BIOL THE
HOUDTIKHI ANAQUE TA XEIROUPTIKH
WORLD Journal of SURGERY 2001 by the Société Internationale de Chirurgie
Adrenocortical Carcinomas: Surgical Trends and Results of a 253-Patient Series from the French Association of Endocrine Surgeons Study Group
Philippe Icard, M.D.,3 Pierre Goudet, M.D.,1 Cyril Charpenay, M.D.,1 Bernard Andreassian, M.D.,2 Bruno Carnaille, M.D.,6 Yves Chapuis, M.D.,4 Patrick Cougard, M.D.,1 Jean-François Henry, M.D., Charles Proye, M.D.6
1Service de Chirurgie Viscérale et Urgences, Hôpital Général, 3 Rue du Faubourg-Raines, BP 1519, 21033 Dijon-Cédex, France
2Service de Chirurgie Thoracique, Hôpital Bichat-Beaujon, 46 Rue Henri-Huchard, 75018 Paris, France
3Service de Chirurgie Thoracique, Hôpital de la Côte de Nacre, Avenue de la Côte-de-Nacre, 14033 Caen-Cédex, France
+Service de Chirurgie Viscérale et Endocrinienne, Hôpital Cochin, 27 Rue du Faubourg-Saint-Jacques, 75674 Paris-Cédex 14, France
$Service de Chirurgie Endocrinienne, Hôpital de la Timone, Boulevard Jean-Moulin, 13005 Marseille, France
6Clinique Chirugicale Est, Hôpital Claude-Hurriez, 6 Rue du Professeur-Laguesse, 59037 Lille-Cédex, France
Abstract. Because of the rarity of adrenocortical carcinoma, survival rates and the prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine Surgery was to evaluate these factors over an 18-year period. A trend study was associated to assess changes in the clinical and biochemical presentations as well as the surgical evolution. A total of 253 patients (158 women, 95 men) with a mean age of 47 years were included. Cushing syndrome was the main clinical presentation (30%), and hormonal studies revealed secreting tumors in 66% of the cases. Altogether, 72% (n = 182) of patients underwent resection for cure, and 41.5% (n = 105) of them had an extensive resection because of metastatic cancer. A lymphadenectomy was performed in 32.5% (n = 89) of the cases. The operative mortality was 5.5% (n = 14). Patients were given mitotane as adjuvant therapy in 53.8% of the cases (n = 135). The results of staging were stage I in 16 patients (6.3%), stage II (local disease) in 126 patients (49.8%), stage III (locore- gional disease) in 57 patients (22.5%), and stage IV (metastases) in 54 patients (21.3%). Neither tumor staging nor the rate of curative surgery changed during the study period. More subcostal incisions were per- formed, and the use of mitotane increased significantly. The 5-year actu- arial survival rates were 38% overall, 50% in the curative group, 66% for stage I, 58% for stage II, 24% for stage III, and 0% for stage IV. Multi- variate analysis showed that mitotane benefited only the group of patients not operated on for cure. A better prognosis was found in patients operated on after 1988 (p = 0.04), in those with precursor-secreting tumors (p = 0.005), and in those at local stages of the disease (p = 0.0003). Thus mitotane benefited only patients not operated on for cure. Curative resection, precursor secretion, recent diagnosis, and local stage were favorably associated with survival.
Adrenocortical carcinoma is a rare malignant tumor with an annual incidence estimated at 0.5 to 2.0 cases per million per year. This tumor accounts for 0.2% of cancer-related deaths per year in the United States [1, 2]. Five-year survival remains poor, varying from 32% to 45%. Reported series are rare because the infre- quent occurrence of this cancer precludes extensive studies. In
1992 the French Association of Endocrine Surgeons (AFCE) reported the first results of a retrospective study on 156 patients operated on for adrenocortical carcinoma (AC) [3], and this French-speaking multidisciplinary network has continued to reg- ister ACs. The 253-patient up-to-date database has been used for the present study. The aims of this reappraisal were to assess trends in the diagnosis and treatment of AC and to determine the predicting factors for survival. Special attention was paid to the effects of mitotane on survival.
