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Operative management of adrenal metastases from lung carcinoma
OPERATIVEMANAGEMENTOFADRENAL METASTASESFROM LUNGCARCINOMA ANDREW J. KIRSCH, M.D. MEHMET C. OZ, M.D. MARK STOOPLER, M.D. MARK GINSBURG, M.D. KENNETH STEINGLASS, M.D. From the Departments of Urology, Surgery, and Medicine, Columbia University, College of Physicians and Surgeons, New York, New York
ABSTRACT-Most surgeons consider patients with solitary adrenal metastasis from a primary lung carcinoma incurable and avoid excision of both the adrenal and primary lung tumors. However, several cases of successful surgical management of these patients recently have been reported. We reviewed 12 surgically treated patients with isolated adrenal and lung disease and identified 2 survivors of greater than fifteen years (17%) and 4 additional patients who are still alive following combined resection (34%). This survival rate, albeit in a selected population, represents an improvement over the natural history of nine months’ survival. We suggest that if after six to twelve months of following patients with lung cancer and isolated adrenal metastasis no other evidence of spread of disease is evident, the tumor biology may be favorable and resection of both adrenal and lung lesions is reasonable.
The adrenal gland is the most common site by weight of lung cancer metastases. Although computed tomography allows preoperative screening for large metastases, 9 percent of patients undergoing otherwise curative resections for lung cancer and dying within one month of operation from unrelated causes have been found to have unrecognized adrenal metastases.l Identification of a solitary adrenal metastasis from a primary lung carcinoma upgrades the patient to a Stage IV status even if the primary lesion is otherwise resectable. Most surgeons consider the patient incurable and excision of both the adrenal and primary lung tumors have been contraindicated in this setting. However, over the past decade several published case reports have described successful management of patients with solitary adrenal metastases. We have reviewed our experience and evaluated the literature in an attempt to formalize a protocol for managing such patients.
Submitted: May 28, 1993, accepted (with revisions): July 21, 1993
716
MATERIAL AND METHODS Two cases treated at the Columbia-Presbyterian Medical Center from 1987 to present are reported in this study In addition, 10 cases from the literature were identified and attempts to identify the current status of the reported cases were made by contacting the original authors and primary physicians of the patients. Table I2-4 outlines the 12 patients reviewed in this retrospective study Among these Stage IV patients, several long-term survivors have been identified. We will report details on the 2 patients from our institution and follow-up on patients previously reported in the literature. CASE REPORTS CASE 1
A seventy-one-year-old woman was hospitalized for surgical excision of a 1.5cm right eyelid basal cell carcinoma. A routine preoperative chest x-ray film showed a spiculated left upper lobe mass. Previous films were unavailable for comparison. She had smoked one package of cigarettes daily for thirty years. She had no specific complaints and denied weight loss, anorexia, or cough.
UROLOGY / DECEMBER1993 I VOLUME42. NUMBER6
TABLE Case 1 2 32 42
53 63
73 84
94
104 114 124
Age
I.
