World Journal of Surgery
CrossMark
Minimally Invasive Adrenalectomy for Adrenocortical Carcinoma: Five-Year Trends and Predictors of Conversion
Natalie A. Calcatera1 . Chi Hsiung-Wang2 . Nicholas R. Suss1 . David J. Winchester1 . Tricia A. Moo-Young1 . Richard A. Prinz1
@ Société Internationale de Chirurgie 2017
Abstract
Background Adrenocortical carcinoma (ACC) is rare but often fatal. Surgery offers the only chance of cure. As minimally invasive (MI) procedures for cancer become common, their role for ACC is still debated. We reviewed usage of MI approaches for ACC over time and risk factors for conversion using a large national database. Methods ACC patients with localized disease were identified in the National Cancer Data Base from 2010 to 2014. A retrospective review examined trends in the surgical approach over time. Patient demographics, surgical approach, and tumor characteristics between MI, open, and converted procedures were compared.
Results 588 patients underwent adrenalectomy for ACC, of which 200 were minimally invasive. From 2010 to 2014, MI operations increased from 26 to 44% with robotic procedures increasing from 5 to 16%. The use of MI operations compared to open was not different based on facility type (p = 0.40) or location (p = 0.63). MI tumors were more likely to be confined to the adrenal (p < 0.001) but final margin status was not different (p = 0.56). Conversion was performed in 38/200 (19%). Average tumor size was 10.2 cm in the converted group compared to 8.6 cm in the MI group (p = 0.09). There was no difference in extent of disease (p = 0.33), margin status (p = 0.12), or lympho- vascular invasion (p = 0.59) between MI and converted procedures. Tumor size > 5 cm was the only significant predictor of conversion (p = 0.04). No patients with pathologic stage I disease required conversion (0/19).
Conclusions The frequency of MI approaches for ACC is increasing. In the final year of the study, 44% of adrenalectomies were MI. Size > 5 cm was the only significant predictor of conversion.
Introduction
Adrenocortical carcinoma is a rare disease affecting less than one person per million. The prognosis is poor and five- year overall survival ranges from 38 to 46% [1]. Open adrenalectomy has traditionally been recommended due to
☒ Natalie A. Calcatera ncalcatera@gmail.com
1 Department of Surgery, NorthShore University HealthSystem, 2650 Ridge Avenue, Walgreen Suite 2507, Evanston, IL 60201, USA
2 Department of Biostatistics and Research Informatics, NorthShore University HealthSystem, Evanston, IL, USA
the large size of these tumors, tendency for local invasion, and high propensity for implantation. Surgeons have been deterred from adopting a MI approach by previously pub- lished reports of poor outcomes after laparoscopic resec- tion including positive margins, earlier time to recurrence, and development of peritoneal carcinomatosis. A complete oncologic resection is critical for ACC because of the lack of effective adjuvant therapy. MI surgery has multiple advantages that are well described for benign adrenal tumors, but evidence to support the safety and efficacy for ACC is lacking. In order to evaluate whether minimally invasive techniques are being used for adrenocortical cancer, we examined the trends in operative approaches for this tumor using the National Cancer Data Base (NCDB).
We examined differences in outcomes between MI and open, as well as possible risk factors for conversion to an open procedure.
Methods
The NCDB was queried for cases of adrenocortical carci- noma from 2010 to 2014. The earliest year of 2010 was chosen because surgical approach data became available then. 1459 patients with adrenocortical carcinoma were identified using histology code 8370 within the NCDB. Patients with more than one malignant diagnosis, meta- static disease, and undefined operative approach were excluded. Using these inclusion and exclusion criteria, 588 patients were included in the study (Fig. 1). Of these, 151 were treated with laparoscopic adrenalectomy, 49 with
Adrenal patients NCDB 2010-2014 n=2,269
Histology 8370 only (adrenocortical carcinoma) n=1,459
Single malignant diagnosis n=1,213
Exclude patients with metastatic disease n=734
Only patients with surgical approach data n=588
Fig. 1 Selection map
robotic adrenalectomy, and 388 with an open procedure. The frequency of each surgical approach during the study period was compared to identify utilization trends over time.
