Primary Retroperitoneal Sarcoma Research Articles

Association Between Ageing and Short-Term Survival Outcomes in Patients Undergoing Surgery for Primary Retroperitoneal Sarcoma.

As the population ages, more elderly patients are receiving surgery for retroperitoneal sarcoma (RPS). However, high-quality data investigating associations between ageing and prognosis are lacking. Our study aimed to investigate whether ageing is associated with inferior short-term survival outcomes after RPS surgery. Patients undergoing surgery for primary RPS between 2008 and 2019 at two tertiary sarcoma centres were analysed. The primary outcome was 1-year mortality, and the primary explanatory variable was patient age, classified as: < 55, 55-64, 65-74 or 75+ years. The 692 patients undergoing surgery (mean age 60.8 ± 13.8 years) had a 1-year mortality rate of 9.4%, which differed significantly by age (p < 0.001), with rates of 7.2%, 6.9%, 8.7% and 22.8% for the < 55, 55-64, 65-74 and 75+ years groups, respectively. The distribution of causes of death also differed significantly by age (p = 0.023), with 22% and 28% of deaths in the 65-74 and 75+ years groups caused by post-operative complications, versus none in the < 55 and 55-64 years groups. On multivariable analysis, age of 75+ years (versus < 55 years) was a significant independent predictor of 1-year mortality [odds ratio (OR) 7.05, 95% confidence interval (CI) 2.63-18.9, p < 0.001]; no significant increase in risk was observed in the 55-64 (OR 0.72, 95% CI 0.28-1.87) or 65-74 (OR 0.89, 95% CI 0.37-2.15) years groups. Post-operative complications are an important cause of deaths in elderly patients. These findings are relevant to decision-making and counselling when surgery is considered for patients with RPS.

Preoperative Radiotherapy in Patients With Primary Retroperitoneal Sarcoma: EORTC-62092 Trial (STRASS) Versus Off-trial (STREXIT) Results.

The aim of the present study was to compare the effect of radiotherapy (RT) on abdominal recurrence-free survival (ARFS) in patients with primary retroperitoneal sarcoma treated in the EORTC-STBSG-62092 (STRASS) phase 3 randomized controlled trial (STRASS cohort) and off-trial (STREXIT cohort) and to pool STRASS and STREXIT data to test the hypothesis that RT improves ARFS in patients with liposarcoma. The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S). All consecutive adult patients not enrolled in STRASS and underwent curative-intent surgery for a primary retroperitoneal sarcoma with or without preoperative RT between 2012 and 2017 (STRASS recruiting period) among ten STRASS-recruiting centres formed the STREXIT cohort. The effect of RT in STREXIT was explored with a propensity score (PS)-matching analysis. Primary endpoint was ARFS defined as macroscopically incomplete resection or abdominal recurrence or death of any cause, whichever occurred first. STRASS included 266 patients, STREXIT included 831 patients (727 after excluding patients who received preoperative chemotherapy, 202 after 1:1 PS-matching). The effect of RT on ARFS in STRASS and 1:1 PS-matched STREXIT cohorts, overall and in patients with liposarcoma, was similar. In the pooled cohort analysis, RT administration was associated with better ARFS in patients with liposarcoma [N=321, hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.42-0.89]. In particular, patients with well-differentiated liposarcoma and G1-2 dedifferentiated liposarcoma (G1-2 DDLPS, n=266) treated with RT+S had better ARFS (HR, 0.63; 95% CI, 0.40-0.97) while patients with G3 DDLPS and leiomyosarcoma had not. At the current follow-up, there was no association between RT and overall survival or distant metastases-free survival. In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS.

Feasibility of Preoperative Dose-Painting Intensity Modulated Radiation Therapy (IMRT) for Borderline-Resectable Primary Retroperitoneal Sarcoma.

