Initial local resection versus early referral for spermatic cord sarcoma: Any impact on treatment timelines and oncological outcomes?

OBJECTIVES: Spermatic cord sarcomas are exceedingly rare, often misdiagnosed and subsequently improperly treated at local hospitals. This retrospective study looked at the oncological outcomes of spermatic cord sarcoma cases managed with curative intent resection at a tertiary referral sarcoma centre. We specifically studied how initial inadequate resections impact the oncologic outcomes compared to primary tumour resections at the reference centre. METHODS: One hundred eighteen consecutive patients affected by primary, localized spermatic cord sarcoma surgically managed at our reference centre from January 2001 through January 2021 were included. Primary endpoints were local relapse free (LRFS), distant metastasis free (DMFS) and overall survival (OS). These outcomes were evaluated with multi-nomial logistic regression and Cox proportional hazards regression models for a co-relation to known patient, tumour and treatment-related prognostic factors, including a prior inadequate resection and time from diagnosis to a complete oncologic resection as independent variables. Secondarily, we compared the above variables and treatment intervals among the subgroups of primary versus re-resection surgery. RESULTS: Over a median follow-up of 54 months (IQR 25-105), 12 patients (10.2%) developed local recurrence (LR) and 14 (11.6%) had distant metastasis (DM). 5-year local relapse (LRFS) and distant metastasis-free survival (DMFS) were 89.3% and 86.5%, respectively. Higher tumour grade and size were associated with a worse DMFS (p=<0.05). Likewise, marginal (R1) resection correlated with an inferior LRFS (p=< 0.05). Eighty-four patients (71.2%) had their initial diagnosis established on an inadequate surgical excision performed in a local hospital, followed by a re-excision at our centre (Re-resection group). During the same period, 34 (28.8%) were managed primarily with biopsy and treatment at our reference centre (Primary-resection group). The two groups had statistically significant differences in tumour size, histopathology, surgery duration, rate of postoperative complication and R0 resection (p < 0.005). Additionally, the difference in time intervals to achieve the treatment targets was statistically insignificant and did not correlate to the risk of recurrence as an independent variable. Residual disease was present in 51.2 % (n = 43) of the re-excision specimens. However, following a complete R0 resection, this did not correlate with a higher risk of recurrence (p = 0.481). CONCLUSION: Prompt referral to a tertiary centre, where multidisciplinary evaluation and sound oncologic resections are the standard of treatment, can align the OS and DFS of patients receiving incomplete surgery elsewhere to those treated primarily in referral centres. The primary determinant of prognosis remains surgical margin, tumour size and grade.

Pathological and radiological response following neoadjuvant treatments in primary localized resectable myxofibrosarcoma and undifferentiated pleomorphic sarcoma of the extremities and trunk wall.

BACKGROUND: To explore the correlation between pathological and radiological response to preoperative treatments and outcome in surgically treated patients with myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). METHODS: All consecutive patients with primary localized MFS and UPS of the extremities and trunk wall surgically treated with curative intent at our center (2005-2021) were included. Clinical data including residual visible tumor (VT%) on surgical specimen and Response Evaluation Criteria in Solid Tumor (RECIST) were retrieved. Kaplan-Meier curves for overall survival and disease-free survival, and cumulative incidence of local relapse and distant metastasis were estimated in a competing risk framework according to RECIST and VT%, overall and by treatment group. Cox and Fine and Gray multivariable models were performed. RESULTS: Of 693 patients affected by primary MFS and UPS, 233 (66 MFS and 167 UPS) were treated by neoadjuvant chemotherapy (naChT), radiotherapy (naRT), or both (naChT-RT). VT% was ≤5% in 13/46 (28.2%), 24/99 (24.2%), and 40/88 (45.4%) patients, respectively. There were 11/46 (29.7%), 22/99 (22.7%), and 23/88 (26.1%) RECIST partial responses and 18/46 (48.6%), 59/99 (60.8%), and 60/88 (68.2%) RECIST stable disease, respectively. In naChT, a trend for a better survival was observed when VT% ≤5% (p = .09), whereas RECIST partial responses and stable disease had the same outcome. VT% was not associated with outcome in naRT or naChT-RT, whereas RECIST response was. CONCLUSION: In primary localized MFS and UPS treated with neoadjuvant therapies, VT% seems more relevant than size reduction after naChT, whereas the opposite is true when naRT is administered alone or concurrent to ChT.

