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Laparoscopic surgery for adrenocortical carcinoma: Estimating the risk of margin-positive resection
Kendyl Carlisle MD1 0 | Kyle W. Blackburn BS1
Emily A. Japp MD2
Patrick F. McArdle PhD3,4
| Douglas J. Turner MD1 ☒
Julia H. Terhune MD1
Brian R. Englum MD, MHS1,4
Philip W. Smith MD5
Yinin Hu MD1,4
1Division of General and Oncologic Surgery, Department of Surgery, University of Maryland Baltimore, Baltimore, Maryland, USA
2Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
3Department of Epidemiology & Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
4Maryland Surgery, Pharmacy, and Anesthesiology Research Collaborative, Baltimore, Maryland, USA
5Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA
Correspondence
Yinin Hu, MD, Division of General and Oncologic Surgery, Department of Surgery, University of Maryland Baltimore, 29 S. Greene St. 6th FL, Baltimore, MD 21201, USA. Email: yinin.hu@som.umaryland.edu
Funding information
T32; National Institutes of Health; American College of Surgeons
Abstract
Background: Over recent years, there has been increasing adoption of minimally invasive surgery (MIS) in the treatment of adrenocortical carcinoma (ACC). However, MIS has been associated with noncurative resection and locoregional recurrence. We aimed to identify risk factors for margin-positivity among patients who undergo MIS resection for ACC. We hypothesized that a simple nomogram can accurately identify patients most suitable for curative MIS resection.
Methods: Curative-intent resections for ACC were identified through the National Cancer Database spanning 2010-2018. Trends in MIS utilization were reported using Pearson correlation coefficients. Factors associated with margin-positive resection were identified among preoperatively available variables using multi- variable logistic regression, then incorporated into a predictive model. Model quality was cross validated using an 80% training data set and 20% test data set.
Results: Among 1260 ACC cases, 38.6% (486) underwent MIS resection. MIS utilization increased over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R = 0.009, p = 0.982). Factors associated with margin-positive MIS resection were increasing age, nonacademic center (odds ratio [OR]: 1.8, p = 0.006), cT3 (OR: 4.7, p < 0.001) or cT4 tumors (OR: 14.6, p <0.001), and right- sided tumors (OR: 2.0, p =0.006). A predictive model incorporating these four factors produced favorable c-statistics of 0.75 in the training data set and 0.72 in the test data set. A pragmatic nomogram was created to enable bedside risk stratification.
Conclusions: An increasing proportion of ACC are resected via minimally invasive operations, particularly at nonacademic centers. Patient selection based on a few key factors can minimize the risk of noncurative surgery.
KEYWORDS
adrenal cancer, adrenocortical cancer, minimally invasive surgical procedures, nomogram, outcomes research, risk factors
Adrenal nodules are common, present in roughly 10% of the population by age 70.1 Adrenocortical carcinoma (ACC), however, is a rare but deadly cancer with an incidence of two per million in the United States annually, and a 5-year survival rate of less than 50%.2-4 According to the National Comprehensive Cancer Network, the current recommendation for adrenal masses with a high suspicion of ACC is open resection to minimize risks of local recurrence, capsule rupture, and peritoneal seeding.5-8
More recent studies have suggested that minimally invasive surgery (MIS) techniques for resection of ACC do not carry an increased risk of positive margins (PM) when compared to an open approach (OA).9,10 Consensus guidelines by the American Association of Endocrine Surgeons (AAES) note that the choice of operative approach should be based on the certainty of a complete R0 resection without tumor disruption. The guidelines acknowledge that this could be accomplished by OA or MIS approach.11 Although evidence from the early 2000s demonstrates a risk for tumor seeding and higher rates of PM following laparoscopic resection of ACC, to date there has been no study assessing the factors that confer risk of PM during a minimally invasive approach.5-8 This knowledge gap limits surgeons’ capacity to reliably identify patients suitable for an MIS resection. Further, a diagnosis of ACC is rarely confirmed before definitive resection, as percutaneous biopsy is not reliable in making the diagnosis and can lead to tumor seeding outside the capsule. Thus, operative planning for patients undergoing adrenalectomy for suspected ACC must rely on preoperatively available clinical and radiographic characteristics.
