- Email: [email protected]
The basis for surgical resection of pulmonary metastases
lnt. I. Radiation Ondo#y
Bid Phys.. 1976. Vol. 1, pp. 149-753.
Pegamm
Press.
Printed in the U.S.A.
THE BASIS FOR SURGICAL RESECTION
OF PULMONARY METASTASES CLIFTON F. MOUNTAIN, M.D. Chief, Section of Thoracic Surgery, M.D. Anderson Hospital & Tumor Institute, Texas Medical Center, Houston, TX 77025, U.S.A. Pulmonary metas-
Surgical excision, Dissemination.
INTRODUCTION
SELECTION OF PATIENTS
In the past relatively little attention has been focused on the control of metastatic disease because of the ominous effect on prognosis that its presence usually signifies and the common supposition that any remote foci of disease indicates widespread dissemination. The rationale for surgical resection of pulmonary metastases derives from observations at autopsy which demonstrate that metastatic disease is confined to the lungs in U-25% of cancer patients who die with pulmonary metastasis.’ The potential of these patients for survival has been reported in the literature since 1939 when Barney and Churchill documented the first long term survival following resection for puhnonary metastases.’ In several series reported in the literature since 1970583*‘4.*s303’ overall survival rates for highly selected groups of patients having surgical resection as the primary treatment of their pulmonary metastases ranged from 25 to 40%. There were 173 five year survivors in a total of 589 patients collected from these series, for a collective crude survival rate of 29.3%. Innumerable factors influence the growth and spread of cancer; although certain growth features portend metastasis it is difficult to determine in what stage of growth secondary spread will take place. It occurs at inconsistent times.6 Careful study of the patients selected for curative resection of pulmonary metastases may yield valuable information as to how spread of cancer can be controlled and the tumor ultimately destroyed.
A greater percentage of failure may be reported as efforts are made to extend the application of surgical resection in the treatment of pulmonary metastases, even though this may result in the salvage and palliation of more patients. Therefore, success with this therapeutic approach depends almost entirely on the selection of patients. Three basic questions must be answered to fulfill the criteria for initial selection of cases. First, can the patient tolerate the contemplated surgery; second, has the primary site of the tumor been definitely and successfully treated without evidence of recurrent disease; and third, can all known metastatic disease be encompassed by the projected pulmonary resection? If these basic criteria can be fulfilled, surgical resection is recommended. In general the factors which favorably affect prognosis are absence of metastatic tumor in regional or mediastinal nodes, slow growth rate of the pulmonary metastasis and a long interval of time from primary treatment to appearance of metastasis. Controversy exists regarding the prognostic implications of this time interval. Indications are that the survival rate increases as the interval between the treatment of the primary tumor and discovery of the metastasis becomes longer. This may be logical since, during the disease free interval, the host resistance to the tumor is strong enough to prevent growth into gross metastases and may be strong enough to further contain the disease.6 However, our studies do not confirm 149
750
Radiation Oncology 0 Biology 0 Physics
1976, Vol. 1. Number 7 and Number 8
limited to the lung, and if it is resectable. Removal of the least amount of tissue which encompasses all discemable metastatic disease (wedge or transegmental resection) is the method of choice in order to conserve functional ventilatory reserve, to permit planDIAGNOSTIC AND EVALUATIVE ned bilateral thoracotomy, and to allow for PROCEDURES resection of additional pulmonary nodules Patients with any evidence of co-existing which subsequently may declare themselves. extra-thoracic metastases or those with diffuse The usual peripheral location of these lesions seeding in the lungs would be eliminated from and the infrequent involvement of the first and surgical consideration by careful screening for fourth order bronchi make this choice of disseminated disease. The first stage of procedure feasible. screening includes full chest tomography, Ongoing studies of patients who were biochemical tests of liver function, bone treated surgically for pulmonary metastases at scintigrams and an electroencephalogram. If the M.D. Anderson Hospital as well as the any abnormahties are encountered in these work of others [Hutchesion and Denner,9 Po01,‘~ Cliffton and Pool41 tests, liver and brain scans are performed. Martini et aLL2*” Because of the frequency of metastatic have shown that multiple metastases should mediastinal adenopathy accompanying pulmo- not necessarily be