Six Surgical Stages in the Resection of Primary Right Retroperitoneal Liposarcoma: A Standardized Comprehensive Approach.

BACKGROUND: Surgery is the treatment mainstay in retroperitoneal sarcoma (RPS), a frontline comprehensive approach based on tumor removal en bloc with adherent viscera is mandatory especially for liposarcoma, where the normal retroperitoneal fat is undistinguishable from the well-differentiated tumor component.1-5 In this video, a reproducible and standardized six-stage approach to a primary right retroperitoneal liposarcoma is presented. PATIENT AND METHODS: A 23-cm right retroperitoneal, well-differentiated liposarcoma was diagnosed in a 68-year-old female patient in December 2021. The tumor involved the right kidney and adrenal gland; displacing anteriorly the right colon, the duodenum, and the pancreatic head; and invading part of the ipsilateral psoas muscle. After the publication of the STRASS trial and STREXIT results,6,7 neoadjuvant radiotherapy was delivered to a total dose of 50.4 Gy in 28 fractions with stable disease. Virtual 3D reconstruction of regional anatomy by Visible Patient was performed preoperatively. RESULTS: The patient underwent right retroperitoneal mass resection en bloc with ipsilateral kidney and adrenal gland, colon, psoas muscle, and portion of ipsilateral diaphragm. Of note, the resection of the psoas muscle was performed to obtain a safe posterior margin and accomplish a better clearance of fat of the posterior abdominal wall. This can be limited to the psoas fascia whenever the tumor is not adherent to it. A six-stage approach was performed, as described in the supplementary video file. CONCLUSIONS: RPS resection is complex and requires a broad range of surgical expertise. A staged approach that can be followed in virtually all cases is highly recommended to achieve an optimal tumor resection.

Organ Infiltration and Patient Risk After Multivisceral Surgery for Primary Retroperitoneal Liposarcomas.

BACKGROUND: The extent of histological organ involvement (HOI) to organs and structures of a retroperitoneal liposarcoma may have prognostic implications. This study investigated incidence, characteristics, and risk association of HOI in these patients. PATIENTS AND METHODS: Data of patients who underwent multivisceral resection for primary liposarcoma (2009-2014) were retrospectively analyzed. HOI was the variable of interest and was classified into four degrees: absent (HOI-0), perivisceral (HOI-1), initial (HOI-2), and advanced (HOI-3). Primary endpoint was overall survival (OS). Secondary endpoint was disease-free survival (DFS). The prognostic value of HOI was adjusted for preoperative treatment and the Sarculator nomogram score. RESULTS: A total of 109 patients were included. HOI-0, HOI-1, HOI-2, and HOI-3 were detected in 9 (8.3%), 11 (10.1%), 43 (39.4%), and 46 (42.2%) patients. Median follow-up was 8.4 years [interquartile range (IQR) 7.2-9.6 years]. There were 68 recurrences and 50 patient deaths observed, resulting in a 10-year OS and DFS of 51.1% [95% confidence interval (CI) 41.9-62.1%] and 34.1% (95% CI 25.2-46.1%), respectively. Clinically relevant HOIs (HOI-2 and HOI-3) were found in 35/45 (77.8%) and 54/64 (84.4%) cases of well- and de-differentiated liposarcomas, respectively. On multivariable survival analysis, patients with HOI-3 had significantly shorter OS (HOI-3 vs HOI-0/HOI-1 HR 2.92; p = 0.012) and DFS (HOI-3 vs HOI-0/HOI-1 HR 2.23; p = 0.045), independently of the nomogram score (OS: HR 2.93; p < 0.001; DFS: HR 1.78; p = 0.003). CONCLUSIONS: Initial and advanced HOIs are frequently detected in both well-differentiated and de-differentiated liposarcomas, supporting that multivisceral resection may be needed. HOI stratifies the risk of patients with primary retroperitoneal liposarcoma.

