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Ann Thorac Surg 1998;65:331-335
© 1998 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Adrenalectomy for a Solitary Adrenal Metastasis From Lung Cancer

Clinique Chirurgicale, Hôpital Calmette, Lille, France

Accepted for publication August 20, 1997.

Dr Porte, Clinique Chirurgicale, Hôpital Calmette, Bd du Pr. J. Leclercq, 59037 Lille Cedex, France.

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
Background. Several case reports have shown that patients with truly solitary adrenal gland metastases can undergo resection with long-term survival.

Methods. We assessed consecutive patients with operable or operated non–small cell lung cancer in whom the presence of a unilateral solitary adrenal metastasis was confirmed histologically. Synchronous homolateral adrenal metastases were resected at the same time as the non–small cell lung carcinoma through a transphrenic approach. Synchronous contralateral or metachronous adrenal metastases were resected through an elective approach.

Results. Of 598 patients with operable or operated non–small cell lung carcinoma, 11 had a unilateral solitary adrenal gland metastasis and underwent adrenalectomy with no additional mortality or morbidity. One patient died of late postoperative complications and 7 patients died of other distant metastases between 4 and 24 months after adrenalectomy. Two patients are still alive and free of recurrent disease and 1 patient is still alive with brain metastasis 66, 6, and 10 months, respectively, after adrenalectomy.

Conclusions. In the absence of selection criteria to identify the subgroup of patients who will benefit from surgical resection, we suggest the resection of synchronous lesions in patients without N2 involvement and the careful selection of patients with metachronous adrenal metastases according to the evolution of their disease.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment References

 
Adrenal metastases originating from non–small cell lung carcinoma (NSCLC) are present in 5% to 10% of patients at initial presentation [1] [2]. The development of computed tomography (CT) has revolutionized the evaluation of patients with NSCLC with respect to the extent of the primary disease as well as metastatic spread to distant sites, including the adrenal glands [3] [4] [5]. It is not defined clearly whether patients with NSCLC and a solitary adrenal metastasis are likely to benefit from surgical resection. This resection remains controversial because the discovery of an adrenal metastasis transfers the patient to an advanced disease stage at which a nonoperative treatment usually is used [6]. However, several case reports have shown that patients with an isolated adrenal metastasis from NSCLC can undergo resection with long-term survival [7] [8] [9] [10] [11] [12] [13]. The current study was initiated to evaluate the incidence of isolated adrenal metastasis in patients with operable NSCLC and the impact on survival of adrenal resection performed synchronously or metachronously with potentially curative lung resection. We discuss the management of truly solitary unilateral adrenal metastases of NSCLC on the basis of our experience and data obtained from the literature.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
Synchronous Adrenal Metastases
All patients with resectable NSCLC who were referred to our institution underwent systematic exploration of the adrenal glands by CT scanning. When a unilateral adrenal mass was discovered, magnetic resonance imaging was performed to rule out the possibility of a pheochromocytoma (indicated by high signal intensity on T2-weighted images). Then, the patients underwent CT-guided biopsy of the adrenal mass.

When histologic studies confirmed the adrenal metastasis, abdominal and cerebral CT scanning and bone scintigraphy were carried out to verify the absence of metastatic spread. Patients with adrenal metastasis identified at the time of initial NSCLC diagnosis were classified as having synchronous metastasis. Adrenalectomy then was performed synchronously with the lung resection through a transphrenic approach in the case of homolateral adrenal metastasis. In the case of contralateral adrenal metastasis, adrenalectomy was performed through a left lumbotomy or a right transverse abdominal incision performed after the lung resection.

Metachronous Adrenal Metastases
Metastases shown to be absent at the time of lung resection were classified as metachronous metastases. When a unilateral adrenal gland mass was discovered more than 12 months after potentially curative lung resection for NSCLC, magnetic resonance imaging was performed, followed by CT-guided biopsy of the mass.

After confirmation of the adrenal metastasis by histopathologic studies, the absence of any other metastatic spread was confirmed by cerebral and abdominal CT scanning and bone scintigraphy. Then a surgical resection was performed through a left lumbotomy or a right abdominal transverse incision. When a unilateral adrenal mass was discovered less than 12 months after lung resection, preoperative biopsy was not performed before adrenalectomy.

Statistical Analysis
Patient survival was expressed by actuarial analysis according to the method of Kaplan and Meier, using time zero as the date of adrenalectomy and death as the end point. Data are presented as frequency distributions and simple percentages. Univariate analysis of selected preoperative variables was accomplished by ² analysis. A statistically significant difference between measurements was defined as p less than or equal to 0.05.