The role of radiation therapy (RT) in resectable retroperitoneal sarcoma (RPS) remains controversial; however, preoperative RT may play an important role in borderline-resectable (at risk of R2 resection) disease. We evaluated the outcome of such patients treated with preoperative dose-painting IMRT followed by planned resection. Between January 2001 and December 2017, 30 patients with borderline-resectable primary nonmetastatic RPS (after multidisciplinary review) received preoperative dose-painting IMRT in this retrospective cohort study. Median follow-up for all patients was 32 months. Median dose to the whole tumor/high-risk margin was 50.4 Gy/60.2 Gy. Sixteen patients were female, 24 were >50 years. Median tumor size was 9.2 cm. After RT, 6 did not have surgery. Of the 24 who were explored, 20 underwent complete gross resection. During RT, 7 of 30 patients developed acute grade 2+ toxicities: 5 fatigue, 1 nausea and vomiting, and 1 cystitis. RT was completed in 29 of 30 patients. Postoperatively, 12 of 20 patients developed grade 2+ complications: 2 gastropathy, 5 intraabdominal collections requiring drainage, 1 retroperitoneal bleed, and 3 delayed wound healing. Late grade 2+ toxicity was observed in 3 of 20 patients: 1 lymphedema with recurrent cellulitis, 1 chronic diarrhea, 1 gastrointestinal bleeding from anastomosis requiring transfusions, and 2 renal insufficiency. In those who underwent complete gross resection (n = 20, median follow-up 47 months), the 5-year local control was 57%, and overall survival was 46%. Preoperative dose-painting IMRT given to borderline-resectable RPS rendered 67% of patients resectable, provided a 5-year local control rate of 57%, which is similar to those with resectable disease, and had an acceptable morbidity profile.

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

Impact of time to first relapse on long-term outcome in adult retroperitoneal sarcoma patients after radical resection

BackgroundLocal recurrence of primary retroperitoneal sarcoma (RPS) is one of the major causes of treatment failure and death. We attempted to assess the effects of time to local recurrence (TLR) on the survival after recurrence (SAR) and overall survival (OS) of RPS.MethodsIncluded in this study were 224 patients who underwent R0 resection for primary RPS at our institution between January 2000 and December 2020, 118 of whom had local recurrence. Based on the median TLR (19.8 months), patients were divided into two groups: early local recurrence (ELR < 20 months) and late local recurrence (LLR > 20 months). The Kaplan–Meier method was employed to calculate the local recurrence-free survival (LRFS), SAR and OS. Univariate and multivariate analyses were conducted to explore the prognostic value of TLR.ResultsThe median follow-up time was 60.5 months for the entire cohort and 58.5 months for the recurrence cohort. There were 60 (50.8%) patients in the ELR group and 58 (49.2%) in the LLR group. The ELR group exhibited a worse SAR (29.2 months vs. 73.4 months, P < 0.001), OS (41.8 months vs. 120.9 months, P < 0.001), and a lower 5-year OS rate (35.9% vs. 73.2%, P = 0.004) than the LLR group. Furthermore, multivariate analysis indicated that TLR was an independent prognostic indicator for SAR (P = 0.014) and OS (P < 0.001).ConclusionsIn patients with RPS, ELR after R0 resection presents adverse effects on OS and SAR than those with LLR, and TLR could serve as a promising predictor for OS and SAR.

Management of recurrent retroperitoneal sarcomas

Recurrent retroperitoneal sarcomas are rare, with patterns of recurrence determined by the histologic subtype. A range of patient characteristics and treatment profiles combined with a myriad of presentations and clinical courses of recurrences make this diverse entity challenging to manage. Although surgical resection improves survival in select patients, the oncological outcomes are inferior to that of primary retroperitoneal sarcomas. Management options for unresectable disease include local ablative therapy, radiation and systemic therapy, with palliative surgery indicated occasionally. Attempts at disease control must be balanced with potential morbidity and impact on the patient's quality of life. This review aims to offer insights into the current understanding of recurrent retroperitoneal sarcomas and provide some guidance on management.

Risk of misclassification during diagnosis of malnutrition in retroperitoneal sarcoma patients.