Long-term survivors with desmoplastic small round cell tumor (DSRCT): Results from a retrospective single-institution case series analysis.

OBJECTIVE: To report on a retrospective study of primary DSRCT aiming at characterizing long-term survivors (LTS). METHODS: All consecutive patients treated at our institution for a primary DSRCT between 2000 and 2021 were retrospectively identified. Patients received multiagent chemotherapy ± surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) ± whole abdomino-pelvic radiotherapy (WAP-RT) ± high-dose chemotherapy ± maintenance chemotherapy (MC). Event-free survival (EFS) and overall survival (OS) were estimated by Kaplan-Meier method. Patients alive, without evidence of disease at ≥36 months from diagnosis, were defined as LTS. RESULTS: Thirty-eight patients were identified. All received multiagent chemotherapy; 27/38 (71%) surgery (7/27 [26%] plus HIPEC), 9/38 (24%) WAP-RT, 12/38 (32%) MC. At a median-follow-up of 37 months (IQR 18-63), overall median-EFS and median-OS were 15 and 37 months, respectively. All events occurred within 35 months. In patients who underwent surgery, median-EFS and median-OS were 19 and 37 months (23 and 43 months after R0/R1, and 10 and 19 months after R2 resection), respectively. LTS were 5/38 (13%), alive at 37, 39, 53, 64, 209 months. None had liver or extra-abdominal metastasis at diagnosis, they all received R0/R1 resection, 3/5 had WAP-RT, 2/5 MC, 1/5 received high-dose chemotherapy, none HIPEC. CONCLUSIONS: In our series cure was likely achieved in 13% of DSRCT. LTS had no liver/extra-abdominal disease, were treated with complete surgery, and possibly WAP-RT/MC.

Long term outcome of complex surgical resection and reconstruction for rare thoracic cancers.

BACKGROUND: Complex surgical resection and reconstruction for rare thoracic cancers (RTCs) represent a major challenge, given their very low frequency, extreme variability of presentation, multi-modality treatment options and inadequate outcome prediction. We analysed the experience of a tertiary referral centre on a consecutive series of patients with thoracic germ cell tumours, thymomas and sarcomas, with the aim of reporting the long-term outcome by cancer type and complexity of surgical procedures. METHODS: From Jan 2003 to Dec 2018, 768 surgical procedures were performed with curative intent on 644 RTC patients. Study endpoints were: post-operative hospital stay (Pod), 30-day and 90-day mortality, 5-year and 10-year overall survival (OS). Median follow-up of alive patients was 7.2 years. RESULTS: Median Pod was 7 days, with a 1.2% 30-day and 2.9% 90-day mortality. OS was 90.8% at one year, 74.2% at five years and 62.8% at 10 years. Ten-year OS was 73.0% in low, 65.3% in intermediate, and 55.6% in high complexity score (Log-rank tests p<0.0001); 66.6% in patients with one or two reconstructions and 46.4% in patients with three or more reconstructions (p<0.0001); 46.0% with vascular and 50.0% with chest wall reconstruction; 71.8% in germ cell tumours, 64.6% in thymoma and 51.3% in sarcoma (p<0.0001). CONCLUSION: Complex surgical resection and reconstruction was associated with acceptable 90-day mortality and good 10-year survival in all RTC types. A predictive score based on surgical complexity and cancer type can help the clinical decision making.

Residual Adrenal Function After Multivisceral Resection With Adrenalectomy in Adult Patients.

