Abstract
Background: Skeletal metastases from renal cell carcinoma are highly
destructive vascular lesions. They pose unique surgical challenges due to the
risk of life-threatening hemorrhage and resistance to other treatments. The
goal of this retrospective study was to evaluate factors that may affect
survival after surgical treatment of metastases of renal cell carcinoma.
Methods: We performed a retrospective review of a series of 295
consecutive patients who had been treated for metastatic renal cell carcinoma
at one institution between 1974 and 2004. There were 226 men and sixty-nine
women. A total of 368 metastases of renal cell tumors to the extremities and
pelvis were treated. The surgical procedures included curettage with cementing
and/or internal fixation (214 tumors), en bloc resection (117), closed nailing
(twenty-seven), amputation (four), and other measures (six). Overall survival
was calculated with Kaplan-Meier analysis. The log-rank test was used to
evaluate the effect of different variables on overall survival.
Results: The overall patient survival rates at one and five years
were 47% and 11%, respectively. The metastatic pattern had a significant
effect on the survival rate (p < 0.0001): patients with a solitary bone
metastasis had the most favorable overall survival rate. Patients with
multiple bone-only metastases had a better survival rate than patients with
pulmonary metastases (p = 0.009). A clear-cell histological subtype was also
associated with better survival (p < 0.0001). The tumor grade did not
predict survival (p = 0.17). Fifteen patients (5%) died within four weeks
after surgery. The causes included acute pulmonary failure (seven patients),
multiorgan failure (six), cerebrovascular accident (one), and hypercalcemia
(one). There were no deaths attributable to intraoperative hemorrhage.
Discussion: Survival beyond twelve months is possible for a
substantial proportion of patients with metastatic renal cell carcinoma.
Patients with a clear-cell histological subtype, bone-only metastases, and a
solitary metastasis have superior survival rates. The presence of pulmonary
metastases does not predict early death in a reliable manner, and some
patients may survive for years with pulmonary and systemic disease. The data
are important for surgeons to consider when choosing treatment for these
patients. For example, local control of disease and implant stability are
important issues for patients with a potential for a long duration of
survival.
Level of Evidence: Prognostic Level II. See Instructions
to Authors for a complete description of levels of evidence.
Osseous metastases from renal cell carcinoma are difficult to
manage1-3.
They tend to be large, highly destructive, hypervascular tumors. The optimal
form of treatment has not been well-established. Conservative operations such
as closed nailing may provide temporary stabilization, but they are
susceptible to failure secondary to local tumor progression since the disease
does not respond reliably to conventional chemotherapy and radiation
(Fig.
1)4-7.
The projected duration of survival of patients is an important factor
affecting the decision regarding management of osseous metastases. Patients
predicted to have a prolonged survival, such as those with a solitary
metastasis, need a durable construct. Patients anticipated to have a short
survival may need only temporary stabilization. Patients who are moribund may
not be surgical candidates at all. Unfortunately, with the conventional
staging system of the American Joint Commission on Cancer, patients with
skeletal metastases are grouped together as having stage-IV
disease8, and there
is no accepted method of stratifying patients with regard to the indications
for surgical
treatment9,10.
We retrospectively analyzed a consecutive series of patients with
metastatic renal cell carcinoma of the appendicular skeleton treated with
surgery. The goal was to document the survival of this cohort of patients and
to determine clinicopathologic factors that affect survival.
Study Design
We performed a retrospective review of a series in patients who had been
treated surgically for metastatic renal cell carcinoma involving the pelvis
and extremities at the M.D. Anderson Cancer Center in Houston, Texas, between
1974 and 2004. The patients were identified through the orthopaedic oncology
surgical da tabase and institutional tumor registry. Medical records,
radiographic studies, operative notes, anesthetic records, and pathology
reports were reviewed. The study was approved by and performed in accordance
with the guidelines of the institutional review board.