Retroperitoneal sarcoma (RPS) is a rare tumour that can reach exceptionally large size at diagnosis and affects body weight with its volume. We investigated the risk of nutritional status misclassification based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in RPS patients. We retrospectively analyzed the baseline data of patients with primary RPS including anthropometry, Malnutrition Universal Screening Tool (MUST) score and skeletal muscle index (SMI) calculated on preoperative CT scan. Phenotypic GLIM criteria considered were non-volitional weight loss, low-BMI and low muscle mass. MUST score, being inclusive of weight loss, was chosen as its surrogate. Reduced muscle mass was defined with SMI cut-offs <38.5-52.4cm2/m2 for female and male respectively. From 2018 to 2020, 100 consecutive patients (male/female: 48/52) were included. Median age was 61 (48-68) years, median BMI 24.6 (21.5-27.4) kg/m2. Seven patients (7%) reported MUST score ≥2 and 80 (80%) score 0. Five patients (5%) were underweight, 44 (44%) overweight and obese. Sixty patients (60%) presented low SMI, of those 56 (93%) were normal or overweight, and 46 (77%) not at nutritional risk according to the MUST score. Both underweight BMI and MUST score ≥2 were not correlated with low SMI (p=0.406, p=0.612, respectively). No relevant discrepancy was found in the postoperative course of patients with low or normal muscle mass, although SMI was able to better characterize nutritional risk in the proportion of patents with high-grade liposarcoma and predicted worst overall survival. GLIM criteria are a useful tool for diagnosis of malnutrition. However, our analysis suggests that phenotypic criteria are not interchangeable with each other. An altered body composition is often hidden in patients with retroperitoneal sarcoma and the use of weight-based classification does not seem to be appropriate, enhancing the role of mass muscle measurement to prevent misdetections of malnourished patient.

Histology-tailored multidisciplinary management of primary retroperitoneal sarcomas

Until recently, the recommendation for primary retroperitoneal sarcomas (RPS) was to perform a complete en-bloc gross excision, (neo) adjuvant treatments being options which were not validated by randomized studies, with a large discrepancy of use between centers. The heterogeneity of RPS, with their different biological behaviour, renders a homogenous therapeutic and surgical approach probably inappropriate. Recent studies, both surgical and dedicated to adjuvant treatments, allow refining these recommendations. This review summarizes recent advances and directions.

Neoadjuvant Therapy for Primary Resectable Retroperitoneal Sarcomas-Looking Forward.

Simple SummaryThis review summarizes the current evidence around neoadjuvant radiotherapy and systemic therapy for retroperitoneal sarcoma (RPS). While surgery is the cornerstone of treatment for these tumors, data from prospective studies, retrospective studies, early phase trials, and—most recently—our first phase III randomized trial for RPS suggest there are clinical scenarios in which neoadjuvant therapy may provide benefit. This review evaluates the STRASS results in the setting of other recent studies, identifies active trials of interest, and suggests future directions of study in this field. The intersection of STRASS and STRASS2 is considered and a summary of current acceptable approaches to neoadjuvant therapy for RPS is provided. The cornerstone of therapy for primary retroperitoneal sarcomas (RPS) is complete surgical resection, best achieved by resecting the tumor en bloc with adherent structures even if not overtly infiltrated. Until recently, trials designed to elucidate the role of neoadjuvant radiation or chemotherapy for RPS have been unable to achieve sufficient enrollment. The completion of the STRASS trial, which explored neoadjuvant radiotherapy for primary resectable RPS, is a major milestone in RPS research, but has prompted further questions about histology-driven treatment paradigms for RPS. Though it was ultimately a negative trial with respect to its primary endpoint of abdominal recurrence-free survival, STRASS produced a signal that suggested improved abdominal recurrence-free survival with neoadjuvant radiotherapy (RT) for patients with liposarcoma (LPS). No effect was seen for leiomyosarcoma (LMS) or high-grade dedifferentiated (DD) LPS, consistent with recent literature suggesting LMS and high-grade DD-LPS have a predominant pattern of distant rather than local failure. These results, along with those from other recent studies conducted at the bench and the bedside, emphasize the importance of a histology-specific approach to RPS research. Recent evidence for patterns of distant failure in LMS and high-grade DD-LPS has prompted the initiation of STRASS2, a study of neoadjuvant chemotherapy for these histologies. As this study unfolds, evidence may emerge for novel systemic therapy options in specific sarcoma histotypes given the explosion in targeted and immunotherapeutic applications over the last decade. This article reviews current and recent evidence around neoadjuvant radiation and chemotherapy as well as avenues for future study to optimize these treatment approaches.