Importance: The risk of developing adrenal insufficiency (AI) following adrenalectomy has been insufficiently studied in the context of multivisceral resection (MVR). Objective: To evaluate the incidence of AI in patients undergoing MVR with en bloc adrenalectomy. Design, Setting, and Participants: Prospective observational longitudinal study in a single referral center including 56 consecutive adult patients undergoing retroperitoneal sarcoma surgery from June 2019 to August 2020. Those who were candidates for MVR with en bloc adrenalectomy and had no preexisting adrenal impairment were considered eligible. Of these, 4 individuals were excluded because they did not receive adrenalectomy at the time of surgery and 2 because they were not considered evaluable for the main end point. Follow-up was set at 4 months after surgery, and 49 patients completed follow-up. Data were analyzed from October 2020 to September 2021. Exposures: Diagnosis of AI was determined by low-dose (1 µg) adrenocorticotropic hormone (ACTH) stimulation test with a threshold of 20 µg/dL in blood samples retrieved 30 and 60 minutes after stimulation. ACTH test was repeated on postoperative days 1 and 10 and at 4 months' follow-up. Main Outcome and Measures: The primary end point was incidence and relevance of AI after MVR. Secondary end points were associations with patient- and tumor-related factors, impact on perioperative hemodynamic management, and association with postoperative morbidity and mortality. Results: Fifty patients (26 female; median [IQR] age, 59 [46-67] years) were evaluable. Incidence of AI was 64% (32 of 50 patients) in the early postoperative period and 38.5% (15 of 39 patients) at follow-up. Patients with AI showed lower postoperative cortisol values. Factors associated with risk of AI at univariate analysis were high American Society of Anesthesiologists score (odds ratio [OR], 0.31; 95% CI, 0.14-0.48) and high malignancy grade (OR, 0.35; 95% CI, 0.24-0.46). Clinical outcomes not associated with AI included morbidity, mortality, reoperation rate, admission to intensive care unit, length of intensive care unit stay, total hospital stay, and long-term quality of life. Conclusions and Relevance: In this study, AI after MVR with en bloc adrenalectomy was frequent, even in patients with adequate preoperative adrenal function. Despite this, adrenalectomy can be safely performed. Patients at risk should be monitored in the long term to exclude underrated impairment of adrenal function.

Treatment strategies and outcomes of primary Myxofibrosarcomas in a large patients cohort.

BACKGROUND: this study analysed primary myxofibrosarcoma (MFS) to investigate patient outcomes focusing on histopathologic margins and perioperative treatments. PATIENTS AND METHODS: data from consecutive patients affected by primary and localized MFS of the extremities or trunk wall who underwent surgery (2002-2017) were analysed. Local recurrence (LR), amputation rate, incidence of distant metastasis (DM), and overall survival (OS) were studied. RESULTS: Of 293 included patients, 52 (17%) patients received perioperative treatments and 54 (18%) had positive microscopic histopathologic margins (R1). Median follow-up was 80 months (IQR, 49-109). 5-yr CCI of LR was 0.12 (SE: 0.02). Status of histopathologic margins (P < 0.001), tumour malignancy grade (P = 0.018) and size (P = 0023) were independent prognostic factor for LR. Nine amputations (amputation rate: 3%) were performed (N = 1 for primary tumour; N = 8 for LR). Larger tumour size (P = 0.015) and higher grade (P = 0.025) were independent prognostic factor for DM. 5-year OS was 0.84 (95%CI 0.79-0.88). Patient age (P = 0.008), tumour size (P = 0.013) and malignancy grade (P = 0.018) were independently associated to OS. In the subgroup of patients who had a re-excision for a primary MFS (N = 116, 40%), the presence of residual disease was not associated with LR, DM, or OS. CONCLUSION: in this study 5-year LR, DM and OS were 12%, 17%, and 84%, respectively. One in six patients had a positive surgical margin, which was a prognostic factor for LR, while DM and OS were predicted by tumour grade and size. Findings from this large patient cohort may set benchmarks for investigating new treatment options for MFS.