Review of 12 cases of adrenal metastases
r/t-s)
Primary’
71
3 cm LUL (adeno) 3 cm LUL (adsquam) 4 cm LUL (lg. cell) 3 cm LUL (lg. cell)
61 62 65
69 67 56 35
43
41 69 54
LUL (unknown) 5 cm (adeno) LUL (adeno) RUL (adeno)
Adrenal Mets
Treatment
3 cm ipsi M 5 cm ipsi [Ml 10 cm contra (Sl 15 cm contra M 7 cm contra (51 a cm M 7 cm (Ml 2 cm contra (Sl
RUL (lg. cell)
bilateral
LUL (lg. cell) RUL, LUL (unknown] RUL [squamous)
7 cm contra
[Sl
[S) 2 cm benign (9 6 cm ipsi (9
Adrenalectomy LUL. chemo Lobectomy chemo Adrenalectomy lobectomy Unresectable lung nephroadrenalectomy XRT Unresectable lung adrenalectomy Pneumonectomy adrenalectomy Lobectomy adrenalectomy Pneumonectomy adrenalectomy XRT, chemo Lobectomy bilat. adrenalectomy chemo Adrenalectomy lobectomy Adrenalectomy bilat. lobectomy Adrenalectomy lobectomy XRT, chemo
Outcome 2 yrt
2 yr 16 yr 15 yr
3 yr 2 yr 2 yr 3 yrt
4 yrt
1 yr 5 yrt
1v
KEY:LUL = left upper lobe of lung, RUL = right upper lobe of lung, XRT= radiation therapy, chemo = chemotherapy, ipsi = contralateral to initial lung carcinoma, yr = years of adrenal hmo~ ipsilaterat toinitial lung carcinoma, contra = adrenal tumor survival, S = synchronous, M = metachronous, adeno = adenocarcinoma, adsquam = adcnosquamous carcinoma, lg. cell = large cell carcinoma. *Histology ofadrenal m&stases identical to primary lung lesion. fPatient is still alive.
Computed tomography (CT) of the chest demonstrated a 3-cm mass in the apex of the left upper lobe, with no evidence of mediastinal lymphadenopathy. Additionally, a 3-cm right adrenal mass was identified. Further radiographic studies, including a CT scan of the brain, total body bone scan, and mammography were negative. Percutaneous adrenal biopsy and transbronchial biopsy both revealed poorly differentiated adenocarcinoma. The diagnosis of Stage IV lung carcinoma was established and she received six cycles of combination chemotherapy (cis-platinum, Velban, mitomycin C). No significant tumor regression nor growth was identified after ten months and no other metastatic foci became apparent. She remained asymptomatic from both lesions. Ten months following the initial diagnosis, right adrenalectomy was performed without complication. There was no evidence of tumor invasion be-
UROLOGY
I DECEMBER 1993 I VOLUME 42, NUMBER 6
yond the adrenal gland. Two months later an uneventful left upper lobectomy was performed. One lymph node adherent to the recurrent laryngeal nerve, demonstrated metastatic involvement. Pathologic specimens from both the adrenal gland and lung revealed poorly differentiated adenocarcinema, most likely metastatic from the lung. Postoperative recovery was uneventful. Since the time of her diagnosis, fifteen months ago, there continues to be no clinical or diagnostic evidence of further metastatic disease. CASE 2
A sixty-one-year-old man underwent uneventful left upper lobectomy for a 2 x 3-cm poorly differentiated adenosquamous carcinoma with no involvement of mediastinal lymph nodes. No postoperative radio- or chemotherapy was given. He was followed regularly and had no problems until 717
three years postoperatively when an x-ray film of the chest showed a question of recurrent lung tumor. A CT scan of the chest showed no abnormality, but incidentally a left adrenal mass was found measuring 4 x 5 cm. Endocrine evaluation revealed that it was a nonfunctioning tumor. Findings on metastatic workup, including total body bone scan and brain CT scan, were negative. The patient had no evidence of other metastases. He was given combination chemotherapy (Velban, cis-platinum, and mitomycin), and the adrenal mass was followed by interval CT scans. By eighteen months, the adrenal mass had enlarged to 8 cm with invasion into the left diaphragmatic crus and celiac axis, as well as the upper pole of the left kidney. By twenty-four months, the mass had enlarged and now more extensively involved the posterior wall of the stomach, tail of the pancreas, and wall of the aorta. He became increasingly weak, and melena, hematuria, and hematemesis developed prior to his death. No postmortem examination was performed. LITERATURE FOUOW-UP
(TABLE I)
Case 3: The patient survived fifteen years after adrenalectomy and lobectomy with death resulting from unrelated causes; however, at autopsy an indolent, asymptomatic residual lung carcinoma was noted (personal communication, Orlo Clark, M.D., Mount Zion Medical Center, San Francisco, CA, July 6, 1992). Case 4: The patient survived sixteen years after nephroureterectromy and radiation therapy and died of an unclear etiology. Although no autopsy was performed, the physician caring for the patient believes recurrent disease was present (personal communication, Orlo Clark, M.D., Mount Zion Medical Center, San Francisco, CA, July 17, 1992). Case 9: The patient has survived four years without evidence of recurrence (personal communication, Hiroshi Takita, M.D., Roswell Park Cancer Institute, Buffalo, NY, June 23, 1992). Case 13: A five-year survival without disease at present is reported; however, the patient underwent an additional pulmonary resection for recurrent local disease (personal communication, Hiroshi Takita, M.D., Roswell Park Cancer Institute, Buffalo, NY, June 23, 1992).