considered inoperable. The nary metastasis from breast cancer, medias- number and distribution of metastasis did not tinoscopy is recommended before thoracot- afIect the crude survival rate significantly in omy is undertaken. In selected cases, arterio- those patients in whom all residual malignant grams and bronchograms may be utilized disease apparently was removable by resecto complete the screening and aid in the pre- tion of bilateral and recurrent lesions. Although some disagreement exists with this operative evaluation. The 6rst evidence of pulmonary metastasis approach, in our judgement consideration of is most often found on routine follow-up chest excision of multiple nodules is warranted by roentgenograms. Fewer than one-fourth of the existence of long term survivors in this patients have presenting symptoms of cough, category. An important factor in the consideration of hemoptysis, chest pain or fever. As mentioned above, tomograms are required and may show resection for pulmonary metastases is the additional lesions not seen on the standard optimum point at which surgical intervention X-ray film. In our preliminary studies of 314 should take place. If the time between the patients under consideration for this treat- primary treatment and discovery of the ment, a retrospective review of X-rays was metastasis is short, it is prudent to observe the undertaken in approximately one third of the patient long enough for occult lesions to patients to evaluate the presence of the lesion become recognized clinically. Surgery should earlier than reported. The lesion was identified not be denied on this basis, however, to a on an earlier film in 12-13%. Since resection of patient who is otherwise a suitable surgical the earlier found and smaller lesions provides candidate. Because of the high incidence of a better opportunity for salvage, regular second primary tumors in the lung, especially follow-up at 3-6 month intervals for 5 years among patients whose primary tumors were in and yearly thereafter is of the utmost impor- the head and neck, and because of the tance in the cancer management program. difEculty of difIerentiating these from metastatic lesions, a period of long observation is SURGICAL RE!3ECTION not recommended in this group of cases. In a Consensus among oncologists regarding patient who has had a previous cancer treated treatment of metastatic pulmonary disease and develops a lung shadow, it is as likely to favors resection if the primary tumor has been be a new lung cancer as a metastatic deposit.16 completely treated, if the metastatic process is The chances are more in favor of a metastasis this thinking. Other important factors such as the cell type and the anatomic site of the primary lesion affect prognosis materially, but if the basic criteria can be fulfilled, surgical resection is recommended. nevertheless.
The basis for surgical resection of pulmonary metastases 0 C. F. MOUNTAIN
than a new primary if the prior lesion had been a soft tissue or bone sarcoma. In Cahan’s’ series of 29 melanoma patients, 5 developed primary lung tumors years after primary melanomas had been excised. A delay in treatment might deprive such patients with primary lung tumors of their only chance for cure. Choski et aL3 point out that the biological behavior of certain types of tumors cause them to present with a solitary pulmonary metastasis more frequently than others. For example, 15% of the solitary metastases that were resected in his series, were from primary sarcomas, with a sign&ant number from tumors of the breast, testis and uterus. In our own series, it was noted that patients who were treated for osteogenic sarcoma, carcinoma of the colon, or malignant melanoma were likely to develop additional nodules within a relatively short time. Biological characteristics of the primary tumor such as the determination of the growth rate (tumor doubling time, TDT) provide accurate evaluation of operability. A long TDT for the primary lesion results in a longer interval between primary tumor resection and the appearance of metastases, suggesting a more aggressive therapeutic approach in those patients with prolonged TDT.” Present knowledge of the acceleration and retarding influences on the growth rate of cancer is incomplete, but the enormous variances within each histological cell type reflect the interrelationship between the virulence of the tumor and the host resistance. From the author’s personal series, the growth rate of the pulmonary metastasis was examined in one third of the patients with serial chest roentgenograms taken 60 days or more apart. The findings emphasized what is common knowledge, namely those patients with slow growing tumors get better results from surgical treatment than patients with fast growing tumors. Prolonged survival is rarely associated with rapid enlargement of the pulmonary metastasis. The presence of regional and mediastinal node metastases portends the same grave prognosis in patients operated upon for pulmonary metastasis as for many primary