ASO Visual Abstract: The Effect of Preoperative Treatment on the Performance of Predictive Nomograms in Primary Retroperitoneal Sarcoma (RPS)

ASO Visual Abstract: The Effect of Preoperative Treatment on the Performance of Predictive Nomograms in Primary Retroperitoneal Sarcoma (RPS)

Delayed Gastric Emptying After Multivisceral Resection for Retroperitoneal Sarcoma.

Delayed gastric emptying (DGE) is a common complication in surgery, but incidence and relevance following multivisceral resection are unknown. Data from 100 consecutive patients treated for primary retroperitoneal sarcoma (RPS) were analyzed from our institutional prospectively maintained database from January 2019 to April 2020. DGE severity was graded according to the International Study Group of Pancreatic Surgery and classified as primary or secondary to other complications. The primary outcome was incidence and grade of clinically relevant DGE (grades B-C). Secondary outcomes were correlation with patient, tumor, and treatment characteristics, and non-DGE morbidity [Clavien-Dindo (CD) grade ≥ 3]. Forty-two patients developed DGE and 28 had clinically relevant DGE. DGE was primary in 10 patients and secondary in 18 patients; the most common associated complications were: infections (11/18, 61.1%), pancreatic leak (7/18, 38.9%), bleeding (6/18, 33.3%), and bowel leak (6/18, 33.3%). DGE was related to longer length of hospital stay (P < 0.001), ICU admission (P = 0.004), ICU length of stay (P = 0.001), postoperative complications (CD [Formula: see text] 3 in 14/28 in DGE patients vs 11/72 in no-DGE; P = 0.04), and re-operation (P = 0.03). With multivariate analysis, the independent risk factors for DGE were patient comorbidities (OR 1.05; 95% CI 1.01-1.1; P = 0.04) and tumor size (OR 1.05; 95% CI 1.0-1.1; P = 0.02). Following multivisceral resection, DGE is a clinically relevant event that can be caused by an underlying complication. Prompt diagnosis and treatment of both DGE and any underlying complications led to full recovery in all cases.

Effect of Preoperative Treatment on the Performance of Predictive Nomograms in Primary Retroperitoneal Sarcoma.

Retroperitoneal sarcoma (RPS)-specific nomograms provide estimates of survival and recurrence risk following resection in the individual patient. The effect of preoperative treatment on nomogram performance has not been previously examined. Our aim was to evaluate the predictive accuracy of existing RPS-specific nomograms in patients managed at our center, where the majority of patients received preoperative radiation. All patients who underwent curative treatment for primary RPS at Mount Sinai Hospital/Princess Margaret Hospital between 1996 and 2016 were identified. The performance of four previously published nomograms was assessed by measuring the agreement between nomogram-predicted and observed outcomes using Harrell's C-Index and level of calibration. Outcomes included in each of the nomograms [overall survival (OS), disease-free survival (DFS), disease-specific death (DSD), local recurrence (LR), distant recurrence (DR)] at each of the specified post-resection timepoints were examined. In total, 253 patients were included. When observed outcomes were compared with those predicted by each of the four nomograms, the C-Index ranged from 0.60 to 0.81, representing a wide range of predictive accuracy. The lowest C-Index was for prediction of LR. Calibration plots revealed that the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram predicted a 5-year LR of 45%, whereas the observed LR was 24%. Overprediction of LR was detected in patients who had undergone preoperative radiotherapy, but not in patients treated with surgery alone. Preoperative radiotherapy appeared to preclude the use of the LR component of existing nomograms for primary RPS. Updated nomograms should be created to reflect this variable, particularly in light of the recently published STRASS trial results.

