Resection of Adrenal Metastases From Non-SmallCell Lung Cancer: A Multicenter StudyHenri Porte, MD, PhD, Joelle Siat, MD, Benoit Guibert, MD,Francoise Lepimpec-Barthes, MD, Rene Jancovici, MD, Alain Bernard, MD,Annick Foucart, MD, and Alain Wurtz, MDClinique Chirurgicale, Hopital A. Calmette Centre Hospitalier et Universitaire de Lille, Lille, France

Background. In recent case reports and limited series,adrenalectomy was recommended for an isolated adrenalmetastasis from non-small cell lung cancer (NSCLC).

Methods. We retrospectively studied patients with asolitary adrenal metastasis from NSCLC who had under-gone potentially curative resection in eight centers.

Results. Forty-three patients were included. Their ad-renal gland metastasis was discovered synchronouslywith NSCLC in 32 patients, and metachronously in 11. Itwas homolateral to the NSCLC in 31 patients and con-tralateral in 12 (p < 0.01). Median survival was 11months, and 3 patients survived more than 5 years. Therewas no difference between the synchronous and meta-

chronous groups regarding recurrence rate or survival.Survival was not affected by the homolateral location ofthe metastasis, the histology of the NSCLC, TNM stage,any adjuvant and neoadjuvant treatment, or, in the meta-chronous group, a disease-free interval exceeding 6months.

Conclusions. We confirm the possibility of long-termsurvival after resection of isolated adrenal metastasisfrom NSCLC, but no clinical or pathologic criteria weredetected to identify patients amenable to potential cure.

(Ann Thorac Surg 2001;71:981–5)© 2001 by The Society of Thoracic Surgeons

Nonsurgical treatment of solitary adrenal metastases(AM) from non-small cell lung cancer (NSCLC) is

associated with poor survival. The impact of adrenalresection cannot be clearly evaluated from the literature,which mainly consists of case reports concerning long-term survivors after lung and adrenal resection [1–4].Furthermore, the few published series include less than20 patients with resected AM from NSCLC [5–11], be-cause of the relative rarity of truly isolated AM. Accord-ingly, in two prospective studies [5, 11] these AM wereevaluated, respectively, at 1.62% and 3.5% of resectableNSCLC. In the present study, we report the results of aretrospective multicenter study of patients with AM fromNSCLC, both of which were surgically treated with apotentially curative aim during the past 10 years, andanalyze the clinical and pathologic factors that may haveaffected survival.

Patients and Methods

From 1987 to 1998, all patients who had been surgicallytreated for NSCLC associated with a solitary resectableAM in eight thoracic surgery centers were included in thestudy. Data were obtained from medical records, physi-cians’ interviews, or clinical examinations. Patients inwhom any other metastatic deposit had been detectedbefore operation were excluded, as were patients who

had a macroscopically incomplete resection of the pri-mary tumor or AM. Patients with involvement of medi-astinal lymph nodes were included in the study. Thesepatients had not systematically received preoperativechemotherapy but they all received postoperative medi-astinal radiotherapy. After adrenalectomy, no particularcriteria were defined to give any adjuvant treatmentincluding radiotherapy focalized on the adrenal bed, orplatinum-based chemotherapy protocols.

Unilateral AM, identified at the time of initial NSCLCdiagnosis, were classified as synchronous. Metastasesshown to be absent at the time of lung resection wereclassified as metachronous. Before operation, all patientsunderwent thoracic, cerebral, and abdominal computedtomographic scan. A positron emission tomographic scanwas never performed. Complete resection was defined asthe absence of any microscopical tumor after lung andadrenal resection. In patients with synchronous metasta-sis, the disease-free interval was defined as zero. Inpatients with metachronous metastasis, it was defined asthe time from the resection of the primary NSCLC toadrenalectomy. In both groups, follow-up was calculatedfrom the date of adrenalectomy. Patient survival wasexpressed by actuarial analysis according to the Kaplan-Meier method, using time zero as the date of adrenalec-tomy and death as the end point. In both groups, disease-free survival was defined as the interval from the date ofadrenalectomy to the date of the last follow-up or diag-nosis of disease recurrence. Data are expressed as fre-quency distributions and simple percentages. Univariateanalysis of the selected variables was done by x2 analysis.