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
Of the 598 patients with otherwise operable NSCLC who were referred to our institution from January 11, 1988, to January 11, 1996, 39 (6.5%) had a unilateral adrenal mass. Twenty-one (3.5%) of the patients had an adrenal metastasis proven by needle aspiration and 18 (3%) had a benign adenoma. Among the 21 metastases, 16 (76%) were homolateral and 5 (24%) were contralateral to the primary NSCLC (p < 0.005). Ten (62%) of the 16 patients with homolateral adrenal metastases and 1 (20%) of the 5 patients with contralateral adrenal metastases had no evidence of metastases at other locations.

Overall, 11 patients, all men, with a mean age of 55 years (range, 42 to 67 years) and a Karnofsky scale superior to 80%, underwent complete resection of both their lung cancer and their adrenal metastasis. The mean adrenal metastasis size was 32 mm (range, 30 to 45 mm).

Surgical Treatment of the 8 Patients With Synchronous Metastases
The mean operative time of synchronous resection through a phrenotomy was 180 minutes (range, 130 to 300 minutes). The mean hospital stay was 40 days (range, 8 to 123 days).

There was no perioperative mortality or morbidity. There was 1 late postoperative death (12.5%). This patient died of pulmonary septic complications 123 days after completion pneumonectomy and adrenal resection; he had no lung cancer recurrence at autopsy.

Three patients (27%) had postoperative morbidity, none as a result of either the phrenotomy or the adrenalectomy. Clinical examinations and biologic tests did not reveal any adrenal secretion deficiency.

Surgical Treatment of the 3 Patients With Metachronous Metastases
The mean operative time was 120 minutes (range, 110 to 150 minutes). The mean hospital stay was 9 days (range, 6 to 14 days). There was no perioperative or postoperative mortality or morbidity and no adrenal secretion deficiency noted on clinical examination or biologic testing.

Survival of Patients Who Underwent Synchronous Adrenal Resection
Only 1 patient is still alive and free of any recurrent disease 66 months after a superior and middle bilobectomy associated with a synchronous homolateral adrenalectomy performed for an adenocarcinoma classified as T3, N0, M1. Another patient is alive 10 months after a synchronous resection with a cerebral metastasis discovered 3 months after operation. Altogether, 4 patients with a synchronous adrenal gland metastasis experienced general spread of the disease within 7 months after operation.

Survival of Patients Who Underwent Metachronous Adrenal Resection
One patient is still alive and free of any recurrent disease 6 months after adrenal resection and 17 months after lung resection. Altogether, 2 patients with a metachronous adrenal metastasis experienced general spread of the disease within 3 months after adrenal resection.

The overall median survival of patients who underwent synchronous or metachronous adrenal resection was 6 months. The characteristics and clinical outcomes of these patients are outlined in Table 1.

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

However, long-term survivors have been reported in the literature. Twomey and co-workers [7] reported two cases of adrenal metastasis from large cell carcinoma in patients who survived 5 and 14 years, respectively, after adrenal resection. In the first of these patients, the primary lung cancer was unresectable and treated by radiation therapy. Raviv and associates [8] performed lung and adrenal resection in 2 patients who survived for 24 and 25 months, respectively. Reyes and colleagues [9] performed four metachronous adrenalectomies for both synchronous and metachronous metastases. Two patients survived for up to 36 months. Kirsch and co-workers, in a review article [12], reported 1 patient with resected homolateral metastases who survived up to 5 months after adrenalectomy.

Higashiyama and co-workers [10] performed three metachronous adrenalectomies for solitary metastases in patients who previously underwent potentially curative lung resection. Two patients were alive without recurrence 24 and 40 months, respectively, after adrenalectomy. The primary lesions of these patients were classified as T2 N0 M0. In contrast, 4 other patients who received chemotherapy died less than 6 months after the diagnosis of metastasis, and the 2 patients who underwent adrenal resection without potentially curative lung resection died of early recurrence. Luketich and Burt [11] described 14 patients with a solitary adrenal metastasis associated with NSCLC. The median survival was 22 months for the 8 patients who were treated surgically compared with 8.5 months for the 6 patients who were treated with platinum-based chemotherapy. Ayabe and associates [13] performed one metachronous and two synchronous resections. Of these 3 patients, 2 survived for more than 5 years. More recently, Lo and colleagues [14] reported 52 patients who underwent adrenalectomy for adrenal metastases originating from different primary lesions (eg, kidney, colon, lung). Eleven metastases originated from NSCLC. Eight of the patients underwent potentially curative resection of their lung cancer. No information was provided about the characteristics of the primary lung cancer or the survival of the patients.

