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Treatment of Osseous Metastases Secondary to Renal Cell Carcinoma
0022-534 7/92/1483-0784$03.00/0 Vol. 148, 784-787, September 1992
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC.
TREATMENT OF OSSEOUS METASTASES SECONDARY TO RENAL CELL CARCINOMA ERIC M. SMITH, ELROY D. KURSH, JOHN MAKLEY
AND
MARTIN I. RESNICK*
From the Division of Urology and Department of Orthopedics, Case Western Reserve University School of Medicine, Cleveland, Ohio
ABSTRACT
Osseous metastases occur in 25 to 50% of the patients with metastatic renal cell carcinoma. We retrospectively reviewed our experience with 14 patients who underwent 20 palliative orthopedic procedures for treatment of bony metastases secondary to renal cell carcinoma. Of the patients 6 presented after nephrectomy (group 1) and 8 presented initially with osseous metastases (group 2). Only 1 of the group 2 patients underwent adjunctive nephrectomy. Overall, 5 of 14 patients (36%) presented with fracture and 9 of 14 (64%) presented with impending fracture. Five patients required multiple procedures. A total of 7 lesions had been previously treated with external radiation. Of the 20 orthopedic procedures 17 (85%) resulted in significant functional improvement and 18 (90%) resulted in significant relief of pain. There were 4 major complications in the series, including 2 culminating in amputation. Average survival after palliative orthopedic procedures was 22 months (range 7 to 64 months) with a 1-year survival rate of 58%. Orthopedic palliation of osseous metastases from renal cell carcinoma is effective, and our experience indicates that the majority of renal cancer patients with bone metastases will survive long enough to benefit from palliative orthopedic procedures. KEY WORDS:
carcinoma, renal cell; kidney neoplasms; neoplasm metastasis; bone neoplasms
limb was recovered, moderate if there was partial use or a prosthetic device was required for function (for example use of a walker), or poor if no function was recovered. Pain relief was rated good if no analgesics were required after the initial postoperative period, moderate if occasional use of analgesics was required or poor if pain was unrelieved or worsened by the procedure.
More than 17,000 new patients with renal cell carcinoma will be diagnosed in the United States this year. Of these patients up to 90% will eventually have metastases and 25 to 50% of this group will have osseous metastases. 1• 2 Therefore, the paramount concern of the clinician who cares for these unfortunate patients should be palliation but the management of painful and disabling bone metastases is often difficult. We retrospectively reviewed our experience with 14 renal carcinoma patients with osseous metastases who underwent 20 palliative orthopedic procedures to evaluate the effectiveness of this approach.
RESULTS
MATERIALS AND METHODS
The charts of 14 patients who presented to our institution from 1981 to 1989 with bone metastases from renal cell carcinoma requiring orthopedic procedures were reviewed. Eight patients who had osseous metastases but who did not undergo orthopedic procedures other than biopsy were excluded. Presentation of the metastatic lesion was classified as pain with impending fracture or fracture. Radiographic criteria for impending fracture were a painful lytic destructive lesion involving greater than 2.5 cm of the cortex, a lytic lesion greater than 50% of the cross-sectional diameter of the bone and pain unrelieved by radiation therapy. Metastatic evaluation at presentation included a chest x-ray, liver function tests, alkaline phosphatase, bone scan and head computerized tomography. In 1 patient alkaline phosphatase was not obtained. Diagnosis of metastatic renal carcinoma was confirmed pathologically for each lesion at the time of orthopedic repair via excisional biopsy in 12 patients. Two patients underwent diagnostic needle aspiration before repair. The patients were divided into 2 groups: group 1 included 6 patients who presented with osseous metastases after nephrectomy and group 2 consisted of 8 patients who initially presented with bone metastases. The effectiveness of palliative orthopedic procedures was graded according to the level of function and pain relief after the initial postoperative period. Function was considered good if full use of the affected Accepted for publication January 31, 1992. *Requests for reprints: Division of Urology, University Hospitals of Cleveland, 2074 Abington Rd., Cleveland, Ohio 44106.
Mean patient age was 61 years (range 41 to 79). There were 8 men and 6 women. Robson stage at presentation of the renal cell cancer was I (tumor confined to capsule) in 1 patient, II (tumor confined to Gerota's fascia) in 1 and IV (distant metastases) in 12. Overall, 5 of 14 patients (36%) presented with a fracture and 9 (64%) presented with impending fracture. The average age of the patients presenting with a pathological fracture was no different from that of all patients. Only 5 of 13 patients (39%) had an elevated alkaline phosphatase at presentation (3 of 5 in group 1 and 2 of 8 in group 2). Of 14 patients 10 had multiple osseous and visceral metastases when the osseous metastases were discovered. A total of 6 patients (43 % ) suffered pulmonary metastases during the course of the disease, and 3 (21 %) presented with pulmonary and osseous metastases. The 6 group 1 patients (43%) who presented after nephrectomy were an average age of 61 years, and presented at an average of 30 months (range 3 to 72 months) after nephrectomy. Only 1 of these patients presented with a pathological fracture. Of the 8 group 2 patients (57%) who presented initially with osseous metastases 1 underwent nephrectomy and 1 underwent tumor embolization. No renal surgery was required for palliation in the remaining 6 patients. The average age of this group was also 61 years. Four of these patients (51 %) presented with a pathological fracture. The location of the osseous metastases requiring surgery is noted in table 1. The femur was the most common bone affected, followed by the humerus. These 2 sites accounted for 16 of the 20 metastases (80%) requiring surgical intervention. The orthopedic procedures performed and their outcomes are also summarized in table 1. A total of 20 procedures was performed on 14 patients: 9 (62%) underwent a single proce-
784
RENAL
TREA~Cl½E!"
Presentation
Pt. No.
Site of Metastases
785
CA.NCER
1. Procedures performed and outcomes Procedure
Pain
Function
Survival (mos.)
