Editorial The Role of Surgery in Adrenal Cancer
Jeffrey A. Norton, MD
Adrenocortical carcinoma is a rare type of cancer that comprises between .05% and .2% of all malignant tu- mors and affects as few as two people per million in the population. Therefore, it is surprising that in this issue of the Annals of Surgical Oncology, Schulick and Brennan from Memorial Sloan-Kettering Cancer Center describe a very large single institution surgical experience with 113 patients.1 Previous studies2 reporting results in sim- ilar numbers of patients are from large data banks that include entire countries. The results of the current study clearly demonstrate the value of complete surgical resec- tion after both initial presentation and recurrence, as the only treatment likely to prolong survival.1 However, in this editorial, I would like to highlight some important issues with these rare tumors that either were not ad- dressed or warrant additional emphasis.
First, the surgeon must realize that the pathological diagnosis of adrenocortical carcinoma may be problem- atic. There are no microscopic features that unequivo- cally indicate that an adrenal cortical tumor is malignant. In fact, it is interesting to realize that the two best criteria for malignancy are metastases and glandular weight.3 If the resected adrenal gland weighs more than 100 g, it is cancerous. The 100 g weight translates into 6 cm size. If the gland weighs between 50-100 g, it may not be malignant. In the MacFarlane criteria used in this paper,4 stage I disease, a tumor less than 5 cm and no metastases, is inconsistent with the modern diagnosis of adrenocor- tical carcinoma. The authors describe five patients with stage I disease and indicate that the smallest adrenal cancer was 4 cm in size and weighed only 4 g. It is not
clear by which criteria these tumors were diagnosed as malignant. Inclusion of benign tumors may falsely in- crease the long-term survival rate.
The second issue is the proper conduct of surgery. Because this is a surgical journal and most readers are surgeons, we are all interested in the technique used to remove adrenal tumors. Increasingly, adrenal surgery is being performed by minimally invasive methods. This is supported by the notion that laparoscopic adrenalectomy causes less pain and results in shorter hospital stays and convalescence.5 However, most experts argue that ma- lignant adrenal tumors should be removed by traditional open methods to ensure complete resection. Recent re- ports indicate that bigger and bigger adrenal tumors can be removed by laparoscopic methods. What size tumor is too large for laparoscopic methods? It is clear from the current study1 that incomplete resection portends a worse prognosis. The authors provide few details about the extent of initial operation. For example, should the kid- ney be removed? How many patients had concomitant nephrectomy? Because of the fact that surgery is the only potentially curative treatment, more studies are needed to define the best method for surgical resection of these rare adrenal tumors.
A third issue is the recovery of adrenal cortical func- tion after removal of adrenal tumors in patients with Cushing’s syndrome. Most adrenal cortical tumors are hormonally functional, 55% in the current series.1 How long must glucocorticoids be administered after removal of a cortisol-secreting adrenal tumor? This is a complex question because normal adrenal cortical function re- quires co-ordination among three glands: the hypothala- mus, the pituitary, and the adrenal. One study indicates that it takes approximately 2 years for a complete recov- ery of the HPA axis.6 This is further complicated in some patients with cancer because elevated serum levels of cortisol may also suggest tumor recurrence. The surgeon
must be able to distinguish between the presence of postoperative Addison’s disease and hypercortisolism in these patients.
Finally, the current article1 clearly documents the ad- vantage of complete resection of recurrent and metastatic adrenal carcinoma on survival because these patients had a 5-year survival of 50%. Previous studies have sug- gested a similar benefit in select patients, but not as dramatic. We reported a 5-year survival of 30% in sim- ilar patients.7 However, late recurrences may occur, and 10-year survival drops to 10%. The fact is that with time, most patients will recur and subsequently do poorly. This suggests that other agents are needed. Certainly, mito- tane is not effective, although previously considered to be the antitumor agent of choice.2 Standard chemother- apy drugs have also been ineffective. Although complete resection of all tumor, whether primary or recurrent and metastatic, will benefit these patients, cure rates will remain low until new effective drugs are available.
REFERENCES
1. Schulick RD and Brennan MF. Long-term survival after complete resection and repeat resection in patients with adrenocortical car- cinoma. Ann Surg Oncology 1999;6:719-726.
2. Luton JP, Cerdas S, Billaud L, et al. Clinical features of adreno- cortical carcinoma, prognostic factors and the effect of mitotane therapy. N Engl J Med 1990;322:1195-1201.
3. Page DL, DeLellis RA, Hough AJ. Tumors of the adrenal. In: Hartmann WH, Cowan WR eds. Atlas of Tumor Pathology. Wash- ington: Armed Forces Institute of Pathology, 1986:1-106.
4. MacFarlane DA. Cancer of the adrenal cortex. The natural history, prognosis and treatment in a study of fifty-five cases. Ann R Coll Surg Engl 1958;23:155-86.
5. Wells SA, Merke DP, Cutler GB Jr, Norton JA, Lacroix A. Therapeutic controversy: The role of laparoscopic surgery in ad- renal disease. J Clin Endo Metabol 1998;83:3041-49.
6. Doherty GM, Nieman LK, Cutler GB, Chrousos GP, Norton JA. Time to recovery of the hypothalamic-pituitary-adrenal axis fol- lowing curative surgery of adrenal tumors in patients with Cush- ing’s syndrome. Surg 1990;108:1085-90.
7. Jensen JC, Pass HI, Sindelar WF, Norton JA. Recurrent or meta- static disease in select patients with adrenocortical carcinoma. Arch Surg 1991;126:457-61.