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  Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 3  |  Page : 420-422
 

The longest tumor diameter in one dimension as a predictor for skeletal metastasis in renal cell carcinoma


1 Department of Radiodiagnosis and Imaging, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
2 Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
3 Department of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Date of Web Publication24-Feb-2017

Correspondence Address:
AND Dwivedi
Department of Radiodiagnosis and Imaging, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.200649

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 » Abstract 

INTRODUCTION: Renal cell carcinoma (RCC) comprises a diverse group of malignant neoplasms that have multifarious histopathological features and biological behavior. One-third of RCC patients develops skeletal metastasis with a poor 5-year survival rate. Data explaining how some of these tumors show sooner bony metastasis than expected is sparse. The objective of this study was to identify whether tumor size can act as a predictor of bony metastases among patients of RCC. MATERIALS AND METHODS: We retrospectively reviewed contrast enhanced computed tomography (CECT) scan and clinical records of 66 patients with RCC, who fulfilled specified inclusion criteria. Patients who had bony metastasis at the time of presentation were selected as case and those without skeletal metastasis were referred to as controls. Receiver operating characteristic (ROC) curve analysis was used to determine the appropriate cut-off value for tumor size, which was measured as the longest tumor diameter (LTD) in one-dimensional (1D). RESULTS: Of the 66 patients selected, 30% developed bone metastasis. The tumor size of RCCs significantly correlated with the presence of skeletal metastasis in our study. None of the patients with 1D LTD <4.8 cm on CECT were found to have skeletal metastasis. ROC analysis revealed that the accuracy of the LTD in predicting bone metastasis was high with an area under ROC curve of 0.823. A cut-off value of 7.5 cm had a sensitivity of 78.9% and specificity of 80.9%. CONCLUSION: The 1D LTD with a cut-off value of 7.5 cm, at the time of presentation is an important predictor of skeletal metastasis. The result of this study may have role in triage of patients into a subgroup which mandates more aggressive treatment and monitoring.


Keywords: Multidetector computed tomography, renal cell carcinoma, skeletal metastasis, sum of the longest diameter, tumor diameter


How to cite this article:
Dwivedi A, Srinivasan A, Kumar S, Trivedi S, Shukla V, Shukla R. The longest tumor diameter in one dimension as a predictor for skeletal metastasis in renal cell carcinoma. Indian J Cancer 2016;53:420-2

How to cite this URL:
Dwivedi A, Srinivasan A, Kumar S, Trivedi S, Shukla V, Shukla R. The longest tumor diameter in one dimension as a predictor for skeletal metastasis in renal cell carcinoma. Indian J Cancer [serial online] 2016 [cited 2017 Sep 20];53:420-2. Available from: http://www.indianjcancer.com/text.asp?2016/53/3/420/200649



 » Introduction Top


Renal cell carcinoma (RCC) is among the most common cancers in the world comprising approximately 2–3% of all malignancies.[1] Skeletal metastasis from RCC is a major cause of death.[2] Approximately one-third of RCC patients present with skeletal metastasis. The number, site, and size of the metastasis determine the overall management and prognosis.[2] We tried to assess whether tumor size is associated with the occurrence of skeletal metastasis in patients with RCC. The objective of this study was to establish whether one-dimensional (1D) longest tumor diameter (LTD) can be used as predictor of bony metastases among RCC patients.


 » Materials and Methods Top


This was a retrospective study based on patients' medical, radiological and histopathological records. Between January 2009 and September 2010, 66 patients aged 36–86 years with RCC fulfilled the inclusion criteria.

  • They had histopathologically confirmed primary RCC
  • They had undergone contrast-enhanced computed tomography (CECT) of the abdomen before treatment, and a corresponding official report of the tumor dimensions and metastasis by radiologists was available.