751
malignant tumors. In cases where this metastatic potential exists, mediastinoscopy is recommended before undertaking thoracotomy. In our first series, no patients in this category survived 5 years free of disease. The prognostic outlook in our own studies also relates to the morphology of the primary tumor and the stage of the primary disease. The most favorable outcome was for patients with metastases from carcinomas of the genitourinary tract, colon, rectum, uterine cervix and corpus uteri. Treatment of pulmonary metastases from lesions arising in the breast or from the head and neck area was less successful; the least successful treatment was for lesions from the upper gastrointestinal tract and pancreas. The prognostic outlook was poor for those patients treated for pulmonary metastases from liposarcoma, (unfibrosarcoma and unclassified differentiated) sarcoma. Promising results were obtained in treatment of metastases from skeletal sarcomas including osteogenic sarcomas. In 1974, Martini et ai.” reported on 86 patients who had surgical treatment of metastatic sarcoma to the lung. Of these, 26% remained alive 5 years after first thoracotomy, 17% free of disease. There was a continued drop in survival during the first 3 years after treatment, from 63% at 1 year to 32% at 3 years leveling off in the 3-5 year period. Cahan2 recently has reported pulmonary resection to be successful with a j-year survival in 4 of 12 melanoma patients. COMBINED THERAPY There is a reasonable expectation that the apparent success of surgical treatment of pulmonary metastases can be enhanced through the use of combined therapy. Recent reports in the literature attest to the value of this approach, even though most series of cases reported are small in number. With respect to pediatric malignances, Cliffton and Pool’ recommend that each patient who develops pulmonary metastases should receive a trial of chemotherapy if the tumor is known to be drug sensitive. If there is no response, or if further progression develops, the lesion should be resected immediately. It is recommended generally that chemotherapy be con-
752
1976. Vol. I, Number 7 and Number 8
Radiation Oncology 0 Biology 0 Physics
Table 1. Cummulative
percent surviving at 3 and 5 years
All cases
Carcinoma
m
Sw3ery alone
Surgery+
m
sarcoma
(o/o)
No.
3yr
5 yr
3 yr
5 yr
3 yr
5 yr
1%
38
25
42
29
26
16
61
37
31
39
33
33
28
planned adjunctive therapy
tinued post-operatively to control or eradicate occult foci of disease. Most authors agree that chemotherapy and/or irradiation is the primary treatment of choice for patients with Wilm’s tumor; surgery is indicated if this treatment fails. Tumbti et al.” reported results of combined therapy in 32 patients with pulmonary metastases; 10 of these patients treated with radiotherapy and/or chemotherapy as adjuncts to surgery have been free of recurrence an average of 4.3 years. Isotope implants were added to partial resections in this series for palliation: in 8 of 14 cases the disease did not progress. In 1973 Marcove and Lewis“ reported that an increase in 5 year survival rate from 17 to 40% has been observed when autogenous vaccine was given immediately after amputation for osteogenic sarcoma; however, vaccine administered after metastases were present was not helpful in prolonging survival. In patients with primary testicular tumors, Skinner et &I9 Samuels et 41.,” Reed and Cleland” and others have reported on combined therapy for pulmonary metastases with good results. In Feldman and Kyrialcos* series in various sarcomas, 6 of 9 patients who survived 5 years had received radiation or chemotherapy as adjuncts to surgery.
Table 1 summarizes briefly our own survival experience in an analysis of 257 patients undergoing surgical resection for pulmonary metastases at M.D. Anderson Hospital and Tumor Institute. In 1% patients, surgery alone was employed as definitive therapy while in 61 adjunctive chemotherapy, radiotherapy, or immunotherapy was utiliied. A detailed study of the variables afkting prognosis and of the survival dynamics of the various morphologic patterns of disease will be published in the near future. Nevertheless, these current end results show an encouraging number of long term survivors and argues for ap aggressive surgical approach in selected cases. COMMENT An appreciable palliative benefit and rewarding long-term, disease-free survival results from the surgical treatment of cancer which has metastasized to the lungs. Even multiple and bilateral lesions may be successfully managed. The morbidity and mortality of such treatment is low. It is apparent, however, that further studies are needed to more precisely define the optimum timing of surgical intervention, the selection of cases for detitive surgery, and the role of adjunctive surgery to reduce the total tumor burden.