The purpose of this study is to identify factors associated with margin-positivity following MIS for ACC to generate a pragmatic nomogram suitable for risk-stratification and patient counseling. We hypothesized that selection based on a small set of preoperatively available risk factors can identify a cohort of patients who are at low- risk for margin-positive resection in the MIS setting.
2 METHODS |
2.1 Patient selection |
The study cohort was derived from the National Cancer Database (NCDB), a joint project between the American College of Surgeons and the American Cancer Society. The NCDB includes data from >70% of all cancer diagnoses from 1500 Commission on Cancer- accredited hospitals.12 We performed a query of the NCDB between years 2010 to 2018 to identify patients with ACC resected with curative intent. We first restricted the data set to adrenal cortical carcinoma via the International Classification of Diseases for Oncology (code 8370) with primary site specified as adrenal gland (C74.0, C74.9). Patients were excluded if they had metastatic disease, if they did not receive surgery, or if it is unknown if they received surgery. We further excluded patients with unknown facility type,
days between diagnosis and surgery, tumor size, or laterality. Cases before 2010 were excluded due to lack of data on surgical approach (MIS vs. OA). The final patient population was then separated by surgical approach: MIS and OA. The MIS category included both robotic and laparoscopic approaches. Based on intention-to-treat principles, MIS cases that underwent intraoperative conversion to laparotomy were categorized as MIS (Figure 1).
2.2 Data collection |
Because the objective of this study was to identify factors that could guide surgical decision-making, we chose predictor variables that are commonly available in the preoperative setting: age, sex, race (White vs. non-White), Charlson-Deyo score (0-1 vs. >1), facility type (academic vs. nonacademic), clinical T-stage, tumor size, clinical N- stage, vascular invasion, laterality, days between diagnosis and surgery, and surgical approach. Academic facilities were defined according to the NCDB as academic or research programs, including National Cancer Institute-designated comprehensive cancer centers. nonacademic facilities included community cancer programs, com- prehensive community cancer programs, and integrated network cancer programs. Clinical T-stage was based on the AJCC 7th/8th edition staging and was separated into three groups: T1-T2 (no extra-adrenal extension), T3 (peri-adrenal extension), T4 (adjacent organ invasion), and unknown. T1 (≤5 cm) and T2 (>5 cm) were grouped together as tumor size was analyzed as a separate variable. We analyzed the following outcomes: surgical margin, length of stay after surgery, unplanned readmission, 30-day mortality, and 90-day mortality. A complete listing of all included variables is available in Supporting Information Materials.
2.3 Statistical analyses |
Demographic and clinical variables were compared between OA and MIS cohorts using x2 for categorical variables and Wilcoxon rank-sum for continuous variables. The annual proportional volume of MIS cases was stratified by facility type and time trends were analyzed using Pearson correlation coefficient. Short-term surgical outcomes were compared by surgical approach for readmission, 30-day mortality, and 90-day mortality.
Univariate and multivariable logistic regression was used to identify risk factors associated with margin-positivity for the complete ACC cohort, including MIS and OA surgery cases. Variables significant (p < 0.05) on univariate analyses were included in multivariable regression. To identify risk factors associated with margin positivity in MIS cases, we repeated these analyses after restricting the cohort to the MIS subgroup. Within this subgroup, only eight patients had vascular invasion, thus this variable was excluded from regression analyses. Factors signifi- cantly associated with margin positivity on multivariable regres- sion were incorporated into a predictive model. Model quality was
Adrenal Cancer NCDB 2010-2018 (N=6,904)
Exclude (N=2,689)
- Histology not adrenocortical carcinoma (Code 8370)
- Primary site not adrenal gland (C74.0, C74.9)
Noninvasive
Adrenocortical Carcinoma (N=4,215)
Exclude: (N=2,867)
- Metasatic disease
- No surgical intervention
- Unknown surgical information
Surgical Adrenocortical Carcinoma (N=1,348)
Exclude (N=88)
- Unknown facility type
- Unknown Days Until Surgery
- Unknown Turmor Size
- Unknown Laterality
Final Patient Population (N=1,260)
Minimally Invasive Surgery (N=486)
Open approach (N=774)
assessed using a cross validation scheme of 10,000 iterations, with 80% of the data used as a training set and 20% used as a test set. The training set was used to fit the model, and concordance (c- statistic) and receiver operating characteristic (ROC) curves were derived for both the training set and the test set based on that model. After validating predictive quality, a nomogram was produced to calculate the estimated risk of margin positivity based on model variables. A p-value of less than 0.05 was considered significant for all analyses. All analyses were performed using R Studio (version 1.4.1717 R Studio).
