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Original Article Clinical Investigation
Comparison between minimally invasive surgery and open surgery in managing localized adrenocortical carcinoma treatment: A retrospective propensity-matched study
Xin Zhao,1 Jiaquan Zhou,2 Xiaohong Lyu,3 Yanan Li,1 Yihong Liu4 and Yushi Zhang1 D
1Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China, 2Department of Urology, Hainan Affiliated Hospital of Hainan Medical University (Hainan General
Hospital), Haikou, Hainan, China, 3Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China, and 4Department of Urology, The 7th People’s Hospital of Zhengzhou, Zhengzhou, China
Abbreviations & Acronyms
ACC = adrenocortical carcinoma
AJCC = American Joint Committee on Cancer
CT = computed tomography MIS = minimally invasive surgery SMD = standardized mean difference
TNM = tumor-node- metastasis UFC = urinary-free cortisol
Correspondence
Yushi Zhang, Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. Email: pumchzhangyushi@163. com
Received 18 September 2024; accepted 6 January 2025. Online publication 21 January 2025
Xin Zhao, Jiaquan Zhou, and Xiaohong Lyu contributed equally to this study and are co-first authors.
Abstract:
Background: It was controversial to use open surgery or minimally invasive surgery (MIS) for adrenocortical carcinoma (ACC). This retrospective study aimed to evaluate the impact on prognosis between MIS and open surgery in patients with clinical stage I-II ACC.
Methods: Patients with stage I-II ACC from December 2000 to October 2022 were retrospectively studied. The primary endpoint was recurrence-free survival time calculated by the Kaplan-Meier curves.
Results: In total, 95 patients were enrolled in this study (50 open surgery and 45 MIS). Propensity score matching identified 32 matched pairs of patients. Compared with the open surgery group, the MIS group had a shorter median operative time (150.0 vs. 120.0 min, p = 0.014), the lesser median volume of intraoperative blood loss (200.0 vs. 60.0 mL, p = 0.006), lower incidence of postoperative complications (59.4% vs. 28.1%, p = 0.023), and shorter median postoperative length of hospital stay (8.0 vs. 7.0 days, p = 0.001). After a median follow-up time of 20.5 months, no significant differences were observed in the local recurrence rate (62.5% vs. 78.1%), distant metastasis rate (15.6% vs. 6.3%), and median time to recurrence (15.0 vs. 20.0 months) between the two groups. The median recurrence-free survival time between the open surgery and MIS groups did not significantly differ (16.0 vs. 21.0 months).
Conclusion: MIS might be a feasible option for treating localized ACC at a high patient’s volume center with experienced surgeons.
Key words: adrenocortical carcinoma, laparoscopic, minimally invasive surgery, oncological outcome, open surgery, surgery.
INTRODUCTION
Adrenocortical carcinoma (ACC) is a rare malignancy that originates from the cortex of the adrenal gland, with an incidence of ~0.7-2 cases per million person-years.1 According to the stage at diagnosis, ACC is associated mainly with a poor prognosis, with an overall 5-year survival rate of 15%-60%.2,3 RO surgical resection without residual tumor is the only curative treatment option for localized stage I/II ACC.4 Following resection of ACC, microscopically and macroscopically positive surgical margins were associated with compromised overall survival5. The 5-year survival rate of patients with stage I-III ACC is ~39%-50%. However, it is lower at 6%-13% in patients with stage IV ACC.6 If RO resection is not achieved, patients will require postoperative adjuvant therapy, such as mitotane therapy, radiotherapy, and chemotherapy. Nevertheless, the efficacy of adjuvant treatment is limited.7 Thus, R0 resection is the only potentially curative treatment option.6,
The current European Society of Endocrinology Clinical Practice guidelines recommends the use of open surgery as the standard surgical approach for patients with ACC. In cases of tumors with a diameter of <6 cm without local inva- sion, minimally invasive surgery (MIS), including laparo- scopic and robot-assisted surgery, may be considered.8 Open surgery has some evident disadvantages. That is, it is associ- ated with trauma, longer operative time and hospital stay, and higher volume of blood loss.9-12 Therefore, several clinicians prefer MIS for treating ACC.13-20 Nonetheless, the oncologi- cal safety has not been supported by high-quality evidence, and the role of MIS in treating ACC remains controversial. Some studies have shown that open surgery is safer and more effective in patients with ACC.9-12,21,22 Meanwhile, others have revealed that the two approaches are similar in terms of safety and efficacy.13-20 Therefore, it was necessary to reeval- uate the safety and efficacy of open surgery and the MIS method to treat ACC in large medical centers.