REFERENCES 1. Barney, J.D., Churchill, E.J.: Adenocarcinoma
of the kidney with metastasis to the lung: cured by nephrectomy and lobectomy. J. Ural. 42: 269-276, 1939. 2. Cahan, W.G.: Excision of melanoma metastasis to lung; problems in diagnosis and management. Ann. Surg. 178: 703-709, 1973.
3. Choski, L.B., Takita, H., Vincent, R.G.: The surgical management of solitary pulmonary metastasis. Surg. Gynecol. Obstet. 134: 47% 482, 1972.
4.
Cliiton, E.E., Pool, J.L.: Treatment of lung metastasis in children with combined therapy. J. Thorac. Cardiovasc. Surg. 54: 403-421,1%7.
The basis for surgical resection of pulmonary metastases 0 C. F. MOUNTAIN
5. Cline, R.E., Young, W.G.: Long-term results following surgical treatment of metastatic pulmonary tumors. Am. Surg. 36: 61-68,1970. 6. Cole, W.H.: The mechanisms of spread of cancer. Surg. Gynecol. Obstet. 137: 853-871, 1973. 7. Farrell, Jr., J.T.: Pulmonary metastasis; a pathologic, clinical roentgenologic study based on 78 cases seen at necropsy. Radiology 24: 444-451, 1935. 8. Feldman, P.S., Kyriakos, M.: Pulmonary resection for metastatic sarcoma. J. Thorac. Cardiovasc. Surg. 64: 7%799, 1972. 9. Hutchison, D.E., Denner, R.M.: Resection of pulmonary secondary tumors. Am. J. Surg. 124: 723-737, 1972. 10. Joseph, W.L.: Prognostic signifkance of tumor doubling time in evaluating operability in pulmonary metastatic disease. J. ‘I’horac. Cardiovasc. Surg. 61: 23-32, 1974. 11. Marcove, R.C., Lewis, MM.: Prolonged survival in osteogenic sarcoma with multiple puhnonary metastasis. J. Bone Joint Surg. 55: 15X-1520, 1973. 12. Martini, N., Bains, M.S., Huvos, A.S., et al.: Surgical treatment of metastatic sarcoma to the lung. Surg. Clin. North Am. 54: 841-844, Aug. 1974. 13. Martini, N., Huvos, A.G., Mike, V., Marcove, R.C., Beattie, Jr., E.J.: Multiple puhnonary resections in the treatment of osteogenic sarcoma. Ann. Thorac. Surg. 12: 271-280,197l. 14. Meyer, V., Cadalbert, M., Jenny, M., Senning,
15.
16.
17.
18.
19.
20.
21.
753
A.: Chirugische behandlung von lungenmetastesen extrapulmonaler premartumoren. Therapeutische UmschaulRevue Therapeutique, Band 30: 824-830, 1973. Mountain, CF.: Surgical management of pulmonary metastasis. Postgrad. Med. 48: 128132, 1970. Pool, J.L.: The treatment of metastasis to the lungs. Report to the Cancer Committee of the American College of Chest Physicians, Oct. 1970 (written communication). Rees, G.M., Cleland, W.P.: Surgical treatment of pulmonary metastasis from testicular tumors. Br. Med. J. 3: 467-470, 1971. Samuels, M.L., Holoye, P.Y., Johnson, D.E.: Bleomycin combination chemotherapy for metastatic testicular carcinoma. Cancer Bull. 25: 53-55, 1973. Skinner, D.G., Leadbetter, W.F., Wilkins, Jr., E.W.: The surgical management of testis tumors metastatic to the lung; a report of 10 cases with subsequent resection of from one to seven pulmonary metastasis. J. Ural. 109: 275-282, 1971. Turnbull, A.D., Pool, J.L., Arthur, K., Golbey, R.B.: The role of radiotherapy and chemotherapy in the surgical management of pulmonary metastasis. Am. J. Roentgenol. Radium Ther. Nucl. Med. 114: 99-105, 1972. Turney , S.Z.. Haight, C.: Pulmonary resection for metastatic neoplasms. J. Thorac. Cardiovasc. Surg. 61: 784-794, 1971.