|
3 RESULTS
Between 2010 and 2018, 6904 patients with ACC were captured in the NCDB. Following exclusions, the final data set included 1260 patients (Figure 1). Among these, 38.6% (N = 486) under- went MIS resection. Within the MIS cohort, 486 cases (14.6%) were laparoscopic converted to open. These cases were included in the MIS cohort using intention to treat. Patient demographics are shown in Table 1. Patients who underwent MIS resection were older, had higher Charlson-Deyo scores, had shorter
| Characteristic | Open surgery (N = 774) | MIS surgery (N = 486) | p Value |
|---|---|---|---|
| Age (%) | |||
| <40 | 129 (16.7) | 51 (10.5) | 0.011 |
| 40-59 | 323 (41.7) | 200 (41.2) | |
| 60-79 | 289 (37.3) | 213 (43.8) | |
| 80+ | 33 (4.3) | 22 (4.5) | |
| Sex | |||
| Male | 298 (38.5) | 182 (37.4) | 0.753 |
| Female | 476 (61.5) | 304 (62.6) | |
| Race | |||
| White | 672 (86.8) | 430 (88.5) | 0.438 |
| Nonwhite | 102 (13.2) | 56 (11.5) | |
| Charlson-Deyo score | |||
| 0-1 | 727 (93.9) | 432 (88.9) | 0.002 |
| 2+ | 47 (6.1) | 54 (11.1) | |
| Facility type | |||
| Nonacademic | 302 (39.0) | 256 (52.7) | <0.001 |
| Academic | 472 (61.0) | 230 (47.3) | |
| Tumor clinical stage | |||
| T1-T2 | 425 (54.9) | 291 (59.9) | <0.001 |
| T3 | 185 (23.9) | 93 (19.1) | |
| T4 | 51 (6.6) | 8 (1.6) | |
| Unknown | 113 (14.6) | 94 (19.3) | |
| Tumor size | |||
| Mean (SD) | 13.1 cm (10.9) | 8.3 cm (61.6) | <0.001 |
| Laterality | |||
| Left | 424 (54.8) | 278 (57.2) | 0.433 |
| Right | 350 (45.2) | 208 (42.8) | |
| Nodal status | |||
| Negative | 604 (78.0) | 395 (79.0) | 0.525 |
| Positive | 12 (1.6) | 4 (0.8) | |
| Unknown | 158 (20.4) | 98 (20.2) | |
| Vascular invasion | |||
| None | 386 (49.9) | 259 (53.3) | 0.009 |
| Invasion | 38 (4.9) | 8 (1.6) | |
| Unknown | 350 (45.2) | 219 (45.1) | |
| Days until surgery | |||
| Mean (SD) | 18.2 (47.5) | 9.7 (25.6) | 0.001 |
| Surgery type | |||
| Open/unknown | 774 (100.0) | --- | NA |
| Characteristic | Open surgery (N = 774) | MIS surgery (N = 486) | p Value |
|---|---|---|---|
| Laparoscopic | --- | 350 (72.0) | |
| Robotic | --- | 136 (28.0) |
intervals from diagnosis to surgery, and were more likely to undergo surgery at nonacademic centers. Patients who under- went OA resection had tumors with higher T stage, larger size, and were more likely to have vascular invasion. MIS utilization increased significantly over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R =0.009, p = 0.982) (Figure 2). Relative to OA, MIS approach was associated with shorter length of stay (4 days vs. 6.58 days; p < 0.001) and lower 30-day unplanned readmission rate (3.3% vs. 6.7%, p = 0.013). There were no differences in rates of 30-day (1.0% vs. 1.8%, p = 0.405) or 90-day mortality (3.2% vs. 2.7%, p = 0.808) by surgical approach.
