British Journal of Radiology (2007) 80, 96-102
© 2007 British Institute of Radiology
doi: 10.1259/bjr/31311739
Renal artery embolisation in the palliative treatment of renal carcinoma
N J Maxwell, MB, MRCPI, FFR
1
N Saleem Amer, MB, FFR
1
E Rogers, MB, FRCSI
2
D Kiely, MB, FRCSI
2
P Sweeney, MB, FRCSI
2 and
A P Brady, MB, FRCR, FFR
1
Departments of 1 Diagnostic Radiology and 2 Urology, Mercy University Hospital, Grenville Place, Cork, Ireland
Correspondence: N J Maxwell, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15213-2582, USA
 |
Abstract
|
|---|
The aim of this study is to review the role and technique of renal artery embolisation (RAE), and assess its effectiveness in the palliative treatment of unresectable or inoperable renal cell carcinoma (RCC) in our institution. The study group consisted of 19 consecutive patients (16 male, 3 female; age range 47–87 years) who underwent palliative RAE for the treatment of renal carcinoma between January 2000 and December 2005. Unresectable disease was present in 11 patients (3 stage IVa, 8 stage IVb). Potentially resectable disease was present in 8 patients (4 stage II, 1 stage IIIa, 1 stage IIIb, 2 stage IIIc); however, these patients were unfit for surgery for other reasons. 13 patients presented with haematuria, which was gross in 7 patients. Nine patients complained of flank pain. RAE was performed using polyvinyl alcohol or embosphere particles, metallic coils and, in some cases, absolute alcohol was necessary. At the time of analysis, 12 patients had died while 7 patients were still alive, with an overall median survival for the study group of 6 months. In the 7 patients with transfusion dependant gross haematuria, there was stabilization of the haemoglobin level post-embolisation. In the 9 patients who presented with flank pain, symptoms improved or resolved in 8 patients. The median length of hospital stay for the 18 patients who were discharged was 5.0 days. RAE is a safe and tolerable management option for patients with inoperable or unresectable renal carcinoma as a means of palliation of local symptoms and improving clinical status, with low morbidity and shorter hospital stay.
|
Introduction
|
|---|
Renal cell carcinoma (RCC) is the most common renal malignancy comprising 85% of all malignant renal tumours, with transitional cell carcinoma comprising 5–7% [1]. It is the eighth most common malignancy, accounting for 3% of all newly diagnosed neoplasms, with an incidence of 11 per 100 000 individuals [1]. It occurs twice as often in men as in women [2]. The incidence of RCC has increased significantly in the past three decades, primarily due to incidental detection of tumours by expanded use of imaging modalities such as CT and ultrasound. The incidence of metastatic disease among patients with newly diagnosed RCC is approximately 30% [3], and the prognosis in these patients with disseminated disease is poor, with a 5 year survival of less than 20% [4].
Minimally invasive treatment modalities for ablation of small RCCs such as percutaneous radiofrequency ablation [5] and high-intensity focused ultrasound [6] have emerged in recent years, but these have no role in the treatment of large unresectable or metastatic tumours. The treatment of patients with advanced RCC continues to pose a major clinical challenge. RCC is notoriously chemorefractory. Radical nephrectomy is the standard treatment for localized primary lesions. However, because curative surgery is almost impossible in metastatic renal carcinoma, the benefits of surgery to a patient with disseminated disease has been disputed. Recent studies [7, 8] in patients with metastatic renal carcinoma have shown a small survival advantage in patients undergoing radical nephrectomy followed by immunotherapy; however, these studies are biased towards patients with good performance status (World Health Organization (WHO) status 0 or status 1). This small survival benefit should also be viewed in light of the morbidity and mortality associated with a large surgical procedure. The increased morbidity associated with radical nephrectomy may preclude or delay the administration of systemic immunotherapy, which has demonstrated reproducible response rates of 10–20% [9].
