The vast array of metabolic adaptations that cancer cells are capable of assuming, not only support their biosynthetic activity, but also fulfill their bioenergetic demands and keep their intracellular reduction–oxidation (redox) balance. Spotlight has recently been placed on the energy metabolism reprogramming strategies employed by cancer cells to proliferate. Knowledge regarding soft tissue and bone sarcomas metabolome is relatively sparse. Further characterization of sarcoma metabolic landscape may pave the way for diagnostic refinement and new therapeutic target identification, with benefit to sarcoma patients. This review covers the state-of-the-art knowledge on cancer metabolomics and explores in detail the most recent evidence on soft tissue and bone sarcoma metabolomics.

Background/Objectives: To review the problem of diagnostic delay in soft tissue sarcomas with the aim of identifying its causes and consequences, understanding how to clinically suspect and refer them, and evaluating the main limitations of the referral guidelines already in use. Methods: A systematic review of the available literature was performed, focusing on the theoretical framework, the elements and time intervals to be considered, causes and consequences, “red flag” symptoms/signs, the main referral guidelines in use, their results, and the methods used to avoid excessive referrals. Results: Diagnostic delay in soft tissue sarcomas is a frequent event that is poorly characterized and has important consequences, including prognostic, medico-legal and psycho-social effects. The common denominator is the lack of knowledge and awareness. Several referral guidelines have been described, and most of them are based on clinical data. Their results have been disappointing. Thus, it is necessary to implement new methods to improve their results and avoid the overload of pre-referral imaging systems, sarcoma diagnostic triage meetings, and telemedicine systems. Conclusions: Sarcoma units and health system leaders need to study this issue to determine the extent of the problem and its causes. Without this information, it is almost impossible to properly address the problem and take corrective actions. Early referral of suspected soft tissue sarcoma lesions, although desirable, is a complex issue due to the non-specificity of the symptoms. Existing clinical referral guidelines need to be modified to improve detection and conversion rates.

Peritoneal sarcomatosis is a rare malignant disease with a poor prognosis, secondary to peritoneal dissemination of abdominopelvic soft tissue sarcomas. Its rarity, together with the characteristic histological heterogeneity and the historically poor response to systemic treatments, has prevented the establishment of widely accepted treatment criteria with curative intent. In this sense, radical cytoreductive surgery (CRS) with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC), widely used in peritoneal carcinomatosis with excellent results, have not had the same evolutionary development in patients with peritoneal sarcomatosis. A multidisciplinary working group of experts in sarcomas and peritoneal oncological surgery established a series of recommendations based on current scientific evidence for the management of peritoneal sarcomatosis, taking into account the different histological subgroups of abdominopelvic sarcomas that can cause it depending on their origin: retroperitoneal sarcomas, uterine sarcomas, and visceral/peritoneal sarcomas of GIST (gastrointestinal stromal tumor) and non-GIST origin. This article shows the results of sarcoma experts’ voting on the recommendations presented during the I Ibero-American Consensus on the Management of Peritoneal Sarcomatosis, which took place during the recent celebration of the III Hispanic-Portuguese Meeting for Updates on the Treatment of Sarcomas.

Background: Soft tissue sarcomas (STSs) histopathological classification system and the clinical and molecular-based tools that are currently employed to estimate its prognosis have several limitations, impacting prognostication and treatment. Clinically driven molecular profiling studies may cover these gaps and offer alternative tools with superior prognostication capability and enhanced precision and personalized treatment approaches identification ability. Materials and Methods /Results: We performed DNA sequencing (DNA-seq) and RNA sequencing (RNA-seq) to portray the molecular profile of 102 samples of high-grade STS, comprising the three most common STS histotypes. The analysis of RNA-seq data using unsupervised machine learning models revealed previously unknown molecular patterns, identifying four transcriptomic subtypes/clusters (TCs). This TC-based classification has a clear prognostic value (in terms of overall survival (OS) and disease-free survival (DFS)), a finding that was externally validated using independent patient cohorts. The prognostic value of this TC-based classification outperforms the prognostic accuracy of clinical-based (SARCULATOR nomograms) and molecular-based (CINSARC) prognostication tools, being one of the first molecular-based classifications capable of predicting OS in STS. The analysis of DNA-seq data from the same cohort revealed numerous and, in some cases, never documented molecular targets for precision treatment across different transcriptomic subtypes. The functional and predictive value of each genomic variant was analyzed using the Molecular Tumor Board Portal. Conclusions : This newly identified TC-based classification offers a superior prognostic value when compared with current gold-standard clinical and molecular-based prognostication tools, and identifies novel molecular targets for precision treatment, representing a cutting-edge tool for predicting prognosis and guiding treatment across different stages of STS.

Liver metastases from soft tissue sarcoma (STS) (excluding gastrointestinal stromal tumors) are rare and more commonly arise from retroperitoneal and intra-abdominal primary sites. Chemotherapy remains the mainstay of treatment for disseminated disease, but its effectiveness is limited and patients typically have a dismal prognosis with short survival. However, when metastases are confined to the liver (without pulmonary involvement), some patients may benefit from local techniques, either surgical or nonsurgical, that can provide long periods of disease-free survival. Due to the rarity of STS, especially with liver metastases, and the heterogeneity of histologies and biological behavior, there is a lack of standardized treatment guidelines and universally accepted criteria for this specific setting. To fill this gap, a multidisciplinary working group of experts in sarcoma and liver surgery reviewed the literature and available evidence and developed a set of clinical recommendations to be voted and discussed in the I Ibero-American Consensus on the Management of Metastatic Sarcoma, held at the III Spanish-Portuguese Update Meeting on the Treatment of Sarcomas in May 2024. Herein, the voting results of this meeting and the resulting consensus recommendations are presented, and their applicability, strengths, and limitations are discussed.

Background: Uterine sarcomas represent a small and heterogeneous subgroup of uterine malignancies (accounting for less than 5%), characterized by high biological aggressiveness, high recurrence rates, and diagnostic complexity; surgical management remains the cornerstone of treatment and, consequently, the primary determinant of patient prognosis. Objective: This review synthesizes current evidence regarding the accurate diagnosis and appropriate surgical management of the main histological subtypes of uterine sarcoma across different stages, within a multidisciplinary therapeutic framework. Methods: A comprehensive narrative review was conducted using recent publications from major biomedical databases, with an emphasis on studies exploring surgical outcomes, molecular profiling, therapeutic strategies, and survival patterns. Results: Leiomyosarcoma and endometrial stromal sarcoma represent more than 80% of histological subtypes, with histological grade being the factor of greatest prognostic significance. Complete disease resection, without tumor fragmentation and with negative surgical margins, is the undisputed standard objective. Variations from the standard treatment—en bloc total hysterectomy with bilateral salpingo-oophorectomy—exist depending on histology and tumor staging. Conclusions: Individualized surgical treatment tailored to the specific histological subtype, combined with multimodal treatment strategies based on accurate tumor staging, molecular characterization, and recurrence patterns, is essential to improve survival. Such management should be conducted in referral centers with expertise in treating these rare and fearsome malignancies.