Group I-Presented after nephrectomy Glenoid
Impending fracture Impending fracture
2
Tibia
Pathological fracture
3
Humerus
Impending fracture
4
Tibia
Impending fracture
5
Lt. tibia, rt. femur
Impending fracture
6
Femur, thoracic spine
Scapulectomy and removal of proximal humerus Excision of metastases with intramedullary Kuntscher nailing Proximal humerus replacement with hemiarthroplasty Excision of metastases with intramedullary Kuntscher nailing Excision of metastases with intramedullary rod and methylmethacrylate, resection of proximal two-thirds of femur and total hip arthroplasty Resection of proximal femur and total hip arthroplasty, laminectomy, tumor removal, luque rod insertion
Poor (sling and swath) Poor
Good
Died (9)
Poor
Died (64)
Moderate
Good
Died (9)
Moderate
Moderate
Alive (7)
Moderate
Good (It.), moderate (rt.)
Died (14)
Moderate
Good (femur), moderate (spine)
Died (24)
Good Moderate
Good Moderate
Died (19) Died (25)
Moderate
Poor
Died (11)
Moderate
Moderate
Died (9)
Moderate
Good
Died (7)
Poor
Good
Lost to followup
Moderate
Poor (It.), moderate (rt. femur and humerus)
Alive (30)
Moderate
Moderate (femur), good (humerus)
Died (24)
Group 2-Presented with skeletal metastases 7
Impending fracture Pathological fracture
8
Pathological fracture
9
Femur Humerus, femur Humerus
Impending fracture
10
Femur
Impending fracture
11
Femur
Pathological fracture
12
Femur
Pathological fracture
13
Lt. femur shaft, rt. femur shaft, humerus
Impending fracture
14
Femur, humerus
Total hip arthroplasty Resection with allograft metal prosthesis construct Curettage, intramedullary Kuntscher rod, nailing, methylmethacrylate Proximal femoral allograft and bipolar femoral arthroplasty Proximal femoral resection and cemented hemiarthroplasty Above knee amputation after failed cast and brace at outside institution Intramedullary nailing and methylmethacrylate (IL), intramedullary nailing (rt.), open reduction internal fixation with Rush rods and intramedullary nailing Stepdown fluted femur rod, open reduction internal fixation
dure, while 5 (38%) underwent more than 1 procedure for multiple metastases. The latter 5 patients were an average age of 62 years, essentially the same age as the group overall. Of these 5 patients 3 had positive bone scans at presentation for other lesions, which later became symptomatic and required prophylactic internal fixation, while the remaining 2 had a negative initial bone scan. Of the 20 procedures 9 involved internal fixation, combined when possible with tumor resection and/or curettage. Seven patients underwent resection of metastases with arthroplasty or hemiarthroplasty. Of the 20 lesions preoperative arterial embolization was attempted in 5 (25 %) at the discretion of the attending surgeon. In 2 patients preoperative embolization of upper extremity lesions was unsuccessful due to technical difficulties in superselectively embolizing feeding vessels. In 3 patients successful embolization of long bone metastases (2 femoral and 1 humeral) was performed. Of the 20 procedures performed 1 resulted in complete and 16 in moderate (adequate) return of function, and only 2 had a poor outcome. One of these failures was patient 1, who required a sling and swathe for an extended period postoperatively. The procedure in patient 2 was complicated by nonunion and inability to ambulate, resulting in above the knee amputation. A
total of 8 (40%) resulted in excellent pain relief and only 3 while 9 patients (45%) had moderate (15%) did not have ,mnw,m = in In patient 9 the was unrelieved until recurrent fracture of the humerus in shoulder disarticulation. Patient 13 suffered tures and the pain was unrelieved after each 2 also suffered nonunion lieved until above the knee was the level of function and pain was most improved by arthroplasty or hemiarthroplasty, with these 7 procedures all resulting in a good outcome and only 1 complication. There was no difference in outcome between groups 1 and 2. In group 1, 7 of 8 procedures (88%) yielded improved function and 7 of 8 (88%) resulted in improved pain, compared to 11 of 12 (92%) and 10 of 12 (83%), respectively in group 2, and 18 of 20 (90%) and 17 of 20 (85% ), respectively, overall. Of the 20 procedures there were 4 major and 2 minor complications. Two patients required amputation. Patient 2 suffered nonunion of the tibia after a second pathological fracture and was advised to undergo above the knee amputation for pain relief. Patient 9 also suffered a recurrent pathological fracture after internal fixation, and because of pain and loss of function shoulder disarticulation was recommended. Two patients re0
~LL
C~A,+~~rn
786
SMITH AND ASSOCIATES
quired reoperation, which ultimately resulted in restoration of function. Patient 7 required revision acetabuloplasty after hip dislocation and patient 13 required replacement of the intramedullary rod after migration of the original intramedullary rod resulted in femur nonunion. Three patients presented with complications of palliative orthopedic procedures attempted elsewhere. Patients 5 and 13 suffered nonunion after treatment of pathological fractures elsewhere. Patient 12 presented with a distal femur fracture treated elsewhere with a cast and brace, and nonunion ultimately resulted in above the knee amputation. Overall, there was 1 complication among those lesions treated with arthroplasty. Two patients had minor wound dehiscence. The records of patients receiving radiation therapy before orthopedic procedures were analyzed. Five patients received radiation for pain to 7 lesions at doses of 2,600 to 14,400 rad (table 2). Of these 7 lesions 4 were characterized as impending fractures and 3 were pathological fractures. Six lesions were treated with adjunctive radiotherapy postoperatively but only 1 (patient 13) was not palliated with a combination of surgery and radiation. The postoperative survival of patients was reviewed. The average documented survival was 22 months (range 7 to 64), with 1 patient lost to followup. Of the 2 patients who presented with a solitary osseous metastasis, patient 2 survived 64 months after the procedure before dying of pulmonary metastases and patient 12 was lost to followup. The mean survival after the initial orthopedic procedure was 22 months in group 1 and 21 months in group 2. DISCUSSION
Bone metastases were noted in 42% of the cases in 1 autopsy series of 1,451 Japanese patients with renal cell carcinoma. 2 Patients with metastases commonly present with pain, and usually pain on weight bearing is the first sign of metastases to a lower extremity. 3 Pain with weight bearing is often a sign of imminent fracture. The majority of these lesions are osteolytic and the characteristic radiographic findings are those of a destructive, regular or slightly indented lesion. 4 Cortical involvement of greater than 2.5 cm., a lytic lesion greater than 50% of the cross-sectional diameter of the bone and persistent pain despite irradiation are all considered radiographic criteria of imminent fracture requiring prophylactic fixation. 5 In our series 9 of 14 patients (64 % ) presented with pain and impending fracture, and 5 (36%) presented with a pathological fracture. Any patient with renal cell carcinoma who complains of bone pain on weight bearing should undergo radiographic evaluation and orthopedic consultation to prevent a potentially disabling pathological fracture. Moreover, any patient with a bone metastasis discovered on x-ray should undergo a bone scan, since 9 of our 14 patients (64 % ) suffered multiple metastases during the course of the disease and 5 (36%) required orthopedic surgery on more than 1 metastasis. A review of other reported series of orthopedically managed bone metastases also shows a high incidence of multiple procedures performed on individual patients. 4 ' 6 Patient age did not affect the mode of presentation, since the average ages of groups 1 and 2 were similar. Moreover, increased TABLE 2.
