Urologia Internationalis
Urol Int 2012;88:400-404 DOI: 10.1159/000336134
Received: August 2, 2011 Accepted after revision: December 27, 2011 Published online: April 5, 2012
Surgical Management and Clinical Prognosis of Adrenocortical Carcinoma
Dexin Dong Hanzhong Li Weigang Yan Zhigang Ji Quanzong Mao
Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
Key Words
Adrenocortical carcinoma . Surgery · Prognosis · Stages I-IV
Abstract
Objective: To study the relationship between surgical man- agement and prognosis of adrenocortical carcinoma (ACC) in order to guide the surgical management of ACC. Methods: Clinical data of 45 cases of ACC treated in our hospital were retrospectively analyzed. The 45 cases included 3 cases in stage I, 12 cases in stage II, 7 cases in stage III, and 23 cases in stage IV. 17 cases underwent complete excision, 14 cases underwent palliative excision, 8 cases had non-operative treatment and 6 cases gave up treatment. All patients were followed up from 2 to 141 months. Results: The average sur- vival time of 31 patients with surgery was 32.46 months, and the average survival time of 14 patients without surgery was 4.75 months. There were statistically significant differences between the two groups (p < 0.01). There were no statisti- cally significant differences between the two groups in sur- vival time in stage III and stage IV (p > 0.05). Conclusions: Surgery is considered to be the only method to cure ACC. For ACC in stage I and II, tumor resection is the most effective treatment, and second surgical operation is recommended for local recurrence. For ACC in stage III, extensive surgical operation is recommended, and for ACC in stage IV, surgical operation has no effect on the prognosis.
Copyright @ 2012 S. Karger AG, Basel
Introduction
Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. The poor prognosis and the scant knowledge pose a clinical problem for both doctors and patients. This article analyzed retrospectively the clinical presentation, clinical stage and the clinical management of 45 cases of ACC treated in our hospital in order to study the relationship between surgical management and prognosis of ACC.
Materials and Methods
General Data
Forty-five patients were pathologically diagnosed as ACC af- ter operation or biopsy in our hospital from September 1984 to September 2010. There were 21 females and 24 males. The mean age at initial examination in our hospital was 23.84 years (range 2-76). The mean course of disease was 3.54 months (range 1-18). The average tumor size was 9.46 cm (range 3.80-21.70). Accord- ing to the TNM staging method modified by Icard et al. [1] and Lee et al. [2], 3 cases were in stage I, 12 were in stage II, 7 were in stage III, and 23 were in stage IV. All the patients were followed up 23.84 months (range 2-141). Using skilled techniques, four surgeons and their teams took part in these operations.
Clinical Presentation
Functional ACC. The 22 cases of functional ACC included 15 cases of Cushing’s syndrome, 4 cases of sexual abnormality (3 an- drophany and 1 male sexual precocity) and 3 cases of primary aldosteronism.
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| Index | Stage I | Stage II | Stage III | Stage IV | Total |
|---|---|---|---|---|---|
| Cases | 3 | 12 | 7 | 23 | 45 |
| Mean survival time, months | 67.33 | 40.38 | 34.50 | 7.17 | 24.29 |
| One-year survival rate, % | 100.00 (3/3) | 66.67 (8/12) | 71.43 (5/7) | 17.39 (4/23) | 44.44 (20/45) |
| Two-year survival rate, % | 100.00 (3/3) | 50.00 (6/12) | 57.14 (4/7) | 4.35 (1/23) | 31.11 (14/45) |
| Five-year survival rate, % | 100.00 (3/3) | 33.33 (4/12) | 28.57 (2/7) | 0.00 (0/23) | 20.00 (9/45) |
Non-Functional ACC. The 23 cases of non-functional ACC in- cluded 9 with low back pain or abdominal distention, 9 with inci- dentaloma, 2 with fever, debility and emaciation, 2 with metasta- sis to lung or liver, and 1 with hematuria.
Clinical Management
Seventeen cases had complete resection of the ACC, 14 had palliative resection, 8 had non-operative treatment, and 6 gave up treatment. The 3 cases in stage I had complete resection (1 had complete resection again after recurrence one time). Among the 12 cases in stage II, 11 had complete resection (2 had complete resection again after recurrence one time, and 1 had complete re- section again after recurrence four times), and 1 case had embo- lism of the carcinoma and O,P’-DDD treatment. Among the 7 cases in stage III, 3 had extensive surgery and 4 had palliative sur- gery. Among the 23 cases in stage IV, 10 had palliative surgery, 13 had non-operative treatment, among which 7 had conservative treatment (1 had chemotherapy, 1 had radiotherapy, 2 had chemo- therapy and radiotherapy, and 3 had mitotane treatment) and 6 cases gave up treatment.