Refining the Approach to Patients with Primary Soft Tissue Sarcoma of the Extremities and Trunk Wall: Outcome Improvement Over Time at a Single Institution.

BACKGROUND: The improved outcome of extremity soft tissue sarcoma patients surgically treated until 2007 at the authors' institution was previously reported. This study updates the analysis at a later follow-up and extends the patients' cohort to assess changes in outcomes over time for extremity and superficial trunk soft tissue sarcoma (ESTSTS) treated at a single referral center. METHODS: All consecutive patients with primary localized adult-type ESTSTS surgically treated at the authors' institution between 1987 and 2017 were included and divided into group 1 (1987-2002) and group 2 (2003-2017) according to primary surgery year. Crude cumulative incidence (CCI) of sarcoma-specific mortality (SSM), local recurrence (LR), and distant metastases (DM) were calculated in a competing-risks framework. DM-free survival (DMFS) and post-DM survival were also assessed. RESULTS: The study identified 2382 patients. The median follow-up was 104 months (range, 63-127 months), and the post-DM follow-up was 76 months (range, 37-126 months). Since 2003, an increased adoption of preoperative treatments was observed: the use of chemotherapy, radiotherapy and combined chemoradiotherapy went from 10.5% to 23.7%, from 1.7% to 17.8%, and from 1% to 11.8% respectively. This change in treatment strategies was associated to an improvement in CCI-SSM (27.8% vs 19.5%; P < 0.001), CCI-LR (14.1 vs 7.5%; P < 0.001), DMFS (57.9% vs 65.8%; P = 0.004), and post-DM (12.2% vs 20.1%; P = 0.012), but not in CCI-DM. CONCLUSIONS: Increased adoption of preoperative treatments and greater availability of medical agents in the recent years were associated to better outcomes. New treatments are eagerly awaited for further improvement of outcome for ESTSTS patients because no major changes have been observed since 2003.

Oncological outcomes after major vascular resections for primary retroperitoneal liposarcoma.

BACKGROUND: The surgical management of retroperitoneal sarcomas frequently involves complex multivisceral resections, however retroperitoneal liposarcoma (LPS) rarely invade major abdominal vessels. The aim of the study was to assess association of major vascular resections with outcome of primary LPS. METHODS: All consecutive patients who underwent resection at our institutions for primary LPS between 2002 and 2019 were included. A propensity matched analysis was performed, adjusting the groups for the variables of Sarculator, to assess the effect of vascular resection on oncological outcomes. RESULTS: Overall 425 patients were identified. Twenty-four (5%) patients had vascular resection. At final pathology 18 patients had vascular infiltration, 2 vascular encasement and 4 involvement without infiltration. Vascular resection was associated with longer operative time (480' vs. 330'; p < 0.001) and greater need for transfusions (4 vs. 0 units; p < 0.001), and was burdened by a higher rate of major complications (54% vs. 25%; p = 0.002). After propensity matched analysis, patients undergoing vascular resection had a lower 5-year OS (60% vs. 81%; p = 0.05), and a higher incidence of local and distant recurrence at 5 years (local: 45% vs. 24%, p = 0.05; distant: 20% vs. 0%, p = 0.04). CONCLUSIONS: Vascular resection is feasible and safe even in the context of multivisceral resection for primary retroperitoneal liposarcomas, although associated to a higher complication rate. However, the independent association between vascular involvement and a higher risk of local recurrence, distant metastases and death may imply a more aggressive biology, which should be factored in the initial management of this complex disease.

Dedifferentiation within well-differentiated liposarcoma of the extremity or trunk: Implications for clinical management.