Pt. No.
Lesion
1 Humerus 2 Tibia 3 Humerus 11 Femur 14 Humerus, It. femur, spine
Effect of radiation on osseous metastases Radiation Dose (rad.)
Outcome
Unknown 4,200 2,600 4,000 2,000 X 2 courses + 2,800 (humerus), 3,600 X 4 courses (It. femur), 3,600 X 2 courses (spine)
Impending fracture Impending fracture Fracture Fracture Fracture (humerus and spine), impending fracture (It. femur)
age did not correlate with an increased likelihood of multiple fractures. The average patient age in our series was 61 years, whereas that in the series of Pongracz et al was 55 years. 6 The average age of the patients in the series of Katzner and Schvingt was not reported. 4 The relatively young patient with metastatic renal cell carcinoma is not immune to the potentially disabling consequence of bone metastases, and once a fracture has occurred is just as likely as the older patient to suffer multiple fractures. Alkaline phosphatase alone is not a sensitive indicator of potentially disabling bone metastases, since only 5 of our 14 patients (36%) had an elevated alkaline phosphatase level at presentation. Blacher et al found that 79% of their patients with bony metastases had elevated alkaline phosphatase levels, 7 while Benson et al found elevated alkaline phosphatase levels in 65% of their patients. 8 Bone pain was present in aU of our patients and was a more sensitive indicator of bone metastases than alkaline phosphatase levels. The sites of metastases requiring surgery were most commonly the femur and humerus (77%). Swanson et al reported that 120 of 252 patients (48%) with osseous metastases had lesions of the humerus or femur and, indeed, 52% of the osseous metastases in their series were to the long bones of the extremities.1 Overall, 26% of their renal cell patients had osseous metastases. In the series of Katzner and Schvingt 37 of 44 patients (84 %) suffered femoral or humeral metastases requiring surgery. 4 Most metastases from renal cell carcinoma are hypervascular and operations on such lesions may result in significant hemorrhage. Preoperative transcatheter embolization of osseous metastases has been shown to be effective in reducing operative blood loss. 9 Embolization was successful in 3 of our patients, and we believe that preoperative arterial embolization should be considered in all cases of osseous renal cell metastases. In general, the results of palliative orthopedic procedures were good. Pongracz et al reported excellent to good pain relief in 46 of 52 patients (88%) and significantly improved function in all but 1. 6 Katzner and Schvingt reported pain relief in 90% of 44 patients and significant recovery of function in 31 (70%). 4 Of our 20 procedures 17 (85%) resulted in significant pain relief and 18 (90%) resulted in significant improvement of function. There was no difference in outcome between our 2 patient groups. Postoperative pain relief was augmented by radiation therapy in 5 patients. Failure of orthopedic palliation was most often due to recurrent pathological fracture or continued osteolytic destruction of bone. Moreover, the more aggressively managed bone lesions, in particular those managed with total joint replacement, fared better than those managed otherwise. All 7 of these lesions were managed successfully with only 1 complication (hip dislocation immediately postoperatively). Katzner and Schvingt likewise advocated arthroplasty as the ideal form of treatment for these lesions, particularly those of the upper femur, because of the early weight bearing achieved in these relatively short-lived patients. 4 The use of internal fixation, particularly intramedullary rodding combined with methylmethacrylate, for lesions in which arthroplasty is not indicated, such as the midshaft of the femur, is well documented in the orthopedic literature. 5 ' 6 • 10- 14 Our results indicate that the use of these techniques is palliative in most cases. While there were 4 major complications in our series, including 2 culminating in amputations, the alternatives to surgical intervention, specifically intractable bone pain in a bedridden patient, make the procedures manifest worth the risk. No patient died of orthopedic repair. A particularly telling outcome of this series was the number of patients who received radiation therapy for palliation before presenting with an orthopedic malady. Of the 7 lesions in 5 such patients 3 continued to be intractably painful after radiation therapy and 4 developed into pathological fractures. High dose radiation therapy for palliation of painful bony metastases
TREATMEl'JT OF OSSEOUS J,1ETAS'TASES SECOf.JDARY ·-fO REL\J-AL CELL CANCER