Several patients with ACC underwent MIS for tumors with a diameter >6 cm.16,19 At our center, the largest tumor treated with MIS had a diameter of 12 cm. Based on clinical experi- ence, we hypothesized that MIS is appropriate for patients with localized stage I/II ACC if the surgeon has sufficient experience. Furthermore, each surgeon must respect the prin- ciples of oncological surgery and evaluate the feasibility of MIS in each patient with ACC. A recently published high-quality meta-analysis also pointed out that laparoscopic surgery could be regarded as an effective and safe operation for selected adrenocortical carcinoma (ACC) cases with appropriate laparoscopic expertise.4
The primary objective of this study was to reassess the efficacy and safety of open surgery and MIS for the treatment of localized ACC using a retrospective cohort study in China. To the best of our knowledge, this is the largest single-center study in China on ACC surgical procedures.
METHODS
Patients and their clinical information
We retrospectively reviewed all patients with ACC who were admitted to the Department of Urology at Peking Union Medical College Hospital between December 2000 and October 2022.
Inclusion criteria: (1) Pathologically confirmed ACC; (2) Patients with stage I (T1N0M0) or stage II (T2N0M0) ACC, according to the 8th edition (2017) classification of the Amer- ican Joint Committee on Cancer (AJCC) tumor-node-metas- tasis (TNM) staging and patients who were predicted to have completed R0 or R1 resection before surgery; (3) Underwent complete adrenalectomy; (4) those who underwent preopera- tive examination via enhanced computed tomography (CT) scan; (5) those with an Eastern Cooperative Oncology Group performance status score of 0 or 1; (6) Complete clinical and follow-up data.
Exclusion criteria: (1) TNM stage III or IV; (2) Received palliative surgery or did not receive surgical treatment; (3) predicted inability to perform R0 or R1 resection before sur- gery; (4) Synchronous contralateral adrenal tumor; (5) History of ipsilateral adrenal surgery; (5) Preoperative adjuvant
treatments such as mitotane therapy, radiotherapy, or chemo- therapy; (6) Incomplete clinical or follow-up data; (7) Com- bined with other malignancies.
Patient selection bias: the open surgical approach was pre- ferred until 2014 and was currently more suitable for those patients with large tumors, while after 2014, MIS has become a preferred approach with the advancement and skillfulness of laparoscopic surgical techniques.
This retrospective comparative study was approved by the institutional review board of Peking Union Medical College Hospital (I-22PJ073). We retrospectively collected clinical data, including sex, age, cortisol level, contrast-enhanced CT scan findings, details of the surgery and perioperative recov- ery, pathological examination results, and postoperative adju- vant therapies. To determine cortisol hypersecretion, the following criteria were used: (1) 24-h urinary-free cortisol (UFC) level of >103.5 µg/24 h twice with Cushing syndrome related symptoms and (2) blood cortisol level of >1.8 µg/dL at 8 am after a 1-mg overnight or low-dose dexamethasone suppression test. Surgical outcomes were assessed, and the patients underwent follow-up.