Patients and Methods
Patients
Among 253 AC patients registered between 1978 and 1997, there were 62.5% (n = 158) female and 37.5% (n = 95) male subjects. The mean age at diagnosis was 47.3 ± 16.4 years (range 5-81 years). All cases were retrieved with the help of the AFCE net- work, including physicians and endocrine surgeons. The histologic criteria of malignancy used by all pathologists were standard, widely accepted criteria (lobulation, architectural disorders, tu- mor cell necrosis, percentage of clear cells, hemorrhage, broad fibrous bands, calcifications, mitotic activity, nuclear polymor- phism, capsular lymph nodes, and vascular invasions) [4]. The sole indisputable criterion was the presence of metastases.
Trend Study
Clinical, biochemical, and surgical data and the postoperative outcome were studied overall and during three periods of time: before 1985 (n = 80), from 1986 to 1990 (n = 87), and after 1990 (n = 86).
50
Number of patients
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30
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0
3.0
10.
20
30.
Tumor size (cm)
Clinical and Biochemical Features
The clinical variables evaluated were gender (62.5% of female patients, n = 158/253), age at diagnosis (47.3 ± 13.0 years, n = 253), weight loss (26.9%, n = 68/253), fever (11.1%, n = 28/253), palpable mass (19,0%, n = 48/253), pregnancy (3.2%, n = 8/253), Cushing syndrome (30.4%, n = 77/253), virilization (24.9%, n = 63/253), feminization (1.6%, n = 4/253), and hypertension (7.9%, n = 20/253). The steroid serum hormones evaluated were glu- cocorticoids (52.1%, n = 114/219), mineralocorticoids (10.0%, n = 22/219), androgens (36.5%, n = 80/219), estrogens (4.6%, n = 10/219), and precursors (pregnenolone, compound S (11-deoxy- cortisol), 14.2%, n = 31/219).
Tumor Staging, Surgical Treatment, and Postoperative Outcome
Tumor size (12.0 ± 6.0 cm, n = 223) and tumor weight (689.4 ± 822 g, n = 202) were noted. Eighteen tumors were 5 cm or less (Fig. 1). Two had spread into the perirenal fat with independent deposits or into the kidney. None of these small tumors were associated with distant metastasis. For staging we used the Mac- Farlane classification, which we slightly modified [5]. A stage I tumor was < 5 cm in diameter (n = 16, 6.3%), whereas a stage II tumor was > 5 cm (n = 126, 49.8%). Neither has nodes, local invasion, or metastases. These two stages define local cancers. The stage III tumor was associated with nodes or local invasion with- out metastases (or both) and defined a locoregional cancer (n = 57, 22.5%). Thus in contrast with the original Mac-Farlane clas- sification, the locoregional invasion of cancer associated with invaded regional lymph nodes was not considered to be stage IV but was included in stage III because complete resection can theoretically be performed in such cases. The stage IV tumor had distant metastases (n = 54, 21.3%).
There were 22.9% (n = 58) unilateral subcostal incisions, 22.9% (n = 58) bilateral subcostal incisions, 19.8% (n = 50) thoracophrenolaparotomies, 22.1% (n = 56) midline incisions, 7.5% (n = 19) lateral incisions, 1.2% (n = 3) posterior ap- proaches, and 3.6% (n = 9) miscellaneous approaches. Surgery was curative in 71.9% (n = 182) of the cases; and a lymphade- nectomy was performed in 32.5% (n = 89). A biopsy alone was performed in 4.4% (n = 14). Other resections were associated in
41.5% (n = 105): kidney 29.2% (n = 74), spleen 10.3% (n = 26), vena cava thrombectomy 5.9% (n = 14), right hepatectomy 3.9% (n = 10), liver segmentectomy 3.6% (n = 9), and left pancreatec- tomy 3.6% (n = 9). Postoperative deaths were defined as occur- ring within the first month following the procedure (5.5%, n = 14).
Mitotane Therapy
Mitotane [o,p’-DDD or 1,1-(o,p’-dichlorodiphenyl)-2,2-dichloro- ethane] was administered in 53.8% (n = 135/251) of the cases without a randomized trial. Patients were given mitotane postop- eratively in 103 cases (76%) and pre- and postoperatively in 27 cases (20%). Five cases (4%) were treated preoperatively only because of severe functional syndrome (n = 3) or operative mortality (n = 2). Mitotane was administered orally in three divided doses at a daily dose of 12 g for 3 to 6 weeks preopera- tively and at a lower dose of 3 to 4 g daily postoperatively, with a maximum dose of 8 g, either until death or the occurrence of severe side effects.