Bid Phys.. 1976. Vol. 1, pp. 149-753.
Pegamm
Press.
Printed in the U.S.A.
THE BASIS FOR SURGICAL RESECTION
OF PULMONARY METASTASES CLIFTON F. MOUNTAIN, M.D. Chief, Section of Thoracic Surgery, M.D. Anderson Hospital & Tumor Institute, Texas Medical Center, Houston, TX 77025, U.S.A. Pulmonary metas-
Surgical excision, Dissemination.
INTRODUCTION
SELECTION OF PATIENTS
In the past relatively little attention has been focused on the control of metastatic disease because of the ominous effect on prognosis that its presence usually signifies and the common supposition that any remote foci of disease indicates widespread dissemination. The rationale for surgical resection of pulmonary metastases derives from observations at autopsy which demonstrate that metastatic disease is confined to the lungs in U-25% of cancer patients who die with pulmonary metastasis.’ The potential of these patients for survival has been reported in the literature since 1939 when Barney and Churchill documented the first long term survival following resection for puhnonary metastases.’ In several series reported in the literature since 1970583*‘4.*s303’ overall survival rates for highly selected groups of patients having surgical resection as the primary treatment of their pulmonary metastases ranged from 25 to 40%. There were 173 five year survivors in a total of 589 patients collected from these series, for a collective crude survival rate of 29.3%. Innumerable factors influence the growth and spread of cancer; although certain growth features portend metastasis it is difficult to determine in what stage of growth secondary spread will take place. It occurs at inconsistent times.6 Careful study of the patients selected for curative resection of pulmonary metastases may yield valuable information as to how spread of cancer can be controlled and the tumor ultimately destroyed.
A greater percentage of failure may be reported as efforts are made to extend the application of surgical resection in the treatment of pulmonary metastases, even though this may result in the salvage and palliation of more patients. Therefore, success with this therapeutic approach depends almost entirely on the selection of patients. Three basic questions must be answered to fulfill the criteria for initial selection of cases. First, can the patient tolerate the contemplated surgery; second, has the primary site of the tumor been definitely and successfully treated without evidence of recurrent disease; and third, can all known metastatic disease be encompassed by the projected pulmonary resection? If these basic criteria can be fulfilled, surgical resection is recommended. In general the factors which favorably affect prognosis are absence of metastatic tumor in regional or mediastinal nodes, slow growth rate of the pulmonary metastasis and a long interval of time from primary treatment to appearance of metastasis. Controversy exists regarding the prognostic implications of this time interval. Indications are that the survival rate increases as the interval between the treatment of the primary tumor and discovery of the metastasis becomes longer. This may be logical since, during the disease free interval, the host resistance to the tumor is strong enough to prevent growth into gross metastases and may be strong enough to further contain the disease.6 However, our studies do not confirm 149
750
Radiation Oncology 0 Biology 0 Physics
1976, Vol. 1. Number 7 and Number 8
limited to the lung, and if it is resectable. Removal of the least amount of tissue which encompasses all discemable metastatic disease (wedge or transegmental resection) is the method of choice in order to conserve functional ventilatory reserve, to permit planDIAGNOSTIC AND EVALUATIVE ned bilateral thoracotomy, and to allow for PROCEDURES resection of additional pulmonary nodules Patients with any evidence of co-existing which subsequently may declare themselves. extra-thoracic metastases or those with diffuse The usual peripheral location of these lesions seeding in the lungs would be eliminated from and the infrequent involvement of the first and surgical consideration by careful screening for fourth order bronchi make this choice of disseminated disease. The first stage of procedure feasible. screening includes full chest tomography, Ongoing studies of patients who were biochemical tests of liver function, bone treated surgically for pulmonary metastases at scintigrams and an electroencephalogram. If the M.D. Anderson Hospital as well as the any abnormahties are encountered in these work of others [Hutchesion and Denner,9 Po01,‘~ Cliffton and Pool41 tests, liver and brain scans are performed. Martini et aLL2*” Because of the frequency of metastatic have shown that multiple metastases should mediastinal adenopathy accompanying pulmo- not necessarily be considered inoperable. The nary metastasis from breast cancer, medias- number