BACKGROUND: In extremity or trunk liposarcoma, the implications of a dedifferentiated (DD) component within a well-differentiated (WD) tumor are unclear. We evaluated outcomes after surgery and identified potential predictors of survival in these patients compared to those with an entirely WD tumor. METHODS: Retrospective data were collected for patients who underwent complete resection from 2009 to 2019. Cumulative incidences of local recurrence (LR) and distant metastasis (DM) were calculated, and overall survival (OS) was estimated. Associations between OS and clinicopathologic variables were evaluated by univariable models. RESULTS: A total of 210 patients with MDM2-verified tumors were studied, including 58 (27.6%) with DD. In primary disease, LR occurred only in DD and worse OS was observed versus WD (p < 0.001). In recurrent disease, the LR incidences were similar between WD and DD (p = 0.559); however, worse OS persisted in DD (p = 0.004). The incidence of DM was extremely low (3.8%) and limited to DD. Higher grade (p < 0.001) and DD size (p = 0.043), but not overall tumor size were associated with worse OS. CONCLUSIONS: In extremity or trunk liposarcoma, the presence of DD leads to significantly worse outcomes in both primary and recurrence diseases. Further study is needed to determine if these patients benefit from adjunct therapies (e.g., radiation).

Complete pathological response to neoadjuvant treatment is associated with better survival outcomes in patients with soft tissue sarcoma: Results of a retrospective multicenter study.

BACKGROUND: Locally advanced soft tissue sarcoma (STS) management may include neoadjuvant or adjuvant treatment by radiotherapy (RT), chemotherapy (CT) or chemoradiotherapy (CRT) followed by wide surgical excision. While pathological complete response (pCR) to preoperative treatment is prognostic for survival in osteosarcomas, its significance for STS is unclear. We aimed to evaluate the prognostic significance of pCR to pre-operative treatment on 3-year disease-free survival (3y-DFS) in STS patients. METHODS: This is an observational, retrospective, international, study of adult patients with primary non-metastatic STS of the extremities and trunk wall, any grade, diagnosed between 2008 and 2012, treated with at least neoadjuvant treatment and surgical resection and observed for a minimum of 3 years after diagnosis. The primary objective was to evaluate the effect of pCR. (≤5% viable tumor cells or ≥95% necrosis/fibrosis) on 3y-DFS. Effect on local recurrence-free survival (LRFS), distant recurrence-free survival (MFS) overall survival (OS) at 3 years was also analyzed. Statistical univariate analysis utilized chi-square independence test and odds ratio confidence interval (CI) estimate, multivariate analysis was performed using LASSO. RESULTS: A total of 330 patients (median age 56 years old, range:19-95) treated by preoperative RT (67%), CT (15%) or CRT (18%) followed by surgery were included. pCR was achieved in 74/330 (22%) of patients, of which 56/74 (76%) had received RT. 3-yr DFS was observed in 76% of patients with pCR vs 61% without pCR (p < 0.001). Multivariate analysis showed that pCR is statistically associated with better MFS (95% CI, 1.054-3.417; p = 0.033), LRFS (95% CI, 1.226-5.916; p = 0.014), DFS (95% CI, 1.165-4.040; p = 0.015) and OS at 3 years (95% CI, 1.072-5.210; p = 0.033). CONCLUSIONS: In a wide, heterogeneous STS population we showed that pCR to preoperative treatment is prognostic for survival.

Unplanned Excision of Extremity and Trunk Wall Soft Tissue Sarcoma: To Re-resect or Not to Re-resect?

PURPOSE: The need for systematic reexcision in patients who underwent unplanned excision (UE) for extremity and superficial trunk soft tissue sarcoma (ESTSTS) has been questioned. We investigated the outcome of patients who underwent reexcision for ESTSTS compared with primarily resected at our institution and the prognostic impact of microscopic residual disease (MR) in the reexcision specimen. METHODS: Primary ESTSTS patients surgically treated at our institution between 1997 and 2017 were divided in three groups: primarily resected (A), reexcised after macroscopically complete UE (B), and incomplete UE (C). Weighted overall survival (OS), crude cumulative incidence of local relapse (CCI-LR), and distant metastasis (CCI-DM) were calculated and compared. In group B, multivariable models were performed to assess factors associated with the outcomes. RESULTS: A total of 1962 patients were identified: 1076, 697 and 189 in groups A, B, and C, respectively. Overall median follow-up was 85 months. Seven-year weighted-OS was 73.8%, 84.1%, and 80.7% (p < 0.001) for groups A, B, and C respectively. Seven-year CCI-LR and DM were 5.0% and 25.3%, 12.1% and 15.8%, and 13.6% and 29.4% (both p < 0.001) for groups A, B, and C, respectively. At multivariable analysis, the presence MR was associated with LR (p < 0.001) but not with OS nor CCI-DM. CONCLUSIONS: UE and the presence of MR at pathology in reexcision specimen are associated to a higher risk of LR but not to a higher risk of DM or lower OS. After macroscopic complete UE, postponing reexcision until a LR occurs may be considered on an individualized basis.