Accepted for publication Oct 18, 2000.

Address reprint requests to Dr Porte, Clinique Chirurgicale, HopitalCalmette, Bd du Professeur Leclercq, 59037 Lille Cedex, France; e-mail:awurtz@ chru-lille.fr.

© 2001 by The Society of Thoracic Surgeons 0003-4975/01/$20.00Published by Elsevier Science Inc PII S0003-4975(00)02509-1

Multivariate analysis was done with the same variablesby Cox regression model. Statistically significant differenceswere defined as p equal to 0.05 or less. The primary NSCLCvariables tested for potential significant association withAM were histology, TN status, and location on the operatedlung (superior lobe, inferior lobe). Variables tested forpotential influence on survival were primary NSCLC his-tology, TNM status, synchronous or metachronous group,disease-free interval in the metachronous group, surgicalapproach to perform adrenalectomy, and any adjuvant orneoadjuvant treatment.

Results

Primary NSCLC Characteristics and TreatmentForty-three patients were included in the study (11 hadbeen included in a previous report [11]); 22 had synchro-nous AM and 21, metachronous AM. They comprised 38men and 5 women whose mean age was 52 years (range,34 to 75 years). Table 1 shows the surgical treatment andpathologic characteristics of primary NSCLC in the 43patients. Except for adenocarcinomatous nature (p ,0.01), none of the pathologic parameters of primaryNSCLC was found to be significantly associated with theoccurrence of an adrenal metastasis. Resection of theprimary NSCLC was complete in 41 patients (95%); therewas microscopical bronchial stump involvement in 1patient, and microscopical chest wall margin involve-ment in 1 patient. Before lung resection, a mean of twocycles (range, 1 to 3 cycles) of platinum-based chemo-therapy (mean dose, 80 mg/m2) was given to 3 patients(7%) who had histologically proved N2 involvement. All

the patients (n 5 16) with N2 involvement ascertainedafter systematic mediastinal lymphadenectomy, receivedpostoperative radiotherapy (mean, 60 Grays) focalized onthe mediastinum.

AM Characteristics and TreatmentThe AM was diagnosed by computed tomographic scanin all 43 patients. It was confirmed by computed tomo-graphic-guided biopsy in 18 patients, and by operation inthe remaining 25 patients. The AM was homolateral tothe primary NSCLC in 31 patients (72%, p , 0.01), 16 ofwhom were synchronous and 15, metachronous. It wascontralateral in 12 patients (6 synchronous and 6 meta-chronous). The mean size of the AM was 5.6 cm (range, 2to 12.5 cm). Adrenalectomy was performed through lum-botomy in 18 patients, laparotomy in 14, and phrenotomyduring thoracotomy in 11. Twelve of the 22 patients withsynchronous AM were resected at the time of lungresection, 6 after lung resection (mean, 5 weeks) and 4before lung resection (mean, 7 weeks). Adrenalectomywas complete in all patients. In 2 patients, associatednephrectomy was necessary because of kidney involve-ment by the AM. Regional lymph node dissection wasnot routinely performed. Mortality during operation andthe 30 days thereafter was nil. During those 30 days,postoperative morbidity affected 8 patients and was al-ways the result of lung operation. Six patients receivedpostoperative radiotherapy (mean, 60 Grays) focalized onthe adrenal bed. Twelve of them received platinum-based chemotherapy after adrenalectomy (mean dose,100 mg/m2; mean, 4 cycles; range, 1 to 6 cycles).

Follow-up and RecurrenceThe mean follow-up period was 23.79 months (range, 2 to94 months); it was 20.36 months for synchronous AM, and25.95 months for metachronous AM. In the metachro-nous group, the postoperative disease-free interval was15.7 months (range, 3 to 40 months). Thirty-four of the 43patients (80%) developed a recurrence of their lungcancer during follow-up, including 15 with synchronousAM (68%) and 19 with metachronous AM (90%, p . 0.05).The cases of recurrence comprised 24 of the 31 patientswith homolateral AM (77%) and 10 of the 12 with con-tralateral AM (83%, p . 0.05). In 19 of the 34 patients whohad a lung cancer recurrence (56%), it developed duringthe 6 months after adrenalectomy, and in 13 (38%),during the first 3 months. The sites of recurrence in the 34patients are given in Table 2; the disease-free survivalperiod and the recurrence rate for the 43 patients aregiven in Table 3. In the 7 patients whose recurrence waslocated in the adrenal gland bed, the AM was resectedthrough lumbotomy in 4 patients, laparotomy in 2, andphrenotomy in 1 patient.

