Vol. 114, December Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1975 by The Williams & Wilkins Co.
SOLITARY METASTASIS FROM RENAL CELL CARCINOMA BHUPENDRA M. TO LIA*
AND
WILLET F. WHITMORE, JR.
From the Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
ABSTRACT
Approximately a quarter to a third of the patients with renal cell carcinoma have evidence of distant metastasis when they are first seen. The incidence of apparently solitary metastasis is 1 to 3 per cent. Patients with apparently solitary metastasis have about a 35 per cent prospect of surviving 5 years after aggressive treatment, although the prospects of further metastasis are high. Our study was conducted to define the incidence and sites of apparently solitary metastasis in a series of patients with renal cell cancer and to indicate the methods and results of treatment in these selected cases. MATERIALS AND METHODS
An analysis was made of all patients with renal cell carcinoma who were registered at our center between January 1, 1949 and January 1, 1969. Of these 586 patients 17 4 had distant metastasis at diagnosis. The metastasis was apparently solitary in 19 cases, including 3 in which it had developed after nephrectomy. Our report involves an analysis of the presenting symptoms, site of metastasis, treatment of the metastasis, development of additional metastases, survival after treatment and cause of death. Survival was calculated from the date of treatment of the metastatic lesion to the date of last followup or death. RESULTS
The over-all incidence of apparently solitary metastasis was 3.2 per cent (19 of 586 cases). Sex and side incidences were about equal (table 1). Apparently solitary lesions showed a clear preponderance of bony over soft tissue metastasis (table 2).
Only 5 of the 19 patients had initial symptoms referable to the primary lesion. These symptoms included flank pain and/or hematuria in 4 patients and weakness and fatigue followed by hematuria in 1 patient. Two patients presented with constitutional symptoms only, such as weight loss, malaise and anorexia, while the remaining 12 patients had initial symptoms referable to the metastatic lesion. Irradiation, surgery and cryosurgery were variously used in the treatment of apparently solitary Accepted for publication May 23, 1975. Read at annual meeting of American Urological Association, Miami Beach, Florida, May 11-15, 1975. • Requests for reprints: Department of Urology, Hospital of the Albert Einstein College of Medicine, 1825 Eastchester Rd., Bronx, New York 10461. 836
metastasis in 17 of the 19 patients. One patient with lung metastasis at the time of diagnosis and another with metastasis to the sternum 31 months after nephrectomy did not receive any specific treatment for an apparently solitary metastasis (table 2). After diagnosis of the metastatic lesion , these 2 patients survived 4 and 10 months, respectively. None of the 19 patients was lost to followup. Autopsy confirmation of the presence of additional metastatic disease was available in only 2 of the 17 patients who died. If metastatic disease was clinically present at the last followup and no definite cause of death was determined death from metastatic disease was presumed. Table 3 shows 3, 5 and 10-year survival rates from the date of treatment of the metastatic lesion. At the time of this report only 13 patients were at risk for 10 years (4 patients having been treated after 1965). Six of the 17 patients survived 5 years or more after treatment. Four of these 6 patients were free of evidence of cancer at 5 years, while the other 2 had evidence of metastasis (table 3). Of the former 4 patients 2 died 9 and 7 years after treatment but were free of evidence of metastasis at the last followup before death and 2 are free of disease 6 and 10 years after treatment. Of the latter 2 patients 1 with metastasis to the right humerus, treated with irradiation followed by shoulder disarticulation, had additional metastasis to the left clavicle 36 months later. The metastasis was treated with irradiation and death occurred an additional 57 months later of cerebral metastasis. The other patient with metastasis to the right hilus was initially treated with irradiation and 32 months later had metastasis to the left lung. The metastasis in this case was not treated and the patient died an additional 33 months later. Development of additional metastatic lesions carried a poor prognosis despite further therapy (table 4). Eight of the 19 patients had clinical evidence of additional metastasis. Three patients received radiation therapy, 3 were treated surgically, 1 was treated with chemotherapy and 1 received no additional treatment. For the irradiated '-
837
SOLITARY METASTASIS FROM RENAL CELL CARCINOMA TABLE
1. Renal cell carcinoma: 1949 to 1969
DISCUSSION
No.(%) Patients with distant metastasis Patients with solitary metastasis Sex of patients with solitary metastasis: Male Female Side involved in patients with solitary metastasis: Right Left
174* (29.7) 19* (3.2)