resection of both a primary lung and single metastatic adrenal lesion seem to place this clinical entity in a unique situation. Furthermore, since the metastatic lesion was the primary cause of the patient’s symptoms and eventual death in Case 2, resection of the metastasis may constitute a form of palliation in selected situations. The incidence of adrenal masses identified by computer tomography in patients with otherwise resectable lung cancers is reported as 4 percent.5 Half of these adrenal masses will be benign, but often require adrenalectomy to confirm the diagnosis. The median survival of patients with adrenal metastases in whom the tumors and the primary lung lesions are left in situ is nine months.5 An additional 5-10 percent of patients will have clinically unsuspected adrenal lesions at the time of their lung resection.’ A small percent of these patients will have tumor localized to the adrenal without further metastases over a lengthy follow-up period. As has been recognized following resection of metastases to the 1ivelP or lung7 in patients with a controlled primary carcinoma, some of these high-risk cases can be cured. An analogous situation already exists in patients with lung cancer and cerebral metastases. These patients are offered surgery because the metastatic lesion often proves to be an unnecessarily early life-limiting lesion and a certain number of these patients can be cured. Since the adrenal bed is so richly perfused and is commonly involved with metastatic lung carcinoma, following patients with adrenal metastases for a pre-determined period, as in Case 1, and reassessing the patient’s clinical status appears warranted. Prior to considering composite resection in these patients a thorough restaging including magnetic resonance imaging (MRI) of the brain, CT imaging of the chest, abdomen, and pelvis, and a bone scan, should be performed. Assessment of differential renal function is also appropriate. If after six to twelve months no other evidence of spread of disease is evident, the tumor biology may be favorable and resection of both adrenal and lung lesions is reasonable. Mehmet C. Oz, M.D. PH Unit 170
622 West 168th Street Columbia-Presbyterian Medical Center New York, New York 10032
COMMENT While Stage IV lung carcinoma is usually treated by chemotherapy and sometimes adjuvant radiation, surgery is rarely performed. However, the presence of several long-term survivors following
718
REFERENCES 1. Mathews MJ, Kanhouwa S, Pickren J, and Robinette D: Frequency of residual and metastatic tumor in patients undergoing curative surgical resection of lung cancer. Cancer
UROLOGY
/ DECEMBER 1993 / VOLUME42, NUMBER6
Chemother Rep 4: 63-67, 1973. 2. Twomey P, Montgomery C, and Clark 0: Successful treatment of adrenal metastases from large-cell carcinoma of the lung. JAMA 248(5): 581-583,1982. 3. Raviv G, Klein E, Yellin A, Schneebaum S, and Ben-Ari G: Surgical treatment of solitary adrenal metastases from lung carcinoma. J Surg Oncol43: 123-124,199O. 4. Reyes L, Parvez Z, Nemoto T, Regal A-M, and Takita H: Adrenalectomy for adrenal metastasis from lung carcinoma. J
UROLOGY
/ DECEMBER1993
I VOLUME42, NUMBER6
Surg Oncol44: 32-34,199O. 5. Ettinghausen SE, and Burt ME: Prospective evaluation of unilateral adrenal masses in patients with operable nonsmall cell lung cancer. J Chn Oncol9(8): 1462-1466,199l. 6. Iwatsuki S, Shaw BW Jr, and Starzl TE: Experience with 150 liver resections. Ann Surg 197: 247-253, 1983. 7. Mountain CF, McMurtrey MJ, and Hermes KE: Surgery for pulmonary metastasis: a 20-year experience. Ann Thorac Surg 38: 323-330,1984.