Renal artery embolisation is an alternative treatment modality to radical nephrectomy which is associated with low morbidity and can be performed in patients with low performance status. The technique of embolising hypervascular renal carcinomas dates back to 1969 when first reported by Lalli et al [10]. Since then, various techniques and embolic materials have been described. Renal artery embolisation has been used pre-operatively to facilitate nephrectomy [11], or to stimulate a possible systemic response in patients with metastases [12]. Renal embolisation has been established as a palliative treatment for unresectable renal carcinoma and in patients with less advanced disease (stage I–III) who, for whatever reason, are unsuitable or unwilling to undergo surgery [13, 14]. In this group of patients the technique reduces tumour bulk and relieves local symptoms such as pain or intractable haematuria. In this study, we present our own experience of palliative embolisation in the treatment of renal carcinoma.
|
Methods and materials
|
|---|
Our study population comprised 19 consecutive patients (16 male, 3 female; age range 47–87 years, mean 66.8 years) who underwent palliative renal artery embolisation for the treatment of renal carcinoma between January 2000 and December 2005. Twenty-one embolisation procedures were performed, including repeat embolisation in two patients. The patients' case notes were retrieved and analysed. 13 of the 19 patients presented with haematuria, which was gross in 7 patients. Nine patients complained of flank pain. In three cases, a renal tumour was found incidentally when the patient was being investigated for another pathology. Table 1
illustrates the staging of the study population. Potentially resectable disease was present in eight patients (four patients at stage II, one patient at stage IIIa, one patient at stage IIIb, two patients at stage IIIc). Unresectable disease was present in 11 patients (3 patients at stage IVa and 8 stage IVb). Table 2 illustrates the indications for embolisation.
In total, six patients had tumour thrombus in the renal vein with three of these patients having further extension into the inferior vena cava. In two cases thrombus was identified in the right atrium. The sites of metastases were liver in three cases, lung in five cases and one case each of adrenal (contralateral side), bone and brain metastases. One patient presented with bilateral RCCs; however, only one of these tumours was embolised. In 16 patients, radiological diagnosis of RCC was made without histological confirmation. In two cases unusual tumour type was confirmed on histology following biopsy – rhabdoid and sarcomatoid renal carcinoma. In one patient, metastatic RCC was confirmed following biopsy of a contralateral adrenal mass.
|
Technique
|
|---|
Following access via the left or right common femoral artery, a flush aortogram was initially performed in all patients to identify the vascular anatomy and define the exact position and number of renal arteries. Selective catheterization and selective renal arteriography were then performed using a cobra catheter. Embolisation was performed using polyvinyl alcohol or embosphere particles, metallic coils and, in some cases, absolute alcohol was also necessary.
In 11 patients the capillary bed was initially filled with polyvinyl alcohol (PVA) particles, ranging in size from 500 µm to 1000 µm. The end point of injection of PVA particles was cessation of flow in small distal branches of the renal artery. In 8 patients (10 procedures), embosphere microspheres (Biosphere Medical, Rockland, MA) ranging in size from 300 µm to 500 µm were employed as the primary embolic agent. The end point of injection of embospheres was marked slowing of blood flow. Angiography was performed following injection of the particles, demonstrating contrast blush from the occluded capillary network or considerably sluggish flow (Figure 1). The main renal artery or arteries were then occluded using metallic coils of various sizes. The coils were inserted while there was still some antegrade flow in the main renal artery. The number of coils used per embolisation ranged from 3 coils to 16 coils, depending on the number of arteries embolised. As most of the patients had end-stage disease, coils were used to achieve as comprehensive vascular occlusion as possible. Absolute alcohol was used in a few cases to complete the occlusion of the capillary bed when stocks of PVA and embospheres in the department were depleted. Its use was only as a last resort in very vascular tumours. It was injected very slowly, mixed with contrast, to a maximum volume of 10 ml.