SurvivalTwenty-eight patients died of their lung cancer (65%),and 4 (9%) of other causes. Five (11.6%) were alive withrecurrent lung cancer, and 6 (14%) were alive and free ofrecurrent disease, respectively 3, 16, 17, 76, 92, and 94

Table 1. Surgical Treatment and Pathological Characteristicsof Primary Non-Small Cell Lung Cancer (NSCLC) in 43Patents Who Underwent Adrenalectomy for Adrenal GlandMetastases (AM)

Primary NSCLCCharacteristics

SynchronousAM (n 5 22)

MetachronousAM (n 5 21)

Total(n 5 43)

Adenocarcinoma 18 16 34Squamous cell 3 3 6Large cell 1 0 1Adenosquamous 0 2 2T1N0 0 1 1T2N0 5 5 10T2N1 5 0 5T2N2 5 8 13T3N0 4 4 8T3N1 2 0 2T3N2 0 2 2T4N2 1 1 2Lobectomy and

bilobectomy9 13 22

Enlarged lobectomyor bilobectomy

2 3 5

Pneumonectomy 9 3 12Enlarged

pneumonectomy2 2 4

982 PORTE ET AL Ann Thorac SurgADRENALECTOMY FOR LUNG CANCER METASTASIS 2001;71:981–5

months after adrenalectomy. The 2-, 3-, and 4-year actu-arial survival were 29%, 14%, and 11%, respectively.Survivals rate of the 43 patients are given in Table 3. TheKaplan-Meier survival curve for the 43 patients is givenin Figure 1. There was no significant difference betweensurvival in the synchronous, metachronous, homolateral,and contralateral groups. In both groups neither survivalnor the disease-free interval (in the metachronous group)was affected by primary NSCLC histology, TNM stage,surgical approach to adrenalectomy, or adjuvant or neo-adjuvant treatment.

Comment

The value of operation in the cure of patients withmetastatic disease has been overlooked during the pasttwo decades, especially for cancers that do not respondwell to systemic chemotherapy. As a general principle,patients with a single site of metastatic disease that canbe resected without major morbidity should undergoresection of that metastasis if the primary neoplastic sitecan be (or was) also surgically treated in a curative intent[12]. In this setting, the surgical management of NSCLCthat has metastasized to other sites has for the most partbeen confined to patients with metastasis to other pul-monary segments or to the brain. As for metastaticdisease to the liver or bone, the surgical treatment forAM from NSCLS has not been widely adopted, first,because of concern about the probability of associated

advanced diffuse metastases, and second, because theincidence of truly solitary AM in patients with operableNSCLC is low. Consequently, it was generally thoughtthat adrenal metastases (even solitary) precluded anyfurther surgical intervention. However, in case reportsand a few small series, it was stressed that selectedpatients with an isolated AM can undergo resection withreasonable long-term survival [1–11]. These observationswere reinforced by studies of patients undergoing resec-tion at other distant metastatic sites, such as patients witha solitary brain metastasis who benefited from the resec-tion of both primary NSCLC and the metastatic tumor[13–15]. Thus, Patchell and coworkers [13], who com-pared surgical resection plus radiotherapy to radiother-apy alone for single brain metastases from many primarysites, mostly the lung, found that the surgical resectiongroup lived longer and had fewer recurrences of NSCLCin the brain than the group given radiotherapy alone.With regard to solitary AM from NSCLC, Luketich andcolleagues [9], who reported a recent series of 14 patients,suggested that in certain cases, chemotherapy followedby surgical resection may be better than chemotherapyalone. The present results confirm that the adenocarci-nomatous type of NSCLC is more frequently associatedwith AM, and that a solitary AM is more frequentlylocated on the same side as the primary NSCLC [11, 16].We also confirm the possibility of long-term survival,although this is certainly rarer than is suggested in someindividual case reports. With respect to metachronousmetastases, we could not confirm the results of Higashi-yama [6] and Kim [10] and their associates, who foundthat a disease-free interval of less than 6 months waslinked to poorer survival, due to the intrinsic biologicalaggressiveness of the tumor and its metastases. Further-more, we did not observe any difference between therecurrence rate or survival of the synchronous and meta-chronous groups. Overall, the present series does notprovide many helpful indications, either with regard tothe identification of patients who would benefit fromoperation, or with regard to how much the surgicalprocedure influenced survival in these patients. Thelong-term survivors probably constitute a selected groupwhose tumors were biologically indolent.