has been shown to be effective in one-half to three-quarters of all renal cancer patients. 15- 18 However, our results show that those lesions in which radiation is ineffective can result in fractures. Previous series demonstrating success in relieving pain with radiation therapy do not document whether subsequent fracture occurred. 15- 18 In 1 series of 306 pathological femur fractures secondary to many different types of primary tumor more than a third had undergone preoperative palliative radiotherapy. 19 Radiation therapy does not prevent fracture and should not be undertaken with this in mind. Patients undergoing radiation therapy for long bone metastases should have orthopedic evaluation, as should those who fail radiation therapy. Radiation therapy for pain relief was an effective adjunct to surgery in this series. The survival of patients with bone metastases has been reviewed in several series. Swanson et al showed that patients with a solitary osseous metastasis at diagnosis had a 1-year survival rate of 74%, while those with multiple osseous metastases or osseous and visceral metastases had a 1-year survival rate of 20%. 1 Montie et al found a 1-year survival rate after adjunctive nephrectomy of 36% in patients with only osseous metastases compared with 18% in patients with other metastatic sites. 20 Maldazys and deKernion showed a 1-year survival rate of 32 to 50% in patients with nonpulmonary metastases.21 Grant and deKernion recommended palliative orthopedic procedures in any suitable patient with a life expectancy of longer than 2 months. 3 In our series the average survival after a palliative orthopedic procedure was 22 months (range 7 to 64) and the 1-year survival rate was 58%. Clearly, most renal cell carcinoma patients with skeletal metastases will survive long enough to benefit from palliative orthopedic procedures. The management of patients with skeletal metastases from renal cell carcinoma is essentially palliative. Palliation can often be most effectively achieved through orthopedic surgical management of bone metastases. Any renal cell carcinoma patient with bone pain or pain on weight bearing should undergo a bone scan, appropriate x-rays and orthopedic consultation. Any patient with bone metastases should have a bone scan to identify other sites of metastases and should be followed closely for signs of new osseous metastases. Radiotherapy does not prevent pathological fractures. Finally, these patient survivals are long enough to justify orthopedic intervention when indicated. REFERENCES 1. Swanson, D. A., Orovan, W. L., Johnson, D. E. and Giacco, G.:
Osseous metastases secondary to renal cell carcinoma. Urology, 18: 556, 1981. 2. Saitoh, H.: Distant metastasis of renal adenocarcinoma. Cancer, 48: 1487, 1981.
787
3. Grant, T. T. and deKernion, J. R: Treatment of skeletal metastases from urologic malignancies. Urology, 11: 563, 1978. 4. Katzner, M. and Schvingt, E.: Operative treatment of bone metastases secondary to renal carcinoma. In: Basic Research and Treatment of Renal Cell Carcinoma Metastasis. Edited by C. G. Bollack and D. Jacqmin. New York: Wiley-Liss, pp. 151-168, 1990. 5. Harrington, K. D.: Orthopaedic Management of Metastatic Bone Disease. St. Louis: The C. V. Mosby Co., 1988. 6. Pongracz, N., Zimmerman, R. I. and Kotz, R.: Orthopaedic man-
agement of bony metastases of renal cancer. Sem. Surg. Oneal., 4: 139, 1988. 7. Blacher, E., Johnson, D. E. and Haynie, T. P.: Value of routine radionuclide bone scans in renal cell carcinoma. Urology, 26: 432, 1985.
8. Benson, M. A., Haaga, J. R. and Resnick, M. I.: Staging renal carcinoma. What is sufficient? Arch. Surg., 124: 71, 1989. 9. Bowers, T. A., Murray, J. A., Charnsangavej, C., Soo, C. S., Chuang, V. P. and Wallace, S.: Bone metastases from renal carcinoma. The preoperative use oftranscatheter arterial occlusion. J. Bone Joint Surg., 64: 749, 1982. 10. Beals, R. K. and Snell, W. E.: Breast cancer metastatic to the femur. J. Bone Joint Surg., 45-A: 660, 1963. 11. Harrington, K. D., Johnston, J. 0., Turner, R.H. and Woten, D. L.: The use of methylmethacrylate as an adjunct in the internal fixation of malignant neoplastic fractures. J. Bone Joint Surg., 54: 1665, 1972. 12. Harrington, K. D., Sim, F. H. and Enis, J. E.: Methylmethacrylate as an adjunct in internal fixation of pathological fractures. Experience with three hundred and seventy-five cases. J. Bone Joint Surg., 58: 1047, 1976. 13. Weber, B. G.: Surgical management of tumor-related limb fractures. Rec. Res. Cancer Res., 108: 160, 1988. 14. Gebhart, M., Roman, A., Ghanem, G. and Lejeune, F.: Surgical treatment of bone metastases of the peripheral skeleton-a review of 33 cases. Eur. J. Surg. Oncol., 15: 520, 1989. 15. Forman, J. D.: The role of radiation therapy in the management of carcinoma of the kidney. Sem. Urol., 7: 195, 1989. 16. Onufrey, V. and Mohiuddin, M.: Radiation therapy in the treatment of metastatic renal cell carcinoma. Int. J. Rad. Oncol. Biol. Phys., 11: 2007, 1985. 17. Halperin, E. C. and Harisiadis, L.: The role of radiation therapy in the management of metastatic renal cell carcinoma. Cancer, 51: 614, 1983. 18. Cutuli, B. F., Methlin, A., Teissier, E., Schumacher, C. and Jung,
G. M.: Radiation therapy in the treatment of metastatic renalcell carcinoma. In: Basic Research and Treatment of Renal Cell Carcinoma Metastasis. Edited by C. G. Bollack and D. Jacqmin. New York: Wiley-Liss, pp. 179-186, 1990. 19. Habermann, E. T., Sachs, R., Stein, R. E., Hirsh, D. M. and Anderson, W. J., Jr.: The pathology and treatment of metastatic disease of the femur. Clin. Orthop., 169: 70, 1982. 20. Montie, J. E., Stewart, B. H., Straffon, R. A., Banowsky, L. H. W., Hewitt, C. B. and Montague, D. K.: The role of adjunctive nephrectomy in patients with metastatic renal cell carcinoma. J. Urol., 117: 272, 1977. 21. Maldazys, J. D. and deKernion, J. B.: Prognostic factors in metastatic renal carcinoma. J. Urol., 136: 376, 1986.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC.