Surgical approach
Our hospital has a dedicated adrenal surgery team composed of experienced surgeons. Over the past 22 years, although techniques have evolved, we have consistently followed the same oncological principle of complete tumor resection. All surgeries were performed by or under the supervision of the same group of surgeons. For complex cases, each patient underwent a departmental discussion to decide on the surgical plan. For MIS, we used either the transabdominal or retroper- itoneal approach. For open surgery, we used the transabdom- inal approach. Regardless of the surgical approach, we always adhered to the following principles: (1) avoid tumor rupture or spillage as much as possible; (2) completely remove the tumor to avoid residual tumor, including the over- lying peritoneum of the tumor, and removal of peri-adrenal adipose tissue; (3) carefully achieve hemostasis to prevent postoperative bleeding; (4) properly handle the specimen for accurate pathological evaluation; (5) Lymph node dissection was not routinely performed in patients with stage I-II ACC, unless there were suspicious findings on preoperative imaging or intraoperative lymph nodes.
Surgical outcome and follow-up
Based on different surgical approaches, the patients who underwent resection were divided into the open surgery and MIS groups. Surgical margin status was classified as R0, R1, and R2 resection according to intraoperative findings and postoperative pathology. R classification was defined based on the following criteria: R0, no residual tumor; R1, micro- scopic residual tumor; and R2, macroscopic residual tumor. Intraoperative tumor rupture was considered part of R1 resec- tion. Perioperative complications were classified according to the Clavien-Dindo classification system.25
All patients alternately underwent chest and abdominal CT scans or abdominal ultrasonography combined with chest
radiography every 3 months within the first 2 years after sur- gery and then every 6 months thereafter. CT scans were per- formed every 6 months within the first 5 years after surgery and at least once during the subsequent years. The primary endpoint of the follow-up was the first occurrence of local recurrence or distant metastasis. For radical adrenalectomy using the retroperitoneal approach, local recurrence was defined as ACC recurrence within the scope of the ipsilateral retroperitoneal operative area. Meanwhile, distant metastasis was defined as intraperitoneal ACC recurrence. For transperi- toneal surgery, local recurrence included tumor recurrence of adjacent abdominal organs and tumor implantation on the surface of the abdominal cavity, which was also called perito- neal carcinomatosis.
Statistical analysis
Statistical analysis was performed using R4.2.2 software. The participants in the open surgery and MIS groups were matched 1:1 using the “MatchIt” package based on sex, age, tumor side and size, surgical margin, adjuvant mitotane ther- apy and radiotherapy, and cortisol hypersecretion, with a matching caliper value set at 0.4. The normality of continu- ous variables was tested using the Shapiro-Wilk test. Contin- uous variables with normal distribution were expressed as mean ± standard deviation and compared between groups using the Student’s t-test. Meanwhile, continuous variables with non-normal distribution were expressed as median with interquartile range and compared between groups using the Wilcoxon rank-sum test. For categorical variables, the differ- ence between groups was tested using the Chi-square test or Fisher’s exact test.
The primary and secondary endpoint of this study were recurrence-free survival (RFS) and surgical complications, respectively. RFS was defined as the time from radical adre- nalectomy to the first occurrence of ACC local recurrence or distant metastasis. Further, it was calculated using the Kaplan -Meier method based on the “survival” package, and differ- ences in RFS between the open surgery and MIS groups were analyzed using the stratified log-rank test. Multivariate Cox proportional hazards regression analyses were conducted using a stepwise procedure to identify independent prognostic covariates associated with RFS. Based on the independent prognostic covariates, sensitivity analyses were performed to evaluate differences in RFS between patients who underwent open surgery and those who underwent MIS in different subgroups.
All the analyses were performed with the statistical soft- ware packages R (http://www.R-project.org, The R Founda- tion) and Free Statistics software versions 1.7.A two-sided p-value of ≤0.05 was considered statistically significant.
RESULTS
Characteristics of the patients
In total, 95 patients diagnosed with ACC were included in this study. Among them, 50 were included in the open sur- gery group and 45 in the MIS group. Univariate analysis was performed to compare the clinical characteristics of the open
surgery and MIS groups. Results showed a significant differ- ence in terms of tumor size alone between the two groups (Table 1).