Tumor dimensions were calculated based on the CT by marking the outermost boundaries of the lesion visible on axial or reconstructed coronal and sagittal images. The dimensions of the tumor were first measured in all three planes (in coronal, sagittal, and axial view), and the LTD in any of these planes was calculated, [Figure 1] and [Figure 2]. The presence of skeletal metastasis was assessed by radiologists using plain radiographs and/or CT scan. Patients, who had skeletal metastasis at the time of presentation or subsequently developed skeletal metastatic lesions during follow-up, were designated as cases and those who did not, were designated as controls. Patients having only skeletal metastasis were exclusively selected for the study and those having other extra-skeletal metastasis (lung/liver etc.,) were excluded from this study. As the study was focussed on correlation between 1D LTD and skeletal metastasis biopsy or histopathological evaluation of the tumor/skeletal metastatic lesions were not done. Data were analyzed using the Statistical Package for Social Sciences (SPSS 16, IBM, Chicago, IL, USA). The association between tumor volume and the occurrence of skeletal metastasis was analyzed using independent t-tests between means. The value of P < 0.05 was considered statistically significant. The cut-off value of tumor longest dimension was determined by the largest area under the receiver operating characteristic (ROC) curve.
Figure 1: Axial section of contrast enhanced multidetector computed tomography of a large left renal cell carcinoma. Width and depth were calculated using axial sections (within calipers)

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Figure 2: Coronal section of contrast enhanced multidetector computed tomography of a large renal cell carcinoma with foci of calcification. Length was calculated using coronal sections and longest tumor diameter in any of these sections (coronal in this case) was calculated

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 » Results Top


Of the 66 patients with RCC, 19 (30%) had evidence of or developed skeletal metastasis during the course of this study [Figure 3] and [Figure 4], whereas 47 (70%) did not. The median follow-up time of the cases until distant metastasis was 1.9 years; the median follow-up time of the controls was 3.7 years. There was significant difference in the value of LTD between cases and controls with higher mean tumor diameter in cases (9.9 cm) compared to controls (6.03 cm); P < 0.001, independent sample t-test, [Table 1] and skeletal metastasis were also assessed in patients of all T stages of primary tumor [Table 2]. None of the patients with 1D LTD <4.8 cm on CECT were found to have skeletal metastasis. ROC analysis revealed that the accuracy of LTD in predicting bone metastasis was high with area under ROC curve of 0.823, [Figure 5]. The cut-off value of 7.5 cm, determined by the coordinate of the ROC curve, had a sensitivity of 78.9% and specificity of 80.9% respectively in predicting bony metastasis. Patients were divided into two categories based on this cut-off value, those with 1D LTD >7.5 cm and those with 1D LTD <7.5 cm. The positive and negative predictive values of the cut-off value 7.5 cm in predicting skeletal metastasis were 61.4% and 90%, respectively. The proportion having bony metastasis in those with a 1D LTD >7.5 cm was about 79%.
Figure 3: Vertebral metastasis involving right pedicle and posterior elements from right renal cell carcinoma

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Figure 4: Coronal section of right renal cell carcinoma presenting with multiple vertebral and sacral metastasis

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Table 1: The one-dimensional longest tumor diameter in patients with and without metastases were significantly different

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Table 2: Frequency of skeletal metastasis in different T stages of patients with renal cell carcinoma

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Figure 5: The cut-off value of 7.5 cm, determined by the coordinate of the receiver operating characteristic curve, had a sensitivity of 78.9% and specificity of 80.9% respectively in predicting bony metastasis

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 » Discussion Top


Tumor size and bony metastasis are predictive factors for patient survival and prognosis in RCC. It has been reported in the literature that at presentation or during disease progression, approximately 30% of patients with RCC have or eventually develop metastatic disease in the bone. Furthermore, about 40% of patients who undergo attempted curative resection of their primary relapse with the metastatic skeletal disease.[3] Bone metastases in patients with RCC are also associated with a high risk of debilitating skeletal complications such as severe bone pain, pathological fractures, spinal cord compression and ramifications of orthopedic surgery or palliative radiotherapy to the bone.[3] It has been observed that presenting tumor size represents a significant predictor of synchronous and asynchronous metastases.[4],[5],[6] Cause of increasing metastatic potential with tumor size has been attributed to corresponding increased risk of clear cell histology (vs. papillary or chromophobe) with increasing size.[7],[8] The incidence of distant metastases at presentation for tumors 1.1–2.0 cm and 2.1–3.0 cm are 4% and 5%.[9],[10] A study by Nguyen and Gill employing the surveillance epidemiology and end results database found that 7.8% of all RCCs <1 cm had M1 RCC at presentation and reported 4–5% incidence of metastasis in patients with tumors <3 cm.[9] However, data correlating the incidence of skeletal metastasis with tumor size at the time of presentation is sparse in the existing literature. Few studies have been explained in the literature linking tumor size to the metastatic potential of the renal masses.[10]