Extraskeletal Myxoid Chondrosarcoma with Molecularly Confirmed Diagnosis: A Multicenter Retrospective Study Within the Italian Sarcoma Group.

BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain origin, marked by specific chromosomal translocations involving the NR4A3 gene, and usually characterized by an indolent course. Surgery (with or without radiotherapy) is the treatment of choice in localized disease. The treatment for advanced disease remains uncertain. In order to better evaluate prognostic factors and outcome, a retrospective pooled analysis of patients with EMC treated at three Italian Sarcoma Group (ISG) referral centers was carried out. METHODS: All patients with localized EMC surgically treated from 1989 to 2016 were identified. Diagnosis was centrally reviewed according to WHO 2013. Only patients with NR4A3 rearrangement were included. RESULTS: Sixty-seven patients were identified: 13 (20%) female, 54 (80%) male. Median age was 56 years (range 18-84). Numbers and type of translocation were: 50 (80%) NR4A3-EWS, 10 (16%) NR4A3-TAF15, 1 (2%) NR4A3-TCF12, and 1 (2%) NR4A3-TFG. Median follow-up was 55 months (range 2-312). Five- and ten-year overall survival rates were 94% (86-100 95%CI) and 84% (69-98 95%CI). Thirty-five (52%) patients relapsed: 9 had local recurrence (LR) and 26 had distant metastasis (5 with concomitant LR). The 5- and 10-year disease-free survival rates (DFS) were 51% (38-65 95%CI) and 20% (7-33 95%CI). Size of the primary tumor was significantly related to distant metastasis-free survival (DMFS) (p = 0.004). Patients carrying the NR4A3-EWS translocation had a trend in favor of better DFS (p = 0.08) and DMFS (p = 0.09) compared with the patients with NR4A3-TAF15. CONCLUSIONS: Prolonged survival can be expected in patients with EMC, in spite of a high rate of recurrence. Size is significantly associated with distant relapse. The type of NR4A3 translocation could influence outcome.

Inoperable Primary Retroperitoneal Sarcomas: Clinical Characteristics and Reasons Against Resection at a Single Referral Institution.

BACKGROUND: The outcome of patients with retroperitoneal sarcomas (RPS) depends mainly on tumor biology and completeness of surgical resection. However, some patients are deemed not resectable for various reasons. This study analyzed a series of primary RPS patients to describe rate and reasons of primary inoperability at a large referral center. METHODS: All consecutive patients affected by primary localized RPS referred for surgical treatment at our institution between January 1, 2013 and December 31, 2017 were analyzed. Patients were split in two groups: those who underwent surgical resection with curative intent, and those who were not resected. RESULTS: A total of 322 patients were available for the current analysis: 285 (88.5%) underwent resection with curative intent, and 37 (11.5%) did not. Twenty of 322 (6.2%) patients who did not undergo resection had a technically unresectable tumor, whereas the remaining 18 of 322 (5.6%) were not amenable to a major surgical procedure due to comorbidities/poor performance status. The dominant technical reason was involvement of the celiaco-mesenteric vessels. At a median follow-up from the diagnosis of 34 months, 24 of 37 (64.9%) nonoperated and 48 of 285 (16.8%) operated patients died. The corresponding 4-year overall survival were 10.3% and 83.4%, respectively (p < 0.001). CONCLUSIONS: Roughly, 10% of patients who presented with localized primary RPS at a large referral institution were not resected. An attempt to standardize the definition of resectability for primary localized RPS should be made considering anatomic, biologic, and patient-related factors.