Propensity score matching was used to address differences in clinical characteristics as given in Table 1. In total, 32 patients were included in each group. All characteristics, except for age (standardized mean difference [SMD] = 0.19) and cortisol hypersecretion (SMD = 0.13), had an SMD of ≤0.1. The tumor sizes between the two groups were compara- ble (p = 0.370). In the propensity score matching cohort, 54.69% (35/64) of patients were women, with an average age of 48.14 ± 10.52 years. Meanwhile, 45.31% (29/64) were men, with an average age of 48.21 ± 11.57 years. The mean tumor size was 7.62 ± 2.51 cm. In addition, 14.1% (9/64) of patients received R1 section; 10.9% (7/64), adjuvant mitotane therapy; and 14.1% (9/64), adjuvant radiotherapy at baseline.
Surgical outcomes
In the MIS group, one patient underwent robot-assisted resec- tion for ACC, and three patients required conversion to open surgery due to hemorrhage and tumor rupture. The MIS group was more likely to undergo radical adrenalectomy using the retroperitoneal approach than the open surgery group (p = 0.003). In the MIS group, no tumor involvement of surrounding tissues and organs was found, while in the open surgery group, five patients chose to resect surrounding tissues or some organs, including the kidney, spleen, and pancreas in order to ensure negative margins. In addition, the MIS group had a shorter operative time (p = 0.014), lesser volume of intraoperative blood loss (p = 0.006), and shorter postoperative discharge time (p = 0.001) than the open sur- gery group (Table 2). The MIS group had a lower overall incidence of postoperative complications than the open sur- gery group (28.1% [n = 9] and 59.4% [n = 19]; p = 0.023). In the open surgery group, three patients experienced Clavien-Dindo grade III/IV complications. However, the MIS group did not present with such complications (Table 2) There were 5 cases of R1 resection, including 1 case of intraoperative tumor rupture in the open surgery group. There were 4 cases of R1 resection, including 1 case of intraopera- tive tumor rupture in the MIS group. There was no statisti- cally significant difference in the rates of R1 resection or tumor rupture between the two groups.
Follow-up outcomes
The median follow-up time in this study was 20.5 (range 3 -144) months. Local recurrence was the most common type of ACC recurrence in the MIS and open surgery groups. The incidence rates of local recurrence (62.5% [n = 20] vs. 78.1% [n = 25]; p = 0.274), including 5 peritoneal carcino- matosis in MIS group and 8 in the open surgery group, did not significantly differ in the two groups. And distant metas- tasis (15.6% [n = 5] vs. 6.3% [n = 2]; p = 0.708) also did not significantly differ between the open surgery and MIS groups. The lungs were the most frequent site of distant metastasis, accounting for 90.9% of all cases (10/11). Three patients in the open surgery group and one patient in the
| TABLE 1 Clinical characteristics of the whole cohort and the propensity score-matched cohort. | ||||||
|---|---|---|---|---|---|---|
| Characteristics | Whole cohort | Propensity score-matched cohort | ||||
| Open surgery group (n = 50) | MIS group (n = 45) | p-value | Open surgery group (n = 32) | MIS group (n = 32) | p-value | |
| Sex (%) | ||||||
| Male | 23 (46.0) | 17 (37.8) | 0.547 | 15 (46.9) | 14 (43.8) | 1.000 |
| Female | 27 (54.0) | 28 (62.2) | 17 (53.1) | 18 (56.2) | ||
| Age (years) | 49.06 ± 11.50 | 49.24 ± 11.77 | 0.939 | 47.13 ± 11.35 | 49.22 ± 10.55 | 0.448 |
| Tumor side (%) | ||||||
| Left | 26 (52.0) | 23 (51.1) | 1.000 | 17 (53.1) | 16 (50.0) | 1.000 |
| Right | 24 (48.0) | 22 (48.9) | 15 (46.9) | 16 (50.0) | ||
| Tumor size (cm) | 8.54 ± 2.36 | 6.70 ± 2.49 | <0.001 | 7.90 ± 2.54 | 7.33 ± 2.49 | 0.370 |
| Surgical margin (%) | ||||||
| R0 | 43 (86.0) | 41 (91.1) | 0.602 | 27 (84.4) | 28 (87.5) | 1.000 |
| R1 | 7 (14.0) | 4 (8.9) | 5 (15.6) | 4 (12.5) | ||
| Adjuvant mitotane therapy (%) | ||||||
| No | 45 (90.0) | 37 (82.2) | 0.422 | 28 (87.5) | 29 (90.6) | 1.000 |
| Yes | 5 (10.0) | 8 (17.8) | 4 (12.5) | 3 (9.4) | ||
| Adjuvant radiotherapy (%) | ||||||
| No | 46 (92.0) | 35 (77.8) | 0.080 | 28 (87.5) | 27 (84.4) | 1.000 |
| Yes | 4 (8.0) | 10 (22.2) | 4 (12.5) | 5 (15.6) | ||
| Cortisol hypersecretion (%) | ||||||
| No | 25 (50.0) | 21 (46.7) | 0.905 | 14 (43.8) | 16 (50.0) | 0.802 |
| Yes | 25 (50.0) | 24 (53.3) | 18 (56.2) | 16 (50.0) | ||
Note: Data were reported as total number with percentage and mean value with standard deviation. Abbreviation: MIS, minimally invasive surgery.