Among patients with resected ACC (OA and MIS), the following variables were associated with positive margins on multivariable regression: nonacademic center (odds ratio [OR]: 2.0, p < 0.001), higher T stage (p<0.001), and clinically positive nodes (OR: 4.3, p = 0.011) (Table 2). Variables not associated with PM included age, sex, race, Charlson-Deyo score, laterality, vascular invasion, and importantly, surgery type (OA vs. MIS). The margin-positive rates for OA and MIS were 18.7% (136/729) and 21.5% (97/451), respectively, corre- sponding to a p value of 0.3. Within the MIS-only subgroup, the following factors were associated with margin-positive resection at the univariate level: increasing age, nonacademic center, advanced primary tumor stage, right-sided tumors, and unknown nodal status. The MIS converted to OA subset within the MIS group had a margin positive rate of 38.5% (25/ 65), which was higher than the margin-positive rate of MIS not converted to OA (72/386, 18.7%). On multivariable regression, the only factors associated with PM were increasing age (OR: 2.5-4.0, p =0.01 to <0.001), nonacademic center (OR: 1.8, p = 0.006), cT3 (OR: 4.7, p <0.001) or cT4 tumors (OR: 14.6, p < 0.001), and right-sided tumors (OR: 2.0, p = 0.006) (Table 3). Robotic versus laparoscopic approach was not associated with margin status.
Using these risk factors, we created a predictive nomogram that estimates the probability of margin-positive MIS resection (Figure 3). Within each clinical variable, points are assigned to each value. For a given patient, totaling points across these variables generates a predicted risk of margin-positive MIS resection. Cross-validating the nomogram using an 80% training set and 20% test set over 10,000 iterations, we calculated the C- statistic of the model to be 0.75 and 0.72, respectively, indicating good predictive performance (Figure 4).
0.7
0.6
r = 0.818
P = 0.007
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% of Surgeries, MIS
0.5
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☐
0.4
r = 0.009
☐
P = 0.982
0.3
0.2
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Academic
☐ Non-Academic
- - Linear (Academic)
Linear (Non-Academic)
0
2010
2011
2012
2013
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2015
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Year of Diagnosis
4 DISCUSSION |
In this nationwide analysis of ACC resections captured through the NCDB, we noted increasing utilization of MIS resection over time, largely driven by nonacademic centers. In line with recently published guidelines by the AAES that acknowledges that appropriate operative approach hinges on skill and experience rather than mandating OA for all cases of ACC, there was no difference in rate of margin- positivity between OA versus MIS resection.11 We highlight four key preoperative variables which can be used to estimate the risk of margin-positive-and therefore noncurative-MIS resection. By translating a traditional multivariable logistic regression model to a pragmatic nomogram, we hope to directly contribute to physician-patient counseling.
Consensus guidelines including the ACC management guidelines from 2018 European Society of Endocrinology in collaboration with the European Network for the Study of Adrenal Tumors have historically recommended that high risk adrenal nodules be removed via an OA surgical approach due to concerns for locoregional recurrence and noncurative resection with a MIS approach.5-8,13 In recent years, adrenalectomies are increasingly being performed via MIS approach.14 Regardless of surgical approach, there is unequivocal consensus that an appropriate oncologic surgery entails an R0 resection with an intact adrenal capsule. It is rarely feasible to determine with confidence whether an adrenal mass is ACC in the preoperative setting. The key step in quality-improvement is therefore not to encourage universal OA resections or-even worse -to encourage routine preoperative biopsy, but rather to develop better risk-stratification tools to select patients who are most appropriate for MIS resection. In line with the concept of
personalized, precision medicine, preoperative biomarkers can be used to improve patient selection for the appropriate surgery.