A Prospective Observational Study of Multivisceral Resection for Retroperitoneal Sarcoma: Clinical and Patient-Reported Outcomes 1 Year After Surgery.

BACKGROUND: Primary retroperitoneal sarcoma (RPS) may require multivisceral resection (MVR). Clinical outcome (morbidity and renal function) and quality of life (QoL) are not as well reported as the oncologic outcome. METHODS: Patients with primary RPS who underwent surgery between 2014 and 2016 were prospectively enrolled in an observational longitudinal study. At baseline, then at 4 and 12 months, the study measured Clavien-Dindo morbidity, estimated glomerular filtration rate (EGFR), EORTC QLQ-C30, QLQ-CR29, DN4 (neuropathic pain [NP]), lower-extremity functional scale (LEFS), and the brief pain inventory. The primary end point was the difference in global health status (GHS/QoL). The secondary end points were EGFR changes, difference in other QLQ-C30 scales, pain intensity, NP, and LEFS. The study is registered at ClinTrials.gov (NCT03480399). RESULTS: Of 74 patients, 58 were evaluable. Morbidity grade 3 or higher was 24.1%, and mortality was 1.3%. After nephrectomy, the mean 1-year EGFR change was -33.9%. The GHS/QoL at baseline was 58.6 and had increased of 6.9 points at 1 year, comparable with that of the general population. A transient worsening in pain and diarrhea had recovered at 12 months. Average pain was mild and did not differ at 12 months. However, NP was found in 41.4% of the patients and was significantly associated with resection of the psoas muscle. At baseline, LEFS was already lower than the normative value, and worsening after surgery was not clinically relevant. CONCLUSION: A QoL measure after MVR in primary RPS is complex and requires multiple tools. Whereas overall MVR is safe and associated with an improvement in GHS/QoL, chronic NP is frequent and deserves specific attention. Pre-surgery rehabilitation tracks may help to prevent or reduce chronic NP.

Intraperitoneal Invasion of Retroperitoneal Sarcomas: A Risk Factor for Dismal Prognosis.

INTRODUCTION: Retroperitoneal sarcomas (RPS) lie in the retroperitoneal space and are covered by a peritoneal layer. However, some RPS have an intraperitoneal component (IPC), which invades into the peritoneal cavity. The significance of such a clinical presentation is unknown. METHODS: We retrospectively analyzed our prospectively maintained institutional database of RPS, along with intraoperative photographs taken to document the primary tumor extent at laparotomy. The effects of IPC on overall survival (OS), local recurrence (LR), and distant metastasis (DM) were evaluated. RESULTS: IPC was present in 81 of 493 patients (16.4%). It was significantly associated with older age (64 vs. 59, p = 0.008), gender (67% vs. 33% males, p = 0.005), and multifocality (11.1% vs. 0.5%; p < 0.0001). IPC was not associated with size or any specific histology, while it showed a weak association with high malignancy grade (40.7% vs. 28.6% in G3 tumors; p = 0.076). At a median follow-up of 32 months IPC was associated with worse 5-year OS (54% vs. 74%, p < 0.001) and crude cumulative incidence (CCI) of LR (5-year CCI of LR: 38% vs. 19%, p = 0.001), but not to CCI of DM. However, multivariable models showed that IPC's effect on OS (HR: 1.52, 95% CI 0.92-2.49, p = 0.1) and LR (HR: 1.34, 95% CI 0.8-2.26, p = 0.27) could be sufficiently explained by other known risk factors. CONCLUSIONS: IPC is associated with increased LR and decreased survival. However, the effect of IPC on prognosis is predominantly related to other tumor characteristics already included in published nomograms. IPC should not be a contraindication to a proper surgical resection.