Our investigation presents an analysis concerning a population-based cohort of ESOS patients derived from the SEER database. It delineates the incidence and prevalence of these patients and characterizes the pattern of survival. In this study grounded in the population, we discerned that the age-adjusted annual prevalence of ESOS escalated from 0.02 per 100,000 in the year 2000 to 0.11 per 100,000 in 2019, signifying a remarkable 5.5-fold surge. Meanwhile, the incidence and mortality of this condition exhibited no noteworthy alteration. Considering that prevalence encompasses both incidence and survival, one may deduce that the overall survival rate of ESOS patients experienced a slight enhancement during this temporal span. The broad-spectrum therapeutic approaches might plausibly contribute to the advancement in prognosis for ESOS patients. The preeminence of the surgical cohort over their non-surgical counterparts within this study underscores the pivotal role of treatment, particularly surgical intervention. Despite the prognosis for ESOS patients remaining relatively unfavourable, there is discernible improvement in overall survival over the temporal course, mirroring advancements in anticancer therapeutics.
The patients afflicted by ESOS exhibited an age range of 47 to 61 years, with an average age of 60.7[8]. Within the present study, the proportion of patients surpassing 50 years of age reached 64.8% among ESOS cases, while it stood at a mere 18.2% for those grappling with osseous osteosarcoma. In alignment with prior reports, advanced age emerged as an independent prognostic peril[16, 17]. This phenomenon could be attributed to the relatively diminished tolerance towards comprehensive therapeutic regimens among elderly patients. Furthermore, older patients are prone to multiple comorbidities, including cardiovascular ailments and diabetes, which are known to exacerbate their prognosis. Notably, there existed no appreciable variance in the male-to-female ratio within the ESOS cohort. In our study, the male-to-female ratio for ESOS closely approximated 1:1, a proportion akin to previously documented observations[16]. Intriguingly, within our dataset, 12.4% of ESOS cases emanated from the female breast and reproductive organs, whereas there existed a solitary instance occurring within the male reproductive organ. This incongruity could potentially be ascribed to the annual influx of cases into the system.
ESOS, by its nature, presents an unfavorable prognosis. According to Chung et al.[17], patients diagnosed with ESOS exhibited a three-year mortality rate exceeding 50%. A European multicenter study involving 266 ESOS patients reported a five-year overall survival rate of 47%[14]. Our study yielded similar findings, with corresponding three-year and five-year overall survival rates of 49.4% and 45.7%, respectively. The potential for enhanced prognosis through primary lesion resection by means of surgical intervention has been documented[5, 13, 14, 18, 19, 20]. Goldstein et al.[21] concluded that complete resection stood as the singular positive prognostic determinant for ESOS. In our current investigation, a noteworthy 84% of ESOS patients underwent surgical procedures, emerging as an independent prognostic factor associated with favorable survival outcomes in multivariate Cox regression analysis. Within the 'Soft Tissue including Heart' subgroup, patients subjected to surgery evidenced one-, three-, and five-year overall survival rates of 78.0%, 60.5%, and 52.1%, respectively. These figures notably surpassed those observed in non-surgically treated patients (22.5%, 7.5%, and 7.5%, respectively). Our findings resonate with prior research conducted by others[15, 22]. Additionally, survival prognoses exhibit variation when stratified according to originating systemic tissues or organs. In our study, 250 ESOS patients were distributed across 11 systemic tissues or organs, with 70% of cases manifesting in the 'Soft Tissue including Heart' category (with over a third localized in the lower limbs). Fewer instances occurred within other systemic tissues, comprising 24 cases within breast tissues and 16 cases in the respiratory system. Notably, patients with ESOS originating in the 'Soft Tissue including Heart' category demonstrated a median survival of 33.0 months, markedly outperforming their counterparts originating from other sites (12.0 months for breast and 19.9 months for lung, respectively). This concurs with previously reported findings[4, 8, 23, 24, 25]. Superficial ESOS masses, being more readily detectable, facilitate early-stage diagnosis and subsequent intervention. Moreover, due to their comparatively modest vascular and lymphatic networks, the likelihood of local progression and distinct metastasis diminishes, thereby enhancing patients' prognostic survival rates and reducing the incidence of local recurrence post-treatment[7, 16, 19, 26, 27, 28, 29]. Additionally, ESOS originating from diverse systemic sites exhibit disparate tissue origins, consequently engendering distinct biological behaviours and, by extension, discernible differences in survival outcomes.