Nevertheless, our study, with 3 of 43 long-term survi-vors and a median survival of 11 months, confirms thedata reported by Kim and colleagues [10], who obtaineda disease-free survival of 11 months in a series of 37patients, including 17 with NSCLC. This strengthens the

Table 2. Site and Number of Lung Cancer Recurrence in 34of 43 Patients Who Underwent Adrenalectomy for AdrenalGland Metastases

Site of Recurrence Synchronous MetachronousAll

Patients

Brain 7 2 9Bone 2 4 6Liver 2 6 8Contralateral adrenal

gland2 1 3

Abdomen 1 4 5Soft tissue 1 0 1Peripheral lymph

node0 1 1

Lung 0 1 1Adrenal gland bed 3 4 7

Some patients had several sites of recurrence.

Table 3. Disease-Free Survival, Recurrence Rate, Mean and Median Survival Rate for the 43 Patients Affected by PrimaryNon-Small Cell Lung Cancer Who Underwent Adrenalectomy for Adrenal Gland Metastases (AM)

Synchronous AM(n 5 22)

(mo)

Metachronous AM(n 5 21)

(mo)

Total(n 5 43)

(mo) p Value

Mean disease-free survival 17.5 5.7 13 . 0.05Recurrence rate 15 (68%) 19 (90%) 34 (80%) . 0.05Mean survival rate 14.7 (SD 6 2.5) 15.3 (SD 6 2.4) 16.2 (SD 6 2.1) NS

NS 5 not significant; SD 5 standard deviation.

983Ann Thorac Surg PORTE ET AL2001;71:981–5 ADRENALECTOMY FOR LUNG CANCER METASTASIS

conclusion that surgical resection seems the best optionfor a potential cure, or at least the best palliative therapycompared to nonsurgical treatments. Accordingly, fewreports have been published on the role of radiotherapyon adrenal metastases [16 –18]. Soffen and colleagues[17] reported the results of palliative radiotherapy in 9patients with lung carcinoma and an isolated AM, whosemedian survival was 6 months. Only Miyaji and co-workers [19] reported a case of long-term survival ex-ceeding 34 months after radiotherapy for a metachronousAM, in a patient who underwent resection of theprimary NSCLC. Similarly dismal results were recentlyreported for chemotherapy in two limited series [6, 9],whose median survival periods were less than 6 and 8.5months, respectively. The longest survival period inthese series was 22 months, and there were no long-termsurvivors.

The main problem of concern is to establish preoper-atively that the AM is truly isolated. In the present series,56% of the patients developed their recurrent lung cancerwithin the 6 months after adrenalectomy, and 38% withinthe first 3 months, which reflected the presence of mul-tiple nondetectable lesions at the time of operation,despite complete staging. These early recurrences lead usto conclude first, that the staging modalities were notaccurate enough, and second, that cases of advancedNSCLC (ie, stage III), which have a high metastaticpotential, should not be surgically treated when associ-ated with isolated AM, despite the nonsignificant inci-dence of TNM stage on survival in our study. Therefore,we now propose that in patients with stage I or II NSCLCand a supposedly solitary AM, preoperative stagingshould at least include a positron emission tomographicscan, cerebral magnetic resonance imaging, and medias-tinoscopy. For patients with synchronous AM, neoadju-vant chemotherapy can be given, as advocated by Luke-tich and associates [15]. With regard to operation for AM,simple adrenalectomy seems enough. Dissection of re-gional lymph nodes of the affected adrenal gland shouldnot always be performed because of this procedure’spotential morbidity, except when AM is associated withan extraglandular extension which has to be treated by

extensive resection of the invaded organs (lymph nodeskidney) through an elective approach. On the contrary,the large number of patients with a recurrence in theadrenal bed regardless of the surgical approach usedargues in favor of systematic adjuvant radiotherapy de-livered to the adrenal bed.

