 1 at ten-years only (Table 6). This trend was not observed when limiting the analysis to AJCC stage 2 and stage 3 (Fig. 6 and Table 7).

Fig. 5.

Five-year and ten-year local recurrence-free survival (LRFS) Plots; ADI = Area Deprivation index; ADI tertiles defined as: ADI Tertile 1 = 0-33, ADI Tertile 2 = 34-66, ADI Tertile 3 = 67-100

Table 6.

Cox proportional hazard model for risk of local recurrence

Variable	Level	5-Year Risk: HR	5-Year Risk: 95% CI	5-Year Risk: P-value	10-Year Risk: HR	10-Year Risk: 95% CI	10-Year Risk: P-value
Age		1.0	0.98–1.02	0.70	1.0	0.98–1.02	0.70
ADI	Group 1
	Group 2	1.69	0.47–6.12	0.42	3.68	1.1–12.32	0.03
	Group 3	2.32	0.66–8.16	0.19	4.93	1.5–16.23	0.01
Race	Black
	Non-Black	1.29	0.48–3.45	0.62	1.39	0.7–2.79	0.35
AJCC Stage	Stage 1
	Stage 2	0.74	0.27–2.04	0.56	3.86	1.88–7.94	0.001
	Stage 3	2.46	1.06–5.73	0.04	5.84	2.7–12.65	0.001

ADI Area Deprivation Index, HR Hazard Ratio, CI Confidence interval, AJCC American Joint Committee on Cancer; bold indicates statistically significant results (alpha < 0.05); ADI groups defined as: ADI Group 1 = 0–33, ADI Group 2 = 34–66, ADI Group 3 = 67–100

Fig. 6.

Five-year and ten-year local recurrence-free survival (LRFS) Plots for AJCC 2 and 3 only; ADI = Area deprivation index; AJCC = American joint committee on cancer; ADI tertiles defined as: ADI Tertile 1 = 0–33, ADI Tertile 2 = 34–66, ADI Tertile 3 = 67–100

Table 7.

Cox proportional hazard model for risk of local recurrence for AJCC 2 and 3 only

Variable	Level	5-Year Risk: HR	5-Year Risk: 95% CI	5-Year Risk: P-value	10-Year Risk: HR	10-Year Risk: 95% CI	10-Year Risk: P-value
Age		1.01	0.98–1.04	0.46	1.01	0.97–1.04	0.72
ADI	Group 1
	Group 2	2.54	0.52–12.47	0.25	2.54	0.52–12.47	0.25
	Group 3	2.62	0.54–12.66	0.23	2.62	0.54–12.66	0.23
Race	Black
	Non-Black	3.52	0.77–16.09	0.10	3.52	0.77–16.09	0.10
Histologic Grade	Grade 2
	Grade 3	6.57	1.44–30.06	0.02	6.57	1.44–30.06	0.02
AJCC Stage	Stage 2
	Stage 3	5.89	2.08–16.65	0.00	5.89	2.08–16.65	0.001

ADI Area Deprivation Index, HR Hazard Ratio, CI Confidence interval, AJCC American Joint Committee on Cancer; bold indicates statistically significant results (alpha < 0.05); ADI groups defined as: ADI Group 1 = 0–33, ADI Group 2 = 34–66, ADI Group 3 = 67–100

Discussion

This study demonstrates that neighborhood socioeconomic disadvantage, as quantified by ADI, is independently associated with worse long-term disease-specific survival in patients with localized extremity and pelvis STS. The magnitude of this association was significant, with patients in the most deprived neighborhoods facing nearly four-to-five times the risk of sarcoma-specific death compared with those in the least deprived group after controlling for age, race, AJCC stage, and histologic grade. These findings underscore the influence of social determinants of health on cancer outcomes and suggest that disparities extend beyond differences in tumor biology or initial treatment.

AJCC stage and histologic grade distributions were not uniformly distributed between ADI groups. ADI 1 demonstrated a tendency toward lower AJCC stage and lower-grade tumors compared with ADI 2 and ADI 3. AJCC stage in soft-tissue sarcoma is partly determined by tumor size, therefore these baseline characteristics could reflect earlier detection or diagnosis in patients who have less socioeconomic deprivation. Due to these differences potentially confounding survival estimates, both AJCC stage and grade were included in our multivariable models. Even after adjustment, ADI remained independently associated with survival. This suggests that socioeconomic disadvantage influences outcomes and is not entirely dependent on tumor characteristics alone. We then repeated the analyses on higher staged tumors (AJCC 2 and 3 only) and found that ADI was still significantly associated with survival.