Statistical Analysis
SPSS 11.5 software was utilized to analyze clinical data. A rank-sum test was utilized for two independent samples, one fac- tor analysis of variance was utilized for multiple samples, and Pearson bivariate correlation analysis was utilized for two related variables (p < 0.05 is considered to be significantly different).
Results
Survival Time and Survival Rate
Fourteen patients survived and 31 had died up to the time of writing. The 3 cases in stage I all survived with a mean follow-up of 67.33 ± 52.01 months. Among the 12 cases in stage II with a mean follow-up of 40.38 ± 43.13 months, 6 survived and 6 died. Among the 7 cases in stage III with a mean follow-up of 34.50 ± 29.76 months, 2 survived and 5 died. Among the 23 cases in stage IV with a mean follow-up of 7.17 ± 6.73 months, 3 survived and 20 died (table 1; fig. 1).
| Stage | Surgical management | Cases | Survival time, months | p value |
|---|---|---|---|---|
| I | Surgical | 3 | 67.33 ±52.01 | – |
| II | Surgical | 11 | 43.14 ±44.11 | – |
| Non-surgical | 1 | 10.0 | ||
| III | Extensive surgery | 4 | 54.33 ±35.22 | >0.05 |
| Palliative surgery | 3 | 19.63 ±16.01 | ||
| IV | Palliative surgery | 10 | 10.04 ±8.95 | >0.05 |
| Non-surgical | 13 | 4.96± 1.86 | ||
| Conservative treatment | 7 | 5.79 ±1.82 | >0.05 | |
| Gave up treatment | 6 | 4.00 ±1.52 | ||
| Total | Surgical | 31 | 32.46 ± 34.88 | 0.000 |
| Non-surgical | 14 | 4.75 ±1.96 |
Rank-sum test (p < 0.05 is considered significantly different).
Stage I
Stage II
Stage III
Stage IV
1.2
Survival rate (%)
1.0
0.8
0.6
0.4
0.2
0
6
12
18
24
30
36
42
48
54
60
Time (months)
Color version available online
Fig. 1. Relationship between survival rate and time.
| Index | Group | Cases | Survival time, months | For P | p value |
|---|---|---|---|---|---|
| Gender | Male | 24 | 18.33 ±26.50 | – | 0.155 > 0.05ª |
| Female | 21 | 30.14±36.22 | |||
| Age | ≤40 years | 18 | 16.36 ±23.16 | 2.562 | 0.278 >0.05b |
| 40-60 years | 16 | 31.47 ± 34.78 | |||
| ≥60 years | 6 | 38.00 ± 49.87 | |||
| Left/right | Left | 15 | 17.03 ±19.74 | – | 0.970 > 0.05ª |
| Right | 29 | 27.97 ±36.36 | |||
| Size | – | 45 | 24.29 ± 33.11 | -0.174 | 0.253 > 0.05€ |
| Function | Non-functional | 23 | 35.60 ± 39.66 | – | 0.005 < 0.05ª |
| Functional | 22 | 11.20 ±12.84 | |||
| Stage | Stage I | 3 | 67.33 ±52.01 | 7.456 | 0.000 < 0.05b |
| Stage II | 12 | 40.38 ±43.13 | |||
| Stage III | 7 | 34.50 ± 29.76 | |||
| Stage IV | 23 | 7.17 ±6.73 |
a Rank-sum test (p < 0.05 is considered significantly different).
b One factor analysis of variance (p < 0.05 is considered significantly different).
” Pearson bivariate correlation analysis (p < 0.05 is considered significantly different).
Correlation between Surgical Management and Survival Time
The average survival time of 31 cases of patients with surgical management was 32.46 ± 34.88 months, and the average survival time of 14 patients without surgical management was 4.75 ± 1.96 months. The difference be- tween the two groups was statistically significant (p < 0.01) (table 2).
The 3 cases with surgical management in stage I all survived with a mean follow-up of 67.33 ± 52.01 months. Among the 12 cases in stage II, 11 with surgical management survived with a mean follow-up of 43.14 ± 44.11 months, and 1 with arterial embolization and treatment of dichloroethane chlorobenzene died after 10.0 months.