Characteristics of the MI group and the open group were compared using an intent-to-treat model (all MI cases were included regardless of conversion status). To evaluate differences between the MI and converted group, the patients having a successful MI surgery were compared to the patients requiring conversion to open. Chi-square test was used for categorical variables and t test for continuous variables. Both univariate and multivariable analyses were performed to identify predictors of conversion. Character- istics analyzed included age at diagnosis, gender, ethnicity, primary tumor size > 5 cm, laterality, insurance status, Charlson-Deyo comorbidity index, presence of lympho- vascular invasion, adjuvant chemotherapy and/or radiation, and American Joint Committee on Cancer (AJCC) patho- logic stage. Facility type was categorized using the NCDB definitions of academic center, community cancer program, comprehensive community cancer program, or integrated network cancer program. Facility location was analyzed by the nine NCDB geographic designations throughout the USA. Margin status was categorized as negative (R0) or positive (R1 or R2). Data on nodal status were missing for the majority of patients (92%) and were consequently excluded from analysis. Extent of disease was categorized as localized or extra-adrenal with any extension beyond the capsule including into adjacent organs. Postoperative out- comes were evaluated using 30-day mortality, 30-day hospital readmission, and length of stay. A Kaplan-Meier survival curve was created to evaluate overall survival, and Cox regression analysis was used to identify independent predictors of a worse outcome. All data analyses were performed using SAS 9.4 (Cary, NC), and a p < 0.05 was considered statistically significant.
Results
During the study period, 1459 patients with ACC were identified, of whom 588 met inclusion criteria (Fig. 1). A MI approach was used in 200 (34%) patients and an open approach in 388 (66%). Between 2010 and 2014, the use of MI surgery increased almost twofold from 26 to 44%, while robotic adrenalectomy increased more than threefold from 5 to 16%. Open adrenalectomy accounted for 74% of the procedures in 2010 and 56% in 2014 (Fig. 2). Among patients undergoing MI surgery, there was no difference in overall conversion rate between laparoscopic adrenalec- tomy and robotic adrenalectomy (21 vs. 12%, p = 0.17). Although the numbers of robotic adrenalectomy grew at a faster rate during the study period, it was trending toward
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MI Adrenalectomy
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Robotic Adrenalectomy
to a lower conversion rate compared to laparoscopic adrenalectomy. However, this was not statistically signifi- cant (Table 1).
Characteristics of patients having MI and open adrenalectomy were compared (Table 2). When consider- ing known preoperative variables, there was no difference in the use of MI surgery based on tumor laterality, insur- ance status, facility type, or geographic location. Only tumor size > 5 cm was significantly different between the two groups (p > 0.001). Average tumor size was greater in the open group as compared to the MI group (12.4 ± 6.9 vs. 8.9 ± 6.2 cm, p < 0.001). The MI group was more likely to have disease confined to the adrenal and present with earlier stage disease; however, there was no difference in final margin status. The open group was more likely to have adjuvant chemotherapy.
To determine factors associated with conversion, the MI surgery group was compared to the converted group (Table 3). There was no difference in age, gender, race, insurance status, Charlson-Deyo comorbidity index, extent of disease, laterality, margin positivity, AJCC pathologic stage, or lymphovascular invasion between the two groups. None of the patients with pathologic stage I disease required conversion (0/19). Twenty-five percent of stage II (13/52), 16% of stage III (5/31), and 30% of stage IV patients (3/10) were converted to open, but the difference was not statistically significant. Size greater than 5 cm was
the only predictor of conversion on multivariable analysis (p = 0.04). The overall conversion rate for tumors > 5 cm was 22%, while the conversion rate for tumors ≤ 5 cm was 7%. The average tumor size was 8.6 cm (± 6.3 SD) for the MI group and 10.2 cm (± 5.1 SD) for the converted group, respectively.
Table 4 summarizes the short-term outcomes between the MI and the converted groups. There were no deaths within 30 days in either group but the data were missing in 27% of the MI group and 32% of the converted group. No difference was seen between the groups for 30-day read- mission (p = 0.77). Average length of stay was shorter for the MI group compared to the converted group (3.7 vs. 6.3 days, p = 0.02).