TREATMENT OF OSSEOUS METASTASES SECONDARY TO RENAL CELL CARCINOMA ERIC M. SMITH, ELROY D. KURSH, JOHN MAKLEY
AND
MARTIN I. RESNICK*
From the Division of Urology and Department of Orthopedics, Case Western Reserve University School of Medicine, Cleveland, Ohio
ABSTRACT
Osseous metastases occur in 25 to 50% of the patients with metastatic renal cell carcinoma. We retrospectively reviewed our experience with 14 patients who underwent 20 palliative orthopedic procedures for treatment of bony metastases secondary to renal cell carcinoma. Of the patients 6 presented after nephrectomy (group 1) and 8 presented initially with osseous metastases (group 2). Only 1 of the group 2 patients underwent adjunctive nephrectomy. Overall, 5 of 14 patients (36%) presented with fracture and 9 of 14 (64%) presented with impending fracture. Five patients required multiple procedures. A total of 7 lesions had been previously treated with external radiation. Of the 20 orthopedic procedures 17 (85%) resulted in significant functional improvement and 18 (90%) resulted in significant relief of pain. There were 4 major complications in the series, including 2 culminating in amputation. Average survival after palliative orthopedic procedures was 22 months (range 7 to 64 months) with a 1-year survival rate of 58%. Orthopedic palliation of osseous metastases from renal cell carcinoma is effective, and our experience indicates that the majority of renal cancer patients with bone metastases will survive long enough to benefit from palliative orthopedic procedures. KEY WORDS:
carcinoma, renal cell; kidney neoplasms; neoplasm metastasis; bone neoplasms
limb was recovered, moderate if there was partial use or a prosthetic device was required for function (for example use of a walker), or poor if no function was recovered. Pain relief was rated good if no analgesics were required after the initial postoperative period, moderate if occasional use of analgesics was required or poor if pain was unrelieved or worsened by the procedure.
More than 17,000 new patients with renal cell carcinoma will be diagnosed in the United States this year. Of these patients up to 90% will eventually have metastases and 25 to 50% of this group will have osseous metastases. 1• 2 Therefore, the paramount concern of the clinician who cares for these unfortunate patients should be palliation but the management of painful and disabling bone metastases is often difficult. We retrospectively reviewed our experience with 14 renal carcinoma patients with osseous metastases who underwent 20 palliative orthopedic procedures to evaluate the effectiveness of this approach.
RESULTS
MATERIALS AND METHODS
The charts of 14 patients who presented to our institution from 1981 to 1989 with bone metastases from renal cell carcinoma requiring orthopedic procedures were reviewed. Eight patients who had osseous metastases but who did not undergo orthopedic procedures other than biopsy were excluded. Presentation of the metastatic lesion was classified as pain with impending fracture or fracture. Radiographic criteria for impending fracture were a painful lytic destructive lesion involving greater than 2.5 cm of the cortex, a lytic lesion greater than 50% of the cross-sectional diameter of the bone and pain unrelieved by radiation therapy. Metastatic evaluation at presentation included a chest x-ray, liver function tests, alkaline phosphatase, bone scan and head computerized tomography. In 1 patient alkaline phosphatase was not obtained. Diagnosis of metastatic renal carcinoma was confirmed pathologically for each lesion at the time of orthopedic repair via excisional biopsy in 12 patients. Two patients underwent diagnostic needle aspiration before repair. The patients were divided into 2 groups: group 1 included 6 patients who presented with osseous metastases after nephrectomy and group 2 consisted of 8 patients who initially presented with bone metastases. The effectiveness of palliative orthopedic procedures was graded according to the level of function and pain relief after the initial postoperative period. Function was considered good if full use of the affected Accepted for publication January 31, 1992. *Requests for reprints: Division of Urology, University Hospitals of Cleveland, 2074 Abington Rd., Cleveland, Ohio 44106.
Mean patient age was 61 years (range 41 to 79). There were 8 men and 6 women. Robson stage at presentation of the renal cell cancer was I (tumor confined to capsule) in 1 patient, II (tumor confined to Gerota's fascia) in 1 and IV (distant metastases) in 12. Overall, 5 of 14 patients (36%) presented with a fracture and 9 (64%) presented with impending fracture. The average age of the patients presenting with a pathological fracture was no different from that of all patients. Only 5 of 13 patients (39%) had an elevated alkaline phosphatase at presentation (3 of 5 in group 1 and 2 of 8 in group 2). Of 14 patients 10 had multiple osseous and visceral metastases when the osseous metastases were discovered. A total of 6 patients (43 % ) suffered pulmonary metastases during the course of the disease, and 3 (21 %) presented with pulmonary and osseous metastases. The 6 group 1 patients (43%) who presented after nephrectomy were an average age of 61 years, and presented at an average of 30 months (range 3 to 72 months) after nephrectomy. Only 1 of these patients presented with a pathological fracture. Of the 8 group 2 patients (57%) who presented initially with osseous metastases 1 underwent nephrectomy and 1 underwent tumor embolization. No renal surgery was required for palliation in the remaining 6 patients. The average age of this group was also 61 years. Four of these patients (51 %) presented with a pathological fracture. The location of the osseous metastases requiring surgery is noted in table 1. The femur was the most common bone affected, followed by the humerus. These 2 sites accounted for 16 of the 20 metastases (80%) requiring surgical intervention. The orthopedic procedures performed and their outcomes are also summarized in table 1. A total of 20 procedures was performed on 14 patients: 9 (62%) underwent a single proce-
784
RENAL
TREA~Cl½E!"
Presentation
Pt. No.
Site of Metastases
785
CA.NCER
1. Procedures performed and outcomes Procedure
Pain
Function
Survival (mos.)