| Characteristics | All patients (N = 64) | Open surgery group (n = 32) | MIS group (n = 32) | p-value |
|---|---|---|---|---|
| Operative time (min) | 140.0 (120.0, 161.0) | 150.0 (130.0, 165.0) | 120.0 (95.0, 150.0) | 0.014 |
| Volume of intraoperative blood loss (mL) | 125.0 (30.0, 575.0) | 200.0 (95.0, 1350) | 60.0 (30.0, 162.5) | 0.006 |
| Surgical approach (%) | ||||
| Transperitoneal | 29 (45.3) | 21 (65.6) | 8 (25.0) | 0.003 |
| Retroperitoneal | 35 (54.7) | 11 (34.4) | 24 (75.0) | |
| Abdominal drain removal time (days) | 4.0 (3.0, 6.0) | 5.0 (3.0, 6.0) | 4.0 (3.0, 5.0) | 0.125 |
| Length of postoperative stay (days) | 7.0 (6.0, 10.0) | 8.0 (6.0, 12.0) | 6.0 (5.0, 7.0) | 0.001 |
| Conversion to open surgery (%) | NA | NA | 3 | NA |
| Postoperative complications (Clavien-Dindo classification) (%) | ||||
| Grade I | 16 (25.0) | 10 (31.3) | 6 (18.8) | 0.072 |
| Grade II | 9 (14.1) | 6 (18.8) | 3 (9.4) | |
| Grade III | 2 (3.1) | 2 (6.3) | 0 (0.0) | |
| Grade IV | 1 (1.6) | 1 (3.1) | 0 (0.0) | |
| Recurrence site (%) | ||||
| Local | 45 (70.3) | 20 (62.5) | 25 (78.1) | 0.270 |
| Distant | 7 (10.9) | 5 (15.6) | 2 (6.3) | |
| Both | 4 (6.3) | 3 (9.4) | 1 (3.1) | |
| Time to recurrence (months) | 16.50 (8.75, 35.00) | 15.00 (7.75, 36.25) | 20.00 (12.0, 31.25) | 0.687 |
Note: Data were expressed as total number with percentage and median value with interquartile range. Abbreviations: ACC, adrenocortical carcinoma; MIS, minimally invasive surgery; NA, not applicable.
FIGURE 1 Kaplan-Meier curves showing recurrence-free survival in patients with adrenocortical carcinoma (ACC) stratified by surgical approach. (A) Analysis of the entire cohort demonstrating recurrence-free survival probability over time. (B) Subgroup analysis of patients with tumor size ≤ 6 cm. (C) Subgroup analysis of patients with tumor size > 6 cm but ≤ 12 cm. Blue lines represent minimally invasive surgery (MIS) group; red lines represent open surgery group. Hazard ratios (HR) with 95% confidence intervals (CI) are shown for each comparison. Vertical tick marks indicate censored data points. Numbers at risk are shown below each graph at specified time intervals. Statistical significance was determined using log-rank test.