Survival Study
Crude survival was studied overall and according to each clinical, surgical, histopathologic, and biochemical factor. The effect of the date of diagnosis was assessed comparing survival before (n = 121) and after (n = 131) 1988.
Statistical Analysis
Categorical data were expressed with their percentage. Continu- ous variables were expressed as the mean ± the standard devia- tion (SD). Percentages were compared using chi-square tests for heterogeneity. Means were compared using Student’s t-tests and ANOVA. The crude survival rates were calculated using Kaplan- Meier methods and were expressed with standard errors [6]. Survival curves were compared using the log-rank test. Factors influencing survival were studied multivariately using a stepwise Cox proportional hazards regression model following both as- cending and descending procedures. A p value of 0.20 or less was required to include a variable in the multivariate analysis. The effect of mitotane was forced in the model, as data in the literature suggested its favorable influence on survival. A 0.05 level was set as the level of significance. No more than one independent vari- able was examined for each of 10 outcomes [7]. The proportional hazards assumption was verified, and interacting terms were as- sessed [8]. BMDP Statistical Software (Los Angeles, CA, USA) was used to carry out the computations (2D, 4F, 3D, 6D, 1L, 2L). Thirty-six patients were excluded from the multivariate analysis because of missing data concerning hormone secretion (n = 33), mitotane treatment (n = 2), or survival (n = 1). Thirty precise tumor size measurements and 21 tumor weight measurements were missing because of incomplete removal of the tumor (biopsy alone or palliative surgery). Because those tumors were > 5 cm or associated with distant metastases, the Mac-Farlane classification was still applicable. This classification, which takes into account the tumor size, was then used to perform the prognosis study. In contrast, tumor size and tumor weight were not included in the multivariate analysis.
Results
Trends in Clinical and Biochemical Features
No significant change in clinical presentation was found during the three study periods. A trend toward more female patients was found after 1990 (60.0%, 55.2%, 72.1% for the three study peri- ods, respectively; p = 0.06). A decrease in precursor secretion was noted over time (21.5%, 15.1%, 7.4%; p = 0.05). No other bio- chemical change was noted.
Trends in Tumor Staging, Treatment, and Postoperative Outcome
Neither the tumor staging nor the rate of curative surgery changed during the entire study period. The rate of associated resections, lymphadenectomies, type of resection, and weight and size of the tumors remained unchanged from 1978 to 1997. In contrast, the surgical approach changed in that more subcostal incisions [15% (n = 12), 26.4% (n = 23), 26.7% (n = 23)] and fewer lateral approaches [16.3% (n = 13), 4.6% (n = 4), 2.3% (n = 2); p = 0.04] were performed. The anticipated significant drop in opera- tive mortality did not occur [7.5% (n = 6), 4.6% (n = 4), 4.7% (n = 4)]. In contrast, a dramatic increase in the use of mitotane was noted [45.0% 36/80), 54.0% (47/87), 61.9% (52/84); p = 0.03]. Mitotane was used in 58.2% of patients (39/67) less than 35 years of age and in 52.2% (96/184) of older patients (p = 0.40), more often in female patients [56.7% vs. 48.9% (89/157 vs. 46/94); p = 0.23], and more often in those with advanced disease (stages III + IV) [58.6% vs. 50.0% (65/111 vs. 70/140); p = 0.18]. Mitotane was used significantly more often among hormone-secreting patients [78.0% vs. 22.0% (96/142 vs. 27/75); p < 0.0001], and less often in cases of surgery for cure [50.0% vs. 63.4% (90/180 vs. 45/71); p = 0.05].
Survival Study
The overall 5-year survival was 38% ± 4%. The univariate analysis (Table 1) showed that local stages (Fig. 2), curative surgery, age less than 35 years, and no other resections were significantly associated with a better survival. Other factors were selected for the multivariate analysis (p < 0.2): lymphadenectomy, precursor secretion, virilization, weight loss, cortisol secretion, and time of diagnosis. The use of mitotane was included (p = 0.70), as some previous studies showed its favorable effect in patients with met- astatic AC. Figure 3 shows the favorable effect of Mitotane in the stage IV subgroup (p < 0.0001).