Overall survival for the converted group was worse compared to the MI group in both unadjusted and adjusted analyses (Fig. 3). The median survival for the MI group was twice that of the converted group (4.7 vs. 2.3 years, p = 0.005). In multivariable Cox analysis, MI converted to open (HR 2.1, 95% CI 1.1-3.9), tumor size > 5 cm (HR 1.02, 95% CI 1.01-1.02) and positive margin (HR 2.4, 95% CI 1.2-4.7) were the independent predictors of worse overall survival among patients undergoing MI adrenalectomy.
Despite the worse survival seen in the converted group, there was no difference in overall survival between the MI and open groups in both unadjusted and adjusted analyses (Fig. 4). Median survival for the MI group was 4.4 years compared to 4.6 years in the open group. In multivariable Cox analysis, positive margin (HR 2.08, 95% CI 1.35-3.20) and lymphovascular invasion (HR 1.60, 95% CI 1.07-2.38) were the independent predictors of worse overall survival.
Discussion
As the use of minimally invasive surgery for cancer becomes more widespread, the oncologic outcomes of these techniques compared to the open approach continue to be scrutinized. Minimally invasive adrenalectomy for
| Year of diagnosis | Total MI cases | Laparoscopic w/o conversion | Laparoscopic conversion | Robotic | w/o conversion | Robotic conversion |
|---|---|---|---|---|---|---|
| 2010 | 35 | 26 | 2 (7.1%) | 7 | 0 | |
| 2011 | 43 | 31 | 6 (16%) | 6 | 0 | |
| 2012 | 34 | 21 | 5 (19%) | 6 | 2 (25%) | |
| 2013 | 33 | 16 | 9 (36%) | 6 | 2 (25%) | |
| 2014 | 55 | 25 | 10 (29%) | 18 | 2 (10%) | |
| Total | 200 | 119 | 32 (21%)* | 43 | 6 (12%)* | |
* The conversion rate was not significantly different between laparoscopic and robotic (p = 0.17)
| MI n = 200 | Open n = 388 | p | |
|---|---|---|---|
| Age (mean) | 55 (std ± 14) | 53 (std ± 15) | 0.17 |
| Gender | 0.24 | ||
| Male | 71 (35.5%) | 157 (40.5%) | |
| Female | 129 (64.5%) | 231 (59.5%) | |
| Ethnicity | 0.47 | ||
| Caucasian | 176 (88.0%) | 323 (83.2%) | |
| African American | 14 (7.0%) | 36 (9.3%) | |
| Asian | 4 (2.0%) | 8 (2.1%) | |
| Pacific Islander | 3 (1.5%) | 15 (3.9%) | |
| Other | 3 (1.5%) | 6 (1.5%) | |
| Insurance | 0.09 | ||
| Not insured | 9 (4.5%) | 25 (6.4%) | |
| Private insurance | 110 (55.0%) | 209 (53.9%) | |
| Medicaid | 11 (5.5%) | 24 (6.2%) | |
| Medicare | 65 (32.5%) | 100 (25.8%) | |
| Other government | 2 (1.0%) | 8 (2.1%) | |
| Unknown | 3 (1.5%) | 22 (5.7%) | |
| Charlson/Deyo score | 0.001 | ||
| 0 | 133 (66.5%) | 311 (80.2%) | |
| 1 | 54 (27.0%) | 63 (16.2%) | |
| 2 | 13 (6.5%) | 14 (3.6) | |
| Facility type | 0.14 | ||
| Community cancer program | 8 (4.0%) | 6 (1.5%) | |
| Comprehensive community cancer program | 53 (26.5%) | 88 (22.7%) | |
| Academic/research program | 86 (43.0%) | 184 (47.4%) | |
| Integrated network cancer program | 21 (10.5%) | 31 (8.0%) | |
| Other | 32 (16.0%) | 79 (20.4%) | |
| Facility location | 0.07 | ||
| New England | 13 (6.5%) | 14 (3.6%) | |
| Middle Atlantic | 34 (17.0%) | 46 (11.9%) | |
| South Atlantic | 32 (16.0%) | 57 (14.7%) | |
| East North Central | 26 (13.0%) | 47 (12.1%) | |
| East South Central | 7 (3.5%) | 25 (6.4%) | |
| West North Central | 14 (7.0%) | 32 (8.2%) | |
| West South Central | 12 (6.0%) | 35 (9.0%) | |
| Mountain | 12 (6.0%) | 19 (4.9%) | |
| Pacific | 50 (25.0%) | 113 (29.1) | |
| Margin | 0.56 | ||