9
10
9
10
* Total number of patients 586. TABLE
2. Treatment of solitary metastasis in 19 cases No. Pts.
Bone-12 cases Humerus: Cryosurgery and internal fixation which led to disarticulation, 1 Internal fixation and radiation therapy which led to interscapulothoracic amputation, 1* Radiation therapy which led to disarticulation, 1t Interscapulothoracic amputation, 1 Radiation therapy which led to interscapulothoracic amputation, 1 Disarticulation, 1 Scapula: Radiation therapy which led to interscapulothoracic amputation, 1 Radiation therapy, 1 Ribcage: Chest wall resection, 1* Chest wall resection, 1 Femur: Curettage, cryosurgery and internal fixation, 1* Sternum: No treatment, 1 Soft tissue-7 cases Lung: Wedge excision, 1* Lobectomy, 1 No treatment, 1 Vagina: Radium needles, 1 Wide excision, total abdominal hysterectomy and bilateral salpingo-oophorectomy, 1 Mediastinum: Radiation therapy, 1t Supraclavicular lymph node: Radical neck dissection, 1
6
2
The reports of Middleton (149 of 503 cases) and Skinner and associates (77 of 309 cases) as well as our series (174 of 586 cases) suggest that a quarter to a third of the patients with renal cell carcinoma have evidence of distant metastasis when first seen. 1 • 2 Skinner and associates, and Middleton reported the incidence of apparently solitary metastasis to be 3.6 and 1.6 per cent, respectively, similar to the 3.2 per cent in this series. 1 • 2 Spontaneous regression of apparent metastasis after nephrectomy is rare. 3 World wide, about 60 cases of spontaneous regression are known and in only 3 patients were the regressed metastases non-pulmonary: 1 case each of intestinal, osseous and cutaneous metastasis.• Regression usually is temporary and may occur in 1 area while metastasis elsewhere continues to grow. One instance of b~opsy-proved cutaneous metastasis that disappeared spontaneously has been reported by Braren and associates.• The 5-year survival rates for patients with multiple metastases range between 6 and 8 per cent. 2 • 6 Survival rates for patients with untreated apparently solitary metastasis ·have not been reported. The first successful surgical excision of an apparently solitary pulmonary metastasis in a patient who had undergone nephrectomy for renal cell carcinoma was reported by Barney and Churchill
2 TABLE
3
3. Survival after treatment of solitary metastasis
Followup (yrs.)
At Risk (No.)
3 5 10
17 17 13
TABLE
Free of Cancer (No.)
Alive With Cancer (No.)
10 6 1
(58.8) (35.3) (7.7)
4 4 1
6 2 0
metastasis in 19 cases No. Cases Development of additional metastasis following treatment of solitary lesion Autopsy evidence of additional metastasis Clinical evidence of additional metastasis
* 5-year survival free of cancer.
patients survival was 58, 22 and 2 months, respectively. For the surgically treated patients survival was 19, 9 and 2 months, respectively. One patient treated with chemotherapy lived for 30 months and the untreated patient lived for 32 months. Survival relative to the pre-nephrectomy or post-nephrectomy occurrence of the solitary metastasis is shown in table 5. In summary, 2 of 19 patients survive without evidence of cancer, 5 died of metastatic cancer, 4 died of cerebrovascular accidents (2 with evidence of metastasis), and 8 died of uncertain causes (7 with evidence of metastasis at last followup).
(%)
Alive
4. Survival following treatment of additional
2
t 5-year survival with evidence of cancer.
No.