A significant interaction was found in the multivariate analysis between curative surgery and mitotane. The effect of mitotane was not comparable depending on the type of surgery performed (cura- tive versus palliative). The four modalities of treatment are presented in Table 2. Mitotane use seemed efficient in the palliative subgroup only where the relative risk reaches 1.13 instead of 4.55 without mitotane. Mitotane did not have any evident effect in the curative group as the relative risks (RR) are equivalent (RR = 1 with mito- tane, RR = 0.77 without mitotane: p = 0.28). Other selected prog- nostic factors were stage, period, and precursor secretion.
Thirty-three patients were excluded from the multivariate anal- ysis because of missing data concerning hormone secretion (n = 33). Those patients had a lower survival rate than had patients
| Factor | No. | % | P |
|---|---|---|---|
| Staging | |||
| { | 16 | 66 ± 14 | |
| II | 126 | 58 ± 5 | |
| III | 57 | 24 ± 6 | |
| IV | 53 | 0 | < 0.0001 |
| Curative surgery | |||
| Yes | 182 | 50 ± 4 | |
| No | 70 | 6±4 | < 0.0001 |
| Age (years) | |||
| ≤ 35 | 67 | 54 ± 7 | |
| > 35 | 185 | 34 ±4 | 0.02 |
| Associated resection | |||
| Yes | 105 | 26 ± 5 | |
| No | 147 | 47 ±5 | 0.02 |
| Lymphadenectomy | |||
| Yes | 89 | 42 ± 6 | |
| No | 163 | 36 ± 4 | 0.06 |
| Virilization | |||
| Yes | 63 | 50 ± 7 | |
| No | 189 | 35 ± 4 | 0.07 |
| Precursors | |||
| Yes | 31 | 61 ± 10 | |
| No | 188 | 36 ± 4 | 0.07 (1 vs. 2) |
| Not done | 33 | 31 ± 10 | 0.05 (1 vs. 2 vs. 3) |
| Weight loss | |||
| Yes | 68 | 43 ± 6 | |
| No | 184 | 36 ± 4 | 0.11 |
| Cortisol | |||
| Yes | 114 | 32 ± 5 | |
| No | 105 | 48 ± 6 | 0.13 (1 vs. 2) |
| Not done | 33 | 31 ± 10 | 0.06 (1 vs. 2 vs. 3) |
| Time of diagnosis | |||
| Before 1989 | 121 | 37 ± 4 | |
| After 1988 | 131 | 39 ± 6 | 0.20 |
| Mitotane | |||
| Yes | 135 | 34 ± 5 | |
| No | 115 | 43 ± 5 | 0.70 |
The following variables were not selected for the multivariate analy- sis: pregnancy (p = 0.99); palpable mass (p = 0.94); feminizing hormones (p = 0.70); aldosterone (p = 0.60); secreting tumors (p = 0.53); femini- zation (p = 0.35); fever (p = 0.35); gender (p = 0.32); high blood pressure (p = 0.32); androgens (p = 0.25); Cushing syndrome (p = 0.24); tumor size > 10 cm (p = 0.11, n = 202); tumor weight > 330 g (p = 0.07, n = 223).
with hormone blood sampling. They were more often associated with weight loss and a fever. These patients were in the older age group and were more often Cushing-free. No dosage was missing in case of virilization or feminization. Those 33 patients were of the same staging pattern (p = 0.86).
Discussion
The first study on AC from the AFCE dates back to 1992 [3]. Multicentric data from 156 patients were collected to evaluate the main prognostic factors for mortality in the hope of confirming the favorable role of surgery and mitotane therapy. Curative surgery, age less than 35 years, extent of disease, and type of hormonal secretion influenced survival. A favorable effect of mi- totane was found only in the metastatic group. The use of retro- spective studies to assess a potential treatment effect is debatable, as many confounding factors may affect the outcomes. Neverthe-
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less, results from some studies are encouraging and prospective randomized studies are not easy to set up for this rare tumor [3, 9-12]. Six years after the first report, this new study of 253 patients aimed at making our previous report more precise [3]. Because patients were operated on between 1960 and 1997, a trend study was also undertaken to assess changes in clinical presentation, therapeutic approaches, or survival.