| Negative | 141 (70.5%) | 289 (74.5%) | |
| Positive | 36 (18.0%) | 58 (14.9%) | |
| Unknown | 23 (11.5%) | 41 (10.6%) | |
| Size in cm (mean) | 8.9 (std ± 6.2) | 12.4 (std ± 6.9) | < 0.001 |
| Size > 5 cm | < 0.001 | ||
| No | 47 (23.5%) | 33 (8.5%) | |
| Yes | 148 (74.0%) | 345 (88.9%) | |
| Unknown | 5 (2.5%) | 10 (2.6%) | |
| Laterality | 0.14 | ||
| Right | 67 (41.4%) | 22 (57.9%) |
| MI n = 200 | Open n = 388 | p | |
|---|---|---|---|
| Left | 93 (57.4%) | 16 (42.1%) | |
| Unknown | 2 (1.0%) | 3 (0.8%) | |
| Extent of disease | < 0.001 | ||
| Confined to adrenal | 132 (66.0%) | 212 (54.6%) | |
| Locally invasive | 53 (26.5%) | 114 (29.4%) | |
| Unknown | 11 (5.5%) | 60 (16%) | |
| Lymphovascular invasion | 0.08 | ||
| No | 70 (43.2%) | 15 (39.5%) | |
| Yes | 63 (38.9%) | 18 (47.4%) | |
| Unknown | 29 (17.9%) | 5 (13.2%) | |
| Stage AJCC | < 0.001 | ||
| 1 | 19 (9.5%) | 9 (2.3%) | |
| 2 | 52 (26.0%) | 122 (31.4%) | |
| 3 | 36 (18.0%) | 78 (20.1%) | |
| 4 | 10 (5.0%) | 49 (12.6%) | |
| Unknown | 80 (40.0%) | 120 (30.9%) | |
| Received chemo | 0.005 | ||
| No | 138 (69.0%) | 223 (60.0%) | |
| Yes | 48 (24.0%) | 145 (37.4%) | |
| Unknown | 14 (7.0%) | 20 (5.6%) | |
| Received radiation | 0.41 | ||
| No | 160 (80.0%) | 296 (76.3%) | |
| Yes | 35 (17.5%) | 85 (21.9%) | |
| Unknown | 5 (2.5%) | 7 (1.8%) |
small, benign lesions has become standard, while there is mixed evidence about the outcomes of these techniques for adrenocortical carcinoma. Adjuvant treatments offer lim- ited benefit for this disease, and therefore a complete oncologic resection is critical. Due to reports of shorter time to recurrence and peritoneal carcinomatosis, the clinical impression has been that prolonged disease-free and overall survival can be best achieved with an open operation [2-5]. Despite these observations, we found in our study that the use of MI techniques in ACC is increasing. This contrasts with the most recently published 2017 recommendation by the National Comprehensive Cancer Network that states open adrenalectomy is the preferred approach for preoperatively suspected adrenal cancer. These recommendations specifically state that there is an increased risk of peritoneal spread and local recur- rence with laparoscopic resection [2]. In our data, the use of MI adrenalectomy accounted for almost half (44%) of procedures in the final year of study.
Characteristics of patients having a MI adrenalectomy were compared to those having an open operation. Smaller tumor size was predictive of having a minimally invasive
procedure (p < 0.001) (Table 2). MI procedures were more likely to have tumors confined to the adrenal, but there was no difference in pathologic margin status between MI and open groups. In our data, despite smaller tumor size pre- dicting the use of MI surgery, large tumor size was not a clear deterrent to the use of a MI approach. The average tumor size was 8.9 cm in the MI group and 12.4 cm in the open group. There were no differences in the use of MI procedures based on facility type or location throughout the USA. In one of the largest studies to date comparing MI to open adrenalectomy, including 13 tertiary care facilities and 201 patients, smaller tumor size was the only preop- erative predictor of MI surgery. Similar to our study, they did not identify any differences in utilization based on institution [6].