Tumor grade and symptoms at presentation are survival risk factors in Chinese patients with primary retroperitoneal sarcoma

No cohort studies have been performed on Chinese primary retroperitoneal sarcoma (RPS) patients. Data derived from western cohort studies may not be directly superimposable on Asian counterparts. Furthermore, the risk factors for survival of RPS are currently unknown for Chinese patients. The objectives were therefore to (1) gain insight into RPS incidence and patient demographics and clinical details; (2) determine the risk factors for overall survival (OS) and disease-free survival (DFS); and (3) critically appraise the Asian cohort data in relation to information obtained in western cohort studies. In this retrospective cohort study, the health records of patients that had been diagnosed with primary localized RPS with curative intent between 2009 and 2020 were analyzed. Cox proportional hazards analysis was conducted to evaluate the risk factors for OS and DFS. A total of 261 patients met the inclusion criteria. Ninety-six (36.8%) patients had been diagnosed with well-differentiated liposarcoma, 63 patients (24.1%) with dedifferentiated liposarcoma, 41 patients (15.7%) with leiomyosarcoma (LMS), 22 patients (8.4%) with solitary fibroma, 7 patients (2.7%) with malignant peripheral nerve sheath tumor (MPNST), and 32 patients (12.3%) with another type of RPS. The study further revealed that (1) the 5-y OS and DFS in RPS patients was 67.8% and 51.3%, respectively, with the highest OS and DFS observed in MPNST (100% and 100%, respectively) and the lowest 5-y OS and DFS attributed to LMS (42.6% and 28.9%, respectively); (2) symptoms at presentation, Federal National Cancer Center (FNCLCC) grade, and number of combined resections are independent risk factors in OS; (3) symptoms at presentation, FNCLCC grade, chemotherapy, and hospital length of stay are independent risk factors for DFS; and (4) patients at high risk (symptoms at presentation and high-grade tumors) have less than half the chance of survival at 5 y post-diagnosis than patients with a low-risk profile. Symptoms at presentation constitute a risk factor for OS and DFS. When combined with tumor grade - another risk factor for both OS and DFS - patients can be classified into a high-risk and low-risk category to gauge a patient's prognosis and, accordingly, frame an optimal clinical trajectory. Moreover, the clinicopathology and overall prognosis of RPS in Asian and Western populations are comparable and hence superimposable. The present study identifies the risk factors of survival in RPS and suggests symptoms at presentation should be considered in the preoperative consultation and added in prognostic grouping.

Measuring the impact of complications after surgery for retroperitoneal sarcoma: Is comprehensive complication index better than Clavien-Dindo Classification?

BackgroundTo compare the Clavien-Dindo classification (CDC) and the Comprehensive Complication Index (CCI) in retroperitoneal sarcoma (RPS) surgery in assessing the real burden of post-operative complications on both post-operative length of stay and total costs of hospitalization (PLOS and TCH, respectively). Study designA series of 417 procedures for both primary and recurrent RPS between January 2000 and December 2017 was analyzed. Complications were classified according to both CDC and CCI. Univariable linear regressions were used to assess predictors associated with PLOS and TCH. Multivariable linear regression models were constructed to identify the factors independently associated with PLOS and TCH. ResultsMedian PLOS was 10 days (interquartile range [IQR] 7–16); median TCH was 7033.5€ (IQR 1350–305.900). Post-operative complications occurred in 170/417 (40.7%) of the procedures and in 75/417 (17.9%) of the procedures CDCs >3 were identified. Sixty-four (15.34%) patients had more than one complication. Univariable linear regression showed that both PLOS and TCH were significantly associated to both CDC and CCI among other factors. Multivariable linear analyses selected CDC and CCI as independent prognostic factors for both PLOS and TCH. According to the AIC and BIC, models including CCI performed better (5559.53 and 5598.18, respectively, compared with 5561.31 and 5599.95 for CDC models). ConclusionThe CCI resulted to perform better than the CDC in describing the overall burden of complications after RPS surgery, both for clinical and economic purposes.