and distribution of metastasis did not tinoscopy is recommended before thoracot- afIect the crude survival rate significantly in omy is undertaken. In selected cases, arterio- those patients in whom all residual malignant grams and bronchograms may be utilized disease apparently was removable by resecto complete the screening and aid in the pre- tion of bilateral and recurrent lesions. Although some disagreement exists with this operative evaluation. The 6rst evidence of pulmonary metastasis approach, in our judgement consideration of is most often found on routine follow-up chest excision of multiple nodules is warranted by roentgenograms. Fewer than one-fourth of the existence of long term survivors in this patients have presenting symptoms of cough, category. An important factor in the consideration of hemoptysis, chest pain or fever. As mentioned above, tomograms are required and may show resection for pulmonary metastases is the additional lesions not seen on the standard optimum point at which surgical intervention X-ray film. In our preliminary studies of 314 should take place. If the time between the patients under consideration for this treat- primary treatment and discovery of the ment, a retrospective review of X-rays was metastasis is short, it is prudent to observe the undertaken in approximately one third of the patient long enough for occult lesions to patients to evaluate the presence of the lesion become recognized clinically. Surgery should earlier than reported. The lesion was identified not be denied on this basis, however, to a on an earlier film in 12-13%. Since resection of patient who is otherwise a suitable surgical the earlier found and smaller lesions provides candidate. Because of the high incidence of a better opportunity for salvage, regular second primary tumors in the lung, especially follow-up at 3-6 month intervals for 5 years among patients whose primary tumors were in and yearly thereafter is of the utmost impor- the head and neck, and because of the tance in the cancer management program. difEculty of difIerentiating these from metastatic lesions, a period of long observation is SURGICAL RE!3ECTION not recommended in this group of cases. In a Consensus among oncologists regarding patient who has had a previous cancer treated treatment of metastatic pulmonary disease and develops a lung shadow, it is as likely to favors resection if the primary tumor has been be a new lung cancer as a metastatic deposit.16 completely treated, if the metastatic process is The chances are more in favor of a metastasis this thinking. Other important factors such as the cell type and the anatomic site of the primary lesion affect prognosis materially, but if the basic criteria can be fulfilled, surgical resection is recommended. nevertheless.
The basis for surgical resection of pulmonary metastases 0 C. F. MOUNTAIN
than a new primary if the prior lesion had been a soft tissue or bone sarcoma. In Cahan’s’ series of 29 melanoma patients, 5 developed primary lung tumors years after primary melanomas had been excised. A delay in treatment might deprive such patients with primary lung tumors of their only chance for cure. Choski et aL3 point out that the biological behavior of certain types of tumors cause them to present with a solitary pulmonary metastasis more frequently than others. For example, 15% of the solitary metastases that were resected in his series, were from primary sarcomas, with a sign&ant number from tumors of the breast, testis and uterus. In our own series, it was noted that patients who were treated for osteogenic sarcoma, carcinoma of the colon, or malignant melanoma were likely to develop additional nodules within a relatively short time. Biological characteristics of the primary tumor such as the determination of the growth rate (tumor doubling time, TDT) provide accurate evaluation of operability. A long TDT for the primary lesion results in a longer interval between primary tumor resection and the appearance of metastases, suggesting a more aggressive therapeutic approach in those patients with prolonged TDT.” Present knowledge of the acceleration and retarding influences on the growth rate of cancer is incomplete, but the enormous variances within each histological cell type reflect the interrelationship between the virulence of the tumor and the host resistance. From the author’s personal series, the growth rate of the pulmonary metastasis was examined in one third of the patients with serial chest roentgenograms taken 60 days or more apart. The findings emphasized what is common knowledge, namely those patients with slow growing tumors get better results from surgical treatment than patients with fast growing tumors. Prolonged survival is rarely associated with rapid enlargement of the pulmonary metastasis. The presence of regional and mediastinal node metastases portends the same grave prognosis in patients operated upon for pulmonary metastasis as for many primary