719
ABSTRACT-Most surgeons consider patients with solitary adrenal metastasis from a primary lung carcinoma incurable and avoid excision of both the adrenal and primary lung tumors. However, several cases of successful surgical management of these patients recently have been reported. We reviewed 12 surgically treated patients with isolated adrenal and lung disease and identified 2 survivors of greater than fifteen years (17%) and 4 additional patients who are still alive following combined resection (34%). This survival rate, albeit in a selected population, represents an improvement over the natural history of nine months’ survival. We suggest that if after six to twelve months of following patients with lung cancer and isolated adrenal metastasis no other evidence of spread of disease is evident, the tumor biology may be favorable and resection of both adrenal and lung lesions is reasonable.
The adrenal gland is the most common site by weight of lung cancer metastases. Although computed tomography allows preoperative screening for large metastases, 9 percent of patients undergoing otherwise curative resections for lung cancer and dying within one month of operation from unrelated causes have been found to have unrecognized adrenal metastases.l Identification of a solitary adrenal metastasis from a primary lung carcinoma upgrades the patient to a Stage IV status even if the primary lesion is otherwise resectable. Most surgeons consider the patient incurable and excision of both the adrenal and primary lung tumors have been contraindicated in this setting. However, over the past decade several published case reports have described successful management of patients with solitary adrenal metastases. We have reviewed our experience and evaluated the literature in an attempt to formalize a protocol for managing such patients.
Submitted: May 28, 1993, accepted (with revisions): July 21, 1993
716
MATERIAL AND METHODS Two cases treated at the Columbia-Presbyterian Medical Center from 1987 to present are reported in this study In addition, 10 cases from the literature were identified and attempts to identify the current status of the reported cases were made by contacting the original authors and primary physicians of the patients. Table I2-4 outlines the 12 patients reviewed in this retrospective study Among these Stage IV patients, several long-term survivors have been identified. We will report details on the 2 patients from our institution and follow-up on patients previously reported in the literature. CASE REPORTS CASE 1
A seventy-one-year-old woman was hospitalized for surgical excision of a 1.5cm right eyelid basal cell carcinoma. A routine preoperative chest x-ray film showed a spiculated left upper lobe mass. Previous films were unavailable for comparison. She had smoked one package of cigarettes daily for thirty years. She had no specific complaints and denied weight loss, anorexia, or cough.
UROLOGY / DECEMBER1993 I VOLUME42. NUMBER6
TABLE Case 1 2 32 42
53 63
73 84
94
104 114 124
Age
I.
Review of 12 cases of adrenal metastases
r/t-s)
Primary’
71
3 cm LUL (adeno) 3 cm LUL (adsquam) 4 cm LUL (lg. cell) 3 cm LUL (lg. cell)
61 62 65
69 67 56 35
43
41 69 54
LUL (unknown) 5 cm (adeno) LUL (adeno) RUL (adeno)
Adrenal Mets
Treatment
3 cm ipsi M 5 cm ipsi [Ml 10 cm contra (Sl 15 cm contra M 7 cm contra (51 a cm M 7 cm (Ml 2 cm contra (Sl
RUL (lg. cell)
bilateral
LUL (lg. cell) RUL, LUL (unknown] RUL [squamous)
7 cm contra
[Sl
[S) 2 cm benign (9 6 cm ipsi (9
Adrenalectomy LUL. chemo Lobectomy chemo Adrenalectomy lobectomy Unresectable lung nephroadrenalectomy XRT Unresectable lung adrenalectomy Pneumonectomy adrenalectomy Lobectomy adrenalectomy Pneumonectomy adrenalectomy XRT, chemo Lobectomy bilat. adrenalectomy chemo Adrenalectomy lobectomy Adrenalectomy bilat. lobectomy Adrenalectomy lobectomy XRT, chemo
Outcome 2 yrt
2 yr 16 yr 15 yr
3 yr 2 yr 2 yr 3 yrt
4 yrt
1 yr 5 yrt
1v
KEY:LUL = left upper lobe of lung, RUL = right upper lobe of lung, XRT= radiation therapy, chemo = chemotherapy, ipsi = contralateral to initial lung carcinoma, yr = years of adrenal hmo~ ipsilaterat toinitial lung carcinoma, contra = adrenal tumor survival, S = synchronous, M = metachronous, adeno = adenocarcinoma, adsquam = adcnosquamous carcinoma, lg. cell = large cell carcinoma. *Histology ofadrenal m&stases identical to primary lung lesion. fPatient is still alive.
