Table 4: Survival according to combinations of depth, size and grade. High grade = III-IV Prognostic factor Deep Large High grade Survival 95% CI Table 5: Survival according to different combinations of depth, size and grade. High grade = IV Prognostic factor Deep Large High grade Table 6: Staging by grade (high grades = III-IV) and tumor size trichotomized. Grade Size (cm) No. of patients Survival 95% CI Table 7: Staging by grade (high grade = IV) and tumor size trichotomized. Grade Size (cm) No. of patients Survival 95% CI Survival 0.94 0.94 0.80 0.83 0.74 0.74 0.65 0.48 95% CI 1.0–0.87 1.0–0.87 0.92–0.68 0.92–0.75 0.89–0.59 0.91–0.58 0.81–0.49 0.56–0.40 1.0–0.81 1.0–0.91 0.91–0.72 0.92–0.70 0.79–0.55 0.60–0.46 0.99–0.96 0.88–0.74 0.69–0.55 0.54–0.30 0.90–0.85 0.80–0.61 0.65–0.46 0.54–0.28 0 0 + + 0 0 + + 0 0 + + 0 0 + + any 1–5 6–10 >10 any 1–5 6–10 >10 0 0 0 0 + + + + 0 0 0 0 + + + + 94 125 198 73 218 95 116 61 n 18 22 15 39 69 56 67 204 n 48 50 41 79 39 28 41 164 BMC Cancer 2003, 3 http://www.biomedcentral.com/1471-2407/3/17 0 + 0 + 0 + 0 + 0 + 0 + 0 + 0 + I-II III-IV III-IV III-IV I-III IV IV IV 1.0 1.0 0.93 0.97 0.81 0.81 0.67 0.53 0.97 0.81 0.62 0.42 0.87 0.70 0.55 0.41 type and strength between histotypes [4]. Our aim with this study was not to suggest a new staging system but to analyze the rationale for using tumor depth as a prognos- tic factor. Histologic malignancy-grade and tumor size are undis- puted strong prognostic factors in soft tissue sarcoma and are consequently included in all staging systems, most of which also include tumor depth. However, there is a well- known association between tumor depth and size and some authors have found similar survival in patients with superficial and deep tumors when stratified according to grade and size [5,6]. The largest prognostic study on soft tissue sarcoma hitherto published, based on 2,136 patients treated at the Memorial Sloan-Kettering Cancer Center, showed that both size and depth were of prognos- tic importance [7]. That study included one fifth retroin- traabdominal and visceral tumors which all by definition are deep-seated and with a poor prognosis, sometimes killing the patient because of uncontrollable local growth despite being low grade without metastatic spread. This may, at least in part, explain the independent prognostic value of depth. Recently two other large studies on staging of soft tissue sarcoma arrived at different conclusions: Wunder et al [2] found that a system utilizing grade, depth, and size (all factors dichotomized) would better predict patient outcome and stratify risk than one using only grade and size whereas Ramanathan et al [8] pro- posed a staging system based on only grade and 4 groups of size. We find it less probable that whether a sarcoma arises and grows in or outside the deep fascia investing the extremi- ties and trunk wall should influence the metastatic proc- ess – tumor growth into blood vessels with release of tumor cells into the circulation followed by adherence and growth of these tumor cells in their new environment. One explanation for a prognostic importance of tumor depth that we have explored could be that certain histo- types are predominantly deep-seated and that these spe- cific histotypes are more prone to metastasize even when adjusted for size and grade. We could not find that this was an explanation for the prognostic importance of depth. Indeed the fraction of deep-seated tumors and the prognostic strength of high malignancy-grade varied between histotypes, however, leiomyosarcoma was the histotype with the highest fraction superficial tumors (even though skin leiomyosarcomas were not included) but also the histotype that had the highest relative risk for metastatic disease associated with high malignancy-grade (data not shown). We therefore chose to closer analyze the relation between size and depth of tumors. Most staging systems dichotomize tumor size (largest diameter) in 1–5 cm/>5 cm. The 5 cm designation some- Page 4 of 5 (page number not for citation purposes)