Although ACC may not always be diagnosed preoper- atively, large tumor size is well known to be associated with an increased risk of cancer [5, 7, 8]. Specifically, a study performed by Sturgeon et al. from Northwestern University comparing data from the Surveillance, Epi- demiology, and End Results Program (SEER) to retro- spective single institution data found that the size of the
| MI n = 162 | MI to open n = 38 | p | |
|---|---|---|---|
| Age (mean) | 55.3 (std ± 14.6) | 54.8 (std ± 15.2) | 0.83 |
| Range 20-87 | Range 24-85 | ||
| Gender | 0.34 | ||
| Male | 55 (34.0%) | 16 (42.1%) | |
| Female | 107 (66.0%) | 22 (57.9%) | |
| Ethnicity | 0.44 | ||
| Caucasian | 144 (88.9%) | 32 (84.2%) | |
| African American | 11 (6.8%) | 3 (7.9%) | |
| Asian | 2 (1.2%) | 2 (5.3%) | |
| Pacific Islander | 2 (1.2%) | 1 (2.6) | |
| Other | 3 (1.9%) | 0 (0.0%) | |
| Insurance | 0.91 | ||
| Not insured | 7 (4.3%) | 2 (5.3%) | |
| Private insurance | 90 (55.6%) | 20 (52.6%) | |
| Medicaid | 9 (5.6%) | 2 (5.3%) | |
| Medicare | 51 (31.5%) | 14 (36.8%) | |
| Other government | 2 (1.2%) | 0 (0.0%) | |
| Unknown | 3 (1.9%) | 0 (0.0%) | |
| Charlson/Deyo score | 0.06 | ||
| 0 | 106 (65.4%) | 27 (71.1%) | |
| 1 | 48 (29.6%) | 6 (15.8%) | |
| 2 | 8 (4.9%) | 5 (13.2%) | |
| Facility type | 0.40 | ||
| Community cancer program | 5 (3.1%) | 3 (7.9%) | |
| Comprehensive community cancer program | 41 (25.3%) | 12 (31.6%) | |
| Academic/research program | 72 (44.4%) | 14 (36.8%) | |
| Integrated network cancer program | 19 (11.7%) | 2 (5.3%) | |
| Other | 25 (15.4%) | 7 (18.4%) | |
| Facility location | 0.07 | ||
| New England | 10 (6.2%) | 3 (7.9%) | |
| Middle Atlantic | 30 (18.5%) | 4 (10.5%) | |
| South Atlantic | 29 (17.9%) | 3 (7.9%) | |
| East North Central | 15 (9.3%) | 11 (28.9%) | |
| East South Central | 7 (4.3%) | 0 (0.0%) | |
| West North Central | 12 (7.4%) | 2 (5.3%) | |
| West South Central | 10 (6.2%) | 2 (5.3%) | |
| Mountain | 9 (5.6%) | 3 (7.9%) | |
| Pacific | 40 (24.7%) | 10 (26.3%) | |
| Margin | 0.12 | ||
| Negative | 119 (73.5%) | 22 (57.9%) | |
| Positive | 25 (15.4%) | 11 (28.9%) | |
| Unknown | 18 (11.1%) | 5 (13.2%) | |
| Size in cm (mean) | 8.6 (std ± 6.3) | 10.2 (std ± 5.1) | 0.09 |
| Size > 5 cm | 0.04 | ||
| No | 44 (27.2%) | 3 (7.9%) | |
| Yes | 114 (70.4%) | 34 (89.5%) | |
| Unknown | 4 (2.5%) | 1 (2.6%) |
| MI n = 162 | MI to open n = 38 | p | |
|---|---|---|---|
| Laterality | 0.30 | ||
| Right | 67 (41.4%) | 22 (57.9%) | |
| Left | 93 (57.4%) | 16 (42.1%) | |
| Extent of disease | 0.33 | ||
| Confined to adrenal | 107 (66.0%) | 25 (65.8%) | |
| Locally invasive | 44 (27.2%) | 9 (23.7%) | |
| Unknown | 7 (4.3%) | 4 (10.5%) | |
| Lymphovascular invasion | 0.59 | ||
| No | 70 (43.2%) | 15 (39.5%) | |
| Yes | 63 (38.9%) | 18 (47.4%) | |
| Unknown | 29 (17.9%) | 5 (13.2%) | |
| Stage AJCC | 0.19 | ||
| 1 | 19 (11.7%) | 0 (0.0%) | |
| 2 | 39 (24.1%) | 13 (34.2%) | |
| 3 | 31 (19.1%) | 5 (13.2%) | |
| 4 | 7 (4.3%) | 3 (7.9%) | |
| Unknown | 64 (39.5%) | 16 (42.1%) | |
| Received chemo | 0.08 | ||
| No | 115 (71.0%) | 23 (60.5%) | |
| Yes | 34 (21.0%) | 14 (36.8%) | |
| Unknown | 13 (8.0%) | 1 (2.6%) | |
| Received radiation | 0.28 | ||
| No | 133 (82.1%) | 27 (71.1%) | |
| Yes | 25 (15.4%) | 10 (26.3%) | |
| Unknown | 4 (2.5%) | 1 (2.6%) |
| MI n = 162 | MI converted to open n = 38 | p | |
|---|---|---|---|
| 30-day mortality | 0.63 | ||
| Alive | 118 (73%) | 26 (68%) | |
| Dead | 0 | 0 | |
| Unknown | 44 (27%) | 12 (32%) | |
| 30-day readmission | 0.78 | ||
| No | 155 (96%) | 37 (97%) | |
| Yes | 7 (4%) | 1 (3%) | |
| Length of stay (days) | 3.7 std 5.1 | 6.3 std 8.7 | 0.02 |
| Range 0-38 | Range 1-56 |