According to already known data, AC is observed more fre- quently among women (62.5% in this study) [1, 2, 5, 10, 13-16]. Moreover, this percentage increased and reached 72.1% during the last study period. The clinical features did not change signif- icantly: Cushing syndrome (30.4%) remained the main clinical presentation [12, 14, 17]. Weight loss dropped from 31.0% to
18.6% at the end of the study. This trend may reflect an earlier diagnosis; but no change in staging, tumor size, or tumor weight confirms this relative optimistic interpretation. Around one-fifth of the patients were still diagnosed at a metastatic stage. Conse- quently, no improvement was found in the rate of curative surgery (71.9%). This percentage compares favorably with curative rates in the literature, which is less than 50% [13, 14, 17-19]. The operative mortality decreased but not significantly, reaching 4.7% at the end of the study period. The lymphadenectomy rate in- creased but did not reach a level of significance (26.3% to 32.2%). Only the type of incision changed dramatically: More subcostal incisions and fewer lateral approaches were performed. Subcostal incisions afford a better surgical approach in terms of cancer
| Factor | No. | Relative risk | Confidence interval | ¥ p* |
|---|---|---|---|---|
| Treatment (surgery = mitotane) | ||||
| Curative ± mitotane | 83 | 1.00 | ||
| Curative | 74 | 0.77 | 0.49-1.24 | |
| Palliative + mitotane | 40 | 1.13 | 0.51-2.51 | |
| Palliative | 20 | 4.55 | 1.71-12.12 | 0.005 |
| Stage | ||||
| I + II | 122 | 1.00 | ||
| III | 49 | 2.83 | 1.80-4.46 | |
| IV | 46 | 4.40 | 1.85-10.50 | < 0.0003 |
| Period | ||||
| During 1988 and after | 116 | 1.00 | ||
| Before 1988 | 101 | 1.52 | 1.02-2.27 | 0.04 |
| Precursors | ||||
| With | 31 | 1.00 | ||
| Without | 186 | 2.09 | 1.21-3.65 | 0.005 |
*For heterogeneity (likelihood ratio test).
treatment, lymphadenectomy, and liver resection. The length of the incision may be adapted to each case and be prolonged bilaterally.
The use of mitotane as perioperative adjuvant chemotherapy changed dramatically over time, reaching 62% at the end of the study. Advanced diseases, and particularly metastatic AC, were not the first element of choice, whereas retrospective data in the literature would have encouraged this attitude [10, 12, 21, 22]. First, mitotane was given to patients with secreting AC (78% vs. 22%) because it is known that the endocrine syndrome is con- trolled in 75% of cases [10]. Patients not operated on for cure represent the second significant indication (63% vs. 50% in pa- tients operated on for cure), indicating that mitotane was often used to treat the remaining disease after incomplete surgery. In terms of survival, our study seems to demonstrate that mitotane benefited a particular subgroup of patients. In patients not oper- ated on for cure the relative risk of death dropped from 4.5 to 1.1 (i.e., they reached the same risk level as patients operated on for cure and receiving mitotane as adjuvant chemotherapy). More- over, patients operated on for cure without mitotane behaved as well as those with mitotane. These results suggest that mitotane is not an efficient adjuvant therapy for survival among patients operated on for cure. This conclusion might explain why, among patients with stage I + II AC, the Anderson Cancer Center found a 43% two-year survival in the mitotane + surgery group and a 100% survival rate in the surgery-alone group [23].
The 5-year survival was 38% ± 4%. Survival has not exceeded 40% in published series of more than 40 operated patients. [10, 13, 14, 17-20, 24, 25].