Postnephrectomy outcomes following en bloc resection of primary retroperitoneal sarcoma: multicentre study.

This article reports on postoperative renal function in the largest series of patients with primary retroperitoneal sarcoma undergoing nephrectomy at three high-volume sarcoma centres. Although half of patients develop chronic kidney disease of stage 3 or higher, rarely do patients develop acute renal failure requiring renal replacement therapy.

Retroperitoneal soft tissue sarcoma: surgical management

Retroperitoneal soft tissue sarcomas are rare and heterogeneous tumors with high recurrence rates that require amultimodal treatment approach and asurgical resection strategy adapted to tumor localization and histological subtype. Based on current scientific data this article intends to provide an overview on subtype-specific features, prognostic factors and operative techniques in the surgical management of retroperitoneal soft tissue sarcomas. Areview of the literature addressing surgical management of retroperitoneal soft tissue sarcomas was performed. Current evidence and recommendations were summarized. Macroscopically complete tumor resection represents the sole curative treatment option for both primary and recurrent retroperitoneal soft tissue sarcomas. To minimize the probability of tumor-infiltrated resection margins, compartmental resection has become astandard treatment for retroperitoneal soft tissue sarcomas. This approach includes resection of all organs and structures adjacent to the tumor. Multivisceral resection is often associated with this approach and it is acceptable in terms of morbidity and mortality if performed at acenter with experience in retroperitoneal sarcoma surgery. Histologic subtype, tumor grading, and quality of initial surgical treatment are major prognostic factors for oncologic overall survival.

Longitudinal prognostication in retroperitoneal sarcoma survivors: Development and external validation of two dynamic nomograms

PurposeThe aim of this study was to create and validate dynamic nomograms to predict overall survival (OS) and disease-free survival (DFS) at different time points during follow-up in patients who had undergone resection of primary retroperitoneal sarcoma (RPS). MethodsPatients with primary RPS operated upon between 2002 and 2017 at four and six referral centres comprised the development and external validation cohorts, respectively. Landmark analysis and multivariable Cox models were used to develop dynamic nomograms. Variables were selected using two backward procedures based on the Akaike information criterion. The prediction window was fixed at 5 years. Nomogram performances were tested in terms of calibration and discrimination on the development and validation cohorts. ResultsDevelopment and validation cohorts totalled 1357 and 487 patients (OS analysis), and 1309 and 452 patients (DFS analysis), respectively. The final OS model included age, landmark time (TLM), tumour grade, completeness of resection and occurrence of local/distant recurrence. The final DFS model included TLM, histologic subtype, tumour size, tumour grade, multifocality and the interaction terms between TLM and size, grade and multifocality. For OS, Harrell C indices were higher than 0.7 in both cohorts, indicating very good discriminative capability. For DFS, Harrell C indices were between 0.64 and 0.72 in the development cohort and 0.62 and 0.68 in the validation cohort. Calibration plots showed good agreement between predicted and observed outcomes. ConclusionValidated nomograms are available to predict the 5-year OS and DFS probability at different time points throughout the first 5 years of follow-up in RPS survivors.

Prognostic implications of histological organ involvement in retroperitoneal sarcoma.