We gathered information on demographic characteristics, the site(s) of the
metastasis, the stage of the disease, the presence of other metastatic
disease, the type of surgery, preoperative embolization, blood loss, blood
replacement, the dose of radiation, administration of systemic treatment,
recurrence of disease, and complications.
The histological subtype and Fuhrman grade were determined from the
pathology reports. The Fuhrman classification assigns nuclear grades of 1
through 4 in increasing order of nuclear size, nuclear irregularity, and
nucleolar
prominence11. Grade
1 indicates round nuclei of approximately 10 µm with no clearly visible
nucleoli. Grade 2 indicates nuclei of 15 µm with a somewhat irregular
outline, and nucleoli visible at 400× magnification. Grade 3 indicates
nuclei of 20 µm with an obviously irregular outline, and nucleoli visible
at 100× magnification. Grade-4 nuclei possess the characteristics of
grade-3 nuclei, but they are also distinguished by bizarre multilobed shapes,
chromatin clumps, and sometimes the presence of spindle cells. Since the
Fuhrman grade was not described until 1982, it did not become widely accepted
and utilized until the late 1980s. One hundred and seventy-seven patients had
a Fuhrman grade assigned to the primary tumor in the pathology report on the
initial biopsy results or on the results of the analysis of the resection
specimen obtained at the nephrectomy.
The date and cause of death were determined from information provided by
the institutional Department of Tumor Registry (available on patient charts),
and this was corroborated by the Social Security Death Index. Radiographs were
reviewed for the presence of fracture, extent of local bone destruction,
recurrence, failure of the implant, and long-term stability of
endoprostheses.
The stage of the disease at the time of surgery was determined by a review
of the charts. Particular attention was directed toward chest radiographs,
skeletal radiographs, bone scans, magnetic resonance imaging scans, and
computed axial tomography scans to document the presence of other metastases.
The findings of physical examinations, pathology reports, and operative notes
were also reviewed to determine the presence of lymph node metastases and
visceral metastases.
Patients
A total of 295 consecutive patients were included in the study. Patient
demographics and follow-up data are shown in
Table I. For inclusion in this
study, patients had to have undergone surgery for metastatic renal cell
carcinoma lesion(s) affecting the appendicular skeleton at our institution.
Exclusion criteria included treatment solely with nonoperative measures,
metastatic disease confined to the cranium or spine, surgery for a metastasis
at another institution, or inadequate follow-up (less than twenty-four months,
unless the patient died before that time).
The mean duration of follow-up was nineteen months (median, ten months;
range, zero to 163 months). One hundred and fifty patients died of
disease-related causes twelve months or less after the operation. An
additional forty-three patients died between twelve and twenty-four months
postoperatively. At the time of the last follow-up, forty-eight patients were
still alive. Nine of them had been lost to follow-up. Data were complete for
all other patients.
Surgery
There were 368 de novo metastatic tumors (index cases) and twenty-nine
cases of locally recurrent metastatic disease. One hundred and sixty-three of
the de novo metastases involved a pathologic fracture, and 205 involved an
impending fracture. Fifty-two patients (18%) had more than one site of
surgery. Forty of these patients had two separate operative sites, and the
remaining twelve patients had three to seven operative sites.
Seven attending surgeons performed the operations during the period of the
study. The surgical treatment was chosen by the surgeon and was predicated on
the patient's health status, the anatomic site of the disease, the local
extent of the lesion, and projected patient survival. The type of surgery
performed for the index cases is shown in
Table II. The surgery included
tumor excision in 335 index cases and did not include tumor excision in
thirty-three.
