Our study retrospectively reviewed the clinicopathological characteristics of 200 patients with BM from CRC, discussing prognostic factors and a novel risk stratification for CSS. Many researches have been reported that spine is the leading site of BM from solid tumors [8, 9]. And the common sites of BM from CRC are reportedly the spine, followed by the pelvis and long bones, which is highly consistent with our study .
The prognosis of patients with BM from CRC is very poor because of advanced disease stage, with a median survival time of 7.0 to 17.8 months after BM diagnosis [6, 10, 11]. In our study, the overall median CSS time was 11 months (95%CI: 9.7–12.3) from the time of BM diagnosis, with 30.0%, 17.0% and 7.0% of 1-, 2- and 3-year CSS rate. Although the median CSS of patients with adenocarcinoma was longest than those with mucinous adenocarcinoma, signet-ring cell carcinoma and other pathological types (11 months, 9 months, 8 months, 4 months, respectively), there was no statistical significance (P = 0.453). Median CSS time of patients with metachronous BM and synchronous BM were both 11 months. The CSS did not differ significantly between the two groups (P = 0.571) in univariate analysis. Hidetaka et al. also found there is no significant difference in survival between metachronous and synchronous groups after BM diagnosis(P = 0.59) .
Then we analyzed the prognostic factors based on multivariable analysis, which revealed the CSS in patients with regional lymph node metastasis was found to be shorter than patients who were without. In addition, patients with positive serum CA199 levels at BM diagnosis had poorer prognosis in CRC patients than those with negative. High CA199 levels is one of indicators of colorectal tumor, but there are rarely reports about the its role in prognosis of CRC, while most of researches show it plays a key role in CRC diagnosis [12, 13]. We also found high serum CEA levels and LHD levels were significant prognostic indicators for CSS by univariate analysis, which had been shown in many reports [10, 14]. So, we suggest careful surveillance in those indicators for patients with BM from CRC.
The multiple bone involvement was found to be an independent prognostic factor for CSS, similar to some previous studies [15, 16]. However, Lun et al. reported there was no association between the number of bone metastases and survival . Such differences might due to the sample size and selection bias in different studies. In our study, KPS scores at BM diagnosis less than 80 were associated with a worse prognosis compared to scores ranging from 80 to 100. This is in line with previous researches that have identified performance status as one of the most valuable prognostic factors for survival of BM patients [16–18].
There exists controversy regarding to the benefit of primary tumor resection in advanced CRC. Many prior studies suggest a clinical benefit to improve survival with surgery [19–21], while others report there is no benefit [22, 23]. We found the patients with BM from CRC could significantly be beneficial from primary tumor resection with improved CSS. That might be because removal of primary tumor could prevent tumor-related complications such as bleeding, obstruction and perforation, further improving quality and survival of patients with BM.
The treatment of bisphosphonates and radiotherapy for CRC patients with BM is strongly recommended. Bisphosphonates have been used for prevention of skeletal-related events and reduction of pain from BM in recent years [24, 25]. According to our study, 42.5% of patients received bisphosphonates therapy for BM and the remaining patients didn’t. The difference in median CSS between two groups is significant (13 months vs. 9 months, respectively), showing that patients who took bisphosphonates were associated with better prognosis.
Radiotherapy was found to be associated with longer CSS, although quality-of-life data were lacking. In patients with palliative radiotherapy for BM, median CSS time after BM diagnosis was prolonged obviously (15 months vs. 9 months, respectively). Previous researches have verified that radiotherapy is the approach most commonly used to treat severe pain from BM, which could improve survival directly and indirectly [26–28]. In addition, the chemotherapy can notably improve survival of BM as many researches have demonstrated [26, 29, 30]. However, because all patients had received adjuvant chemotherapy in our study, the utility of chemotherapy in improving CSS was not investigated.
Here, we developed a weighted scoring system to facilitate risk stratification for patients with BM from CRC. As an example, a CRC patient, with regional lymph node metastasis, negative CA199 levels, KPS ≥ 80 and multiple bone involvement, received primary tumor resection, bisphosphonates therapy and radiotherapy for BM, then he would be assigned for 0 point with a median CSS benefit of up to 35 months (95%CI: 20.6–49.4). In contrast, patients with all adverse factors (10 points) showed the worst CSS of only 5 months (95%CI: 3.6–6.4). So, we suggest that more medical care might be necessary for high risk patients. And individualized medical care should be considered for patients in different risk groups. This risk stratification had good discrimination and calibration, implying a clinical value in predicting prognosis of CRC patients with BM.
Our study had some limitations. First, this was a retrospective designed study, and some data might have missed. For example, not every patient showed complete AJCC TNM stage. In addition, this was a single-center study. Because of the low incidence of BM from CRC, the number of patients was small, which limited the external validation. Nonetheless, we believe our study will be useful to both clinicians and patients.