Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study

Abstract

Background Alveolar soft part sarcoma (ASPS) is a rare histological subtype of soft-tissue sarcoma, which remains refractory to conventional cytotoxic chemotherapy. We aimed to characterize ASPS and investigate whether the oncological outcome has improved over the past decade. Methods One hundred and twenty patients with newly diagnosed ASPS from 2006 to 2017, identified from the Bone and Soft-Tissue Tumor Registry in Japan, were analyzed retrospectively. Results The study cohort comprised 34 (28%) patients with localized ASPS and 86 (72%) with metastatic disease at presentation. The 5-year disease-specific survival (DSS) was 68% for all patients and 86% and 62% for localized and metastatic disease, respectively (p = 0.019). Metastasis at presentation was the only adverse prognostic factor for DSS (hazard ratio [HR]: 7.65; p = 0.048). Patients who were > 25 years (80%; p = 0.023), had deep-seated tumors (75%; p = 0.002), and tumors > 5 cm (5–10 cm, 81%; > 10 cm, 81%; p < 0.001) were more likely to have metastases at presentation. In patients with localized ASPS, adjuvant chemotherapy or radiotherapy did not affect survival, and 13 patients (45%) developed distant metastases in the lung (n = 12, 92%) and brain (n = 2, 15%). In patients with metastatic ASPS (lung, n = 85 [99%]; bone, n = 12 [14%]; and brain n = 9 [11%]), surgery for the primary or metastatic site did not affect survival. Prolonged survival was seen in patients who received pazopanib treatment (p = 0.045), but not in those who received doxorubicin-based cytotoxic chemotherapy. Overall, improved DSS for metastatic ASPS has been observed since 2012 (5-year DSS, from 58 to 65%) when pazopanib was approved for advanced diseases, although without a statistically significant difference (p = 0.117). Conclusion The national study confirmed a unique feature of ASPS with frequent metastasis to the lung and brain but an indolent clinical course. An overall trend toward prolonged survival after the introduction of targeted therapy encourages continuous efforts to develop novel therapeutic options for this therapeutically resistant soft-tissue sarcoma.

Evaluation of TRIM63 RNA in situ hybridization (RNA-ISH) as a potential biomarker for alveolar soft-part sarcoma (ASPS)

“…Nevertheless, accurate diagnosis is important, as disease management is currently evolving. Targeted therapies toward VEGF, MET signaling, and immune modulation are being studied, and while some clinical trials are agnostic of subclassification in treating soft tissue sarcomas, growing familiarity with recurrent molecular features and implicated pathogenic pathways have led to clinical trials being designed specifically for advanced ASPS (e.g., atezolizumab and bevacizumab, in NCT03141684) [ 24 , 25 ]. Accurate and efficient diagnosis of ASPS is also crucial to accrue patients with this rare tumor type.…”

Alveolar Soft Part Sarcoma of the Nasolabial Fold: A Case Report and Literature Review

“…The five-year survival rate for ASPS is estimated at 86% for those without metastatic spread and 62% for patients reported with metastasis [ 10 ]. Metastasis is the main predictor of prognosis, with age being a secondary contributing factor as older individuals are more susceptible to metastasis [ 1 , 3 , 4 , 10 , 11 ].…”

“…The five-year survival rate for ASPS is estimated at 86% for those without metastatic spread and 62% for patients reported with metastasis [ 10 ]. Metastasis is the main predictor of prognosis, with age being a secondary contributing factor as older individuals are more susceptible to metastasis [ 1 , 3 , 4 , 10 , 11 ]. Other predictors of a worse prognosis in ASPS include male sex, tumor size greater than 5 cm in local lesions, 10 cm in metastatic lesions, and a primary site other than the extremity [ 1 , 4 , 10 ].…”

“…Metastasis is the main predictor of prognosis, with age being a secondary contributing factor as older individuals are more susceptible to metastasis [ 1 , 3 , 4 , 10 , 11 ]. Other predictors of a worse prognosis in ASPS include male sex, tumor size greater than 5 cm in local lesions, 10 cm in metastatic lesions, and a primary site other than the extremity [ 1 , 4 , 10 ]. Recurrence of ASPS after resection is a known complication of this malignancy; Wang et al reported an estimated overall local recurrence rate of 38.9%, with a 33% recurrence rate in their observational study.…”

“…Currently, complete surgical resection is the first-line treatment for ASPS, as it offers the greatest benefit [ 4 , 10 , 15 ]. ASPS is characteristically resistant to chemotherapy, as a less than 10% response rate to conventional anthracycline-based chemotherapy has been noted [ 16 , 17 ].…”