Yrs. Survived 1 2 3 4 5
TABLE
10 2 8
Treated (7 cases)
Untreated (1 case) 1 1
4
2 1 1 0
0 0 0
5. Survival after treatment of metastasis Yrs. Survived
Metastasis absent at time of diagnosis (2 cases) Metastasis present at time of diagnosis (15 cases)
2
3 2
5 2
9
6
3
10 0
838
V:EITMORE
ir: 1939. 7 1'he li'vsd for 23 years and dj_ed of coronary artery disease. 8 This remarkable case has prompted other surgeons to treat apsolitary metastatic lesions in patients with renal cell carcinoma. After reviewing accumulated literature and adding 8 cases, Middleton reported a 34 per cent 5-year survival rate after removal of an apparently solitary metastasis in 59 cases. 1 The present experience supports the data reported by Middleton. with a 35.3 per cent 5-year survival rate in patients with apparently solitary metastasis aggressively treated. Since metastasis may first appear 20 years or more after nephrectomy 5 and 10-year survivals are not indicative of cure. 9 Both patients whose solitary metastasis appeared post-nephrectomy survived 5 years, whereas only 3 of 15 patients whose solitary metastasis was present before nephrectomy survived 5 years. This small experience supports the observations of Skinner and associates that the success rate for treatment of solitary metastasis is greater in the former than in the latter situation. 2 Talley and associates reported a significantly longer period of survival when metastasis appeared more than 18 months after nephrectomy. 10 The limited total experience, the differences in the sites of metastasis and the variability in therapeutic approach prevent generalizations regarding therapy. The small and recent experience of Marcove and associates with the cryosurgical destruction of bone lesions suggests a high degree of local tumor control with minimal risks and functional sacrifices in a setting in which long-term prognosis is poor. 11 There is a high incidence of development of additional metastasis after treatment of an apparently solitary lesion. In our series 10 patients had additional metastasis at intervals varying from 3 to 39 months after the initial treatment. No definite relation between the site of the original lesion and the site of further metastasis was evident. Arkless suggested a role of the para vertebral venous plexus of Batson in the spread of metastasis to the bone. 12
He also noticed that in 15 of tl12 19 in v.rhom involvement was confined to 1 side. it was ipsilateral to the primary. No significant relation to the side of the primary tumor 'Nas noted in the present series. REFERENCES 1. Middleton, R. G.: Surgery for metastatic renal cell
carcinoma. J. Urol., 97: 973, 1967. 2. Skinner, D. G., Colvin, R. B., Vermillion, C. D., ' Pfister. R. C. and Leadbetter, W. F.: Diagnosis and management of renal cell carcinoma. A clinical and pathologic study of 309 cases. Cancer, 28: 1165, 1971. 3. Garfield, D. H. and Kennedy, B. J.: Regression of metastatic renal cell carcinoma following nephrectomy. Cancer, 30: 190, 1972. 4. Holland, J. M.: Cancer of the kidney-natural history, and staging. Cancer, 32: 1030, 1973. 5. Braren. V., Taylor, J. N. and Pace, W.: Regression of metastatic renal carcinoma following nephrectomy. Urology, 3: 777, 1974. 6. Grabstald, H.: Renal-cell cancer. I. Incidence, etiology, natural history, and prognosis. N. Y. State J. Med., 64: 2539, 1964. 7. Barney, J. D. and Churchill, E. J.: Adenocarcinoma of the kidney with metastasis to the Iung: cured by nephrectomy and lobectomy. J. Ural., 42: 269, 1939. 8. Wilkins, .I:
THE JOURNAL OF UROLOGY
Copyright © 1975 by The Williams & Wilkins Co.
SOLITARY METASTASIS FROM RENAL CELL CARCINOMA BHUPENDRA M. TO LIA*
AND
WILLET F. WHITMORE, JR.
From the Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York
ABSTRACT
Approximately a quarter to a third of the patients with renal cell carcinoma have evidence of distant metastasis when they are first seen. The incidence of apparently solitary metastasis is 1 to 3 per cent. Patients with apparently solitary metastasis have about a 35 per cent prospect of surviving 5 years after aggressive treatment, although the prospects of further metastasis are high. Our study was conducted to define the incidence and sites of apparently solitary metastasis in a series of patients with renal cell cancer and to indicate the methods and results of treatment in these selected cases. MATERIALS AND METHODS
An analysis was made of all patients with renal cell carcinoma who were registered at our center between January 1, 1949 and January 1, 1969. Of these 586 patients 17 4 had distant metastasis at diagnosis. The metastasis was apparently solitary in 19 cases, including 3 in which it had developed after nephrectomy. Our report involves an analysis of the presenting symptoms, site of metastasis, treatment of the metastasis, development of additional metastases, survival after treatment and cause of death. Survival was calculated from the date of treatment of the metastatic lesion to the date of last followup or death. RESULTS
The over-all incidence of apparently solitary metastasis was 3.2 per cent (19 of 586 cases). Sex and side incidences were about equal (table 1). Apparently solitary lesions showed a clear preponderance of bony over soft tissue metastasis (table 2).