Tumor excision was performed with curettage, en bloc resection, or
amputation. Curettage was generally performed prior to internal fixation with
an intramedullary nail, a long-stem prosthesis, a plate, or another device. A
meticulous, aggressive curettage was performed typically to remove all gross
tumor. Surgical adjuvants were employed in eighteen cases (5%), at the
surgeon's discretion, and included intracavitary argon beam coagulation (ten),
liquid nitrogen (four), phenol (three), and hydrogen peroxide (one). The
cavities were filled with polymethylmethacrylate in 212 cases (99%) after
curettage. The indications for en bloc resection included bone destruction
that precluded standard internal fixation or joint arthroplasty, a solitary
bone metastasis, or a locally recurrent tumor associated with established or
impending fixation failure. The indication for amputation was extensive
multifocal recurrence of disease (three patients) or the inability to perform
limb-sparing reconstruction (one).
Statistical Analysis
Overall survival and local relapse-free survival rates were calculated with
Kaplan-Meier analysis with use of the log-rank test to compare different
groups. Analysis of variance and the Student t test were used to compare the
means of different groups. Statistical calculations were performed with SPSS
version 12.0 (SPSS, Chicago, Illinois). Significance was defined as p =
0.05.
Patient Survival
The overall patient survival rate after the first operation for metastatic
bone metastasis was 47% at twelve months, 30% at two years, and 11% at five
years. The variables that did not have a significant effect on survival
included age, gender, surgeon, and the decade during which the surgery was
performed (Table III).
The clear-cell histological subtype, which accounted for 84% of the cases,
was associated with more favorable patient survival than other variants (p
< 0.0001). At one year, the overall survival rate was 51% for the patients
with the clear-cell subtype compared with 25% for those with a non-clear-cell
subtype. At five years, the overall survival rates were 12% and 0%,
respectively. With the numbers studied, there was no difference in survival
among the various non-clear-cell subtypes.
The Fuhrman grade of the initial primary renal cell tumor was not
predictive of long-term patient survival (p = 0.17). At one year, the overall
survival rate was worse for patients with grade-4 disease than for those with
other grades, but by five years, with the numbers studied, there was no
significant difference in overall survival
(Table III).
Patients were grouped according to four different modes of metastatic
presentation: solitary bone metastasis, multiple osseous metastases without
other metastases, osseous metastasis with non-pulmonary metastases only, and
osseous metastasis with pulmonary metastases (with or without visceral
metastases). The largest group of patients (49%) had pulmonary metastases.
The pattern of skeletal metastasis affected overall survival. Patients with
a solitary bone metastasis had a significantly better survival rate than all
other groups (p < 0.0001), with 78% and 35% survival rates at one and five
years after the surgery, respectively (Fig.
2). Patients with bone-only metastases also had a better prognosis
than patients with pulmonary metastases (p = 0.009).
Only one patient survived for longer than ten years. That patient had a
solitary bone metastasis and was still free of disease at the time of writing.
Although nineteen patients survived for at least five years, fifteen died of
the disease between five and ten years. Three patients survived between five
and ten years and were alive at the time of the last follow-up. Fifteen
patients survived more than five years but died before ten years.
With the numbers studied, we could not identify a significant difference
between en bloc resection and intralesional curettage with regard to survival
of patients with a solitary bone metastasis
(Fig. 3). Thirty-three patients
with a solitary bone metastasis underwent resection, and fifteen patients
underwent curettage. The median duration of survival following en bloc
resection was forty-five months, and the survival rate was 80% at one year and
38% at five years. The median duration of survival following curettage was
twenty-two months, and the survival rate was 73% at one year and 24% at five
years.
Fifteen patients (5%) died in the perioperative period (within four weeks
after the surgery). The most common cause of death was acute respiratory
failure in the presence of pulmonary metastases (seven patients). Rapid
progression of visceral disease resulted in multiorgan failure in six
patients. Hypercalcemia and a cerebrovascular accident contributed to one
death each. Five of the patients who died in the perioperative period had been
treated with conservative surgery (no tumor excision). Eight patients treated
with curettage of the tumor and internal fixation and two patients who had an
en bloc tumor resection died in the perioperative period.