Group I-Presented after nephrectomy Glenoid
Impending fracture Impending fracture
2
Tibia
Pathological fracture
3
Humerus
Impending fracture
4
Tibia
Impending fracture
5
Lt. tibia, rt. femur
Impending fracture
6
Femur, thoracic spine
Scapulectomy and removal of proximal humerus Excision of metastases with intramedullary Kuntscher nailing Proximal humerus replacement with hemiarthroplasty Excision of metastases with intramedullary Kuntscher nailing Excision of metastases with intramedullary rod and methylmethacrylate, resection of proximal two-thirds of femur and total hip arthroplasty Resection of proximal femur and total hip arthroplasty, laminectomy, tumor removal, luque rod insertion
Poor (sling and swath) Poor
Good
Died (9)
Poor
Died (64)
Moderate
Good
Died (9)
Moderate
Moderate
Alive (7)
Moderate
Good (It.), moderate (rt.)
Died (14)
Moderate
Good (femur), moderate (spine)
Died (24)
Good Moderate
Good Moderate
Died (19) Died (25)
Moderate
Poor
Died (11)
Moderate
Moderate
Died (9)
Moderate
Good
Died (7)
Poor
Good
Lost to followup
Moderate
Poor (It.), moderate (rt. femur and humerus)
Alive (30)
Moderate
Moderate (femur), good (humerus)
Died (24)
Group 2-Presented with skeletal metastases 7
Impending fracture Pathological fracture
8
Pathological fracture
9
Femur Humerus, femur Humerus
Impending fracture
10
Femur
Impending fracture
11
Femur
Pathological fracture
12
Femur
Pathological fracture
13
Lt. femur shaft, rt. femur shaft, humerus
Impending fracture
14
Femur, humerus
Total hip arthroplasty Resection with allograft metal prosthesis construct Curettage, intramedullary Kuntscher rod, nailing, methylmethacrylate Proximal femoral allograft and bipolar femoral arthroplasty Proximal femoral resection and cemented hemiarthroplasty Above knee amputation after failed cast and brace at outside institution Intramedullary nailing and methylmethacrylate (IL), intramedullary nailing (rt.), open reduction internal fixation with Rush rods and intramedullary nailing Stepdown fluted femur rod, open reduction internal fixation
dure, while 5 (38%) underwent more than 1 procedure for multiple metastases. The latter 5 patients were an average age of 62 years, essentially the same age as the group overall. Of these 5 patients 3 had positive bone scans at presentation for other lesions, which later became symptomatic and required prophylactic internal fixation, while the remaining 2 had a negative initial bone scan. Of the 20 procedures 9 involved internal fixation, combined when possible with tumor resection and/or curettage. Seven patients underwent resection of metastases with arthroplasty or hemiarthroplasty. Of the 20 lesions preoperative arterial embolization was attempted in 5 (25 %) at the discretion of the attending surgeon. In 2 patients preoperative embolization of upper extremity lesions was unsuccessful due to technical difficulties in superselectively embolizing feeding vessels. In 3 patients successful embolization of long bone metastases (2 femoral and 1 humeral) was performed. Of the 20 procedures performed 1 resulted in complete and 16 in moderate (adequate) return of function, and only 2 had a poor outcome. One of these failures was patient 1, who required a sling and swathe for an extended period postoperatively. The procedure in patient 2 was complicated by nonunion and inability to ambulate, resulting in above the knee amputation. A
total of 8 (40%) resulted in excellent pain relief and only 3 while 9 patients (45%) had moderate (15%) did not have ,mnw,m = in In patient 9 the was unrelieved until recurrent fracture of the humerus in shoulder disarticulation. Patient 13 suffered tures and the pain was unrelieved after each 2 also suffered nonunion lieved until above the knee was the level of function and pain was most improved by arthroplasty or hemiarthroplasty, with these 7 procedures all resulting in a good outcome and only 1 complication. There was no difference in outcome between groups 1 and 2. In group 1, 7 of 8 procedures (88%) yielded improved function and 7 of 8 (88%) resulted in improved pain, compared to 11 of 12 (92%) and 10 of 12 (83%), respectively in group 2, and 18 of 20 (90%) and 17 of 20 (85% ), respectively, overall. Of the 20 procedures there were 4 major and 2 minor complications. Two patients required amputation. Patient 2 suffered nonunion of the tibia after a second pathological fracture and was advised to undergo above the knee amputation for pain relief. Patient 9 also suffered a recurrent pathological fracture after internal fixation, and because of pain and loss of function shoulder disarticulation was recommended. Two patients re0
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SMITH AND ASSOCIATES
quired reoperation, which ultimately resulted in restoration of function. Patient 7 required revision acetabuloplasty after hip dislocation and patient 13 required replacement of the intramedullary rod after migration of the original intramedullary rod resulted in femur nonunion. Three patients presented with complications of palliative orthopedic procedures attempted elsewhere. Patients 5 and 13 suffered nonunion after treatment of pathological fractures elsewhere. Patient 12 presented with a distal femur fracture treated elsewhere with a cast and brace, and nonunion ultimately resulted in above the knee amputation. Overall, there was 1 complication among those lesions treated with arthroplasty. Two patients had minor wound dehiscence. The records of patients receiving radiation therapy before orthopedic procedures were analyzed. Five patients received radiation for pain to 7 lesions at doses of 2,600 to 14,400 rad (table 2). Of these 7 lesions 4 were characterized as impending fractures and 3 were pathological fractures. Six lesions were treated with adjunctive radiotherapy postoperatively but only 1 (patient 13) was not palliated with a combination of surgery and radiation. The postoperative survival of patients was reviewed. The average documented survival was 22 months (range 7 to 64), with 1 patient lost to followup. Of the 2 patients who presented with a solitary osseous metastasis, patient 2 survived 64 months after the procedure before dying of pulmonary metastases and patient 12 was lost to followup. The mean survival after the initial orthopedic procedure was 22 months in group 1 and 21 months in group 2. DISCUSSION
Bone metastases were noted in 42% of the cases in 1 autopsy series of 1,451 Japanese patients with renal cell carcinoma. 2 Patients with metastases commonly present with pain, and usually pain on weight bearing is the first sign of metastases to a lower extremity. 3 Pain with weight bearing is often a sign of imminent fracture. The majority of these lesions are osteolytic and the characteristic radiographic findings are those of a destructive, regular or slightly indented lesion. 4 Cortical involvement of greater than 2.5 cm., a lytic lesion greater than 50% of the cross-sectional diameter of the bone and persistent pain despite irradiation are all considered radiographic criteria of imminent fracture requiring prophylactic fixation. 5 In our series 9 of 14 patients (64 % ) presented with pain and impending fracture, and 5 (36%) presented with a pathological fracture. Any patient with renal cell carcinoma who complains of bone pain on weight bearing should undergo radiographic evaluation and orthopedic consultation to prevent a potentially disabling pathological fracture. Moreover, any patient with a bone metastasis discovered on x-ray should undergo a bone scan, since 9 of our 14 patients (64 % ) suffered multiple metastases during the course of the disease and 5 (36%) required orthopedic surgery on more than 1 metastasis. A review of other reported series of orthopedically managed bone metastases also shows a high incidence of multiple procedures performed on individual patients. 4 ' 6 Patient age did not affect the mode of presentation, since the average ages of groups 1 and 2 were similar. Moreover, increased TABLE 2.