Extrarenal supply to the tumour was identified in some patients, mostly from lumbar arteries. These were embolised where found. An aortogram was performed before choosing the vessels to be occluded in each case. In one patient, recurrent tumour was identified in the renal bed 19 years after nephrectomy for renal carcinoma. Arterial supply to this recurrent tumour was from a lumbar artery which was selectively catheterized and occluded with embospheres and coils. In another patient who presented with a large right renal carcinoma and significant paracaval adenopathy, both the renal artery supplying the renal tumour and the lumbar artery supplying the paracaval adenopathy were embolised using embospheres and coils with good result. Two patients required repeat embolisation. The first patient presented with recurrent haematuria and required repeat arterial embolisation of new supply to the renal tumour from a lumbar artery 12 months after the initial procedure. In the second case, repeat embolisation of arterial supply to the upper pole renal tumour was required 6 months after the initial procedure as follow-up imaging confirmed residual perfusion to the tumour, which had increased in size.
In addition to the renal embolisation, adjunctive chemotherapy or immunotherapy was administered to five patients who were deemed suitable by the oncology service in the weeks following the procedure. Follow up radiological imaging included CT (Figure 2), renal ultrasound, radioisotope bone imaging and chest radiograph. Three patients died before scheduled follow-up imaging. All patients were also clinically reviewed either by the urology or medical oncology service. Survival time was calculated from the date of embolisation until time of death.
|
Results
|
|---|
At the time of analysis, 12 patients had died with a median survival of 6 months (range 0 months to 23.5 months) with 7 patients still alive and a median survival of 6 months (range 1 month to 66 months) (Table 3). Table 4 shows the breakdown of survival by tumour stage. The overall median survival time for the group was 6 months.
Three patients died within 1 month post-embolisation. One of these patients had advanced metastatic disease, while a second patient who presented with nephrotic syndrome died from deteriorating renal and cardiac failure. The third patient died from coexisting metastatic prostate carcinoma. One patient with stage II disease who is still alive 66 months post-embolization suffers from severe ankylosing spondylitis particularly affecting his cervical spine. This condition made him a high anaesthetic risk, and therefore unsuitable for surgery.
One of the aims of palliative embolisation in our study was to improve quality of life by obtaining symptomatic improvement with significant reduction in haematuria, flank pain and systemic manifestations. 13 patients in our study population presented with haematuria, with transfusion dependant gross haematuria in 7 cases. There was stabilization of the haemoglobin level in all of the symptomatic patients post-embolisation. In the nine patients who presented with flank pain, symptoms improved or resolved in eight patients. One patient who presented with flank pain died within 2 weeks post-embolisation due to rapid progression of metastatic disease.
The post-embolisation syndrome occurs 1–3 days post-procedure. In our study group eight patients experienced mild flank pain with only one of these patients requiring additional analgesia. Five patients developed pyrexia post-procedure. One of these patients had a gram negative infection which resolved with antibiotics. Two patients experienced nausea.
Three patients were readmitted within 1 month of discharge with renal failure. One of these patients had pre-existing nephrotic syndrome with poor cardiac function and died shortly after admission. The second patient's renal failure resolved with medical management and dialysis was not required. In the third case, the renal failure was predominantly due to dehydration and this resolved with fluid replacement.
In two cases, an embolisation coil was dislodged into the common femoral artery during the procedure. These were subsequently retrieved with an intravascular snare device. In a third case, a coil was dislodged into a branch of the left internal iliac artery; however, on this occasion attempted retrieval of the coil was unsuccessful. The patient made an uneventful recovery. The mean length of hospital stay for the 18 patients who were discharged was 7.4 days with a median of 5 days (range 3 days to 25 days). Only two patients remained in hospital longer than 9 days.
|
Discussion
|
|---|
Up to 30% of patients diagnosed with RCC have metastatic disease at presentation [3]. Despite its sometimes favourable course, patients with metastatic RCC generally die within 2 years of diagnosis. DeKernion et al [4] found that cumulative survival in 86 patients with metastatic RCC was 53% at 6 months, 43% at 1 year, 26% at 2 years and 13% at 5 years. The treatment of patients with metastatic RCC has not improved over the years and continues to pose a problem for clinicians. Surgery is not curative in this group; however, recent advances in immunotherapy have rekindled interest in cytoreductive nephrectomy. A combined analysis [15] of two prospective randomized trials, EORTC [7] and Southwest Oncology Group (SWOG) [8], found a small survival advantage (5.8 months) in patients who underwent nephrectomy followed by interferon-alpha based immunotherapy compared with immunotherapy alone. This survival benefit relates to patients with a good performance status whose primary tumour has been assessed to be surgically operable and who are good candidates for subsequent immunotherapy. Unfortunately, many elderly patients with disseminated RCC do not fit these criteria and have significant comorbidity. Radical nephrectomy may cause significant morbidity post-surgery, particularly in elderly patients, and in some cases precludes the use of systemic therapy. It is in this situation that renal artery embolisation appears to have a role.
