Abstract
Background/Aim: We hypothesized that regional tumor growth into L1 and L2 vertebral bodies from renal pelvis carcinoma was linked to the development of bone metastases. Materials and Methods: Criteria for the study were: (i) Metastatic renal pelvis carcinoma confirmed via pathology and computed tomographic (CT) scan, (ii) L1 and L2 invasion confirmed from retrospective CT scan review, and (iii) detection of bone metastases using radionuclide images/CT scans. Results: A total of 71 cases were enrolled in the study. Initial L1 and L2 vertebral body invasion. were detected in 45 (63%) patients. As well as L1 and L2 invasion, 32 (71%) had development of bone metastases. All bone lesions were osteolytic. Initial L1 and L2 invasion (p<0.00001) was associated with the development of bone metastasis. Conclusion: CT scan can help to detect L1 and L2 vertebral body invasion in patients with renal pelvis carcinoma. Early identification and optimal management of such patients is necessary.
Adult kidneys are located at the T12-L3 level lateral to the psoas muscle and vertebral body (1). The left and right kidney hilum lie at vertebral levels L1 and L2, respectively (1). Tumors originating in the renal pelvis can spread directly to the regional areas along L1 and L2 and then grow into the vertebral bone. Bone metastasis occurs either via direct invasion of bone tissue or secondarily to bone marrow, with the latter being most common (2). Renal pelvis carcinoma involving the renal vein or inferior vena cava (IVC) has been linked to early-onset lung metastasis, as noted in our previous study (3). Direct invasion of renal pelvis carcinoma to L1 and L2 vertebral bodies may play a role in the pathogenesis of bone metastasis development. Computed tomographic (CT) scans of the abdomen are useful for tumor staging and can detect invasion of L1 and L2 vertebral bodies (4).
In this study, we retrospectively identified direct regional invasion of L1 and L2 from metastatic renal pelvis carcinoma based on CT scans. We hypothesized that regional tumors directly growing into L1 and L2 vertebral bodies in patients with renal pelvis carcinoma is linked to the development of bone metastases.
Materials and Methods
Study population. We conducted a retrospective case series study using data collected from patients with metastatic renal pelvis cancer admitted to the Oncology Ward of Chang-Gung Memorial Hospital, Taoyuan, Taiwan, between January 2010 and December 2017. A single medical oncologist specializing in urological cancer provided most of the data. All patients were hospitalized due to chemotherapy treatment and palliative care for complications. CT scans were performed in all cases to evaluate the extent of the tumor. The criteria were: (i) Metastatic renal pelvis carcinoma confirmed via pathology and CT scan, (ii) identification of direct invasion of L1 and L2 vertebral bodies from retrospective CT scan review, and (iii) detection of bone metastases using radionuclide images/CT scans. Representative CT scans of L1 and L2 vertebral body invasion are shown in Figure 1.
Evaluation. We next evaluated whether direct regional growth into L1 and L2 vertebral bodies from renal pelvis carcinoma is linked to the development of bone metastases. Bone metastases were defined as the detection of metastatic bone lesions other than in the L1 and L2 vertebral bodies. Bone metastases were detected using CT scans in all patients and radionuclide images were used in 42 patients with 99mtechnetium-methylene diphosphonate (99mTc-MDP) whole-body bone scan. For staging, 18F-fluorodeoxyglucose positron-emission tomography/CT (18F-FDG PET/CT) was used in four cases. Evaluation for bone metastasis included initial L1 and L2 vertebral body invasion, initial renal vein/IVC involvement, suspicion of peritoneal spread, para-aortic lymph node (LN) metastases, and lung metastases.
Statistical analysis. Chi-squared test was used to detect differences between subgroups and differences with p<0.05 were considered statistically significant.
Results
This study included 71 consecutive patients with metastatic renal pelvis cancer. They consisted of 39 men and 32 women, aged between 39 and 88 years (median age=65 years). Of them, 24 patients did not undergo nephrourectomy procedures. Fifteen patients had multiple primary sites of urinary cancer, including five cases involving the bladder (one case simultaneously), nine cases involving the ureter (six cases simultaneously), and one case involving the bladder and the ureter. One case had undergone previous renal transplantation and one case had end-stage renal disease.
The patients' clinical characteristics are shown in Table I. The most common pathology in this study was urothelial carcinoma. Initial L1 and L2 vertebral body invasion were detected in 45 (63%) patients; all presented with various degrees of back and radicular pain. Initial renal vein/IVC involvement was found in 43 (61%) patients and lung metastasis occurred in 44 (62%).