This study did not show a difference in likelihood of curative resection between MIS and OA adrenalectomies, corroborating several prior works. Using an earlier NCDB data set including all ACC resections regardless of curative intent, Skertich et al. noted that predictors of PM included extra-adrenal extension, nodal metastasis, and distant metastasis.10 However, margin-positivity is less relevant in the setting of distant metastatic disease, as these patients likely underwent surgery for pathologic confirmation or palliation. While Tseng et al. previously reported a higher risk of PM relative to OA surgery with laparoscopic but not robotic resection, our data set showed no difference between modalities of MIS surgery.9 To expand upon these prior works, we chose to focus specifically on the MIS subgroup, and found that variables incurring a higher risk for PM included older age, tumor stage, nonacademic facility, and right laterality. In concordance with the study hypothesis, our novel nomogram comprised of only these ubiquitous variables was able to estimate risk of PM following MIS resection with robust accuracy (c-statistic: 0.72-0.75).
The predictive nomogram generated by our study is pragmatic and intuitive. Extra-adrenal extension has been consistently shown to be a strong predictor of noncurative resection, highlighting the importance of multidisciplinary imaging review.1º The European Society of Endocrinology guidelines recommend adrenal-specific expertise in radiology as a part of every multidisciplinary expert team for patients with ACC.13 Right-sided tumors have been described to have worse survival due to invasion of important structures and involvement of the liver.15 Notably, tumor size alone was not a risk factor for margin positive resection. Prior work by
| Logistic regression (margins) | ||||
|---|---|---|---|---|
| Characteristics | Univariate analysis | Multivariate analysis | ||
| OR | p Value | OR | p Value | |
| Age | ||||
| <40 | Ref | --- | ||
| 40-59 | 0.95 | 0.811 | ||
| 60-79 | 1.53 | 0.673 | ||
| 80+ | 1.38 | 0.404 | ||
| Sex | ||||
| Male | Ref | --- | ||
| Female | 1.33 | 0.065 | ||
| Race | ||||
| White | Ref | --- | ||
| Nonwhite | 0.84 | 0.452 | ||
| Charlson-Deyo score | ||||
| 0-1 | Ref | --- | ||
| 2+ | 1.44 | 0.144 | ||
| Facility type | ||||
| Nonacademic | Ref | --- | Ref | --- |
| Academic | 0.55 | <0.001 | 0.49 | <0.001 |
| Tumor stage | ||||
| T1-T2 | Ref | --- | Ref | --- |
| T3 | 3.26 | <0.001 | 3.29 | <0.001 |
| T4 | 5.47 | <0.001 | 5.31 | <0.001 |
| Unknown | 1.93 | 0.002 | 1.66 | 0.046 |
| Tumor size | 1.00 | 0.081 | ||
| Laterality | ||||
| Right | Ref | --- | ||
| Left | 0.88 | 0.399 | ||
| Nodal status | ||||
| Negative | Ref | --- | Ref | --- |
| Positive | 5.12 | 0.002 | 4.27 | 0.011 |
| Unknown | 1.38 | 0.070 | 1.22 | 0.358 |
| Vascular invasion | ||||
| None | Ref | --- | Ref | --- |
| Invasion | 2.02 | 0.043 | 1.22 | 0.596 |
| Unknown | 1.44 | 0.015 | 1.33 | 0.085 |
| Days till surgery | 1.00 | 0.672 | ||
| Surgery type | ||||
| Open/unknown | Ref | --- | ||
| Laparoscopic | 1.26 | 0.153 | ||
| Robotic | 1.03 | 0.917 | ||
| Logistic regression (margins) | ||||
|---|---|---|---|---|
| Characteristics | Univariate analysis | Multivariate analysis | ||
| OR | p Value | OR | P Value | |
| Age | ||||
| <60 | Ref | --- | Ref | --- |
| 60-79 | 2.30 | <0.001 | 2.49 | <0.001 |
| 80+ | 2.92 | 0.032 | 4.00 | 0.010 |
| Sex | ||||
| Male | Ref | --- | ||
| Female | 1.26 | 0.328 | ||
| Race | ||||
| White | Ref | --- | ||
| Non-White | 0.74 | 0.435 | ||
| Charlson-Deyo Score | ||||
| 0-1 | Ref | --- | ||
| 2+ | 1.41 | 0.322 | ||
| Facility type | ||||
| Nonacademic | Ref | --- | Ref | --- |
| Academic | 0.61 | 0.033 | 0.56 | 0.006 |
| Tumor stage | ||||
| T1-2 | Ref | --- | Ref | --- |
| T3 | 4.08 | <0.001 | 4.65 | <0.001 |
| T4 | 10.93 | 0.001 | 14.64 | <0.001 |
| Unknown | 2.43 | <0.001 | 2.56 | 0.003 |
| Tumor size | 1.00 | 0.734 | ||
| Laterality | ||||
| Right | Ref | --- | Ref | --- |
| Left | 0.57 | 0.014 | 0.50 | 0.006 |
| Nodal status | ||||
| Negative | Ref | --- | ||
| Positive | 2.11 | 0.544 | ||
| Unknown | 1.82 | 0.023 | ||
| Days till surgery | 1.00 | 0.611 | ||
| Surgery type | ||||
| Laparoscopic | Ref | --- | ||
| Robotic | 0.81 | 0.429 | ||