A favorable survival trend was seen after 1988, which has been found in other cancer studies when the study period lasted more than 15 years [26]. Advances in perioperative care (anesthesiolo- gy, intensive care units) and the decrease in operative mortality (from 7.5% to 4.7%) may also account for this trend. Other prognostic factors, such as stage and hormone secretions, were confirmed after our previous study. As shown in Figure 2. stage I and stage II patients had the same survival rates, and they have been studied together in the multivariate analysis. The 5 cm cutoff point that separates them does not seem to make any difference in terms of survival. Nevertheless, it is of importance to underline
that, overall, only tumors < 5 cm were free of synchronous metastasis. One can even raise the issue of a correct AC diagnosis for some stage I patients. Of 16 stage I patients, 4 were still alive after a 2- to 12-year follow-up without recurrence or metachro- nous metastasis. The pathologist mentioned a “highly probable” AC diagnosis because they met several but not all of the criteria for malignancy [4]. Therefore, these four cases were kept in the study. This large collection of patients (253 instead of 156) have helped us to be more precise about the protective role of precur- sor secretion. However, some bias cannot be excluded in our retrospective multiinstitutional study, especially because in each case the various potential hormonal secretions may not have been properly evaluated. Survival among patients without hormonal workups is significantly worse (31 ± 10%, n = 33). This subset of patients could not be included in the multivariate analysis. They represent patients with peculiar features: more fever, more weight loss, occurrence in older patients, and less frequent occurrence of Cushing’s disease. Thus, these hormonal prognosis factors must be considered cautiously and be confirmed by others because they have not been found in other large studies [19].
Conclusions
The prognosis of CA remains poor, with a 38% five-year survival. Nevertheless, this survival improved significantly after 1988. No major change in clinical presentation was found. Except for the surgical approach, no significant change in surgical technique was noted. The use of mitotane increased and benefited patients who did not undergo surgery for cure.
Résumé
Introduction: La survie et le pronostic des patients opérés d’un corticosurrénalome restent mal connus car il s’agit d’une tumeur rare. L’Association Française de Chirurgie Endocrinienne s’est fix pour but d’évaluer ces facteurs pendant une période de 18 ans. Les changements de présentation clinique, biochimique et l’évolution de la prise en charge chirurgicale ont également fait l’objet d’une analyse. Méthode: Deux cent cinquante trois patients (158 femmes, 95 hommes), d’une moyenne d’âge de 47 ans, ont été étudiés. Un syndrome de Cushing a été la situation clinique la plus fréquente (30%), et les études hormonales ont montré une tumeur sécrétante dans 66% des cas. Soixante-douze pour cent (n = 182) des patients ont bénéficié d’une chirurgie à visée curative et 41,5% (n = 105) ont eu une résection étendue en raison des métastases. Un curage ganglionnaire a été réalisé dans 32,5% (n = 89) des cas. La mortalité post-opératoire a été de 5,5% (n = 14). Du mitotane a été utilisé dans 53,8% des cas (n = 135). La classification tumorale a montré : 16 stades I (6,3%); 126 stades II (maladie locale) (49,8%), 57 stades III (maladie loco- régionale) (22,5%); et 54 stades IV (métastases) (21,3%). Résultats: Le stade des tumeurs et le pourcentage de chirurgie à visée curative n’ont pas évolué. II a été réalisé plus d’incisions sous-costales et l’utilisation du mitotane n’a cessé de croître de façon significative. La survie actuarielle à 5 ans a été de 38% : 50% dans le groupe opéré à visée curative, 66% dans les stades I, 58% dans les stades II, 24% dans les stades III, et 0% dans les stades IV. L’analyse multivariée a montré que le mitotane a apporté un bénéfice de survie au groupe de patients opérés à visée palliative. Une amélioration du pronostic a été notée après 1988
(p = 0,04), chez les patients sécrétant des précurseurs (p = 0,005) et dans les stades locaux (p = 0,0003). Conclusion: Le mitotane n’a été profitable qu’aux patients opérés à visée palliative. Le caractère curatif de la chirurgie, le type de sécrétion hormonale, la période récente de diagnostic et le stade local ont été des facteurs favorables de survie.