Only 5 of the 19 patients had initial symptoms referable to the primary lesion. These symptoms included flank pain and/or hematuria in 4 patients and weakness and fatigue followed by hematuria in 1 patient. Two patients presented with constitutional symptoms only, such as weight loss, malaise and anorexia, while the remaining 12 patients had initial symptoms referable to the metastatic lesion. Irradiation, surgery and cryosurgery were variously used in the treatment of apparently solitary Accepted for publication May 23, 1975. Read at annual meeting of American Urological Association, Miami Beach, Florida, May 11-15, 1975. • Requests for reprints: Department of Urology, Hospital of the Albert Einstein College of Medicine, 1825 Eastchester Rd., Bronx, New York 10461. 836
metastasis in 17 of the 19 patients. One patient with lung metastasis at the time of diagnosis and another with metastasis to the sternum 31 months after nephrectomy did not receive any specific treatment for an apparently solitary metastasis (table 2). After diagnosis of the metastatic lesion , these 2 patients survived 4 and 10 months, respectively. None of the 19 patients was lost to followup. Autopsy confirmation of the presence of additional metastatic disease was available in only 2 of the 17 patients who died. If metastatic disease was clinically present at the last followup and no definite cause of death was determined death from metastatic disease was presumed. Table 3 shows 3, 5 and 10-year survival rates from the date of treatment of the metastatic lesion. At the time of this report only 13 patients were at risk for 10 years (4 patients having been treated after 1965). Six of the 17 patients survived 5 years or more after treatment. Four of these 6 patients were free of evidence of cancer at 5 years, while the other 2 had evidence of metastasis (table 3). Of the former 4 patients 2 died 9 and 7 years after treatment but were free of evidence of metastasis at the last followup before death and 2 are free of disease 6 and 10 years after treatment. Of the latter 2 patients 1 with metastasis to the right humerus, treated with irradiation followed by shoulder disarticulation, had additional metastasis to the left clavicle 36 months later. The metastasis was treated with irradiation and death occurred an additional 57 months later of cerebral metastasis. The other patient with metastasis to the right hilus was initially treated with irradiation and 32 months later had metastasis to the left lung. The metastasis in this case was not treated and the patient died an additional 33 months later. Development of additional metastatic lesions carried a poor prognosis despite further therapy (table 4). Eight of the 19 patients had clinical evidence of additional metastasis. Three patients received radiation therapy, 3 were treated surgically, 1 was treated with chemotherapy and 1 received no additional treatment. For the irradiated '-
837
SOLITARY METASTASIS FROM RENAL CELL CARCINOMA TABLE
1. Renal cell carcinoma: 1949 to 1969
DISCUSSION
No.(%) Patients with distant metastasis Patients with solitary metastasis Sex of patients with solitary metastasis: Male Female Side involved in patients with solitary metastasis: Right Left
174* (29.7) 19* (3.2)
9
10
9
10
* Total number of patients 586. TABLE
2. Treatment of solitary metastasis in 19 cases No. Pts.
Bone-12 cases Humerus: Cryosurgery and internal fixation which led to disarticulation, 1 Internal fixation and radiation therapy which led to interscapulothoracic amputation, 1* Radiation therapy which led to disarticulation, 1t Interscapulothoracic amputation, 1 Radiation therapy which led to interscapulothoracic amputation, 1 Disarticulation, 1 Scapula: Radiation therapy which led to interscapulothoracic amputation, 1 Radiation therapy, 1 Ribcage: Chest wall resection, 1* Chest wall resection, 1 Femur: Curettage, cryosurgery and internal fixation, 1* Sternum: No treatment, 1 Soft tissue-7 cases Lung: Wedge excision, 1* Lobectomy, 1 No treatment, 1 Vagina: Radium needles, 1 Wide excision, total abdominal hysterectomy and bilateral salpingo-oophorectomy, 1 Mediastinum: Radiation therapy, 1t Supraclavicular lymph node: Radical neck dissection, 1
6
2
The reports of Middleton (149 of 503 cases) and Skinner and associates (77 of 309 cases) as well as our series (174 of 586 cases) suggest that a quarter to a third of the patients with renal cell carcinoma have evidence of distant metastasis when first seen. 1 • 2 Skinner and associates, and Middleton reported the incidence of apparently solitary metastasis to be 3.6 and 1.6 per cent, respectively, similar to the 3.2 per cent in this series. 1 • 2 Spontaneous regression of apparent metastasis after nephrectomy is rare. 3 World wide, about 60 cases of spontaneous regression are known and in only 3 patients were the regressed metastases non-pulmonary: 1 case each of intestinal, osseous and cutaneous metastasis.• Regression usually is temporary and may occur in 1 area while metastasis elsewhere continues to grow. One instance of b~opsy-proved cutaneous metastasis that disappeared spontaneously has been reported by Braren and associates.• The 5-year survival rates for patients with multiple metastases range between 6 and 8 per cent. 2 • 6 Survival rates for patients with untreated apparently solitary metastasis ·have not been reported. The first successful surgical excision of an apparently solitary pulmonary metastasis in a patient who had undergone nephrectomy for renal cell carcinoma was reported by Barney and Churchill
2 TABLE
3
3. Survival after treatment of solitary metastasis
Followup (yrs.)
At Risk (No.)