(a) All patients with ACC
Surgical pattern - Open surgery MIS
1.00
HR : 1.10
Probability of Recurrence-free Survival (%)
(95%CI:0.64-1.89)
p: 0.723
0.75
0.50
0.25
0.00
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
Time (Months)
Number at risk
Open surgery
32
22
11
10
7
7
7
5
5
3
3
2
1
1
1
0
MIS
32
25
17
9
4
3
3
1
1
1
1
0
0
0
0
0
(b) Patients with ACC ≤ 6cm in size
1.00
HR : 1.78
Probability of Recurrence-free Survival (%)
(95%CI:0.60-5.29)
p: 0.299
0.75
0.50
0.25
0.00
0
10
20
30
40
50
60
70
80
90
100
110
120
Time (Months)
Number at risk
Open surgery
7
6
4
4
2
2
2
2
2
2
2
1
0
MIS
12
11
9
5
2
1
1
0
0
0
0
0
0
(c) Patients with ACC > 6cm but ≤ 12cm in size
Surgical pattern - Open surgery - MIS
1.00
Probability of Recurrence-free Survival (%)
HR : 1.01 (95%CI:0.53-1.93)
p: 0.969
0.75
0.50
0.25
0.00
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
Time (Months)
Number at risk
Open surgery
25
16
7
6
5
5
5
3
3
1
1
1
1
1
1
0
MIS
20
14
8
4
2
2
2
1
1
1
1
0
0
0
0
0
Patients with local recurrence of ACC
(a)
Surgical pattern
Open surgery
MIS
1.00
HR : 1.31
(95%CI:0.73-2.36)
p: 0.360
Probability of Recurrence-free Survival (%)
0.75
0.50
0.25
0.00
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
Time (Months)
Number at risk
Open surgery
27
20
11
10
7
7
7
5
5
3
3
2
1
1
1
0
MIS
30
23
16
8
3
2
2
1
1
1
1
0
0
0
0
0
Patients with diatant metastasis of ACC
(b)
Surgical pattern
Open surgery
MIS
1.00
HR : 0.49
(95%CI:0.13-1.85)
p: 0.292
Probability of Recurrence-free Survival (%)
0.75
0.50
0.25
0.00
0
10
20
30
40
50
60
70
80
00
100
110
120
130
140
150
Time (Months)
Number at risk
Open surgery
12
7
4
3
3
3
3
2
2
1
1
1
1
1
1
0
MIS
7
6
4
3
2
2
2
1
1
1
1
0
0
0
0
0
MIS group presented with ACC recurrence including local recurrence and distant metastasis. Nevertheless, there was no significant difference between the two groups in terms of recurrence site (p = 0.270) (Table 2). The median time to recurrence in all patients was 16.5 (range 3-144) months. The probabilities of 1-, 3-, and 5-year RFS were 68.1%, 21.1%, and 14.1%, respectively.
According to the stratified log-rank test, at the last follow-up evaluation, the median RFS rates did not signifi- cantly differ between the open surgery and MIS groups (16.0 vs. 21.0 months) (Figure 1a). The matched cohort was further divided into two subgroups based on a tumor size threshold of 6 cm. In the subgroup with a tumor size of ≤6 cm, the median RFS of patients who underwent open surgery and those who underwent MIS were 36.0 and 21.0 months, respectively. In the other subgroup, the median RFS of
patients who underwent open surgery and those who under- went MIS were 14.0 and 15.0 months, respectively. Hence, there was no significant difference in terms of RFS between patients who underwent open surgery and those who under- went MIS in either subgroup (p > 0.05) (Figure 1b,c).
Furthermore, the cohort was divided into two subgroups based on the presence of local recurrence or distant metastasis, with censored patients included in both subgroups. In the local recurrence subgroup, the median RFS of patients who underwent open surgery and those who underwent MIS were 18.0 and 21.0 months, respectively. In the distant metastasis subgroup, the median RFS of patients who underwent open surgery and those who underwent MIS were 14.0 and 60.0 months, respec- tively. Thus, there was no significant difference in terms of RFS between patients who underwent open surgery and those who underwent MIS in either subgroup (p > 0.05) (Figure 2a,b).