In a 1992 survey of general urologists in the UK and Ireland, a questionnaire sought data on urologists' experience with the technique of renal artery embolisation and their view of its current role [16]. The survey outlined the general abandonment by urologists of embolisation as a routine component of the management of renal malignancy. Previous studies had reported that delayed nephrectomy following embolisation of RCC may be of clinical benefit to high risk patients with reduction in the size and vascularity of the primary tumour prior to surgery [17]. Subsequent studies have, however, found no survival benefit for patients with metastatic disease undergoing embolisation and nephrectomy [18]. The survey also indicated that a significant proportion of respondents (35%) still believed that the technique had a role in palliation of haematuria or pain in unfit or inoperable cases, or as the sole treatment modality in patients with metastatic disease.
If permanent occlusion is desired, embolisation of the capillary bed is initially accomplished with polyvinyl alcohol particles (PVA) followed by central occlusion of the main renal artery with stainless steel coils or platinum coils. In the past few years, embosphere particles have been introduced which are gradually replacing PVA particles. One of the perceived shortcomings of PVA particles is that they tend to aggregate and clump within vessels after injection [19]; however, in our study we found this embolic material to be very effective. Embosphere Microspheres (Biosphere Medical, Rockland, MA) are trisacryl microspheres embedded with gelatin. They are precisely calibrated spherical embolisation agents, easy to deliver through microcatheters and unlikely to clump in vessels. Embospheres penetrate more distally into the lesion than PVA particles of similar size with more progressive reduction of the arterial blood supply to the lesion [20].
There was excellent control of local symptoms in our study population. Only one patient required repeat embolisation, due to recurrent haematuria 12 months after the initial procedure. This was due to new supply to the tumour from a lumbar artery. Nurmi et al [13] and Munro et al [21] reported very successful palliation of local symptoms in their respective studies.
We performed arterial embolisation on four patients (Cases 1, 4, 6 and 16) who had no local symptoms related to their renal tumour. In three of these patients, the tumour was diagnosed incidentally when the patient was being investigated for another reason. Two of these patients had metastatic disease. Both patients were reviewed regularly by the urology service. Both patients remained asymptomatic from a renal prospective for a long period following embolisation. One patient survived 10.5 months (dying from coexisting ischaemic heart disease), while the other patient survived 17.5 months post-embolisation. The third patient, who was diagnosed incidentally, was still alive at the time of analysis (6 months post-embolisation). This patient had stage II disease and was unfit for surgery due to coexisting ischaemic heart disease and a poorly functioning contralateral kidney. The fourth patient with no local symptoms died within 1 month post-embolisation secondary to end-stage cardiac failure. It is our experience that arterial embolisation has a role in slowing progression of the disease process in asymptomatic patients who have potentially resectable or inoperable metastatic disease. In the study by Munro et al [21], 24% (6 patients) of their study group had arterial embolisation for asymptomatic localized RCC.
The post-embolisation syndrome comprises fever, loin pain, nausea and vomiting, and can occur between 1–3 days post-embolisation [22]. This was experienced to a varying degree by 13 patients. This was expected and resolved in all cases within a few days.
18 patients were discharged with an average hospital stay of 7.4 days and a median stay of 5 days (range 3 days to 25 days). In a recent study by Tigrani et al [23], the median hospital stay was 8 days (range 4 days to 25 days) for patients who underwent nephrectomy for metastatic RCC without prior embolisation. In the study by Lanigan et al [16], the average hospital stay for their nephrectomy group was 10.45 days. This may have hospital cost implications.