3 5 10
17 17 13
TABLE
Free of Cancer (No.)
Alive With Cancer (No.)
10 6 1
(58.8) (35.3) (7.7)
4 4 1
6 2 0
metastasis in 19 cases No. Cases Development of additional metastasis following treatment of solitary lesion Autopsy evidence of additional metastasis Clinical evidence of additional metastasis
* 5-year survival free of cancer.
patients survival was 58, 22 and 2 months, respectively. For the surgically treated patients survival was 19, 9 and 2 months, respectively. One patient treated with chemotherapy lived for 30 months and the untreated patient lived for 32 months. Survival relative to the pre-nephrectomy or post-nephrectomy occurrence of the solitary metastasis is shown in table 5. In summary, 2 of 19 patients survive without evidence of cancer, 5 died of metastatic cancer, 4 died of cerebrovascular accidents (2 with evidence of metastasis), and 8 died of uncertain causes (7 with evidence of metastasis at last followup).
(%)
Alive
4. Survival following treatment of additional
2
t 5-year survival with evidence of cancer.
No.
Yrs. Survived 1 2 3 4 5
TABLE
10 2 8
Treated (7 cases)
Untreated (1 case) 1 1
4
2 1 1 0
0 0 0
5. Survival after treatment of metastasis Yrs. Survived
Metastasis absent at time of diagnosis (2 cases) Metastasis present at time of diagnosis (15 cases)
2
3 2
5 2
9
6
3
10 0
838
V:EITMORE
ir: 1939. 7 1'he li'vsd for 23 years and dj_ed of coronary artery disease. 8 This remarkable case has prompted other surgeons to treat apsolitary metastatic lesions in patients with renal cell carcinoma. After reviewing accumulated literature and adding 8 cases, Middleton reported a 34 per cent 5-year survival rate after removal of an apparently solitary metastasis in 59 cases. 1 The present experience supports the data reported by Middleton. with a 35.3 per cent 5-year survival rate in patients with apparently solitary metastasis aggressively treated. Since metastasis may first appear 20 years or more after nephrectomy 5 and 10-year survivals are not indicative of cure. 9 Both patients whose solitary metastasis appeared post-nephrectomy survived 5 years, whereas only 3 of 15 patients whose solitary metastasis was present before nephrectomy survived 5 years. This small experience supports the observations of Skinner and associates that the success rate for treatment of solitary metastasis is greater in the former than in the latter situation. 2 Talley and associates reported a significantly longer period of survival when metastasis appeared more than 18 months after nephrectomy. 10 The limited total experience, the differences in the sites of metastasis and the variability in therapeutic approach prevent generalizations regarding therapy. The small and recent experience of Marcove and associates with the cryosurgical destruction of bone lesions suggests a high degree of local tumor control with minimal risks and functional sacrifices in a setting in which long-term prognosis is poor. 11 There is a high incidence of development of additional metastasis after treatment of an apparently solitary lesion. In our series 10 patients had additional metastasis at intervals varying from 3 to 39 months after the initial treatment. No definite relation between the site of the original lesion and the site of further metastasis was evident. Arkless suggested a role of the para vertebral venous plexus of Batson in the spread of metastasis to the bone. 12
He also noticed that in 15 of tl12 19 in v.rhom involvement was confined to 1 side. it was ipsilateral to the primary. No significant relation to the side of the primary tumor 'Nas noted in the present series. REFERENCES 1. Middleton, R. G.: Surgery for metastatic renal cell
carcinoma. J. Urol., 97: 973, 1967. 2. Skinner, D. G., Colvin, R. B., Vermillion, C. D., ' Pfister. R. C. and Leadbetter, W. F.: Diagnosis and management of renal cell carcinoma. A clinical and pathologic study of 309 cases. Cancer, 28: 1165, 1971. 3. Garfield, D. H. and Kennedy, B. J.: Regression of metastatic renal cell carcinoma following nephrectomy. Cancer, 30: 190, 1972. 4. Holland, J. M.: Cancer of the kidney-natural history, and staging. Cancer, 32: 1030, 1973. 5. Braren. V., Taylor, J. N. and Pace, W.: Regression of metastatic renal carcinoma following nephrectomy. Urology, 3: 777, 1974. 6. Grabstald, H.: Renal-cell cancer. I. Incidence, etiology, natural history, and prognosis. N. Y. State J. Med., 64: 2539, 1964. 7. Barney, J. D. and Churchill, E. J.: Adenocarcinoma of the kidney with metastasis to the Iung: cured by nephrectomy and lobectomy. J. Ural., 42: 269, 1939. 8. Wilkins, .I:
