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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 1  |  Page : 80-83

Colorectal cancer presenting as bone metastasis


1 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
2 Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India

Date of Web Publication16-May-2017

Correspondence Address:
Sunny Garg
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Dr. M. H. Marigowda Road, Bengaluru - 560 029, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.181177

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 > Abstract 

Introduction: Bone metastasis is a rare site of metastasis, seen in only 3.7–11% of clinical cases. Isolated bone involvement has been reported very rarely in literature. Moreover, the patients who have bone metastasis at presentation are even rare.
Objectives: To discuss the demographic characteristics, carcinoembryonic antigen (CEA) levels, pattern of bone involvement, and their correlation with survival in patients of colorectal cancer that have bone metastasis at the time of presentation.
Materials and Methods: Retrospectively, tumor registry was analyzed for the cases of colorectal cancer presenting with bone metastasis between 2008 and 2013. Survival curves were generated by Kaplan–Meier method and analyzed using the log-rank test.
Results: Ten such patients were identified (male:female = 7:3) of the total 410 patients. Median age was 41 years (22–50 years). All patients were <50 years of age. Median CEA level was 147.5 (45–840). Three patients had bone-only metastasis. Most common metastatic site involved was liver (six patients) and lungs (three patients). The most common sites of bone metastasis were vertebra and pelvis (4 each). Chemotherapy was given in seven patients. Median overall survival was 5.5 months (2–36 months). It was higher in males, in those with bone-only involvement and those without liver involvement. Vertebral involvement, pelvic involvement, CEA levels, and chemotherapy did not show any significant survival implication.
Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

Keywords: Bone metastasis, colorectal cancer, pelvis, vertebra


How to cite this article:
Suresh Babu M C, Garg S, Lakshmaiah K C, Babu K G, Kumar RV, Loknatha D, Abraham LJ, Rajeev L K, Lokesh K N, Rudresha A H, Rao SA. Colorectal cancer presenting as bone metastasis. J Can Res Ther 2017;13:80-3

How to cite this URL:
Suresh Babu M C, Garg S, Lakshmaiah K C, Babu K G, Kumar RV, Loknatha D, Abraham LJ, Rajeev L K, Lokesh K N, Rudresha A H, Rao SA. Colorectal cancer presenting as bone metastasis. J Can Res Ther [serial online] 2017 [cited 2019 Jun 20];13:80-3. Available from: http://www.cancerjournal.net/text.asp?2017/13/1/80/181177


 > Introduction Top


Colorectal cancer is one of the most common malignancies in the world. Most common sites of metastasis are liver (57.6%), abdominal lymph nodes (48.3%), and lungs (37.6%).[1] Bone metastasis is a rare site of metastasis, seen in only 3.7–11% of clinical cases.[2],[3],[4],[5] However, on autopsy, it is seen in 8.6–27% of the cases.[1],[6] This particular predisposition may be attributed to the pattern of blood flow and molecular protein signals. However, isolated bone involvement has been reported very rarely in literature. Moreover, the patients who have bone metastasis at presentation are even rare. Here, we discuss the demographic characteristics, carcinoembryonic antigen (CEA) levels, pattern of bone involvement, and their correlation with the survival in patients of colorectal cancer that have bone metastasis at the time of presentation.


 > Materials and Methods Top


Tumor registry was analyzed retrospectively for the cases of colorectal cancers diagnosed between 2008 and 2013. Henceforth, a review of patients presenting as metastasis to bone was performed, and 10 such patients were identified of the total 410 patients (ratio = 41:1). Clinical data including age, clinical presentation, tumor markers, radiographic findings, and outcome were extracted from the hospital records. SPSS version 19 was used for statistical analysis. The survival curves were generated using the Kaplan–Meier method and log-rank test was used to calculate the differences. P<0.05 was considered to be significant. Fischer's t-test was used to compare the variables.


 > Results Top


Ten patients of colorectal cancer were diagnosed with bone metastasis at the presentation, 7 males and 3 females. Median age was 41 years (22–50). All patients were <50 years, with 5 <40 years, and 2 <25 years. Median CEA level was 147.5 (45–840). Out of 10, three patients had bone-only metastasis; whereas, 7 had metastasis to other sites also. Bone pain was the most common symptom seen in eight patients. Out of eight patients with metastasis to vertebra and spine, two patients complained of lower limb weakness and one patient had complete paralysis. One patient was asymptomatic. For the symptomatic patients, plain radiograph followed by magnetic resonance imaging was performed, whereas asymptomatic patient was picked up on bone scan [Table 1].
Table 1: The patient characteristics and the pattern of colonic and metastatic involvement

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Primary site was the rectosigmoid region in six patients, while 1 each in hepatic flexure, splenic flexure, cecum, and rectum. The most common sites of bone metastasis were vertebra and pelvis (4 each), followed by radius, humerus, ankle, and femur (1 each). Three patients presented with only bone metastasis [Table 2]. Among the other sites of metastasis, most commonly involved were the liver (six patients), lungs (three patients; 2 parenchymal and 1 pleural effusion). Rarely metastasis to ovary and peritoneum was seen (1 each).
Table 2: Each of the patient characteristics separately

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Supportive treatment was given to all patients in the form of analgesics for pain relief. Six patients were given radiotherapy, and four patients were given bisphosphonates for pain relief. Chemotherapy was given in seven patients, 2 were unfit and one patient refused. It was 5-fluorouracil/leucovorin based in all seven patients.

Median overall survival (OS) was 5.5 months (2–36). It was higher in males as compared to females with a trend toward statistical significance (10 months vs. 3 months; P = 0.058) [Table 3]. Patients with vertebral involvement had a poorer survival as compared to those without vertebral involvement with a trend toward statistical significance (3 months vs. 10 months; P = 0.082) [Table 3]. Patients with involvement of pelvic bone had a better survival as compared to those without it, but statistically insignificant (6 months vs. 3 months; P = 0.454) [Table 3]. Patients with CEA <100 had a median survival higher than those with CEA >100 but that was not significant (18 months vs. 5 months; P = 0.274). Median OS was significantly higher in patients with bone-only involvement as compared to those with extraosseous involvement also (22 months vs. 3 months; P = 0.008) [Table 3] and [Figure 1]. Patients without liver involvement also had a significantly higher survival as compared to those with liver involvement (18 months vs. 3 months; P = 0.032) [Table 3] and [Figure 2]. The median OS in patients who received chemotherapy was higher than those who did not receive but statistically insignificant (6 months vs. 5 months; P = 0.321) [Table 3].
Table 3: The univariate analysis for the prognostic factors

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Figure 1: The comparison between median overall survival in those with bone-only and bone+other sites of metastasis. Red line – bone-only involvement, blue line – bone+other sites

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Figure 2: The comparison between median overall survival in those with and without liver involvement. Red line – liver metastasis present, blue line – liver metastasis absent

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 > Discussion Top


Colorectal cancer patients with bone metastasis constitute only 3.7–27% of the total cases.[1],[2],[3],[4],[5],[6],[7] In this respect, colorectal cancers are different from the breast, lung, and prostate cancers where the propensity for bone involvement is much higher, to the tune of 70% in patients with Stage IV breast cancer.[8] Cascade hypothesis explains the higher incidence of bone metastasis in patients with lung and liver involvement.[9],[10],[11] Isolated skeletal metastasis is very rarely seen, to the tune of 1.1%.[5] Moreover, the spread to spine and pelvis is much higher owing to the spread via arterial blood and Batson's plexus.[11] Other sites include the skull, pelvis femur, and humerus.[12],[13],[14] Isolated scapular metastasis has also been reported.[15]

In our study, three patients had isolated bone metastasis, i.e., without concomitant involvement of liver or lungs. Another study by Nozue et al. has shown similar results where 3 out of 12 cases had isolated bone metastasis.[16] A study by Jimi et al. showed 5 out of 32 patients with isolated bone metastasis.[17] On the other hand, Roth et al. conducted a positron emission tomography/computerized tomography evaluation of colorectal cancer patients in which no patient was found to have an isolated bone metastasis, without liver lung involvement.[18] They concluded that early metastasis is always present in these sites before involvement of the bone, which are sometimes not detected by the routine imaging techniques. Furthermore, early liver and lung metastasis are asymptomatic; whereas, bone metastasis are often symptomatic, hence their earlier detection. Thus, concluding that bone could be the first organ of metastasis and careful attention must be paid.

On univariate analysis of risk factors, those with bone-only metastasis and those without liver metastasis had a significantly better survival. In addition, female sex and vertebral metastasis had a poorer survival that showed a trend towards statistical significance. However, CEA levels, pelvic involvement, and chemotherapy administration did not show any survival significant results. A study by Jimi et al. showed lung involvement and CEA levels to have a significant correlation with survival.[17]

Median OS, in our study, was 5.5 months, with a range of 2–36 months, with 1-year survival rate of 30%. Similar to our study, Nozue et al. reported a median survival of 5 months, with 1-year survival rate 20%.[16] Jimi et al. reported median OS of 9.3 months, with a range of 1–72 months.[17] The higher survival in the latter could be explained by the fact that bone metastasis could have been detected earlier in the patients as they were already on follow-up in the institution. Therefore, as evident from these studies, the prognosis is grim after the bone metastasis in patients with colorectal cancer. Hence, early detection of bone metastasis is very important to improve the outcomes. Moreover, more attention should be paid to palliation of pain, prevention of pathological fractures, paralysis, and weakness.


 > Conclusions Top


In our study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement, and the other probable factors are female sex and vertebral involvement. However, no particular conclusion could be embarked upon owing to the small number of patients. Above-mentioned prognostic variables need to be analyzed in larger studies for any correlation with survival.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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Nozue M, Oshiro Y, Kurata M, Seino K, Koike N, Kawamoto T, et al. Treatment and prognosis in colorectal cancer patients with bone metastasis. Oncol Rep 2002;9:109-12.  Back to cited text no. 16
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Jimi S, Yasui T, Hotokezaka M, Shimada K, Shinagawa Y, Shiozaki H, et al. Clinical features and prognostic factors of bone metastases from colorectal cancer. Surg Today 2013;43:751-6.  Back to cited text no. 17
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Roth ES, Fetzer DT, Barron BJ, Joseph UA, Gayed IW, Wan DQ. Does colon cancer ever metastasize to bone first? A temporal analysis of colorectal cancer progression. BMC Cancer 2009;9:274.  Back to cited text no. 18
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    Figures

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    Tables

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