Resumen
Introducción: Dada la poca frecuencia del cáncer adreno-cortical el pronóstico y la supervivencia de los pacientes intervenidos no es bien conocido. La Asociación Francesa de Cirugía Endocrina se ha marcado como objetivo valorar estos factores durante un periodo de tiempo de 18 años. Además, pretendemos analizar los cambios clínicos y bioquímicos, así como la evolución del tratamiento quirúrgico. Método: Se estudiaron 253 pacientes (158 hembras y 95 varones) cuya edad media fue de 47 años. El cuadro clínico más frecuente fue el del síndrome de Cushing (30%) y los análisis hormonales demostraron la existencia de un tumor secretor en el 66% de los casos. El 72% (n = 182) de los pacientes fueron intervenidos quirúrgicamente con fines curativos y en el 41.5% (n = 105) hubieron de efectuarse resecciones ampliadas por metástasis. Una linfadenectomia se realizó en el 32.5% (n = 89) de los casos. La mortalidad operatoria fue del 5.5% (n = 14). El 53.8% (n = 135) de los pacientes recibieron como terapia adyuvante Mitotane. La clasificación tumoral registra: 16 estadios I (6.3%); 126 estadios II (enfermedad local) (49.8%). 57 estadios III (enfermedad loco-regional) (22.5%) y 54 estadios IV (con metástasis) (21.3%). Resultados: El porcentaje de tumores en los diferentes estadios no se ha modificado, ni tampoco la cirugía con fines curativos. La vía de abordaje más frecuente ha sido la subcostal y el empleo, como terapia adyuvante, de Mitotane no ha cesado de aumentar significativamente. La supervivencia actuarial global a 5 años fue del 38%; 50% en el grupo operado con fines curativos; 66% en pacientes en estadio I, 58% en los del estadio II, 24% en los del estadio III y 0% en los del estadio IV. Un análisis multivariante ha demostrado los beneficiosos efectos del Mitotane, por lo que a la supervivencia se refiere, en el grupo de pacientes intervenidos con fines paliativos. El pronóstico ha mejorado desde 1988 (p = 0.04), en los pacientes secretores de precursores (p = 0.005) y en los pacientes con enfermedad local (p = 0.0003). Conclusiones: El Mitotane sólo es útil en casos de cirugía paliativa. La cirugía radical, el tipo de secreción hormonal, el diagnóstico precoz y el estadio de enfermedad local, son los factores más favorables en cuanto a la supervivencia se refiere.
Acknowledgments
We acknowledge and thank Professors Bruno Vergès and Jean- Paul Jullien for proofreading and correcting the English language in this paper and Mrs. Chantal Milan (Department of Statistics and Epidemiology) for the statistical support. Coauthors of the AFCE group are Pr. André, Dr. Andry, Pr. Argeme, Dr. Avila, Pr. Bacourt, Pr. Barbier, Dr. Berger, Dr. Bizard, Pr. Boissel, Dr. Bouchet, Pr. Boulez, Dr. Bresler, Dr. Bronn, Dr. Chevert, Pr. Chigot, Dr. Courant, Pr. De Calan, Dr. De-Micco, Dr. De- fechereux, Dr. Denizot, Pr. Dubost, Dr. Duclos, Dr. Fabre, Pr. Favre, Dr. Franz, Pr. Gouzi, Dr. Gregoire, Dr. Hamoir, Pr. Jeack, Dr. Janser, Pr. Kinnaert, Pr. Kraimps, Dr. Landecy, Dr. Lantz, Dr. Le Neel, Pr. Leborgne, Dr. Lehut, Dr. Lequin, Dr. Letessier, Pr.
Lhermine, Dr. Luciani, Dr. Malaise, Dr. Marchand, Pr. Mares- caux, Dr. Marmousez, Dr. Martinot, Pr. Mathieu, Pr. Melliere, Dr. Menegaux, Pr. Meurisse, Pr. Michel, Pr. Michot, Pr. Morin, Dr. Mutter, Pr. Nihoul-Fekete, Pr. Nussaume, Dr. Oudar, Pr. Pailler, Dr. Paineau, Dr. Paris, Pr. Partensky, Dr. Patoir, Pr. Peix. Dr. Pelleray, Dr. Picard, Pr. Pinget, Dr. Pitre, Pr. Reys, Dr. Richet, Dr. Rind, Pr. Ronceray, Dr. Saint-Eve, Dr. Saint-Marc, Pr. Samama, Pr. Sarfati, Dr. Sautier, Dr. Solovei, Pr. Squifflet, Dr. Techer, Pr. Tissot, Dr. Van-Box-Som, Pr. Visset, Dr. Vix, Dr. Wagner.
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