In conclusion, long-term survival may be achievedin some patients after adrenalectomy for AM fromNSCLC in a small percentage of patients, but thesecases cannot be identified by any of the preoperativeresults studied here. Nevertheless, we propose the fol-lowing prerequisites as a guide to patient selection: (1)complete potential control of the primary NSCLC; (2)exclusion of patients with stage III NSCLC; (3) the mostup-to-date explorations before operation, to confirm thesolitary nature of the AM and minimize the chances ofearly recurrence; (4) similar management of synchronousand metachronous AM with regard to staging and oper-ative strategy, and (5) the transdiaphragmatic approachas the method of choice for synchronous AM resectionwhen no other structure is invaded by the neoplasticprocess.

References

1. Twomey P, Montgomery C, Clark O. Successful treatment ofadrenal metastases from large-cell carcinoma of the lung.JAMA 1982;248:581–3.

2. Raviv G, Klein E, Yellin A, Schneebaum S, Ben-Ari G.Surgical treatment of solitary adrenal metastases from lungcarcinoma. J Surg Oncol 1990;45:123–31.

3. Reyes L, Parvez S, Nemoto T, Regal AM, Takita H. Adrenal-ectomy for adrenal metastasis from lung carcinoma. J SurgOncol 1990;44:32–4.

4. Kirsch AJ, Oz MC, Stoopler M, Ginsburg M, Steinglass K.Operative management of adrenal metastases from lungcarcinoma. Urology 1993;42:716–9.

5. Ettinghausen S, Burt ME. Prospective evaluation of unilat-eral adrenal masses in patients with operable non small celllung cancer. J Clin Oncol 1991;9:1462–6.

6. Higashiyama M, Doi O, Kodama K, Yokouchi H, Imaoka S,Koyama H. Surgical treatment of adrenal metastasis fol-lowing pulmonary resection for lung cancer: comparisonof adrenalectomy with palliative therapy. Int Surg 1994;79:124–35.

Fig 1. Survival of the 43 patients who un-derwent surgical treatment of primary non-small cell lung cancer and solitary adrenalgland metastasis calculated with theKaplan-Meier method. (* 5 Effective sam-ple size for the compilate of the actuariallife curve.)

984 PORTE ET AL Ann Thorac SurgADRENALECTOMY FOR LUNG CANCER METASTASIS 2001;71:981–5

7. Ayabe H, Tsuji H, Hara S, Tagawa Y, Kawahara K, Tomita M.Surgical management of adrenal metastasis from broncho-genic carcinoma. J Surg Oncol 1995;58:149–54.

8. Lo CY, Van Heerden JA, Soreide JA, Grant CS, ThompsonGB, Lloyd RV, Harmsen WS. Adrenalectomy for metastaticdisease to the adrenal glands. Br J Surg 1996;83:528–3.

9. Luketich JD, Burt ME. Does resection of adrenal metastasesfrom NSCLC improve survival? Ann Thorac Surg 1996;62:1614–6.

10. Kim SH, Brennan MF, Russo P, Burt ME, Coit DG. The roleof surgery in the treatment of clinically isolated adrenalmetastasis. Cancer 1998;82:389–5.

11. Porte H, Roumilhac D, Graziana JP, et al. Adrenalectomy fora solitary adrenal metastasis from lung cancer. Ann ThoracSurg 1998;65:331–5.

12. Rosenberg SA. Principles of cancer management: surgicaloncology. In: De Vita VT, Hellman S, Rosenberg SA. Cancer:principles and practice of oncology. Philadelphia: Lippincott–Raven, 1997:304.

13. Patchell R, Tibbs P, Walsh J, et al. A randomized trial ofsurgery in the treatment of single metastases to the brain.N Engl J Med 1990;322:494–500.