Park et al [14] investigated the effectiveness of renal artery embolisation with a mixture of ethanol and lipiodol in 27 patients with unresectable RCC. 10 of the patients had stage III disease with 15 of the 27 patients having stage IV disease. Overall the median survival of the 27 patients was 8.5 months. The median survival was 23 months in the 10 patients with stage III disease and 7 months in 15 patients with stage IV disease. A similar study by Onishi et al [24] compared two groups of patients with unresectable RCC with stage IV disease. 24 patients underwent renal embolisation with ethanol while 30 patients did not have any intervention. The median survival for the renal embolisation group was 229 days and for the control group 116 days. Those undergoing renal embolisation had a significantly better prognosis than those who did not (p = 0.019). Other authors, including Nurmi et al [13], Marx et al [25] and Wallace et al [26], have reported median survival times for patients treated with renal embolisation ranging from 4 months to 8.4 months. Our experience to date has shown an overall median survival time of 6 months, which is comparable with the survival times reported by these authors. This equates to a 1 year survival rate of 36.8% and a 2 year survival rate of 15.8%. Our findings support the view that embolisation is not a curative treatment and probably only minimally alters the natural course of the disease, but it gives palliation of local symptoms related to advanced renal malignancy and is a safe alternative to radical nephrectomy, with low morbidity and complication rate and shorter hospital stay. The role of cytoreductive embolisation has been raised by previous authors; however, few clinical trials have evaluated this treatment option in patients with metastatic renal carcinoma. Comparison of cytoreductive embolisation and cytoreductive nephrectomy should be included in future studies of patients with metastatic renal carcinoma.
In conclusion, renal artery embolisation is a convenient, relatively tolerable management option in patients with unresectable renal tumours and in patients unfit or unwilling to undergo surgery as a means of palliation of local symptoms and improving clinical status. We believe there is also a role for this procedure in asymptomatic patients who have potentially resectable disease who are unfit or unwilling to undergo surgery, and in asymptomatic patients with inoperable metastatic disease.
View larger version (68K):
[in this window]
[in a new window]
|
Figure 1. (a) Pre-embolisation CT showing a large tumour of the left kidney with tumour extending into and around the left renal vein. (b) CT 6 weeks post-embolisation showing necrosis of the tumour.
|
|
View larger version (67K):
[in this window]
[in a new window]
|
Figure 2. (a) Selective renal catheterization and embolisation using embospheres and metallic coils. The embosphere particles were mixed with contrast prior to injection to ensure visibility. (b) Stagnant contrast/embospheres within the renal parenchyma and the tumour capillary bed. (c) Post-embolisation angiogram shows complete devascularization of the renal tumour.
|
|
Received for publication January 31, 2006.
Revision received July 11, 2006.
Accepted for publication July 17, 2006.
|
References
|
|---|
- Parker S, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. Cancer J Clin 1996;46:5–27.
- Stenzel A, deKernion JB. Pathology, biology, and clinical staging of renal cell carcinoma. Sem Oncol (Suppl.) 1989;16:3–11.[Medline]
- Ritchie AW, deKernion JB. The natural history and clinical features of renal carcinoma. Semin Nephrol 1987;7:131–9.[Medline]
- deKernion JB, Ramming KP, Smith RB. The natural history of metastatic renal cell carcinoma: a computer analysis. J Urol 1978;120:148–52.[Medline]
- Mahnken AH, Rohde D, Brkovic D, Gunther RW, Tacke JA. Percutaneous radiofrequency ablation of renal cell carcinoma – preliminary results. Acta Radiol 2005;46:208–14.[Medline]
- Marberger M, Schatzl G, Cranston D, Kennedy JE. Extracorporeal ablation of renal tumours with high-intensity focused ultrasound. BJU Int 2005;95(Suppl. 2):52–5.
- Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R. European Organisation for Research and Treatment of Cancer (EORTC). Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal cell carcinoma: a randomized trial. Lancet 2001;358:966–70.[CrossRef][Medline]
- Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal cell cancer. N Engl J Med 2001;345:1655–9.[Abstract/Free Full Text]
- Motzer RJ, Russo P. Systemic therapy for renal cell carcinoma. J Urol 2000;163:408–17.[CrossRef][Medline]
- Lalli AF, Peterson N, Bookstein JJ. Roentgen-guided infarctions of kidney and lungs: a potential therapeutic technique. Radiology 1969;93:434–5.[Medline]
- Kaisary AV, Williams G, Riddle PR. The role of preoperative embolization in renal cell carcinoma. J Urol 1984;131:641–6.[Medline]
- Nakano H, Nihira H, Toge T. Treatment of renal cancer patients by transcatheter embolization and its effects on lymphocyte proliferative responses. J Urol 1983;130:24–7.[Medline]
- Nurmi M, Satokari K, Puntala P. Renal artery embolization in the palliative treatment of renal adencarcinoma. Scand J Urol Nephrol 1987;21:93–6.[Medline]
- Park JH, Kim SH, Han JK, Chung JW, Han MC. Transcatheter arterial embolization of unresectable renal cell carcinoma with a mixture of ethanol and iodised oil. Cardiovasc Intervent Radiol 1994;17:323–7.[Medline]
- Flanigan RC, Mickisch G, Sylvester R, Tangan C, van Poppel H, Crawford ED. Cytoreductive nephrectomy in patients with metastatic renal cancer: A combined analysis. J Urol 2004;171:1071–6.[CrossRef][Medline]
- Lanigan D, Jurriaans E, Hammonds JC, Wells IP, Choa RG. The current status of embolization in renal cell carcinoma – a survey of local and national practice. Clin Radiol 1992;46:176–8.[CrossRef][Medline]
- Christensen K, Dyreborg U, Andersen JF, Nissen HM. The value of transvascular embolization in the treatment of renal carcinoma. J Urol 1985;133:191–3.[Medline]
- Flanigan RC. The failure of infarction and/or nephrectomy in stage IV renal cell cancer to influence survival or metastatic regression. Urol Clin North Am 1987;14:757–62.[Medline]
- Bendszus M, Klein R, Burger R, Warmuth-Metz M, Hofmann E, Solymosi L. Efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles in the preoperative embolization of meningiomas. Am J Neuroradiol 2000;21:255–61.[Abstract/Free Full Text]
- Derdeyn C, Graves V, Salamat M, Rappe A. Collagen-coated acrylic microspheres for embolotherapy: in vivo and in vitro characteristics. Am J Neuroradiol 1997;18(4):647–53.
- Munro NP, Woodhams S, Nawrocki JD, Fletcher MS, Thomas PJ. The role of transarterial embolization in the treatment of renal cell carcinoma. BJU Int 2003;92:240–4.[CrossRef][Medline]
- Bono AV, Caresano A. The role of embolization in the treatment of kidney carcinoma. Eur Urol 1983;9:334–7.[Medline]
- Tigrani VS, Reese DM, Small EJ, Presti JC, Carroll PR. Potential role of nephrectomy in the treatment of metastatic renal cell carcinoma: A retrospective analysis. Urology 2000;55:36–40.[CrossRef][Medline]
- Onishi T, Oishi Y, Suzuki Y, Asano K. Prognostic evaluation of transcatheter arterial embolization for unresectable renal cell carcinoma with distant metastases. BJU Int 2001;87:312–5.[CrossRef][Medline]
- Marx FJ, Chaussy C, Moser E. Grenzea and gefahren der palliativen embolization inoperable nierentumoren. Urologe A 1982;21:206–10.[Medline]
- Wallace S, Chuang VP, Swanson D, Bracken B, Hersh EM, Ayala A, et al. Embolization of renal carcinoma. Radiology 1981;138:563–70.[Abstract/Free Full Text]
This article has been cited by other articles:
|
|
|
|
 
M MAY, S BROOKMAN-AMISSAH, S PFLANZ, J ROIGAS, B HOSCHKE, and F KENDEL
Pre-operative renal arterial embolisation does not provide survival benefit in patients with radical nephrectomy for renal cell carcinoma
Br. J. Radiol.,
September 1, 2009;
82(981):
724 - 731.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