primary tumor was highly predictive of the presence of ACC. Tumors > 8 cm had a likelihood ratio of 16.9 of being ACC compared with tumors < 8 cm [8]. Similarly, in an institutional prospective series from Oxford Univer- sity Hospitals in the UK reviewing adrenal tumors > 8 cm seen from 2000 to 2013, Abdel-Aziz et al. found that 81% (31/37) were ACC on final pathology [7]. With the average tumor size in our study > 8 cm, it can be inferred that the
majority of MI cases were done with the suspicion for malignancy.
The advantages of laparoscopic and robotic adrenalec- tomy are well described. These include decreased postop- erative pain, decreased hospital length of stay, less blood loss, and earlier return to normal activity when compared to open surgery [9]. Our data showed an average length of stay of 3.7 days for MI surgery compared to 6.3 days for
Product-Limit Survival Estimates
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MI
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Unadjusted HR=2.4 (95% CI 1.3-4.4), p=0.005
Adjusted HR=2.1 (95%CI 1.1-3.9), p=0.02
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Product-Limit Survival Estimates
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Unadjusted HR= 1.03 (95% CI 0.75-1.42), p=0.85 Adjusted HR= 1.01 (95% CI .0.70-1.48), p=0.93
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Fig. 4 Overall survival for patients with ACC with a minimally invasive procedure versus open operation
converted procedures (Table 4). Compared to laparoscopy, robotic adrenalectomy offers additional technical advan- tages. Three-dimensional camera magnification of the operative field and wristed instruments aid in difficult dissection, careful handling of delicate adrenal tissue and vascular structures during adrenalectomy. Although most series describing robotic adrenalectomy are small and were performed for benign tumors, based on our data it does appear that this technique is being used for ACC more frequently [10-12]. The largest review series at this time for robotic adrenalectomy was a review of technique and outcomes in 26 studies published in 2016 by Xin et al. from Singapore. Most patients included had benign disease. However, they concluded that robotic adrenalectomy in general is safe and effective when compared to laparoscopy [10]. There is a paucity of literature describing outcomes of
robotic adrenalectomy for ACC. More data are needed to evaluate this practice as it becomes more common.
Previous reports have identified MI surgical approach as a risk factor for the development of peritoneal carcino- matosis (PC) in ACC. Leboullex et al. reported a single institution retrospective cohort study of 64 French patients with ACC having surgery from 2003 to 2009 [3]. Only six patients in this group had laparoscopic surgery. However, they did find an association with development of PC during the follow-up period since 67% of the laparoscopic oper- ations developed PC compared to 27% of the open oper- ations. Gonzalez et al. from MD Anderson Cancer Center reported an 8% risk of PC in patients treated with open adrenalectomy and a startling 83% risk of PC in patients having a laparoscopic adrenalectomy [4]. A retrospective series from the University of Michigan of 17 patients undergoing laparoscopic adrenalectomy also found earlier time to recurrence (9.6 vs. 19.2 months for open) and recommended against MI adrenalectomy [5]. Although there is no consensus about the ideal approach for resection of an adrenal cancer, R0 resection is associated with a recurrence rate of 23% versus 51% for R1 and R2 resec- tions [13]. Further study is needed to determine if there is an independent relationship between the surgical approach, time to recurrence, and disease-specific survival.