Hue et al. similarly showed that, among MIS-resected ACC, local invasion and conversion to OA were more powerful predictors of PM than tumor size.16 These data challenge the notion that adrenal nodules beyond a certain diameter must be approached via OA resection. In our practice, for patients with a <20% chance of positive margins we strongly consider a laparoscopic approach. For
| 0 | 10 | 20 | 30 | 40 | 50 | 60 | 70 | 80 | 90 | 100 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Points Age | 60-79 | ||||||||||
| <59 | 80+ | ||||||||||
| Facility Type | Non-Academic | ||||||||||
| Academic | |||||||||||
| Tumor Stage | T1-T2 | T4 | |||||||||
| T3 | |||||||||||
| Left | Right | ||||||||||
| Laterality | |||||||||||
| Total Points | 0 | 20 | 40 | 100 | 160 | 180 | 200 | ||||
| 60 | 80 | 120 | 140 | ||||||||
| Predicted Risk | 0.05 | 0.1 | 0.2 | 0.3 | 0.4 | 0.5 | 0.6 0.7 | 0.8 | |||
ROC Curve, CV Training Set
ROC Curve, CV Test Set
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LL AUC = 0.595
UL AUC = 0.805
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FIGURE 4 Concordance and ROC curve calculations for nomogram cross-validation. Training set included 80% of the data (left), while test set included 20% of the data (right). Average, upper (UL) and lower (LL) concordance limits (AUC) derived from 10,000 iterations.
intermediate risk patients, an initial laparoscopic exploration may be considered, provided there is a low threshold for conversion to open should direct extra-adrenal invasion be suspected. For patients who are clearly at high-risk for margin positivity based on preoperative factors, we start with an open exploration.
One notable predictor of noncurative resection was treatment at a nonacademic institution. Substantiating a recent study by Delman et al., we found that MIS resection of ACC is rapidly expanding in the United States.14 Our results further show that this increase is almost entirely
attributable to nonacademic centers. Of note, however, laparoscopic resection at nonacademic institutions was associated with a twofold higher risk of positive margins compared to treatment at academic centers. This finding highlights the importance of multidisciplinary preoperative evaluation including experienced imaging review and surgical planning. In line with consensus guidelines, we strongly recommend that patients who possess one or more risk factors for margin-positive resection should be referred to an academic institution or comprehensive cancer center for multidisciplinary review.1
There are several limitations to this study. While our study focuses on patient selection to minimize margin-positive resection via an MIS approach, it is unclear whether offering high-risk patients an OA resection could reduce the risk of an R1 or R2 resection. Second, due to intention to treat principles, 14.6% of our MIS cases were operations that began minimally invasive but were converted to open. This allows for a misclassification of exposure, which given the small percentage, is unlikely to affect the overall results and would be expected to bias the results towards the null. Furthermore, given the retrospective nature of the study, it is impossible to determine if the MIS converted to open cases were done so because of inability to maintain an MIS approach, or they were a planned first look that was immediately aborted and converted to open. There is a potential for selection bias at the discretion of the surgeon in any study using NCDB data. The study does not include information about removal of benign lesions, which makes it difficult to model the real-time surgical decision making that surgeons face-for example, a lesion of unclear malignant potential. Additionally, this nomogram would require prospective testing to clearly define its utility. Multivariable regres- sion may control for confounding variables captured within the data set, but the possibility of unrepresented confounders remains a persistent limitation. Finally, patients who develop local or peritoneal recurrence commonly have distant recurrence as well.18 The relationship between margin positive resection on overall survival is unclear. Anderson et al. previously showed a reduction of survival from 58 months with curative resection to 22 months with microscopic PM and 14 months for macroscopic positive margins.19 Whether these trends reflect treatment efficacy or confounding native disease biology is unknown.