Sensitivity analysis
In the univariate Cox regression analysis, surgical margin (R0 vs. R1) was significantly associated with RFS (p < 0.001) (Table 3). According to the multivariate Cox regression anal- ysis using a stepwise procedure, the independent prognostic variables of RFS were sex, age (≤48 vs. >48 years), T stage (T1 vs. T2), and surgical margin (R0 vs. R1) (Table 3). A sensitivity analysis was conducted to evaluate the interactions between the four prognostic variables and the surgical approach (open surgery vs. MIS) (Figure 3). As shown in Figure 3, there was no significant association between the surgical approach and the four prognostic variables.
DISCUSSION
This was the largest retrospective cohort study in China on whether MIS should be used for ACC procedures. This study evaluated the efficacy, prognosis, and safety of open surgery and MIS in patients with ACC in stage I-II. This study has shown that for patients with ACC in stage I-II, MIS per- formed better than open surgery in terms of operative time, operative bleeding, complications, and length of hospitaliza- tion. There was no statistically significant difference between the performance of MIS and open surgery in terms of prog- nosis of ACC in stage I-II, especially RFS. This proved that MIS may be a viable surgical modality for experienced mini- mally invasive surgical centers as the treatment of choice for
stage I-II ACC patients. Not only is the prognosis compara- ble, but it also saves time and reduces complications.
The results of this study are consistent with those of a recent meta-analysis,24 which showed no significant differ- ence in terms of survival outcomes between the two surgical approaches, with the MIS group having a faster recovery. However, some meta-analysis studies have shown that MIS may be associated with earlier recurrence, higher surgical margin positivity, and greater peritoneal recurrence rates.24 Our study did not find such differences between the two groups, which may be attributed to the fact that the meta-analysis included patients with different tumor stages, thereby resulting in confounders that may affect outcomes. For example, a multicenter study,15 which is included in the meta-analysis, enrolled 481 patients with ACC, and results showed that the MIS group had a higher margin-positive rate than the open surgery group.
In our cohort, three patients required conversion to open surgery in the middle of the procedure, primarily due to bleeding and tumor capsule rupture. Numerous studies docu- mented this type of conversion. However, the number of cases is extremely small to provide a clear prognostic value for ACC.12,15,16,19,21 Nevertheless, considering the principles of oncological surgery, surgeons must maintain the integrity of the tumor capsule during the procedure. Further, we should actively assess and select an appropriate approach. During surgery, the MIS can be actively converted to open surgery at any time according to the intraoperative situation.
| TABLE 3 Cox proportional hazards regression model showing the association between variables and recurrence-free survival. | ||||
|---|---|---|---|---|
| Characteristics | Univariate analysis | Multivariate analysis | ||
| HR (95% CI) | p-value | HR (95% CI) | p-value | |
| Sex | ||||
| Male | 1 [Reference] | NA | 1 [Reference] | NA |
| Female | 1.47 (0.85-2.52) | 0.167 | 2.68 (1.44-5.01) | 0.002 |
| Age (years) | ||||
| ≤48 | 1 [Reference] | NA | 1 [Reference] | NA |
| >48 | 1.23 (0.72-2.12) | 0.446 | 2.24 (1.22-4.10) | 0.009 |
| Tumor side | ||||
| Left | 1 [Reference] | NA | NA | NA |
| Right | 0.79 (0.47-1.33) | 0.370 | NA | NA |
| T stage | ||||
| I | 1 [Reference] | NA | 1 [Reference] | NA |
| II | 1.58 (0.79-3.15) | 0.192 | 2.37 (1.15-4.88) | 0.020 |
| Surgical margin | ||||
| R0 | 1 [Reference] | NA | 1 [Reference] | NA |
| R1 | 5.35 (2.41-11.85) | <0.001 | 15.40 (5.65-41.97) | <0.001 |
| Adjuvant mitotane therapy | ||||
| No | 1 [Reference] | NA | NA | NA |
| Yes | 2.67 (0.91-7.84) | 0.074 | NA | NA |
| Adjuvant radiotherapy | ||||
| No | 1 [Reference] | NA | NA | NA |
| Yes | 1.48 (0.66-3.29) | 0.339 | NA | NA |
| Cortisol hormone abnormality | ||||
| No | 1 [Reference] | NA | NA | NA |
| Yes | 1.23 (0.73-2.09) | 0.442 | NA | NA |
Abbreviations: CI, confidence interval; HR, hazard ratio; NA, not applicable.
