Establishment of an innovative staging system for extramedullary plasmacytoma

EMP is an extremely rare malignant disease. The lack of a unified staging criteria system makes it difficult to predict survival outcome and to define treatment choice. The present study analyzed a large cohort (48 patients) with a long follow-up, allowing us to draw reliable conclusions with regard to prognostic factors in EMP. The OS rates for 5-year (72 %) and 10-year (60 %), and the 5-year (56 %) and 10-year DFS(39 %) were similar to that of other series [12–14]. Therefore, the results from our population are comparable to those previously described. This study showed that large primary tumor and lymph node metastasis were independent prognostic factors for survival. According to the prognosis factors and similar relative risks, the EMP patients were classified into three grades. This staging system had a better prognostic value for OS than the MM staging system. Furthermore, this new staging system can select high-risk EMP patients and help design individualized therapeutic regimens.

Although EMP can arise throughout the body, almost 90 % of tumors arise in the head and neck, especially in the upper respiratory tract [9, 13–16]. The rate of cervical lymph node involvement for patients with EMP of the head and neck varies between 10 % and 15 % [17]. In a previous report, the presence of a cervical lymph node plasmacytoma should suggest an upper respiratory tract or oropharynx plasmacytoma rather than a primary lymph node plasmacytoma [18]. This study showed that the presence of lymph node metastasis was indicative of a primary tumor, although the size and location of the primary tumor were different. Furthermore, patients with lymph node metastasis had a shorter survival time compared to those without lymph node metastasis. Additionally, lymph node metastasis was an independent prognostic factor for EMP patients. Based on these observations, lymph node metastasis was the first factor included in our staging system. Ryohei et al. confirmed that tumor size was not a significant factor for local control in 42 EMP patients [19]. Tsang et al. [6] and Holland et al. [7] suggested that patients with tumors more than 5 cm are at higher risk of treatment failure. In the present study, patients with a tumor equal to or more than 5 cm had shorter OS and DFS. Moreover, tumor size may be an independent prognostic factor for poorer OS and DFS in patients with EMP. Based on these results, tumor size was the second factor considered in our staging system.

Some authors believe that EMP and MM are different phases of the same disease process [20] and used the same clinical grading criteria, whereas others believe that they are different diseases. If solitary EMP is an initial stage of MM, chemotherapy might play a more important role in management of the disease [21]. However, several studies showed that chemotherapy does not reduce relapse rates or improve survival rates and, at present, has no role in the primary management of EMP [10–12]. Moreover, in this study, only 2 (2/48) patients progressed to MM within 5 years. This fact prompted us to develop the specialized staging system for EMP. As shown in our study, the survival curves were distinctly different between the clinical stages. The staging system is a significant independent prognostic factor for OS. Furthermore, the comparison of the new staging system and the MM staging system showed a better prognostic value for OS.

Radiotherapy is a basic/primary treatment for EMP [2]. One study showed that a dose greater than 45Gy to the target volume improves the local control of EMP in the head and neck [19]. In our study, patients treated with total dose greater than 45Gy were showed higher OS than the patients treated with total dose less than or equal to 45 Gy. However, there were no association between total dose and DFS/LRFS, which may be influence by the diversity of combination treatment polices. Surgery can also achieve a high rate of local control in certain situations [9]. In our study, 41 (41/48) patients were treated with radiotherapy or surgery, and the overall 5- and 10-year LRFS rates were 95 % and 86 %, respectively. This result confirmed that radiotherapy and surgery play critical roles in the treatment of EMP. However, the surgical margin of EMP still lacks unified standards, which need further study. The UK Myeloma Forum has suggested that adjuvant chemotherapy is considered for EMP in the following cases: patients with tumors larger than 5 cm, patients with high-grade tumors, patients with refractory and/or relapsed disease, and patients with MM [7]. The present analysis found that patients treated with the simple treatment regimen had poorer OS and DFS than the patients treated with the combined treatment in the late stages (Stage II and III). Using this novel clinical staging, we can identify high-risk patients, which may help to design more aggressive therapeutic regimens and improve the overall survival rate in EMP patients. However, we could not put forward the exact combination treatment scheme for the limited number of patients in subgroup analysis.

This retrospective study and the method of determining the criteria for the stages had several limitations. First, this study demonstrated independent survival factors for EMP patients involving long time spans and a heterogeneous radiotherapy technique. Second, for the limited number of patients in the subgroup, further prospective or larger numbers of cases are required.