Detection of bone metastases other than L1 and L2 invasion from image examination, and pattern and location of bone metastases are shown in Table II. Of the 45 patients with initial L1 and L2 vertebral body invasion, invasion in all was detected from retrospective CT scan review. Detection method included CT scan only in 21 (66%) patients (one initially) and a combination of CT scan with radionuclide imaging in 11 (10 initially). A total of 11 cases was positive for radionuclide image studies, including 10 bone scans and one PET/CT. Ten out of 42 patients were positive for bone scans. PET/CT scans were checked in four patients and one was positive for bone metastasis. All bone lesions found on CT scans were osteolytic. Bone metastatic sites of 22 (65%) patients were located in the lumbar spine only.
CT scans showed direct lumbar vertebral body invasion from renal pelvis carcinoma (Figure 2A). PET-CT scan showed multiple bone metastases Figure 2B). A CT scan with an axial view of the right renal pelvis malignancy is shown in Figure 3A and a tumor with direct L2 vertebral body invasion in Figure 3B. CT scans also showed left scapular bone metastasis. In Figure 3C, a bone scan showed multiple bone metastases. Figure 4A shows a CT scan of L2 invasion from renal pelvis carcinoma. Disease progression following chemotherapy with an increase in L2 vertebral invasion and L3 vertebraI metastases can be seen in Figure 4B and C.
A total of 71 patients were evaluated for associations of factors of bone metastasis (Table III). We found that initial L1 and L2 vertebral body invasion (p<0.00001) was associated with the development of bone metastases.
Discussion
The most common sites of metastasis from renal pelvis cancer are the LNs, bones, lungs, liver, and peritoneum (5, 6). Similarly to the literature, 48% of patients with metastatic renal pelvis carcinoma in this study had metastasis to bone. The spread of urological malignancies to bone is a poor prognostic factor. Early detection of metastatic bony lesions can improve quality of life with therapy (7).
Diagnosis of L1 and L2 vertebral body invasion and bone metastasis is possible based on symptoms, CT scan, and radionuclide images (8). The development of radicular pain, which is characterized by pain radiating along the dermatome of a nerve (9), as well as back pain, is related to invasion L1 and L2 vertebral bodies, which cause nerve root compression or irritation (3). CT scans are useful for the staging and detection of L1 and L2 vertebral body invasion and osteolytic bone metastasis (4, 10). However, initial L1 and L2 vertebral body invasion is mainly detected from retrospective review of CT scans. 99mTc-MDP is commonly used as the bone scanning agent, whose uptake is related to osteoblastic activity in response to the cancer (10). Early bone invasion or the presence of some osteolytic metastases such as from multiple myeloma or hepatoma, can lead to false-negative bone scans (10-12). L1 and L2 vertebral body invasion are osteolytic lesions and can be identified from CT scan rather than from bone scan. 18F-FDG PET/CT has a higher diagnostic value than whole-body 99mTc-MDP bone scan for the detection of osteolytic bone metastases, especially in the vertebrae (12, 13). PET/CT scans used in this study to detect the tumor extent only showed one case positive for bone metastasis.
Metastasis via a direct invasion of bone tissue is a mechanism for the development of bone metastases (2). We hypothesized that direct regional tumor growth into the L1 and L2 vertebral bodies in patients with renal pelvis carcinoma was linked to the development of bone metastases. Chemokines play a vital role in tumor progression and metastasis (14, 15), with the CXC chemokine ligand 12–CXC chemokine receptor type 4 (CXCL12–CXCR4) axis playing a pivotal role in bone metastasis (14-16). The bone microenvironment also plays an important role in the development of bone metastases and tumor progression (17, 18). Expression of inflammatory mediators that are critical for cancer growth is increased in bone metastasis (19). Only initial invasion of L1 and L2 vertebral bodies was a factor associated with the development of bone metastases in our study.
There were several limitations to this study. Firstly, the case series data were collected retrospectively. Secondly, the diagnoses of L1 and L2 vertebral body invasion and bone metastases were based only on images and were not confirmed by pathology.
In conclusion, initial L1 and L2 vertebral body invasion was a factor significantly associated with the development of bone metastases. An initial CT scan can help detect L1 and L2 vertebral body invasion, but this feature can easily be overlooked. Early identification and optimal management of these patients is necessary.
Acknowledgements
The Authors wish to thank the oncology nursing staff for providing the best possible care for the patients of this study. We would like to thank Uni-edit (www.uni-edit.net) for editing and proofreading this manuscript.
Footnotes
Authors' Contributions
L T-Y performed data analysis and manuscript writing/editing; L C-C and T K-H contributed cases and management, and J Y-H contributed imaging knowledge. All Authors read and provided final approval of the manuscript.
This article is freely accessible online.
Conflicts of Interest
There are no conflicts of interest regarding this study.
- Received January 23, 2019.
- Revision received February 15, 2019.
- Accepted February 25, 2019.
- Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved