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Reassessing the impact of tumor size on operative approach in adrenocortical carcinoma
Jonathan J. Hue MD ® Katherine Bingmer MD Heming Zhao MD
John B. Ammori MD ® Scott M. Wilhelm MD Christopher W. Towe MD
Luke D. Rothermel MD, MPH
Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
Correspondence Luke D. Rothermel, MD, MPH, Department of Surgery, Division of Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH, 11100 Euclid Ave. Cleveland, OH 44106, USA.
Email: Luke.Rothermel@UHHospitals.org
Abstract
Background: Adrenocortical carcinoma (ACC) is often a contraindication to minimally invasive adrenalectomy (MIA). We used an administrative data set to analyze post- operative outcomes. We hypothesized that small tumors would have better short- and long-term outcomes, independent of the operative approach.
Methods: The National Cancer Database (2010-2016) identified patients with ACC who underwent adrenalectomy. Tumors were grouped: < 5 cm (n = 125), 5-10 cm (n = 431), and >10 cm (n = 443). The primary and secondary outcomes were margin positivity and overall survival, respectively.
Results: Nine hundred and ninety-nine patients were analyzed: 37% MIA and 63% open adrenalectomy (OA). As the size increased, the rate of attempted MIA decreased. Larger tumors were associated with conversion to open. Although tumors with local invasion and those which required conversion to open were associated with an increased likelihood of a positive margin, tumor size was not. Although “complete” MIA (vs. OA) and tumor size were not associated with differences in survival, conversion (HR = 1.83, p = . 02), positive margins (HR = 1.54, p =. 01), and local invasion (HR = 1.84, p <. 001) were associated with poor survival.
Conclusion: Positive margins are associated with poor survival in ACC. Tumors ≥ 5 cm were associated with an increased conversion rate and subsequent increase in margin positivity. MIA may be considered for select patients with small tumors but adequate oncologic resection is critical.
KEYWORDS
adrenalectomy, adrenocortical carcinoma, minimally invasive surgery, survival analysis
1 INTRODUCTION
Adrenalectomy plays a prominent role in the treatment of localized adrenocortical carcinoma (ACC) and represents a patient’s best chance of long-term survival.1 Due to concern for local recurrence, tumor capsule violation, and positive resection margin, open adrenalectomy (OA), in- dependent of tumor size, is recommended by several consensus groups in the United States, including the National Comprehensive Cancer
Network, the American Association of Clinical Endocrinologists, the American Association of Endocrine Surgeons, and the Society of Gas- trointestinal and Endoscopic Surgeons (SAGES).2-5 However, minimally invasive adrenalectomy (MIA) for ACC has been described in numerous studies.6-9 Importantly, guidelines from the European Society of Endo- crine Surgeons (ESES) suggest that MIA may be performed by experi- enced surgeons for ACC tumors < 6 cm (previously 10 cm10), but state that the surgeon must ensure a negative resection margin without tumor
capsule rupture.11 ESES and SAGES additionally recommend conversion to open if MIA is attempted for early-stage ACC but adhesions, local invasion, or lymphadenopathy are encountered intraoperatively.5
This variability in guidelines is likely due to inconsistencies in the literature detailing outcomes among patients with ACC, as almost all past reports are stratified by operative approach. In certain studies, MIA has been associated with an increased likelihood of local recurrence with subsequent poor disease-free survival.12-14 Other studies have demon- strated comparable outcomes when evaluating OA and MIA for ACC < 10 cm.15-19 These data highlighting tumor size as an important factor in determining the safety of an open versus minimally invasive approach are limited by low numbers of patients in institutional datasets. There is a paucity of data directly analyzing the association between tumor size and surgical outcomes.
As past studies and guidelines stress the importance of a margin- negative resection, our primary aim was to use the National Cancer Database (NCDB) to analyze the margin positivity rate primarily based on tumor size. Secondary aims included analyzing overall survival and other short-term postoperative outcomes. We hypothesized that small tumors would have better short- and long-term outcomes, independent of the operative approach.
2 METHODS
2.1 Institutional assurances
The Institutional Review Board at University Hospitals Cleveland Medical Center has deemed that retrospective analyses of public, deidentified data sets are exempt from review.
2.2 Data source
The NCDB receives patient information from Commission on Cancer- accredited hospitals across the nation and contains deidentified
information on approximately 70% of all new malignancies diagnosed in the United States each year. This database is jointly maintained by the American College of Surgeons and the American Cancer Society. The NCDB Participant User File data dictionary contains definitions of variables used in this study.20 The accuracy of the data reported and statistical analyses performed are not verified by the American College of Surgeons or American Cancer Society. The conclusions represent those of the authors.
2.3 | Patient cohort
Adult patients diagnosed with ACC were identified between 2010 and 2016, using International Classification for Diseases in Oncology (3rd Edition) codes 8010 and 8370. All ACC in the NCDB are categorized as invasive (NCDB behavior code 3). Patients were excluded if they received nonoperative management, had clinical N-stage 1 disease, had metastatic disease at presentation, or if tumor size was unknown. Before 2010, the operative approach was not recorded in NCDB, thus these patients were excluded. A consort diagram can be seen in Figure 1.
Data on local tumor invasion was abstracted from the “cx_extension” data field within the NCDB. Local invasion was defined as invasion into adjacent connective tissue (i.e., Gerota’s fascia), kidney, retroperitoneal structures, pancreas, diaphragm, liver, or spleen. Local invasion also in- cluded tumors classified as T3 or T4 within the “cx_extension” data field, as this is consistent with current American Joint Committee on Cancer (AJCC) staging.21 Venous extension was abstracted from the “cs_site- specific_factor_3” data field within the NCDB and was defined as invasion of the adrenal vein, renal vein, inferior vena cava, large vessel venous invasion not otherwise specified, or any combination.
2.4 | Exposure
Patients were stratified by tumor size: < 5, 5-10, and >10 cm. This grouping was chosen based on AJCC staging21 and past reports
All NCDB adrenocortical carcinoma (2004-2016) N = 3,834
ACC, year ≥2010 N =2,233
Year <2010 N = 1,601
1
Underwent adrenalectomy N =1,400
Managed non-operatively N = 833
Tumor size available for review N=1,340
Missing tumor size data N = 60
2
Operative approach recorded N = 1,168
Missing operative approach N = 172
Clinically node-negative disease N = 1,112
Clinical N-stage 1 N=56
2
Final analytic cohort N = 999
Clinical M-stage 1 N=13
E
examining the feasibility of MIA in tumors <10 cm.15-19 Patients were also stratified by starting operative approach: OA or MIA (laparoscopic or robotic-assisted). Analyses were performed accounting for patients who required conversion to an open operation.
2.5 | Outcomes
The primary outcome of this analysis was margin positivity. This was defined as microscopic residual tumor, macroscopic residual tumor, or residual tumor not otherwise specified. Secondary outcomes included conversion to an open procedure (yes/no) and overall survival. Overall survival was defined as the number of months from the patient’s date of diagnosis to their date of death or last follow-up. Disease-specific outcomes cannot be evaluated using the NCDB, as data pertaining to recurrence or cause of death are not captured. The NCDB does not include survival data for patients diagnosed in 2016, thus these patients were not included in survival analyses.
2.6 Statistical analysis
Statistical comparisons between groups were performed using the Wilcoxon rank-sum or Kruskal-Wallis tests for continuous variables and Pearson’s x2-test for categorical variables. Demographics and clinical characteristics are described using median and range or in- terquartile range (IQR) for continuous variables, and frequency and percentages for categorical variables. A multivariable logistic re- gression was used to determine if there was an association between clinical/demographic/operative details and margin positivity. A simi- lar multivariable regression was used to analyze factors associated with conversion to an open operation. The Kaplan-Meier method was used to estimate survival and was compared by the log-rank test. Multivariable Cox proportional hazards regression was used to analyze overall survival. Variables included in multivariable analyses were those deemed clinically salient. StataSE v16.0 (Statacorp LLC) was used for statistical analyses. A p-value ≤ .05 was used to indicate statistical significance.
3 RESULTS
3.1 Demographics and clinical data
A total of 999 patients were included in the analysis: 12.5% had a tumor <5 cm, 43.1% had a tumor between 5 and 10 cm, and 44.3% had a tumor >10 cm (Table 1). Patients with tumors >10 cm were younger and less likely to be female as compared to the smaller tumor groups. There were no differences in race, Charlson-Deyo comorbidity index, or insurance payor between the tumor size groupings. Most patients received care at an academic hospital. There was no differ- ence in tumor laterality. Tumors > 10 cm were more likely to have a local invasion or vascular invasion as compared to smaller tumors.
Patients with larger tumors more commonly underwent a planned open operation (<5 cm: 35.2%; 5-10 cm: 52.2%; >10 cm: 81.3%, p <. 001). There was no difference in the starting MIA approach (laparoscopic, robotic) between tumor size groups.
3.2 | Margin positivity
The overall positive margin rate was 19.0%. There was no difference in margin positivity based on tumor size (p = . 988, Table 2). Tumors with local or vascular invasion were more likely to have a positive margin. Among patients within a specific tumor size category, the rate of positive margins was greater among patients who required conversion to open (Table S1). As an example, among those who underwent an OA, MIA, or converted procedure for tumors >10 cm, the positive margin rate was 17.3%, 18.2%, and 47.6%, respectively (p =. 003). This association was further explored using multivariable logistic regression (Table 3). Tumor size was not independently as- sociated with positive margins (5-10 vs. < 5 cm: OR, 0.805; p = . 568; > 10 vs. < 5 cm: OR, 0.515; p = . 099). However, patients who required conversion to open had a higher likelihood of a positive margin as compared to OA (OR, 2.852; p = . 030). Additionally, locally invasive tumors were associated with an increased likelihood of po- sitive margins (OR, 5.362; p <. 001).
3.3 | Conversion
Among those who underwent an MIA, the overall conversion rate was 16.5%. On univariable analysis, the conversion rate increased as tumor size increased (<5 cm: 3.7%; 5-10 cm: 16.5%; >10 cm: 28.9%; p < . 001, Table S2). Multivariable logistic regression demonstrated that increasing tumor size was associated with a greater likelihood of conversion (5-10 vs. < 5 cm: OR, 9.598; p = . 031; >10 vs. < 5 cm: OR, 22.942; p = . 004, Table 4). Left-sided tumors were less likely to re- quire conversion as compared to right (OR, 0.280; p = . 004).
3.4 | Survival analysis
The median survival among patients with tumors <5, 5-10, and >10 cm were 59.5, 60.7, and 48.8 months (p =. 106), respec- tively. Patients with evidence of local invasion had a median survival of just 32.8 months, which was significantly lower as compared to patients without local invasion (median survival 72.1 months, p < . 001). This survival trend was seen among all tumor size groups (data not shown). The median survival of patients who had a positive margin was significantly decreased as compared to those with a margin-negative resection (21.8 vs. 71.8 months, p <. 001). Survival curves stratified by operative approach can be seen in Figure 2 (A, Tumors < 5 cm; B, Tumors 5-10 cm; C, Tumors > 10 cm). Among patients with tumors 5-10 cm, those who required conversion to an open operation (median survival 32.8 months) had the shortest
| <5 cm (n = 125) | 5-10 cm (n = 431) | > 10 cm (n = 443) | p value* | |
|---|---|---|---|---|
| Age (years), median (IQR) | 59 (47, 67) | 58 (47, 68) | 54 (41, 65) | <. 001 |
| Female, N (%) | 83 (66.4%) | 278 (64.5%) | 246 (55.5%) | .010 |
| Race, N (%) | .564 | |||
| White | 104 (83.2%) | 366 (84.9%) | 389 (87.8%) | |
| Black | 15 (12.0%) | 43 (10.0%) | 34 (7.7%) | |
| Other | 6 (4.8%) | 22 (5.1%) | 20 (4.5%) | |
| Charlson-Deyo score, N (%) | .092 | |||
| 0 | 87 (69.6%) | 297 (68.9%) | 337 (76.0%) | |
| 1 | 31 (24.8%) | 98 (22.7%) | 84 (19.0%) | |
| ≥2 | 7 (5.6%) | 36 (8.4%) | 22 (5.0%) | |
| Private insurance, N (%) | 69 (55.2%) | 216 (50.1%) | 256 (57.8%) | .073 |
| Academic program, N (%) | 77 (71.3%) | 248 (65.3%) | 251 (72.1%) | .115 |
| Left-sided tumor, N (%) | 59 (55.2%) | 220 (51.0%) | 234 (52.8%) | .311 |
| Local invasion, N (%)ª | <. 001 | |||
| Absent | 77 (61.6%) | 235 (54.2%) | 204 (46.0%) | |
| Present | 34 (27.2%) | 113 (26.2%) | 182 (41.1%) | |
| Unknown | 14 (11.2%) | 83 (19.3%) | 57 (12.9%) | |
| Vascular invasion, N (%)b | <. 001 | |||
| Absent | 62 (49.6%) | 255 (59.2%) | 219 (49.4%) | |
| Present | 31 (24.8%) | 80 (18.6%) | 142 (32.1%) | |
| Unknown | 32 (25.6%) | 96 (22.3%) | 82 (18.5%) | |
| Operative approach, N (%) | <. 001 | |||
| Open | 44 (35.2%) | 225 (52.2%) | 360 (81.3%) | |
| Minimally invasive | 81 (64.8%) | 206 (47.8%) | 83 (18.7%) | |
| Laparoscopic | 56 (69.1%) | 157 (76.2%) | 62 (74.7%) | .464 |
| Robotic | 25 (30.9%) | 49 (23.8%) | 21 (25.3%) |
ªIncludes adjacent connective tissue (i.e., Gerota’s fascia), kidney, retroperitoneal structures, pancreas, diaphragm, liver, and spleen. Also includes tumors classified as T3 or T4. bIncludes adrenal vein, renal vein, inferior vena cava, and large vessel venous invasion not otherwise specified.
*p values are representative of comparisons between all three tumor size groupings.
median survival, as compared to OA (median survival 64.2 months, p =. 016) or complete MIA (median survival 74.4 months, p = . 064). Multivariable Cox proportional hazards regression demonstrated that MIA was not associated with a difference in survival as com- pared to OA (HR, 1.066; p =. 691, Table 5). However, patients who required conversion had poor survival as compared to OA (HR, 1.830; p =. 021). Other factors associated with worse survival in- cluded local tumor invasion (HR 1.839, p <. 001), positive surgical margin (HR, 1.535; p = . 012), and advanced age (HR, 1.030; p < . 001). Tumor size was not independently associated with survival (5-10 vs. < 5 cm: HR, 1.262; p = . 324; >10 vs. 5 cm: HR, 1.354; p = . 205).
4 DISCUSSION
Although most guidelines recommend OA for patients with ACC,2-5 our data demonstrate that minimally invasive resections are being
performed for tumors of all sizes. Herein, we performed an analysis stratified by tumor size and highlight several important points. First, increasing tumor size and right-sided tumors were associated with an increased likelihood of conversion from MIA to OA. Second, opera- tions that required conversion to open and tumors with evidence of local invasion were associated with an increased likelihood of a po- sitive surgical margin; however, tumor size was not an independent predictor of margin status. Third, positive margins, local invasion, and operations that required conversion to open were all associated with poor survival; however, tumor size was not an independent predictor of survival. Taken together, these collective data suggest that evi- dence of local invasion and operative technique play a significant role in the treatment of patients with ACC, but tumor size by itself may not be the most important metric. This analysis adds granularity to the existing literature regarding the most important factors when determining the operative approach. MIA may be cautiously con- sidered in tumors with a relatively low risk of conversion (small size,
| Negative margin (n = 739) | Positive margin (n = | 173) | p value | |
|---|---|---|---|---|
| Age (years), median (IQR) | 56 (44, 69) | 60 (45, 68) | .098 | |
| Female, N (%) | 446 (60.4%) | 116 (67.1%) | .103 | |
| Race, N (%) | .530 | |||
| White | 627 (84.8%) | 152 (87.9%) | ||
| Black | 76 (10.3%) | 13 (7.5%) | ||
| Other | 36 (4.9%) | 8 (4.6%) | ||
| Charlson-Deyo score, | .479 | |||
| N (%) | ||||
| 0 | 545 (73.7%) | 120 (69.4%) | ||
| 1 | 146 (19.8%) | 41 (23.7%) | ||
| ≥2 | 48 (6.5%) | 12 (6.9%) | ||
| Private insurance, | 410 (55.5%) | 84 (48.6%) | .100 | |
| N (%) | ||||
| Academic program, | 439 (71.0%) | 96 (68.6%) | .563 | |
| N (%) | ||||
| Left-sided tumor, N (%) | 398 (53.9%) | 80 (46.2%) | .280 | |
| Tumor size, N (%) | .988 | |||
| <5 cm | 91 (12.3%) | 22 (12.7%) | ||
| 5-10 cm | 319 (43.2%) | 74 (42.8%) | ||
| >10 cm | 329 (44.5%) | 77 (44.5%) | ||
| Local invasion, N (%)ª | <. 001 | |||
| Absent | 433 (58.9%) | 39 (22.5%) | ||
| Present | 193 (26.1%) | 104 (60.1%) | ||
| Unknown | 113 (15.3%) | 30 (17.3%) | ||
| Vascular invasion, | <. 001 | |||
| N (%)b | ||||
| Absent | 426 (57.6%) | 71 (41.0%) | ||
| Present | 177 (24.0%) | 60 (34.7%) | ||
| Unknown | 136 (18.4%) | 42 (24.3%) | ||
| Operative approach, | .270 | |||
| N (%) | ||||
| Open | 469 (63.5%) | 102 (59.0%) | ||
| Minimally invasive | 270 (36.5%) | 71 (41.0%) | ||
| Laparoscopic | 198 (73.3%) | 57 (80.3%) | .230 | |
| Robotic | 72 (26.7%) | 14 (19.7%) | ||
ªIncludes adjacent connective tissue (i.e., Gerota’s fascia), kidney, retroperitoneal structures, pancreas, diaphragm, liver, and spleen. Also includes tumors classified as T3 or T4.
bIncludes adrenal vein, renal vein, inferior vena cava, and large vessel venous invasion not otherwise specified
left-sided) and margin positivity (no evidence of local invasion pre- operatively). Otherwise, OA should remain the standard of care.
Tumor size is recognized as an important staging metric in ACC.2,21 Despite this, most analyses of operatively managed patients with ACC are stratified by starting operative approach, not tumor size, as was performed in the current analysis. Our analysis provides
| OR | 95% CI | p value | ||
|---|---|---|---|---|
| Operative approach | ||||
| Minimally invasive versus open adrenalectomy | 1.601 | 0.901 | 2.845 | .109 |
| Converted versus open adrenalectomy | 2.852 | 1.108 | 7.344 | .030 |
| Tumor size | ||||
| 5-10 versus <5 cm | 0.805 | 0.383 | 1.695 | .568 |
| >10 versus <5 cm | 0.515 | 0.234 | 1.132 | .099 |
| Left versus right | 0.769 | 0.466 | 1.268 | .303 |
| Local invasion | 5.362 | 3.111 | 9.242 | <. 001 |
| Vascular invasion | 1.285 | 0.755 | 2.188 | .355 |
| Academic program versus other | 0.881 | 0.510 | 1.523 | .650 |
| Age | 1.018 | 0.996 | 1.040 | .102 |
| Charlson-Deyo score: ≤1 versus 0 | 0.803 | 0.456 | 1.414 | .447 |
Abbreviations: CI, confidence interval; OR, odds ratio.
additional information that can help guide operative planning. OA was more frequently utilized among larger tumors. Size has previously been shown to be a predictor of operative approach,7,22 which is in line with ESES guidelines.11 Herein, we demonstrate that tumor size was independently associated with an increased likelihood of conversion on multivariable analysis; however, when controlling for other factors was not associated with margin positivity or overall survival. Con- versely, local invasion, independent of tumor size, was associated with margin positivity and survival. Previous reports using administrative data and institutional data similarly demonstrated that tumor size was
| OR | 95% CI | p value | ||
|---|---|---|---|---|
| Tumor size | ||||
| 5-10 versus <5 cm | 9.598 | 1.230 | 74.881 | .031 |
| >10 versus <5 cm | 22.942 | 2.778 | 189.458 | .004 |
| Left versus right | 0.298 | 0.131 | 0.680 | .004 |
| Local invasion | 1.088 | 0.457 | 2.590 | .849 |
| Vascular invasion | 1.237 | 0.502 | 3.050 | .644 |
| Academic program versus other | 1.484 | 0.585 | 3.768 | .406 |
| Age | 0.983 | 0.951 | 1.017 | .325 |
| Charlson-Deyo score: ≤1 versus 0 | 1.410 | 0.612 | 3.251 | .420 |
Abbreviations: CI, confidence interval; OR, odds ratio.
(A)
(B)
1.00
1.00
0.75
0.75
0.50
0.50
0.25
0.25
0.00
Tumor size: < 5 cm
0.00
Tumor size: 5-10 cm
0
12
24
36
48
60
0
12
24
36
48
Analysis Time (months)
60
Analysis Time (months)
Open
MIA
Open
Converted
MIA
(C)
1.00
0.75
0.50
0.25
0.00
Tumor size: >10 cm
0
12
24
36
48
Analysis Time (months)
60
Open
Converted
MIA
| HR | 95% CI | p value | ||
|---|---|---|---|---|
| Operative approach | ||||
| Minimally invasive versus open adrenalectomy | 1.066 | 0.779 | 1.458 | .691 |
| Converted versus open adrenalectomy | 1.830 | 1.095 | 3.059 | .021 |
| Tumor size | ||||
| 5-10 versus <5 cm | 1.262 | 0.795 | 2.004 | .324 |
| >10 versus <5 cm | 1.354 | 0.847 | 2.165 | .205 |
| Left versus right | 0.852 | 0.650 | 1.118 | .248 |
| Local invasion | 1.839 | 1.377 | 2.456 | <. 001 |
| Vascular invasion | 1.129 | 0.845 | 1.509 | .411 |
| Positive margin | 1.535 | 1.099 | 2.145 | .012 |
| Academic program versus other | 1.102 | 0.809 | 1.502 | .536 |
| Age | 1.030 | 1.018 | 1.041 | <. 001 |
| Charlson-Deyo score: ≤1 versus 0 | 1.019 | 0.758 | 1.370 | .900 |
Abbreviations: CI, confidence interval; HR, hazard ratio.
not a predictor of survival, whereas advanced T-stage (i.e., local invasion21) was associated with poor survival.23,24 Past studies have reported a trend toward a higher likelihood of margin positivity among tumors ≥ 10 cm when resected via a minimally invasive approach as compared to OA,25 but this was not demonstrated in our study. Similar to our report, greater tumor size has been associated with an in- creased likelihood of conversion from MIA to OA.6,7,19 We conclude that preoperative tumor size is one of many factors (e.g. surgeon ex- perience, laterality, cross-sectional imaging characteristics) that should be used to help surgeons appropriately choose patients for MIA with the goal to minimize the number of conversions required.