There were no intraoperative or perioperative deaths attributable to
massive hemorrhage. The mean intraoperative blood loss was 1123 mL (median,
500 mL; range, 100 to 14,000 mL). The mean intraoperative blood transfusion
was 2.2 units of packed red blood cells (median, 1.0 unit; range, zero to
thirty units). Twenty cases (5%) involved blood loss of more than 5 L.
Selective transcatheter arterial embolization was used prior to surgery in 199
cases (54%). The mean intraoperative blood loss was 1441 mL for patients who
underwent embolization compared with 875 mL for those who did not have
embolization (p = 0.002). The two groups were not randomized, and embolization
was used routinely for larger, more central tumors at sites where a tourniquet
could not be applied to control intraoperative hemorrhage.
Local Tumor Control
Nineteen patients (6.4%) underwent surgery for local recurrence of disease.
The local relapse-free survival rate was 84% at five years. The local
relapse-free survival rates at one and five years were 94% and 91% after the
117 en bloc resections and 97% and 74% after the 214 curettage procedures (p =
0.43). Within the subset of forty-eight patients with a solitary bone
metastasis, we could not demonstrate a significant difference in the local
relapse-free survival rate at five years between en bloc resection
(thirty-three patients), which was 100%, and curettage (fifteen patients),
which was 92% (p = 0.13).
Sixteen of the nineteen cases of recurrent disease were controlled with
limb-sparing surgery. This consisted of en bloc resection of the involved
segment of bone in seven cases, repeat curettage with internal fixation in
five, and wide excision of a soft-tissue recurrence in four. Amputation of the
extremity was necessary in three patients.
Radiation did not appear to significantly affect the local relapse-free
survival rate. For the fifty-seven primary metastatic lesions (20%) for which
postoperative radiation was employed, the local relapse-free survival rate at
five years was 88%. For the 230 lesions (80%) for which postoperative
radiation was not employed, the local relapse-free survival rate at five years
was 82% (p = 0.79, Fig. 4).
However, the two treatment groups were not comparable, and radiation treatment
was not randomized. The mean dose of radiation was 30 Gy (a median of ten
fractions) with a range of 20 to 40 Gy.
Complications
Perioperative mortality is discussed above in the section on patient
survival. Nonfatal perioperative complications included five cases of deep
wound infection or necrosis that required a reoperation. One case of infection
occurred after closed nail fixation and was treated with surgical irrigation
and débridement. A second case of infection occurred after bipolar hip
hemiarthroplasty and was also treated with irrigation and débridement.
A third case occurred after a proximal humeral resection and endoprosthetic
reconstruction. This infection necessitated removal of the implant. Two cases
of muscle flap necrosis necessitated surgical débridement.
Other nonfatal perioperative complications included superficial wound
necrosis (two cases), pneumonia (three), a retained foreign body (two),
symptomatic deep venous thrombosis (two), prosthetic dislocation (two), nerve
palsy (two), symptomatic pulmonary embolus (one), fat embolism syndrome (one),
upper gastrointestinal bleeding (one), hematoma requiring drainage (one),
prolonged ileus (one), and sepsis from an infected central venous catheter
(one).
Notable late complications following endoprosthetic replacement included
aseptic loosening of the ulnar component of a total elbow replacement in three
patients. There were no other cases of aseptic loosening of endoprostheses at
other sites. There were no late cases of periprosthetic infection. One patient
with a total hip replacement had recurrent dislocations and underwent revision
of the acetabular component to a constrained cup. One patient had breakage of
an intramedullary femoral nail, but this was associated with a massive local
recurrence. There were no instances of nail failure without local
recurrence.
Survival data for patients with metastatic renal cell carcinoma are
relevant to physicians who are confronted with the difficult problem of
managing pathologic fractures. The surgeon must consider issues of local
control and implant stability for patients who have the potential for extended
survival. For patients with a short life expectancy, the surgeon must avoid
hastening death through overly aggressive treatment.