14. Burt M, Wronski M, Arbit E, Galicich JH. Resection ofbrain metastasis from non-small-cell lung carcinoma. Re-sults of therapy. Memorial Sloan-Kettering Cancer CenterThoracic Surgical Staff. J Thorac Cardiovasc Surg 1992;103:399–411.

15. Luketich JD, Martini N, Ginsberg RJ, Rigberg D, Burt ME.Successful treatment of solitary extracranial metastases fromnon-small cell lung cancer. Ann Thorac Surg 1995;60:1609–11.

16. Karolyi P. Do adrenal metastases from lung cancer developby the lymphogenous or hematogenous route? J Surg Oncol1990;43:154–6.

17. Soffen EM, Solin LJ, Rubenstein JH, Hanks GE. Palliativeradiotherapy for symptomatic adrenal metastases. Cancer1990;65:1318–20.

18. Short S, Chaturvedi A, Leslie MD. Palliation of symptomaticadrenal gland metastases by radiotherapy. Clin Oncol 1996;8:387–2.

19. Miyaji N, Miki T, Itoh Y, et al. Radiotherapy for adrenalgland metastasis from lung cancer: report of three cases.Radiation Med 1999;17:71–4.

New Requirements for Recertification/Maintenance ofCertification in 2001Diplomates of the American Board of Thoracic Surgerywho plan to participate in the recertification/maintenance of certification process in 2001 should payparticular attention to this notice because the require-ments have changed.

In addition to an active medical license and institu-tional clinical privileges in thoracic surgery, effective in2001, a valid certificate is an absolute requirement forentrance into the recertification/maintenance of certifica-tion process. If your certificate expired, the only pathwayfor renewal of a certificate will be to take and pass thePart I (written) and the Part II (oral) certifying examina-tions.

In 2001, the American Board of Thoracic Surgery willno longer publish the names of individuals who have notrecertified. In the past, a designation of “NR” (not recer-tified) was used in the American Board of MedicalSpecialties directories if a Diplomate had not recertified.The Diplomate’s name will be published upon successfulcompletion of the recertification/maintenance of certifi-cation process.

The CME requirements have also changed. The newCME requirements are 70 Category I credits in eithercardiothoracic surgery or general surgery earned duringthe 2 years prior to application. SESATS and SESAPS arethe only self-instructional materials allowed for credit.Category II credits are not allowed. The Physicians Rec-ognition Award for recertifying in general surgery is notallowed in fulfillment of the CME requirements. Inter-ested individuals should refer to the 2001 Booklet ofInformation for a complete description of acceptable CMEcredits.

Diplomates should maintain a documented list of theirmajor cases performed during the year prior to applica-tion for recertification. This practice review should con-sist of 1 year’s consecutive major operative experiences.If more than 100 cases occur in 1 year, only 100 should belisted.

Candidates for recertification/maintenance of certifica-tion will be required to complete both the general tho-racic and the cardiac portions of the SESATS self-assessment examination. It is not necessary forcandidates to purchase SESATS individually because itwill be sent to candidates after their application has beenapproved.

Diplomates may recertify the year their certificateexpires, or if they wish to do so, they may recertify up totwo years before it expires. However, the new certificatewill be dated 10 years from the date of expiration of theiroriginal certificate or most recent recertification certifi-cate. In other words, recertifying early does not alter the10-year validation.

Recertification/maintenance of certification is alsoopen to Diplomates with an unlimited certificate and willin no way affect the validity of their original certificate.

The deadline for submission of applications for therecertification/maintenance of certification process isMay 1 each year. A brochure outlining the rules andrequirements for recertification/maintenance of certifica-tion in thoracic surgery is available upon request fromthe American Board of Thoracic Surgery, One RotaryCenter, Suite 803, Evanston, IL 60201; telephone number:(847) 475-1520; fax: (847) 475-6240; e-mail: abts_evanston@msn.com.

985Ann Thorac Surg PORTE ET AL2001;71:981–5 ADRENALECTOMY FOR LUNG CANCER METASTASIS

© 2001 by The Society of Thoracic Surgeons Ann Thorac Surg 2001;71:985 • 0003-4975/01/$20.00Published by Elsevier Science Inc