BackgroundThe prognostic significance of histological organ involvement by retroperitoneal sarcoma subtype is unknown. The present study aimed to describe organ involvement across the subtypes, and the implications for survival.MethodsPatients undergoing surgery for primary retroperitoneal sarcoma at the Queen Elizabeth Hospital, Birmingham from April 2005 to September 2018 were identified retrospectively. Histological organ involvement was classed as pushing, infiltrative or neither. Univariable and multivariable Cox regression models were produced to analyse the association between histological organ involvement and both overall (OS) and recurrence-free (RFS) survival for the cohort as a whole, and by histological subtype.ResultsData were available for a total of 197 patients, of whom 171 (86.8 per cent) had at least one organ resected. Infiltrative organ behaviour was seen in 37 patients (18.8 per cent), and pushing behaviour in 67 (34.0 per cent). For the cohort as a whole, infiltration (hazard ratio (HR) 4.32, 95 per cent c.i. 2.35 to 7.93; P < 0.001), but not pushing (HR 1.62, 0.90 to 2.92; P = 0.106), was associated with significantly shorter OS, in comparisons with a group with neither of these behaviours. However, this effect was found to differ significantly by histological subtype (P = 0.009). For patients with dedifferentiated liposarcoma, there was no significant association between tumour behaviour and either OS (P = 0.508) or RFS (P = 0.313). However, in leiomyosarcoma, infiltrative behaviour was associated with shorter OS (P = 0.002), and both infiltrative (P < 0.001) and pushing (P = 0.010) behaviours were associated with shorter RFS, compared with tumours with neither behaviour. Multivariable analyses of both OS and RFS returned similar results.ConclusionThe prognostic implications of organ involvement in retroperitoneal sarcoma vary by histological subtype.

Multidisciplinary Management of Retroperitoneal Sarcoma: Diagnosis, Prognostic Factors and Treatment

Simple SummaryThe management of retroperitoneal sarcomas can be challenging due to the variety of their presentation, histopathological types, and behaviours. This literature review provides a comprehensive and practical overview of the management of retroperitoneal sarcomas, focusing on diagnostic challenges, prognostic factors, multidisciplinary aspects of treatment and new research perspectives.Retroperitoneal sarcomas (RPS) are rare cancers whose management can be challenging due to various presentation patterns, multiple organ involvement, and a high local and distant recurrence rate. Histopathology and prognostic factors analysis are essential to predict the behaviour of the disease and plan the best therapeutic strategy. To date, surgery is still the main therapeutic option that guarantees a chance of cure from the primary disease. While chemotherapy and radiotherapy seem to be good options for controlling metastatic and recurrent irresectable disease, their role in the treatment of primary RPS remains unclear. This literature review aims to provide a comprehensive overview of the multidisciplinary aspects of RPS management in high-volume centres, summarising the diagnostic path, the prognostic factors, and the most suitable therapeutic options.

Primary Adult Retroperitoneal Sarcoma: A Comprehensive Genomic Profiling Study

Background: Adult primary retroperitoneal sarcomas (RPSs) are a group of heterogeneous tumors with different histological subtypes. Comprehensive genomic profiling (CGP) analyses have recently provided significant insights into the biology of sarcomas by identifying genomic alterations (GAs) which could benefit from targeted therapies. Methods: RPS were evaluated by CGP using next-generation sequencing of up to 406 cancer-related genes. Tumor mutational burden (TMB) was determined on 0.83 to 1.14 mut/Mb of sequenced DNA. Finally, PD-L1 expression was determined. Results: Overall, 296 cases of primary RPS were analyzed. Liposarcoma (LPS) subtype had more GA/tumor than leiomyosarcoma (LMS) subtypes, with follicular dendritic cell sarcomas harboring the highest and synovial sarcomas the lowest. TP53 and Rb1 alterations were the highest in LMS, and CDK4/6 and MDM2 in LPS. However, both the TMB and targetable GA rates were low across subtypes. PD-L1 immunostaining was low positive in 21% and high positive in 5% of patients, respectively. Conclusions: CGP analysis revealed that potentially actionable genomic targets were rare in our cohort of RPS. Moreover, RPSs seem less likely to respond to immune checkpoint inhibitors based on putative biomarkers status. Nevertheless, genomic stratification according to histological subtypes led to description of GAs that can inform future clinical trials design.