The pathways through which socioeconomic disadvantage translates into worse outcomes in sarcoma patients are likely multifactorial and require further investigation. Patients from disadvantaged neighborhoods may face a number of barriers which could include: longer travel times, transportation challenges, and financial or logistical burdens that may delay or interrupt care [17–20]. Treatment adherence may also be impacted by financial constraints, competing work or family responsibilities, or difficulty attending follow-up visits and surveillance imaging [17–22]. Health literacy may also be reduced in higher ADI populations, which could impact compliance with treatment recommendations and/or surveillance. Insurance coverage and out-of-pocket costs may further limit the ability to fully adhere to recommended therapies [23, 24]. Physician bias may also play a role due to potential differences in treatment recommendations dependent on perceived support system or follow-up reliability.

Although unadjusted MFS curves did not show significant differences between ADI groups, adjusted Cox models demonstrated that ADI 3 had a higher risk of metastasis compared with ADI 1 after controlling for grade and stage. Since grade and stage account for tumor size and inherent tumor aggressiveness, the persistence of an effect in the adjusted model suggests that factors outside the tumor itself, such as host biology, may be a contributing factor. One hypothesis is that patients in higher ADI groups may have a greater burden of chronic disease and inflammation, making metastatic progression more likely despite similar tumor characteristics. This difference remains in the AJCC stage 2/3 subgroup analysis. Future work should therefore evaluate whether higher ADI patients are more sick and whether accounting for comorbidity changes the relationship between ADI and metastasis.

Although the unadjusted LRFS curves appeared to show substantially higher local recurrence rates than reported in literature, roughly approaching 30–50% in some groups by ten years, these estimates are largely driven by small number of patients remaining under observation at late follow-up. Therefore, a single recurrence produces a disproportionately large drop in the curve and exaggerates the survival rate. The crude LR rate for ADI 1 was 7.9% (3/38), ADI 2 was 13% (14/107), and ADI 3 was 16% (15/93), which is more consistent with expected local recurrence rates [25, 26].

Beyond financial and logistical barriers, broader structural and social determinants of health likely play a role for the findings of the study. Patients from disadvantaged neighborhoods may experience higher psychosocial stress, reduced health literacy, and weaker social support networks, all of which can affect coping, recovery, and long-term survivorship [27–30]. Systemic factors such as implicit bias and structural inequities in healthcare access may further exacerbate these challenges. Thus, even when baseline disease characteristics appear similar across ADI groups, these non-biologic factors may collectively contribute to the survival disparities observed.

Within the field of orthopedic surgery, our findings parallel prior research in arthroplasty populations, where higher ADI has been associated with reduced achievement of patient-reported outcome thresholds and increased healthcare utilization [16]. Together, these data highlight the need to consider ADI as a meaningful risk factor in musculoskeletal malignancy, with implications for both clinical practice and health policy.

Clinically, incorporation of ADI into prognostic models could allow for more accurate risk stratification. Identifying patients at elevated risk based on neighborhood deprivation may enable proactive interventions such as enhanced patient navigation, social work engagement, and tailored survivorship planning. At a systems level, the findings suggest the importance of addressing structural barriers that disproportionately affect disadvantaged populations. Policies that support transportation services, expand insurance coverage, and incentivize care coordination across networks may help to narrow disparities [20, 31]. Efforts to increase geographic distribution of sarcoma expertise, including telemedicine consultation and regional referral pathways, may also mitigate inequities in access.

Several limitations should be acknowledged. First, the retrospective design carries inherent risks of selection and information bias. Second, although ADI provides a validated measure of neighborhood deprivation, it does not capture individual-level socioeconomic variation and may misclassify certain patients. Third, the absence of treatment adherence data limits analysis of the variables that drive differences in ADI. Furthermore, variables related to initial treatment were not analyzed and as a result, potential differences in treatment approaches across ADI groups could not be evaluated. Nonetheless, the inclusion of patients treated across different states improves the geographic diversity of the cohort and strengthens the generalizability of the findings.

In conclusion, we demonstrate here that outcomes in patients with localized extremity soft-tissue sarcoma are significalty impacted by social determinants of health. Efforts to identify the causes of these differences are needed to optimize outcomes and ensure equity in sarcoma care. Future research should incorporate multi-institutional cohorts with greater geographic and racial diversity. Additional next steps include quantifying time from symptom onset to diagnosis, evaluating differences in treatment delivery and treatment adherence, and developing targeted interventions for patients from high-ADI neighborhoods. Ultimately, the integration of social determinants into sarcoma research represents not only an academic endeavor but a critical need to ensure equitable cancer care.

Authors’ contributions

Conceptualization, B.B., L.M.N., Z.D.B.; methodology, B.B., L.M.N., Z.D.B.; formal analysis, B.B.; investigation, B.B., R.T., M.H.; writing—B.B.; writing—review and editing, B.B., R.T., M.H., J.W., D.S., S.R.C., J.G.S., N.W.M., L.M.N., Z.D.B. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of the Cleveland Clinic. As this was a retrospective chart review involving existing data and posed minimal risk to participants, the requirement for informed consent was waived by the IRB.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.