In Table 2 we summarize the data from the literature regarding patients who have undergone potentially curative lung resection and synchronous or metachronous adrenal resection. All these studies report small series of patients and the stage of the primary NSCLC is not always specified. Only one prospective study similar to ours was published, involving 291 patients, 4 of whom had histologically confirmed adrenal metastasis and were treated by chemotherapy. They all died of widespread metastatic disease 8 to 23 months after initial presentation [6]. Altogether, no selection criteria can be drawn from the literature except the favorable biology of slowly evolving tumors with a long disease-free interval in the case of metachronous metastasis.

Some of these criteria already can be drawn from the literature and from our experience. Concerning the therapeutic management of a solitary adrenal mass from operable NSCLC, the first step is to determine whether it represents a metastasis or an adenoma [4]. The sensitivities and specificities of CT scanning and magnetic resonance imaging, even when combined, are not sufficient to distinguish between benign and malignant lesions [15] [16] [17]. Proper treatment planning, therefore, mandates pathologic confirmation of the true nature of a unilateral adrenal mass in patients with NSCLC. In cases of metachronous metastases, when imaging examinations performed during follow-up clearly demonstrate the recent occurrence of an adrenal mass, adrenalectomy can be performed without histologic confirmation of the metastasis.

The second challenge is to confirm the absence of any other metastatic sites. Three of our patients died of early cerebral metastases that were not apparent before operation. In this endeavor, CT scanning is more sensitive in detecting small tumors, whereas magnetic resonance imaging allows for improved visualization of the brain stem [18].

Synchronous Homolateral Metastases
Our study demonstrates the feasibility of adrenal resection through a phrenotomy performed at the same time as lung resection. The additional resection does not cause any extra morbidity and the patient undergoes only one episode of general anesthesia.

Moreover, the significantly more frequent incidence of homolateral adrenal metastasis (p < 0.005) reinforces the hypothesis of lymphatic spread as the metastatic mechanism postulated by Karolyi [19]. He showed in a large autopsy series that in the early stages, adrenal metastases from NSCLC are more likely to be located homolateral to the primary lesion. Consequently, homolateral synchronous metastases should be resected at the same procedure with a potentially curative aim, except in patients with advanced lung cancer with macroscopic N2 involvement, in whom multiple micrometastatic lesions often are present at other sites (eg, brain, bone, liver).

Synchronous Contralateral Metastases
Synchronous contralateral metastases are likely to be the first manifestation of disseminated disease because they develop mainly by the hematogenous route. Aggressive operative intervention does not seem to be indicated in these patients, particularly because it requires two episodes of general anesthesia. However, because of the small number of patients in our series and the long-term survivors reported by others [7] [8] [9] [13], more patients who have undergone resection need to be evaluated before this approach is abandoned. These patients require a minimum 3-month interval between lung resection and adrenalectomy, as well as confirmation of the absence of any other metastatic sites. Patients with histologically proven N2 involvement should not undergo resection. Radiation therapy or chemotherapy should be considered instead.

Metachronous Homolateral or Contralateral Metastases
Despite the short interval between adrenal resection and cancer recurrence for the 2 patients in our series who died, most of the long-term survivors reported in the literature have undergone adrenal resection for metachronous metastases [10] [12]. Most of these long-term survivors had a disease-free interval of several months between lung resection and the diagnosis of adrenal metastasis. Some authors suggest that patients whose disease progresses slowly after lung resection are the only clearly defined subgroup that is amenable to aggressive composite resection [10] [12]. They advocate a minimum 10-month interval between the diagnosis and the resection of adrenal gland metastasis to confirm the absence of any other metastatic sites. Patients who have a shorter interval between lung resection and the diagnosis of adrenal metastasis should be amenable to radiation therapy or chemotherapy.

Conclusion
Few patients have operable NSCLC associated with a truly solitary adrenal metastasis. Long-term survival can be obtained after aggressive surgical resection of both lesions, but most of these patients experience rapid dissemination of their disease. If a unilateral adrenal mass is found in a patient with operable NSCLC, a percutaneous needle aspiration biopsy must be performed, along with evaluation of other potential metastatic sites. If the adrenal metastasis is homolateral to the primary lesion, a synchronous complete removal can be performed without any added morbidity or mortality. In a patient with a synchronous contralateral metastasis, restaging is required 3 months after lung resection. In a patient with a metachronous metastasis, thorough restaging with careful multidisciplinary consultation is required before resection is undertaken.

	References

Top Abstract Introduction Patients and Methods Results Comment References

 

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