Pt. No.
Lesion
1 Humerus 2 Tibia 3 Humerus 11 Femur 14 Humerus, It. femur, spine
Effect of radiation on osseous metastases Radiation Dose (rad.)
Outcome
Unknown 4,200 2,600 4,000 2,000 X 2 courses + 2,800 (humerus), 3,600 X 4 courses (It. femur), 3,600 X 2 courses (spine)
Impending fracture Impending fracture Fracture Fracture Fracture (humerus and spine), impending fracture (It. femur)
age did not correlate with an increased likelihood of multiple fractures. The average patient age in our series was 61 years, whereas that in the series of Pongracz et al was 55 years. 6 The average age of the patients in the series of Katzner and Schvingt was not reported. 4 The relatively young patient with metastatic renal cell carcinoma is not immune to the potentially disabling consequence of bone metastases, and once a fracture has occurred is just as likely as the older patient to suffer multiple fractures. Alkaline phosphatase alone is not a sensitive indicator of potentially disabling bone metastases, since only 5 of our 14 patients (36%) had an elevated alkaline phosphatase level at presentation. Blacher et al found that 79% of their patients with bony metastases had elevated alkaline phosphatase levels, 7 while Benson et al found elevated alkaline phosphatase levels in 65% of their patients. 8 Bone pain was present in aU of our patients and was a more sensitive indicator of bone metastases than alkaline phosphatase levels. The sites of metastases requiring surgery were most commonly the femur and humerus (77%). Swanson et al reported that 120 of 252 patients (48%) with osseous metastases had lesions of the humerus or femur and, indeed, 52% of the osseous metastases in their series were to the long bones of the extremities.1 Overall, 26% of their renal cell patients had osseous metastases. In the series of Katzner and Schvingt 37 of 44 patients (84 %) suffered femoral or humeral metastases requiring surgery. 4 Most metastases from renal cell carcinoma are hypervascular and operations on such lesions may result in significant hemorrhage. Preoperative transcatheter embolization of osseous metastases has been shown to be effective in reducing operative blood loss. 9 Embolization was successful in 3 of our patients, and we believe that preoperative arterial embolization should be considered in all cases of osseous renal cell metastases. In general, the results of palliative orthopedic procedures were good. Pongracz et al reported excellent to good pain relief in 46 of 52 patients (88%) and significantly improved function in all but 1. 6 Katzner and Schvingt reported pain relief in 90% of 44 patients and significant recovery of function in 31 (70%). 4 Of our 20 procedures 17 (85%) resulted in significant pain relief and 18 (90%) resulted in significant improvement of function. There was no difference in outcome between our 2 patient groups. Postoperative pain relief was augmented by radiation therapy in 5 patients. Failure of orthopedic palliation was most often due to recurrent pathological fracture or continued osteolytic destruction of bone. Moreover, the more aggressively managed bone lesions, in particular those managed with total joint replacement, fared better than those managed otherwise. All 7 of these lesions were managed successfully with only 1 complication (hip dislocation immediately postoperatively). Katzner and Schvingt likewise advocated arthroplasty as the ideal form of treatment for these lesions, particularly those of the upper femur, because of the early weight bearing achieved in these relatively short-lived patients. 4 The use of internal fixation, particularly intramedullary rodding combined with methylmethacrylate, for lesions in which arthroplasty is not indicated, such as the midshaft of the femur, is well documented in the orthopedic literature. 5 ' 6 • 10- 14 Our results indicate that the use of these techniques is palliative in most cases. While there were 4 major complications in our series, including 2 culminating in amputations, the alternatives to surgical intervention, specifically intractable bone pain in a bedridden patient, make the procedures manifest worth the risk. No patient died of orthopedic repair. A particularly telling outcome of this series was the number of patients who received radiation therapy for palliation before presenting with an orthopedic malady. Of the 7 lesions in 5 such patients 3 continued to be intractably painful after radiation therapy and 4 developed into pathological fractures. High dose radiation therapy for palliation of painful bony metastases
TREATMEl'JT OF OSSEOUS J,1ETAS'TASES SECOf.JDARY ·-fO REL\J-AL CELL CANCER