Over the last three decades, surgeons have studied the role of MIA in various adrenal tumors.9,26 Despite advances in minimally invasive technology and technique,27 MIA for ACC remains controversial. Sev- eral previous reports have demonstrated increased rates of margin positive resections, tumor spillage, and local recurrence with MIA as compared to OA.12-14,28,29 Still others have reported equivalent onco- logic outcomes, including development of peritoneal carcinomatosis, tumor capsule violation, and recurrence-free survival.16,17,29,30 Some publications have even discussed the strategy of laparoscopic explora- tion followed by conversion to open if dissection is difficult.16,31 In our current report, we demonstrate that when adjusting for tumor char- acteristics and patient factors, successful MIA was not associated with
an increased likelihood of margin positivity or poor survival as com- pared to a planned OA. A previous NCDB analysis (data from 2010 to 2013) demonstrated that MIA was associated with a greater likelihood of a positive margin as compared to OA; however, this association did not remain if procedures that were converted to open were censored.25 Our report highlights the importance of conversion, showing that 16.5% of MIA required conversion to open with a subsequent increase in margin positivity rates and associations with poor survival. This asso- ciation was explored in a recent NCDB analysis (data from 2000 to 2014) investigating the importance of MIA conversion.7 Although data are not available in the NCDB, the authors speculated that this may be a marker of intra-operative difficulties (bleeding, difficult dissection, concern for tumor rupture).7
Despite using large sample size, our study has notable limitations. Perhaps most importantly, we do not have information on why a certain starting operative approach was selected (i.e., surgeon pre- ference, hospital resources, patient factors, etc.) or data pertaining to individual surgeon adrenalectomy volume. We also do not have spe- cific operative details regarding approach (transperitoneal or retro- peritoneal), reasons for conversion (e.g., hemodynamic issues, blood loss, adhesions, concern for tumor capsule violation, etc.), or other important operative metrics (e.g., estimated blood loss, operative time, tumor disruption). We also cannot account for differences in a sur- geon’s definition of conversion, whether it was a diagnostic laparo- scopy followed by primarily open dissection or significant minimally invasive dissection followed by conversion due to intra-operative dif- ficulty. We also do not have access to cross-sectional imaging, which limits our ability to provide a standard assessment for evidence of local/vascular invasion preoperatively. Data on recurrences are not recorded, thus our analysis of long-term outcomes is limited to overall survival. Detailed patient comorbidities are not recorded, thus the Charlson-Deyo score was used as a surrogate marker. The NCDB only receives data from Commission on Cancer-accredited hospitals, thus these findings may not be applicable to all centers in the United States. Despite these limitations, our analysis of a large number of patients with ACC suggests that carefully selected patients may undergo MIA for ACC, but OA should likely remain the standard of care for the majority of patients.
5 CONCLUSION
Patients who undergo adrenalectomy for ACC can achieve long-term survival. MIA could be considered among patients at low risk for con- version (<5 cm in size, left-sided) or positive margin (absence of local invasion). However, due to the significant association with poor survival among minimally invasive operations which required conversion to open or patients with a positive margin, OA should remain the standard of care for most patients.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
ORCID
Jonathan J. Hue (D https://orcid.org/0000-0002-1608-8874
John B. Ammori iD https://orcid.org/0000-0003-2131-0369
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SUPPORTING INFORMATION
Additional supporting information may be found online in the Supporting Information section.
How to cite this article: Hue JJ, Bingmer K, Zhao H, et al. Reassessing the impact of tumor size on operative approach in adrenocortical carcinoma. J Surg Oncol. 2021;123: 1238-1245. https://doi.org/10.1002/jso.26418