751
malignant tumors. In cases where this metastatic potential exists, mediastinoscopy is recommended before undertaking thoracotomy. In our first series, no patients in this category survived 5 years free of disease. The prognostic outlook in our own studies also relates to the morphology of the primary tumor and the stage of the primary disease. The most favorable outcome was for patients with metastases from carcinomas of the genitourinary tract, colon, rectum, uterine cervix and corpus uteri. Treatment of pulmonary metastases from lesions arising in the breast or from the head and neck area was less successful; the least successful treatment was for lesions from the upper gastrointestinal tract and pancreas. The prognostic outlook was poor for those patients treated for pulmonary metastases from liposarcoma, (unfibrosarcoma and unclassified differentiated) sarcoma. Promising results were obtained in treatment of metastases from skeletal sarcomas including osteogenic sarcomas. In 1974, Martini et ai.” reported on 86 patients who had surgical treatment of metastatic sarcoma to the lung. Of these, 26% remained alive 5 years after first thoracotomy, 17% free of disease. There was a continued drop in survival during the first 3 years after treatment, from 63% at 1 year to 32% at 3 years leveling off in the 3-5 year period. Cahan2 recently has reported pulmonary resection to be successful with a j-year survival in 4 of 12 melanoma patients. COMBINED THERAPY There is a reasonable expectation that the apparent success of surgical treatment of pulmonary metastases can be enhanced through the use of combined therapy. Recent reports in the literature attest to the value of this approach, even though most series of cases reported are small in number. With respect to pediatric malignances, Cliffton and Pool’ recommend that each patient who develops pulmonary metastases should receive a trial of chemotherapy if the tumor is known to be drug sensitive. If there is no response, or if further progression develops, the lesion should be resected immediately. It is recommended generally that chemotherapy be con-
752
1976. Vol. I, Number 7 and Number 8
Radiation Oncology 0 Biology 0 Physics
Table 1. Cummulative
percent surviving at 3 and 5 years
All cases
Carcinoma
m
Sw3ery alone
Surgery+
m
sarcoma
(o/o)
No.
3yr
5 yr
3 yr
5 yr
3 yr
5 yr
1%
38
25
42
29
26
16
61
37
31
39
33
33
28
planned adjunctive therapy
tinued post-operatively to control or eradicate occult foci of disease. Most authors agree that chemotherapy and/or irradiation is the primary treatment of choice for patients with Wilm’s tumor; surgery is indicated if this treatment fails. Tumbti et al.” reported results of combined therapy in 32 patients with pulmonary metastases; 10 of these patients treated with radiotherapy and/or chemotherapy as adjuncts to surgery have been free of recurrence an average of 4.3 years. Isotope implants were added to partial resections in this series for palliation: in 8 of 14 cases the disease did not progress. In 1973 Marcove and Lewis“ reported that an increase in 5 year survival rate from 17 to 40% has been observed when autogenous vaccine was given immediately after amputation for osteogenic sarcoma; however, vaccine administered after metastases were present was not helpful in prolonging survival. In patients with primary testicular tumors, Skinner et &I9 Samuels et 41.,” Reed and Cleland” and others have reported on combined therapy for pulmonary metastases with good results. In Feldman and Kyrialcos* series in various sarcomas, 6 of 9 patients who survived 5 years had received radiation or chemotherapy as adjuncts to surgery.
Table 1 summarizes briefly our own survival experience in an analysis of 257 patients undergoing surgical resection for pulmonary metastases at M.D. Anderson Hospital and Tumor Institute. In 1% patients, surgery alone was employed as definitive therapy while in 61 adjunctive chemotherapy, radiotherapy, or immunotherapy was utiliied. A detailed study of the variables afkting prognosis and of the survival dynamics of the various morphologic patterns of disease will be published in the near future. Nevertheless, these current end results show an encouraging number of long term survivors and argues for ap aggressive surgical approach in selected cases. COMMENT An appreciable palliative benefit and rewarding long-term, disease-free survival results from the surgical treatment of cancer which has metastasized to the lungs. Even multiple and bilateral lesions may be successfully managed. The morbidity and mortality of such treatment is low. It is apparent, however, that further studies are needed to more precisely define the optimum timing of surgical intervention, the selection of cases for detitive surgery, and the role of adjunctive surgery to reduce the total tumor burden.