Among the 7 cases in stage III, 3 had extensive surgery and 4 had palliative surgery. The survival time was re- spectively 54.33 ± 35.22 and 19.63 ± 16.01 months with- out statistically significant differences (p > 0.05).
Among the 23 cases in stage IV, 10 had palliative sur- gery and 13 had non-operative treatment. The survival time was respectively 10.04 ± 8.95 and 4.96 ± 1.86 months without statistically significant differences (p > 0.05). Among the 13 cases treated with non-operative treatment, 7 had conservative treatment and 6 gave up treatment. The survival time was respectively 5.79 ± 1.82 and 4.00 ± 1.52 months without statistically significant differences (p>0.05).
Correlation between Certain Indexes and Survival Time
There was no statistical correlation between the index (gender, age, side, size) and survival time (p > 0.05). The 23 cases of non-functional ACC were followed up for 35.60 + 39.66 months, and the 22 cases of functional ACC were followed up for 11.20 ± 12.84 months, and there were sta- tistically significant differences between the two groups (p<0.05). There was a statistical correlation between clin- ical stage and survival time (F = 11.078, p<0.05) as well as between the clinical stages (p <0.05) (table 3).
Discussion
ACC is a rare disease with a poor prognosis. The inci- dence is 1.5-2 per million population [3, 4]. The age dis- tribution is reported as bimodal with a first peak in child- hood and a second higher peak in the fourth and fifth decades [5, 6]. The male:female ratio in our series was 1.14:1, which is consistent with the literature.
The pathogenesis of ACC is poorly understood and the prognosis is extremely poor. The average survival time of our group was 24.29 ± 33.11 months, and the survival rate of 1, 2 and 5 years was 44.44% (20/45), 31.11% (14/450) and 20.00% (9/45), respectively. Therefore, it is essential to study clinical factors affecting the prognosis of ACC in order to guide the diagnosis and treatment of ACC.
The most important influencing factor is clinical stage. The Pearson correlation analysis demonstrated that the correlation between the survival time and the clinical stage was significant (p < 0.05). There were sta- tistically significant differences in the clinical prognosis between each group and the mean survival time and sur- vival rate was consistent with the literature [7].
Surgery is considered to be the only method to cure ACC of in the early stage [7-10]. There were 15 cases of ACC in stages I and II in total. 14 cases had complete re- section of the carcinoma and 1 refused to have the opera- tion, but had embolism of the carcinoma and mitotane treatment instead. Among the 14 cases, 1 in stage I and 3 in stage II had complete resection again after local recur- rence, and the 4 cases are still alive at the time of writing. Therefore, complete resection of the tumor is the effective treatment for ACC in stages I and II. Close follow-up is necessary after the operation, and operation is recom- mended after local recurrence [11, 12].
With respect to 7 cases in stage III, 3 had extensive surgery and 4 had palliative surgery. The data demon- strated that there were no statistically significant differ- ences between the two methods in survival time (p > 0.05), but the survival time of patients with extensive sur- gery was somewhat longer than that with palliative sur- gery (54.33 ± 35.22 vs. 19.63 ± 16.01). There is appar- ently no alternative treatment for a reasonable compari- son because of small number of cases in stage III. According to the literature, intentionally curative surgery increases the 5-year survival in stage I-III disease. There- fore, extensive surgery with adjunctive therapy is recom- mended for ACC in stage III [13, 14].
With respect to 23 cases in stage IV, 10 had palliative surgery and 13 had non-operative treatment, and there were no statistically significant differences between the two groups in survival time (p> 0.05). The reasons are as follows: Firstly, the ACC in stage IV have encroachment and metastasis, and surgery cannot remove the carcino- ma completely [15]. Secondly, surgery can cause marked damage to the patient in the advanced stage, which might aggravate the progression of disease [16]. Thirdly, surgery is extensive with a high risk, high death rate and poor prognosis. Among the 13 cases treated with non-opera- tive treatment, 7 had conservative treatment and 6 gave up treatment, and there were no statistically significant differences between the two groups in survival time (p > 0.05). Therefore, surgery is not recommended for ACC patients in stage IV [17]. Mitotane, chemotherapy and ra- diotherapy are recommended [13, 18, 19], but the results are not certain.
Conclusions
Surgery is considered to be the only method to cure ACC. For ACC in stages I and II, complete resection is the most effective treatment, and second surgery is recom- mended for local recurrence. For ACC in stage III, exten- sive surgery is recommended. For ACC in stage IV, sur- gery is not recommended.
Disclosure Statement
The authors have no conflicts of interest to declare.
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