BMC Cancer 2003, 3 http://www.biomedcentral.com/1471-2407/3/17 than that of the superficial tumors. A prognostic effect of tumor depth could then be related to size and should be strongest in the large size group in which the size span is greater. We tested this hypothesis in a large population- based series of soft tissue sarcoma of the extremity and trunk wall in adults. Patients and methods The southern Sweden soft tissue sarcoma database is pop- ulation-based, i.e. all patients diagnosed with a soft tissue sarcoma within a defined geographical region (currently 1.5 million inhabitants) are included, irrespective of whether treated at our sarcoma center in Lund or at other hospitals in the region. Patients not referred to our center are identified via the Regional Tumor Registry. All patients with malignant tumors are reported to this Registry by a double-reporting system: every clinician and every pathol- ogist who diagnoses a malignant tumor is obliged to report to the registry. For patients not referred to out sar- coma center, clinical data are obtained from the medical records and archived tumor material is reviewed by our center pathologists. The database includes all adult patients with a soft tissue sarcoma in the extremity or trunk wall. Strictly cutaneous sarcomas (most of them small leiomyosarcomas of the skin which almost never metastazise), dermatofibrosarcoma protuberans, syn- drome-related sarcomas (e.g. sarcomas in patients with neurofibromatosis) and radiation induced sarcomas are not included. For a detailed description of the database, see Gustafson [4]. During the 25-year period 1973–1997, 578 patients were included. 44 patients who had metastases demonstrated already at diagnosis of the primary tumor and 44 patients who had had tumors that were not at least marginally excised were excluded, which left 490 patients for this study. 300 were referred to our tumor center before sur- gery (half of them after needle biopsy), 127 immediately after surgery (most often marginal excision of small and superficial tumors), 21 first after local recurrence, and 42 patients were not referred at all. 90 patients were given local radiotherapy (most often postoperatively) and 34 patients were given adjuvant chemotherapy for the pri- mary tumor according to several regimens. These patients were not separately analyzed; local radiotherapy influ- ences mainly the local recurrence rate and the chemother- apy used has no major effect on distant metastases. The mean age at diagnosis was 62 (17–94) years. 52 % of the patients were men. Nine tenths of the tumors were located in the extremities, almost half of them in the thigh and hip girdle. Two thirds (321/490) of the tumors were deep-seated. The mean size was 8.3 cm for deep-seated tumors and 5,2 cm for superficial tumors. Two thirds of the tumors (325/490) were larger than 5 cm. Malignant fibrous histiocytoma (219) was the commonest histotype (most of these tumors were diagnosed in the 1980's) fol- lowed by leiomyosarcoma (73), liposarcoma (54), syno- vial sarcoma (38) and malignant peripheral nerve sheath tumors (18). The tumors were malignancy-graded on a 4- tiered scale with decreasing survival rates associated with increasing grade. Most staging systems dichotomize grade but the definition of low and high malignancy grade is not clear-cut. Therefore, we used two alternative dichotomiza- tions being: grades I and II versus grades III and IV and grades I-III versus grade IV (Table 1). Follow-up was complete for a minimum of 4.5 years or until death. The median follow-up time for the survivors was 11 (min 4.5, max 26) years. During the observation period 151 patients developed metastatic disease, 122 of these have died because of tumor. Local recurrence occurred in 55/300 (18%) of patients referred before sur- gery and in 64/190 (34%) patients referred after surgery or not referred for the primary tumor. Terminology and Statistics Tumors superficial to the deep fascia are called superficial, all others are called deep. Small tumors are 5 cm or less in largest diameter, all other tumors are called large. High grade refers to either grades III-IV tumors or grade IV tumors as indicated in text. Survival was analyzed in terms of metastasis-free survival; death and other metastasis-free causes for ending follow-up were treated as censoring. Presented rates indicate 5-year metastasis-free survival and were calculated using the Kaplan-Meier method. Mul- tiple prognostic factors were analyzed simultaneously using Cox's proportional hazards model. The statistical analyses were performed by Jonas Ranstam, PhD, CStat, Lund, Sweden. Abbreviations in the Tables: RR relative risk, CI confi- dence interval. Results Size related to depth (Table 2) In the small (1–5 cm) tumor group the mean tumor size was similar for superficial and deep tumors. However, in the large (>5 cm) tumor group the mean size of deep tumors was one third larger than that of superficial tumors. The findings were almost identical if only high grade tumors (irrespective of the classification of high- grade) were analyzed (data not shown). Prognostic factors in total material (Table 3) Multivariate analysis of size, depth, and grade (dichot- omized in two ways) showed size and grade to be of inde- pendent prognostic value, irrespective of definition of high grade. When size and grade were taken into account, depth had no major effect on survival, neither in the total Page 2 of 5 (page number not for citation purposes)