Tumor size is frequently discussed in adrenal surgery concerning both the feasibility of minimally invasive approaches and rates of conversion. The tumor size threshold for surgeons to attempt MI resection has increased over time with individual and institutional experience, as well as improving laparoscopic and robotic technologies [11, 14]. In addition to size, the tendency for local invasion is frequently but not always suspected based on preoperative imaging and may alter the surgical approach if suspected preoperatively or encountered during the operation. Previous reports cite bleeding, tumor size, local tumor invasion, adhesions, and body habitus as contributing factors for conversion to open adrenalectomy [10, 13, 15, 16]. Our analysis showed that tumor size greater than 5 cm was associated with conversion (p = 0.04). All patients with stage I tumors had a successful minimally invasive procedure. The overall conversion rate for tumors > 5 cm was 22 versus 7% for tumors less than 5 cm. Interestingly, tumor extension outside the adrenal gland was not more common in the converted group (p = 0.33). In the MI group, 27% (44/162) had locally invasive tumors com- pared to 24% (9/38) in the converted group.
To evaluate perioperative morbidity, we used data points available through the NCDB as surrogate markers including 30-day mortality, 30-day readmission, and length of hospital stay. Mortality and readmission rates were not different. However, 30-day mortality must be interpreted with caution due to a large amount of missing data (28% of patients). Length of stay for MI adrenalectomy was
3.7 days (range 0-38) and 6.3 days (range 1-56) for con- verted procedures (p = 0.02). Surgery-specific factors that may have contributed to conversion cannot be identified such as surgeon experience or volume, intra-operative blood loss, operative time, or patient body mass index. Based on our findings of an increased conversion rate, we suggest that tumor size > 5 cm should warrant caution when choosing a MI resection for a suspected ACC.
In our study, we saw a decreased overall survival for the converted group. This was present in both the unadjusted and adjusted analysis when controlling for multiple factors, including positive margin and tumor size. Previous studies have reported that complete surgical resection confers a five-year survival of 32 to 50% in patients with localized ACC. The risk of recurrence after surgical resection for ACC can be as high as 50 to 85% [16]. In our data, overall survival for the converted group was 60% at one year versus 80% for the minimally invasive group. There was no difference in positive margins, 30-day readmission, or mortality. The converted group did have a larger tumor size, which has been associated with worse disease-free survival [16]. However, when controlling for these factors, overall survival was still worse in the converted group, indicating there are other factors influencing this outcome.
When the MI group was compared to open, we did not see a difference in overall survival on unadjusted or adjusted analysis (Fig. 4). The MI group had smaller tumors on average, and more disease confined to the adrenal. Positive margin status and presence of lympho- vascular invasion did not differ between groups (Table 2). In multivariable Cox analysis, positive margin (HR 2.08, 95% CI 1.35-3.20) and lymphovascular invasion (HR 1.60, 95% CI 1.07-2.38) were the independent predictors of worse overall survival.
In addition to the retrospective nature of this study, there are several limitations. We cannot examine contributing factors such as surgeon experience, tumor capsule rupture or spillage of tumor, perioperative blood loss, operative time, tumor functionality, development of local recurrence, or metastatic disease. The NCDB does not identify time to recurrence or disease-specific survival. Caution should be used when interpreting the survival data, especially the worse overall survival in the converted group, due to the limitations men- tioned above. Further study is needed to compare disease- specific outcomes for MI versus open adrenalectomy for ACC.
Conclusion
The frequency of minimally invasive surgery for adreno- cortical carcinoma is increasing. Up to 44% of all adrenalectomies were performed using a MI approach in
the final study year. Smaller tumor size predicted the use of minimally invasive surgery. Size > 5 cm was the only significant predictor of conversion to open.
Compliance with ethical standards
Conflicts of interest None.
References
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