 » Conclusion Top


There are few notable finding in this study. First, tumor size (1D LTD) is reported to correlate with the rate of bony metastasis in tumor in this study. The cut-off value of 7.5 cm had high sensitivity of 78.9% and specificity of 80.9% respectively in predicting bony metastasis. Second, the cut-off value of 7.5 cm had high negative predictive value (90%) and moderate positive predictive value (61.4%) in predicting skeletal metastasis. Third, none of the patients with 1D LTD <4.8 cm on CECT were found to have skeletal metastasis. However, we recognize that in this study period of follow-up was relatively less. This was a retrospective study. We await, with interest, a much larger multi-institutional prospective study along with therapeutic trials to ascertain as to whether or not the information embedded in our data could be directly applicable to clinical domains.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
McLaughlin JK, Lipworth L. Epidemiologic aspects of renal cell cancer. Semin Oncol 2000;27:115-23.  Back to cited text no. 1
    
2.
Sahi C, Knox JJ, Clemons M, Joshua AM, Broom R. Renal cell carcinoma bone metastases: Clinical advances. Ther Adv Med Oncol 2010;2:75-83.  Back to cited text no. 2
    
3.
Lipton A, Colombo-Berra A, Bukowski RM, Rosen L, Zheng M, Urbanowitz G. Skeletal complications in patients with bone metastases from renal cell carcinoma and therapeutic benefits of zoledronic acid. Clin Cancer Res 2004;10(18 Pt 2):6397S-403S.  Back to cited text no. 3
    
4.
Kunkle DA, Crispen PL, Li T, Uzzo RG. Tumor size predicts synchronous metastatic renal cell carcinoma: Implications for surveillance of small renal masses. J Urol 2007;177:1692-6.  Back to cited text no. 4
    
5.
Thompson RH, Hill JR, Babayev Y, Cronin A, Kaag M, Kundu S, et al. Metastatic renal cell carcinoma risk according to tumor size. J Urol 2009;182:41-5.  Back to cited text no. 5
    
6.
Lughezzani G, Jeldres C, Isbarn H, Perrotte P, Shariat SF, Sun M, et al. Tumor size is a determinant of the rate of stage T1 renal cell cancer synchronous metastasis. J Urol 2009;182:1287-93.  Back to cited text no. 6
    
7.
Umbreit EC, Thompson RH. Metastatic potential of the small renal mass: Why can't we agree? Eur Urol 2011;60:983-5.  Back to cited text no. 7
    
8.
Guðmundsson E, Hellborg H, Lundstam S, Erikson S, Ljungberg B; Swedish Kidney Cancer Quality Register Group. Metastatic potential in renal cell carcinomas ≤7 cm: Swedish Kidney Cancer Quality Register data. Eur Urol 2011;60:975-82.  Back to cited text no. 8
    
9.
Nguyen MM, Gill IS. Coded tumor size may be unreliable for small metastatic renal cancers in the surveillance, epidemiology, and end results dataset. Urology 2010;75:266-70.  Back to cited text no. 9
    
10.
Ingimarsson JP, Sigurdsson MI, Hardarson S, Petursdottir V, Jonsson E, Einarsson GV, et al. The impact of tumour size on the probability of synchronous metastasis and survival in renal cell carcinoma patients: A population-based study. BMC Urol 2014;14:72.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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