| Subgroups | No. of open surgery | (%) No. of MIS (%) | HR (95% CI) |
|---|---|---|---|
| All Patients | 32 (100) | 32 (100) | 1.10 (0.64 to 1.89) |
| Gender | |||
| Male | 15 (46.9) | 14 (43.8) | . 1.74 (0.74 to 4.10) |
| Female | 17 (53.1) | 18 (56.2) | 0.77 (0.38 to 1.58) |
| Age | |||
| ≤48 | 21 (65.6) | 17 (53.1) | 1.25 (0.63 to 2.46) |
| >48 | 11 (34.3) | 15 (46.9) . | 0.74 (0.29 to 1.86) |
| T stage | |||
| I | 4 (12.5) | 7 (21.9) | 3.34 (0.64 to 17.53) |
| II | 28 (87.5) | 25 (78.1) | 0.96 (0.53 to 1.72) |
| Surgical margin | |||
| R0 | 27 (84.4) | 28 (87.5) | 1.18 (0.65 to 2.14) |
| R1 | 5 (15.6) | 4 (12.5) | 1.14 (0.28 to 4.63) |
0
1
2
3
4
€ Open surgery Better
MIS Better
This was a single-center retrospective cohort study, and it had some limitations. First, similar to all retrospective studies, selection bias could not be eliminated. Second, the current cohort only included patients with stage I/II ACC at a single center. This finding is in contrast to that of other studies that included patients with stage I-IV ACC from multiple centers or even nationwide, which could have limited the generaliz- ability of our findings. Third, we only used RFS and surgical complications as primary endpoints and did not assess overall survival. Nonetheless, RFS and surgical complications are the main indicators of the efficacy of the surgical approach. Meanwhile, overall survival is more related to tumor biology and postoperative adjuvant therapy.
In summary, MIS is a safe and effective treatment approach for localized ACC if selected cautiously. Compared with the open surgery group, the MIS group had a lower inci- dence of postoperative complications, lesser volume of intrao- perative blood loss, shorter operative time, and faster postoperative recovery time.
ACKNOWLEDGMENTS
We want to thank the participants of the current study for their outstanding support, and our colleagues for their valu- able assistance. The authors are grateful to Huizhen Jiang (Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China) for providing valuable advice regarding data collection.
AUTHOR CONTRIBUTIONS
Xin Zhao: Conceptualization; writing - original draft; writ- ing - review and editing. Jiaquan Zhou: Methodology;
formal analysis; writing - review and editing. Xiaohong Lyu: Writing - original draft; writing - review and editing. Yanan Li: Writing - review and editing. Yihong Liu: Inves- tigation; methodology. Yushi Zhang: Funding acquisition; visualization; resources; writing - review and editing.
CONFLICT OF INTEREST STATEMENT
The authors declare that the research was conducted without any commercial or financial relationships that could be con- strued as a potential conflict of interest.
APPROVAL OF THE RESEARCH PROTOCOL BY AN INSTITUTIONAL REVIEWER BOARD
The current study was approved by the Regional Ethics Com- mittee of Peking Union Medical College Hospital (I- 22PJ073).
INFORMED CONSENT
All patients participating in the study have signed a written informed consent.
REGISTRY AND THE REGISTRATION NO. OF THE STUDY/TRIAL
N/A.
ANIMAL STUDIES
N/A.
FUNDING INFORMATION
This work was supported by grants from the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-010).
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Supporting information
Additional Supporting Information may be found in the online version of this article at the publisher’s web-site: Data S1.