ESOS shares a nomenclature and histological resemblances with osseous osteosarcoma, yet diverges in terms of occurrence sites and clinicopathological attributes. Regrettably, ESOS displays a notable insensitivity to chemotherapy, as evidenced in previous reports[5, 18, 30, 31]. The role of chemotherapy in managing ESOS patients remains a contentious topic[13, 14, 32, 33]. In the context of localised ESOS, the amalgamation of surgical intervention with diverse chemotherapy regimens appears to hold promise for enhancing overall survival[21, 34]. A comprehensive examination by Longhi et al.[14] across multiple centres illustrated elevated survival rates among individuals subjected to perioperative chemotherapy, with an inclination towards potential effectiveness of osteosarcoma chemotherapy protocols. Conversely, Lin Qi et al.[35] partitioned 310 ESOS patients into cohorts with and without chemotherapy exposure, arriving at the conclusion that the chemotherapy group didn't manifest significant prognostic amelioration. For advanced ESOS cases marked by distant metastases, assorted chemotherapeutic protocols offer feasible alternatives, yet these regimens fail to impart a survival advantage[5, 36]. Furthermore, given the advanced age demographic and potential for systemic dysfunction among ESOS patients, the associated complexities of chemotherapy pose an unsuitable proposition for elderly cohorts[14]. Consequently, there exists a rationale to abstain from routinely endorsing chemotherapy as a standard ESOS treatment[37]. Within this study, the utilization of chemotherapy accounted for 49.2%, a percentage notably lower than that of surgery. Multivariate Cox regression analysis corroborated that chemotherapy failed to emerge as an independent, favorable prognostic factor.
The therapeutic scope of radiotherapy within ESOS remains circumscribed, resulting in its non-routine adoption[18, 30, 38]. Generally, radiotherapy serves a palliative function for ESOS patients either burdened with inoperable primary lesions or grappling with metastatic afflictions[31, 34, 39, 40]. The coupling of surgical intervention with radiotherapy has demonstrated efficacy in diminishing tumour size and local recurrence rates. However, it falls short of significantly influencing ESOS prognosis[15, 16]. Wang Hao-tong et al.[15] demonstrated an augmentation in the overall survival rate among patients harbouring ESOS with surgically positive margins who underwent radiotherapy. Within our study, over two-thirds of ESOS patients received radiotherapy, a practice ostensibly aimed at curtailing tumour recurrence and attaining negative surgical margins.
ESOS represents an exceedingly uncommon malignancy, marked by a dearth of clinical evidence elucidating its prognosis. Furthermore, prior investigations have often concentrated on therapeutic aspects, neglecting the utilization of a nomogram for prognostic prediction[14]. Thus, our initiative encompassed the construction of a nomogram, designed to prognosticate outcomes for ESOS patients. Following univariate and multivariate Cox regression analysis, four key variables emerged as predictive factors: advanced age at diagnosis, metastatic disease stage, the presence of bone metastasis, and primary tumour surgical intervention. The validation of this nomogram underscored its robust discriminative and calibration capabilities. The visually intuitive format of the nomogram aptly conveys predictive model outcomes, simplifying the intricate task of simultaneous prognostic assessment. This tool not only offers a straightforward and precise means of prognosticating outcomes for ESOS patients, but also equips clinicians with a point of reference to inform subsequent medical decisions.
While our study shares limitations akin to preceding research endeavours, its retrospective design being one. Future prospects necessitate prospective randomised clinical trials to furnish high-calibre clinical evidence for application. Additionally, the SEER database omits certain data points, including tumour size, growth depth, and resection specimen margin status. Neglecting these factors could potentially overlook facets with bearing upon patient prognosis. It is noteworthy, however, that our present study holds the distinction of being the most expansive of its kind, and the first to pioneer a survival prognostic model for ESOS. As the database accumulates a greater corpus of cases, this to a considerable extent addresses the scarcity of ESOS studies, thereby furnishing a more comprehensive epidemiological perspective.
In conclusion, our retrospective analysis of a sizeable, population-based, single-institution dataset offers insights into the distinguishing features of ESOS compared to osseous osteosarcoma. Discerned through our investigation, advanced age at diagnosis, distant disease stage, and the presence of bone metastasis independently emerged as adverse prognostic determinants, while primary tumour excision surgery displayed potential to enhance ESOS patient outcomes. Our observations also indicate that neither radiotherapy nor chemotherapy confers survival advantages in ESOS cases. Thus, our findings advocate for the prioritisation of primary lesion excision surgery in ESOS, coupled with adjuvant radiotherapy contingent on individual patient circumstances. Furthermore, the employment of our nomogram aids clinicians in anticipating patient prognoses, facilitating the tailoring of treatment strategies accordingly.