Two features of the survival of these patients are notable. First, there is
a steep descent in the first year, and many patients die of the disease in the
first few months. Second, the death rate diminishes with the passage of time,
and a substantial fraction of patients live well beyond one year.
Approximately one tenth of the patients survive for more than five years, and
prolonged survival is not restricted to patients with a solitary metastasis.
Patients with pulmonary and visceral disease may survive for years, and
one-quarter of these patients survive at least two years.
The present study identifies several predictors of survival. Patients with
a clear-cell histological subtype had a better survival rate than did those
with other subtypes. Patients with metastases confined to osseous sites had a
better survival rate than did those with metastases in the vital organs.
Finally, patients with a solitary bone metastasis had the best survival rate.
This finding is consistent with those of previous
reports12-15.
It should be noted that prior to the 1980s, computed tomography scans of the
chest, abdomen, and pelvis were not routinely available and some of the
patients treated during this time period may not have had a solitary
metastasis.
Surprisingly, there were few long-term survivors. Previous authors have
reported a relatively high rate of survival (>25%) of patients with a
solitary bone
metastasis12,14,16.
We found that, despite an overall survival rate of 35% at five years, there
was only one documented survivor beyond ten years. This observation suggests
that patients with a solitary bone metastasis have more indolent disease but
are not easily cured of the disease.
A variety of treatments were employed in the present study. En bloc
resection, which was used in approximately one-third of the cases, was favored
for treatment of solitary metastasis, large tumors, periarticular disease, and
recurrent tumors. Intralesional excision with curettage, combined with
cementing and internal fixation, was performed for most other tumors (58% of
the series), particularly small-to-moderately sized diaphyseal tumors. Since
this was a retrospective case series, the exact indications for treatment
could not always be determined, and they may not have been applied
consistently. No meaningful conclusion can be reached by comparing one type of
treatment to another under these circumstances. Nevertheless, it is worth
noting that, despite the difficulty with performing surgery for these
hypervascular tumors, preservation of the limb and local control of disease
were achieved in nearly all patients, and the rate of amputation for
recurrent, uncontrollable disease was 1%.
It is not feasible, in the framework of the present study, to determine
whether curettage of the tumor improved patient outcome. A small subset of
patients (7%) underwent closed nailing without excision of the tumor. These
patients had more advanced disease than the patients who underwent curettage
and open nailing. Most died in less than a year, and none survived beyond two
years. Thus, the group treated with closed nailing could not be compared
directly with the group treated with open nailing. The potential benefits of
tumor excision with curettage include less intramedullary spread of tumor
during nail placement, a greater rigidity of the construct after cementing,
reduction of the local tumor mass, and slower progression of the tumor.
It was beyond the scope of this study to examine the other important
outcomes of surgery, such as functional results and durability of pain relief.
A prospective study is needed to determine if these benefits can be realized
consistently and for the duration of a patient's lifetime.
It was not possible to ascribe a survival advantage to en bloc tumor
resection over curettage. A previous study demonstrated improved survival of
patients who had undergone resection, but there may have been a selection bias
toward resection for patients with a solitary
metastasis17.
Another study showed better survival following surgical excision compared with
that following no surgery in patients with a solitary metastasis, but en bloc
resection resulted in no significant improvement in survival compared with
that associated with
curettage13. With
the numbers studied, we also did not find a significant improvement in overall
survival after en bloc resection compared with that after curettage in a
patient with a solitary metastasis. A retrospective power analysis indicated
that the number of evaluable patients in this study provided only a 68% power
to detect a difference of twenty-three months in median survival. Despite the
lack of statistical justification, we believe en bloc resection remains
preferable for treatment of a solitary metastasis because it is the most
reliable means of eradicating disease in the extremities and of providing
durable control of the disease over a potentially long period of survival. En
bloc resection is certainly more attractive when it can be performed with
minimal compromise of limb function.