Computed tomography (CT) of the chest demonstrated a 3-cm mass in the apex of the left upper lobe, with no evidence of mediastinal lymphadenopathy. Additionally, a 3-cm right adrenal mass was identified. Further radiographic studies, including a CT scan of the brain, total body bone scan, and mammography were negative. Percutaneous adrenal biopsy and transbronchial biopsy both revealed poorly differentiated adenocarcinoma. The diagnosis of Stage IV lung carcinoma was established and she received six cycles of combination chemotherapy (cis-platinum, Velban, mitomycin C). No significant tumor regression nor growth was identified after ten months and no other metastatic foci became apparent. She remained asymptomatic from both lesions. Ten months following the initial diagnosis, right adrenalectomy was performed without complication. There was no evidence of tumor invasion be-
UROLOGY
I DECEMBER 1993 I VOLUME 42, NUMBER 6
yond the adrenal gland. Two months later an uneventful left upper lobectomy was performed. One lymph node adherent to the recurrent laryngeal nerve, demonstrated metastatic involvement. Pathologic specimens from both the adrenal gland and lung revealed poorly differentiated adenocarcinema, most likely metastatic from the lung. Postoperative recovery was uneventful. Since the time of her diagnosis, fifteen months ago, there continues to be no clinical or diagnostic evidence of further metastatic disease. CASE 2
A sixty-one-year-old man underwent uneventful left upper lobectomy for a 2 x 3-cm poorly differentiated adenosquamous carcinoma with no involvement of mediastinal lymph nodes. No postoperative radio- or chemotherapy was given. He was followed regularly and had no problems until 717
three years postoperatively when an x-ray film of the chest showed a question of recurrent lung tumor. A CT scan of the chest showed no abnormality, but incidentally a left adrenal mass was found measuring 4 x 5 cm. Endocrine evaluation revealed that it was a nonfunctioning tumor. Findings on metastatic workup, including total body bone scan and brain CT scan, were negative. The patient had no evidence of other metastases. He was given combination chemotherapy (Velban, cis-platinum, and mitomycin), and the adrenal mass was followed by interval CT scans. By eighteen months, the adrenal mass had enlarged to 8 cm with invasion into the left diaphragmatic crus and celiac axis, as well as the upper pole of the left kidney. By twenty-four months, the mass had enlarged and now more extensively involved the posterior wall of the stomach, tail of the pancreas, and wall of the aorta. He became increasingly weak, and melena, hematuria, and hematemesis developed prior to his death. No postmortem examination was performed. LITERATURE FOUOW-UP
(TABLE I)
Case 3: The patient survived fifteen years after adrenalectomy and lobectomy with death resulting from unrelated causes; however, at autopsy an indolent, asymptomatic residual lung carcinoma was noted (personal communication, Orlo Clark, M.D., Mount Zion Medical Center, San Francisco, CA, July 6, 1992). Case 4: The patient survived sixteen years after nephroureterectromy and radiation therapy and died of an unclear etiology. Although no autopsy was performed, the physician caring for the patient believes recurrent disease was present (personal communication, Orlo Clark, M.D., Mount Zion Medical Center, San Francisco, CA, July 17, 1992). Case 9: The patient has survived four years without evidence of recurrence (personal communication, Hiroshi Takita, M.D., Roswell Park Cancer Institute, Buffalo, NY, June 23, 1992). Case 13: A five-year survival without disease at present is reported; however, the patient underwent an additional pulmonary resection for recurrent local disease (personal communication, Hiroshi Takita, M.D., Roswell Park Cancer Institute, Buffalo, NY, June 23, 1992).
