Retroperitoneal sarcomas, or retroperitoneal soft tissue sarcomas, are rare mesenchymal tumors accounting for ~0.15% of all malignancies (1,2). Retroperitoneal sarcomas display a vast array of histological subtypes, among which liposarcomas are the most common (30–50%), followed by leiomyosarcomas and malignant fibrous histiocytomas, also referred to as undifferentiated pleomorphic sarcomas, according to the updated World Health Organization (WHO) classification of soft tissue tumors (1,3). Retroperitoneal liposarcoma typically presents as advanced disease and often carries a poor prognosis (4). However, its rarity means that its prognostic factors are poorly understood. Furthermore, the majority of previously published series on primary malignant retroperitoneal tumors have included retroperitoneal liposarcomas together with other retroperitoneal sarcomas with heterogeneous histologies, thus preventing the independent characterization of this specific subtype (3,5–8).

Retroperitoneal liposarcomas usually present as an asymptomatic abdominal mass, incidentally detected during abdominal examination or abdominal imaging studies performed for other purposes, while others are detected due to the presence of clinical symptoms (4). Although symptoms at diagnosis have been identified as prognostic markers in several malignancies (9–12), their prognostic value for retroperitoneal liposarcoma has yet to be evaluated. In this study, we assessed the prognostic factors in primary retroperitoneal liposarcoma, focusing on the presence or absence of clinical symptoms at diagnosis.

In the present study, the presence of symptoms at diagnosis in patients with primary retroperitoneal liposarcoma was an independent predictor of poor PFS, and tended to be associated with poor SSS. To the best of our knowledge, this is the first assessment of the prognostic value of symptoms at diagnosis in patients with retroperitoneal liposarcoma.

The rarity of retroperitoneal liposarcoma means that its prognostic factors have yet to be clearly determined. Furthermore, the majority of previous studies on primary malignant retroperitoneal tumors have included patients with other retroperitoneal sarcomas with heterogeneous histologies together with retroperitoneal liposarcomas, thus preventing independent characterization (3,5–8). However, a limited number of studies have specifically investigated retroperitoneal liposarcomas. Singer et al (13) retrospectively reviewed 177 patients with primary retroperitoneal liposarcoma and demonstrated that dedifferentiated histology (HR=4, P<0.0001) and contiguous organ resection (HR=2, P=0.04) were significantly associated with PFS according to the Cox regression analysis, while dedifferentiated histology (HR=6, P<0.0001), gross positive margins (HR=4, P<0.0001), contiguous organ resection (HR=2, P=0.05) and age (HR=1.03, P=0.03) were significantly associated with SSS. A recent comprehensive review of retroperitoneal liposarcomas also reported that the most consistent prognostic factor was completeness of surgical resection, with negative margins (4). Our results supported these findings, given that the univariate analysis revealed an association of dedifferentiated components and positive surgical margins with both PFS and SSS, while the multivariate analysis identified the presence of positive surgical margins as an independent predictor of SSS.

Regarding the presence of symptoms, we were only able to find one study that evaluated the prognostic impact of symptoms on survival in retroperitoneal sarcoma. In a review of 49 patients with primary malignant retroperitoneal tumors, including 25 (51%) with liposarcomas (6), 44 patients (90%) had symptoms, but these were not associated with overall survival (P=0.282, log-rank test).

By contrast, several studies have investigated the prognostic value of tumor size in malignant retroperitoneal tumors (5–8,13), mostly using a cut-off value of 10 cm, particularly in studies conducted over a decade ago (5–7). A relatively small-scale (n=49) study reported a prognostic value of tumor size >10 cm (6), whereas another larger (n=500) study did not report such an association (7). More recently, in a review of 1,091 patients with soft tissue sarcoma of any primary site (including extremities, trunk and retroperitoneum), Lahat et al (14) demonstrated that patients with tumors sized >15 cm were at increased risk of developing distant recurrence and exhibited higher disease-specific mortality compared with those with smaller tumors; they suggested that tumor size should be revised in the current American Joint Committee on Cancer (AJCC) staging system used for soft tissue sarcomas. The AJCC system currently uses a 5-cm threshold, which is better suited for extremity sarcomas, but has limited discriminative power for retroperitoneal liposarcomas, almost all of which are >5 cm (4,15). Indeed, all the patients in the present study had tumors >10 cm (median, 19.0 cm), and tumor size was not associated with PFS or SSS.

The mechanisms underlying the association between symptoms at diagnosis and poor outcome in patients with retroperitoneal liposarcomas may be associated with the fact that an aggressive tumor may be recognized by the host more easily than an indolent one. The most common symptoms (13/16, 81%) in the present study were palpability of the tumor and pain/fullness of the abdomen/flank, as previously reported (3). In the case of two tumors of the same size but with different growth rates, the faster-growing tumor (i.e., more aggressive tumor) would be more likely to cause pain/fullness compared with the slower-growing tumor, due to the greater change. However, tumor size itself is also an important factor, which is supported by the fact that all the symptomatic patients in our cohort had tumors sized >15 cm. In addition to growth rate and tumor size, local invasion of the retroperitoneal structures may cause neurological, musculoskeletal and urinary/bowel symptoms (4), which are also considered to be specific characteristics of aggressive tumors. Of the 16 (19%) symptomatic patients in our cohort, 1 had lower extremity pain due to neural invasion, 1 had testicular pain due to varicocele as a consequence of tumor infiltration of the left gonadal vein, and 1 presented with discomfort on urination due to tumor infiltration of the urinary bladder. Since several inflammatory markers, such as neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio and C-reactive protein, have been reported to be prognostic factors in soft tissue sarcomas (16–19), we also evaluated certain laboratory parameters; however, none were found to be associated with prognosis in the present study (Tables II and III).

This study was limited by its retrospective design and small sample size. Therefore, further confirmatory studies with larger populations are required to validate these results. However, these preliminary results suggest that the presence of symptoms at diagnosis may be an easily available, useful prognostic factor to complement existing markers in retroperitoneal liposarcoma.

In conclusion, retroperitoneal liposarcomas diagnosed by clinical symptoms are associated with a poorer prognosis compared with incidentally diagnosed retroperitoneal liposarcomas. Furthermore, the presence of symptoms at diagnosis was found to be an independent predictor of PFS, which may prove to be a useful additional prognostic factor in primary retroperitoneal liposarcoma.