has been shown to be effective in one-half to three-quarters of all renal cancer patients. 15- 18 However, our results show that those lesions in which radiation is ineffective can result in fractures. Previous series demonstrating success in relieving pain with radiation therapy do not document whether subsequent fracture occurred. 15- 18 In 1 series of 306 pathological femur fractures secondary to many different types of primary tumor more than a third had undergone preoperative palliative radiotherapy. 19 Radiation therapy does not prevent fracture and should not be undertaken with this in mind. Patients undergoing radiation therapy for long bone metastases should have orthopedic evaluation, as should those who fail radiation therapy. Radiation therapy for pain relief was an effective adjunct to surgery in this series. The survival of patients with bone metastases has been reviewed in several series. Swanson et al showed that patients with a solitary osseous metastasis at diagnosis had a 1-year survival rate of 74%, while those with multiple osseous metastases or osseous and visceral metastases had a 1-year survival rate of 20%. 1 Montie et al found a 1-year survival rate after adjunctive nephrectomy of 36% in patients with only osseous metastases compared with 18% in patients with other metastatic sites. 20 Maldazys and deKernion showed a 1-year survival rate of 32 to 50% in patients with nonpulmonary metastases.21 Grant and deKernion recommended palliative orthopedic procedures in any suitable patient with a life expectancy of longer than 2 months. 3 In our series the average survival after a palliative orthopedic procedure was 22 months (range 7 to 64) and the 1-year survival rate was 58%. Clearly, most renal cell carcinoma patients with skeletal metastases will survive long enough to benefit from palliative orthopedic procedures. The management of patients with skeletal metastases from renal cell carcinoma is essentially palliative. Palliation can often be most effectively achieved through orthopedic surgical management of bone metastases. Any renal cell carcinoma patient with bone pain or pain on weight bearing should undergo a bone scan, appropriate x-rays and orthopedic consultation. Any patient with bone metastases should have a bone scan to identify other sites of metastases and should be followed closely for signs of new osseous metastases. Radiotherapy does not prevent pathological fractures. Finally, these patient survivals are long enough to justify orthopedic intervention when indicated. REFERENCES 1. Swanson, D. A., Orovan, W. L., Johnson, D. E. and Giacco, G.:
Osseous metastases secondary to renal cell carcinoma. Urology, 18: 556, 1981. 2. Saitoh, H.: Distant metastasis of renal adenocarcinoma. Cancer, 48: 1487, 1981.
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3. Grant, T. T. and deKernion, J. R: Treatment of skeletal metastases from urologic malignancies. Urology, 11: 563, 1978. 4. Katzner, M. and Schvingt, E.: Operative treatment of bone metastases secondary to renal carcinoma. In: Basic Research and Treatment of Renal Cell Carcinoma Metastasis. Edited by C. G. Bollack and D. Jacqmin. New York: Wiley-Liss, pp. 151-168, 1990. 5. Harrington, K. D.: Orthopaedic Management of Metastatic Bone Disease. St. Louis: The C. V. Mosby Co., 1988. 6. Pongracz, N., Zimmerman, R. I. and Kotz, R.: Orthopaedic man-
agement of bony metastases of renal cancer. Sem. Surg. Oneal., 4: 139, 1988. 7. Blacher, E., Johnson, D. E. and Haynie, T. P.: Value of routine radionuclide bone scans in renal cell carcinoma. Urology, 26: 432, 1985.
8. Benson, M. A., Haaga, J. R. and Resnick, M. I.: Staging renal carcinoma. What is sufficient? Arch. Surg., 124: 71, 1989. 9. Bowers, T. A., Murray, J. A., Charnsangavej, C., Soo, C. S., Chuang, V. P. and Wallace, S.: Bone metastases from renal carcinoma. The preoperative use oftranscatheter arterial occlusion. J. Bone Joint Surg., 64: 749, 1982. 10. Beals, R. K. and Snell, W. E.: Breast cancer metastatic to the femur. J. Bone Joint Surg., 45-A: 660, 1963. 11. Harrington, K. D., Johnston, J. 0., Turner, R.H. and Woten, D. L.: The use of methylmethacrylate as an adjunct in the internal fixation of malignant neoplastic fractures. J. Bone Joint Surg., 54: 1665, 1972. 12. Harrington, K. D., Sim, F. H. and Enis, J. E.: Methylmethacrylate as an adjunct in internal fixation of pathological fractures. Experience with three hundred and seventy-five cases. J. Bone Joint Surg., 58: 1047, 1976. 13. Weber, B. G.: Surgical management of tumor-related limb fractures. Rec. Res. Cancer Res., 108: 160, 1988. 14. Gebhart, M., Roman, A., Ghanem, G. and Lejeune, F.: Surgical treatment of bone metastases of the peripheral skeleton-a review of 33 cases. Eur. J. Surg. Oncol., 15: 520, 1989. 15. Forman, J. D.: The role of radiation therapy in the management of carcinoma of the kidney. Sem. Urol., 7: 195, 1989. 16. Onufrey, V. and Mohiuddin, M.: Radiation therapy in the treatment of metastatic renal cell carcinoma. Int. J. Rad. Oncol. Biol. Phys., 11: 2007, 1985. 17. Halperin, E. C. and Harisiadis, L.: The role of radiation therapy in the management of metastatic renal cell carcinoma. Cancer, 51: 614, 1983. 18. Cutuli, B. F., Methlin, A., Teissier, E., Schumacher, C. and Jung,
G. M.: Radiation therapy in the treatment of metastatic renalcell carcinoma. In: Basic Research and Treatment of Renal Cell Carcinoma Metastasis. Edited by C. G. Bollack and D. Jacqmin. New York: Wiley-Liss, pp. 179-186, 1990. 19. Habermann, E. T., Sachs, R., Stein, R. E., Hirsh, D. M. and Anderson, W. J., Jr.: The pathology and treatment of metastatic disease of the femur. Clin. Orthop., 169: 70, 1982. 20. Montie, J. E., Stewart, B. H., Straffon, R. A., Banowsky, L. H. W., Hewitt, C. B. and Montague, D. K.: The role of adjunctive nephrectomy in patients with metastatic renal cell carcinoma. J. Urol., 117: 272, 1977. 21. Maldazys, J. D. and deKernion, J. B.: Prognostic factors in metastatic renal carcinoma. J. Urol., 136: 376, 1986.