resection of both a primary lung and single metastatic adrenal lesion seem to place this clinical entity in a unique situation. Furthermore, since the metastatic lesion was the primary cause of the patient’s symptoms and eventual death in Case 2, resection of the metastasis may constitute a form of palliation in selected situations. The incidence of adrenal masses identified by computer tomography in patients with otherwise resectable lung cancers is reported as 4 percent.5 Half of these adrenal masses will be benign, but often require adrenalectomy to confirm the diagnosis. The median survival of patients with adrenal metastases in whom the tumors and the primary lung lesions are left in situ is nine months.5 An additional 5-10 percent of patients will have clinically unsuspected adrenal lesions at the time of their lung resection.’ A small percent of these patients will have tumor localized to the adrenal without further metastases over a lengthy follow-up period. As has been recognized following resection of metastases to the 1ivelP or lung7 in patients with a controlled primary carcinoma, some of these high-risk cases can be cured. An analogous situation already exists in patients with lung cancer and cerebral metastases. These patients are offered surgery because the metastatic lesion often proves to be an unnecessarily early life-limiting lesion and a certain number of these patients can be cured. Since the adrenal bed is so richly perfused and is commonly involved with metastatic lung carcinoma, following patients with adrenal metastases for a pre-determined period, as in Case 1, and reassessing the patient’s clinical status appears warranted. Prior to considering composite resection in these patients a thorough restaging including magnetic resonance imaging (MRI) of the brain, CT imaging of the chest, abdomen, and pelvis, and a bone scan, should be performed. Assessment of differential renal function is also appropriate. If after six to twelve months no other evidence of spread of disease is evident, the tumor biology may be favorable and resection of both adrenal and lung lesions is reasonable. Mehmet C. Oz, M.D. PH Unit 170
622 West 168th Street Columbia-Presbyterian Medical Center New York, New York 10032
COMMENT While Stage IV lung carcinoma is usually treated by chemotherapy and sometimes adjuvant radiation, surgery is rarely performed. However, the presence of several long-term survivors following
718
REFERENCES 1. Mathews MJ, Kanhouwa S, Pickren J, and Robinette D: Frequency of residual and metastatic tumor in patients undergoing curative surgical resection of lung cancer. Cancer
UROLOGY
/ DECEMBER 1993 / VOLUME42, NUMBER6
Chemother Rep 4: 63-67, 1973. 2. Twomey P, Montgomery C, and Clark 0: Successful treatment of adrenal metastases from large-cell carcinoma of the lung. JAMA 248(5): 581-583,1982. 3. Raviv G, Klein E, Yellin A, Schneebaum S, and Ben-Ari G: Surgical treatment of solitary adrenal metastases from lung carcinoma. J Surg Oncol43: 123-124,199O. 4. Reyes L, Parvez Z, Nemoto T, Regal A-M, and Takita H: Adrenalectomy for adrenal metastasis from lung carcinoma. J
UROLOGY
/ DECEMBER1993
I VOLUME42, NUMBER6
Surg Oncol44: 32-34,199O. 5. Ettinghausen SE, and Burt ME: Prospective evaluation of unilateral adrenal masses in patients with operable nonsmall cell lung cancer. J Chn Oncol9(8): 1462-1466,199l. 6. Iwatsuki S, Shaw BW Jr, and Starzl TE: Experience with 150 liver resections. Ann Surg 197: 247-253, 1983. 7. Mountain CF, McMurtrey MJ, and Hermes KE: Surgery for pulmonary metastasis: a 20-year experience. Ann Thorac Surg 38: 323-330,1984.
719