Although some tumors may be responsive to radiation, the effectiveness of
postoperative adjuvant radiation is
uncertain18. In the
present study, the lack of a decrease in the rate of local recurrence in the
group treated with radiation could be the result of selection bias. The
results do not warrant dismissal of postoperative radiation as a viable
adjuvant to achieve local tumor control, but they do cause us to question
whether radiation can be relied on for local control, particularly after
closed nailing. A prospective randomized trial may be necessary to address
this question. Likewise, the scope of the current study did not permit
analysis of the efficacy of other treatments, such as chemotherapy,
bisphosphonates, and radiofrequency
ablation19-23.
An inherent risk of surgery for renal cell metastases to bone is massive
intraoperative hemorrhage. Our study suggests that, for most patients, the
extent of blood loss is manageable. The mean intraoperative transfusion was
two units of packed red blood cells, despite the fact that only one-half of
the patients underwent preoperative embolization. The fact that embolization
in this series was associated with greater blood loss suggested that there was
a strong selection bias toward embolization for more locally advanced tumors.
Although not specifically demonstrated in this study, the use of embolization
is an accepted practice to reduce blood
loss24.
In summary, approximately one-half of all patients survive for one year
after surgery for renal cell metastases, and one-tenth survive for longer than
five years. Patients with a clear-cell histological subtype, bone-only
metastases, and a solitary metastasis survive longer. The presence of
pulmonary metastases does not predict an early death. These data are important
to consider when determining the surgical treatment of a particular patient.
Local control of disease and implant stability are important issues for a
patient with a potential for a long duration of survival. ?
Kollender Y, Bickels J, Price WM, Kellar
KL, Chen J, Merimsky O, Meller I, Malawer MM. Metastatic renal cell carcinoma
of bone: indications and technique of surgical intervention. J
Urol. 2000;164:
1505-8.1641505
2000
[PubMed][CrossRef]
Les KA, Nicholas RW, Rougraff B, Wurtz
D, Vogelzang NJ, Simon MA, Peabody TD. Local progression after operative
treatment of metastatic kidney cancer. Clin Orthop Relat Res.
2001;390:
206-11.390206
2001
[PubMed][CrossRef]
Smith EM, Kursh ED, Makley J, Resnick
MI. Treatment of osseous metastases secondary to renal cell carcinoma.
J Urol. 1992;148:
784-7.148784
1992
[PubMed]
Cutuli BF, Methlin A, Teissier E,
Schumacher C, Jung GM. Radiation therapy in the treatment of metastatic
renal-cell carcinoma. Prog Clin Biol Res.
1990;348:
179-86.348179
1990
[PubMed]
Durr HR, Maier M, Pfahler M, Baur A,
Refior HJ. Surgical treatment of osseous metastases in patients with renal
cell carcinoma. Clin Orthop Relat Res.
1999;367:
283-90.367283
1999
[PubMed]
Onufrey V, Mohiuddin M. Radiation
therapy in the treatment of metastatic renal cell carcinoma. Int J
Radiat Oncol Biol Phys. 1985;11:
2007-9.112007
1985
[CrossRef]
Flanigan RC, Campbell SC, Clark JI,
Picken MM. Metastatic renal cell carcinoma. Curr Treat Options
Oncol. 2003;4:
385-90.4385
2003
[CrossRef]
Greene FL, Page DL, Fleming ID, Fritz A,
Balch CM, Haller DG, Morrow M. AJCC Cancer staging manual. 6th
Ed. New York: Springer; 2002. p
323-5.323
2002
Guinan P, Stuhldreher D, Frank W,
Rubenstein M. Report of 337 patients with renal cell carcinoma emphasizing 110
with stage IV disease and review of the literature. J Surg
Oncol. 1997;64:
295-8.64295
1997
[CrossRef]
Russo P. Renal cell carcinoma:
presentation, staging, and surgical treatment. Semin
Oncol. 2000;27:
160-76.27160
2000
Fuhrman SA, Lasky LC, Limas C.