REFERENCES 1. Barney, J.D., Churchill, E.J.: Adenocarcinoma
of the kidney with metastasis to the lung: cured by nephrectomy and lobectomy. J. Ural. 42: 269-276, 1939. 2. Cahan, W.G.: Excision of melanoma metastasis to lung; problems in diagnosis and management. Ann. Surg. 178: 703-709, 1973.
3. Choski, L.B., Takita, H., Vincent, R.G.: The surgical management of solitary pulmonary metastasis. Surg. Gynecol. Obstet. 134: 47% 482, 1972.
4.
Cliiton, E.E., Pool, J.L.: Treatment of lung metastasis in children with combined therapy. J. Thorac. Cardiovasc. Surg. 54: 403-421,1%7.
The basis for surgical resection of pulmonary metastases 0 C. F. MOUNTAIN
5. Cline, R.E., Young, W.G.: Long-term results following surgical treatment of metastatic pulmonary tumors. Am. Surg. 36: 61-68,1970. 6. Cole, W.H.: The mechanisms of spread of cancer. Surg. Gynecol. Obstet. 137: 853-871, 1973. 7. Farrell, Jr., J.T.: Pulmonary metastasis; a pathologic, clinical roentgenologic study based on 78 cases seen at necropsy. Radiology 24: 444-451, 1935. 8. Feldman, P.S., Kyriakos, M.: Pulmonary resection for metastatic sarcoma. J. Thorac. Cardiovasc. Surg. 64: 7%799, 1972. 9. Hutchison, D.E., Denner, R.M.: Resection of pulmonary secondary tumors. Am. J. Surg. 124: 723-737, 1972. 10. Joseph, W.L.: Prognostic signifkance of tumor doubling time in evaluating operability in pulmonary metastatic disease. J. ‘I’horac. Cardiovasc. Surg. 61: 23-32, 1974. 11. Marcove, R.C., Lewis, MM.: Prolonged survival in osteogenic sarcoma with multiple puhnonary metastasis. J. Bone Joint Surg. 55: 15X-1520, 1973. 12. Martini, N., Bains, M.S., Huvos, A.S., et al.: Surgical treatment of metastatic sarcoma to the lung. Surg. Clin. North Am. 54: 841-844, Aug. 1974. 13. Martini, N., Huvos, A.G., Mike, V., Marcove, R.C., Beattie, Jr., E.J.: Multiple puhnonary resections in the treatment of osteogenic sarcoma. Ann. Thorac. Surg. 12: 271-280,197l. 14. Meyer, V., Cadalbert, M., Jenny, M., Senning,
15.
16.
17.
18.
19.
20.
21.
753
A.: Chirugische behandlung von lungenmetastesen extrapulmonaler premartumoren. Therapeutische UmschaulRevue Therapeutique, Band 30: 824-830, 1973. Mountain, CF.: Surgical management of pulmonary metastasis. Postgrad. Med. 48: 128132, 1970. Pool, J.L.: The treatment of metastasis to the lungs. Report to the Cancer Committee of the American College of Chest Physicians, Oct. 1970 (written communication). Rees, G.M., Cleland, W.P.: Surgical treatment of pulmonary metastasis from testicular tumors. Br. Med. J. 3: 467-470, 1971. Samuels, M.L., Holoye, P.Y., Johnson, D.E.: Bleomycin combination chemotherapy for metastatic testicular carcinoma. Cancer Bull. 25: 53-55, 1973. Skinner, D.G., Leadbetter, W.F., Wilkins, Jr., E.W.: The surgical management of testis tumors metastatic to the lung; a report of 10 cases with subsequent resection of from one to seven pulmonary metastasis. J. Ural. 109: 275-282, 1971. Turnbull, A.D., Pool, J.L., Arthur, K., Golbey, R.B.: The role of radiotherapy and chemotherapy in the surgical management of pulmonary metastasis. Am. J. Roentgenol. Radium Ther. Nucl. Med. 114: 99-105, 1972. Turney , S.Z.. Haight, C.: Pulmonary resection for metastatic neoplasms. J. Thorac. Cardiovasc. Surg. 61: 784-794, 1971.