Prognostic significance of morphologic parameters in renal cell carcinoma.
Am J Surg Pathol. 1982;6:
655-63.6655
1982
[PubMed][CrossRef]
Althausen P, Althausen A, Jennings LC,
Mankin HJ. Prognostic factors and surgical treatment of osseous metastases
secondary to renal cell carcinoma. Cancer.
1997;80:
1103-9.801103
1997
[PubMed][CrossRef]
Fuchs B, Trousdale RT, Rock MG. Solitary
bony metastasis from renal cell carcinoma: significance of surgical treatment.
Clin Orthop Relat Res.
2005;431:
187-92.431187
2005
[PubMed][CrossRef]
Tongaonkar HB, Kulkarni JN, Kamat MR.
Solitary metastases from renal cell carcinoma: a review. J Surg
Oncol. 1992;49:
45-8.4945
1992
[CrossRef]
van der Poel HG, Roukema JA, Horenblas
S, van Geel AN, Debruyne FM. Metastasectomy in renal cell carcinoma: a
multicenter retrospective analysis. Eur Urol.
1999;35:
197-203.35197
1999
[PubMed][CrossRef]
Jung ST, Ghert MA, Harrelson JM, Scully
SP. Treatment of osseous metastases in patients with renal cell carcinoma.
Clin Orthop Relat Res.
2003;409:
223-31.409223
2003
[PubMed][CrossRef]
Takashi M, Takagi Y, Sakata T, Shimoji
T, Miyake K. Surgical treatment of renal cell carcinoma metastases: prognostic
significance. Int Urol Nephrol.
1995;27:
1-8.271
1995
[PubMed][CrossRef]
Lee J, Hodgson D, Chow E, Bezjak A,
Catton P, Tsuji D, O'Brien M, Danjoux C, Hayter C, Warde P, Gospodarowicz MK.
A phase II trial of palliative radiotherapy for metastatic renal cell
carcinoma. Cancer.
2005;104:
1894-900.1041894
2005
[PubMed][CrossRef]
Lipton A, Zheng M, Seaman J. Zoledronic
acid delays the onset of skeletal-related events and progression of skeletal
disease in patients with advanced renal cell carcinoma. Cancer.
2003;98:
962-9.98962
2003
[PubMed][CrossRef]
Brinkmann OA, Bruns F, Gosheger G, Micke
O, Hertle L. Treatment of bone metastases and local recurrence from renal cell
carcinoma with immunochemotherapy and radiation. World J Urol.
2005;23:
185-90.23185
2005
[PubMed][CrossRef]
van Spronsen DJ, de Weijer KJ, Mulders
PF, De Mulder PH. Novel treatment strategies in clear-cell metastatic renal
cell carcinoma. Anticancer Drugs.
2005;16:
709-17.16709
2005
[PubMed][CrossRef]
Kerst JM, Bex A, Mallo H, Dewit L,
Haanen JB, Boogerd W, Teertstra HJ, de Gast GC. Prolonged low dose IL-2 and
thalidomide in progressive metastatic renal cell carcinoma with concurrent
radiotherapy to bone and/or soft tissue metastasis: a phase II study.
Cancer Immunol Immunother.
2005;54:
926-31.54926
2005
[PubMed][CrossRef]
Adiga GU, Dutcher JP, Larkin M, Garl S,
Koo J. Characterization of bone metastases in patients with renal cell cancer.
BJU Int. 2004;93:
1237-40.931237
2004
[PubMed][CrossRef]
Roscoe MW, McBroom RJ, St Louis E,
Grossman H, Perrin R. Preoperative embolization in the treatment of osseous
metastases from renal cell carcinoma. Clin Orthop Relat Res.
1989;238:
302-7.238302
1989
[PubMed]