5 CONCLUSION |
Minimally invasive adrenalectomy for presumed ACC is expanding rapidly in the United States, particularly at nonacademic centers. Older patients with right-sided adrenal masses demonstrating extra-adrenal extension are at high risk for noncurative resection. Simple steps to improve short- term oncologic outcomes include adopting a predictive nomogram for patient counseling and advocating for treatment centralization.
ACKNOWLEDGMENTS
This work was supported by the ACS Faculty Research Fellowship (Yinin Hu), a NIH NCATS KL2TR003099, and a T32 in Epidemiology of Aging-funded postdoctoral fellowship (Kendyl Carlisle) (T32 AG000262).
CONFLICT OF INTEREST STATEMENT
The authors declare no conflict of interest.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are openly available in National Cancer Database (NCDB) at https://www.facs.org/ quality-programs/cancer-programs/national-cancer-database/.
ORCID
Kendyl Carlisle İD http://orcid.org/0000-0002-4139-3686
REFERENCES
1. Arnaldi G, Boscaro M. Adrenal incidentaloma. Best Pract Res Clin Endocrinol Metab. 2012;26:405-419.
2. Terzolo M, Angeli A, Fassnacht M, et al. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med. 2007;356(23): 2372-2380.
3. Bilimoria KY, Shen WT, Elaraj D, et al. Adrenocortical carcinoma in the United States: treatment utilization and prognostic factors. Cancer. 2008;113(11):3130-3136.
4. Stigliano A, Chiodini I, Giordano R, et al. Management of adrenocortical carcinoma: a consensus statement of the Italian Society of Endocrinology (SIE). J Endocrinol Invest. 2016;39(1):103-121.
5. Gonzalez RJ, Shapiro S, Sarlis N, et al. Laparoscopic resection of adrenal cortical carcinoma: a cautionary note. Surgery. 2005;138(6): 1078-1086.
6. Leboulleux S, Deandreis D, Al Ghuzlan A, et al. Adrenocortical carcinoma: is the surgical approach a risk factor of peritoneal carcinomatosis? Eur J Endocrinol. 2010;162(6):1147-1153. https:// doi.org/10.1530/EJE-09-1096
7. Miller BS, Ammori JB, Gauger PG, Broome JT, Hammer GD, Doherty GM. Laparoscopic resection is inappropriate in patients with known or suspected adrenocortical carcinoma. World J Surg. 2010;34(6):1380-1385.
8. . Shah MH, Goldner WS, Benson AB, et al. Neuroendocrine and adrenal tumors, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Comprehen Cancer Network. 2021;19(7):839-868.
9. Tseng J, Diperi T, Gonsalves N, et al. Operative approach and case volume are associated with negative resection margins for adreno- cortical carcinoma. Surg Endosc. 2022;36:9288-9296.
10. Skertich NJ, Tierney JF, Chivukula SV, et al. Risk factors associated with positive resection margins in patients with adrenocortical carcinoma. Am J Surgery. 2020;220(4):932-937.
11. Yip L, Duh QY, Wachtel H, et al. American Association of Endocrine Surgeons Guidelines for adrenalectomy: executive summary. JAMA Surg. 2022;157(10):870-877.
12. American College of Surgeons. National Cancer Database. Accessed June, 2022. https://www.facs.org/quality-programs/cancer/ncdb. 2021.
13. Fassnacht M, Dekkers OM, Else T, et al. European society of endocrinology clinical practice guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the study of adrenal tumors. Eur J Endocrinol. 2018;179:G1-G46.
14. Delman AM, Turner KM, Griffith A, Schepers E, Ammann AM, Holm TM. Minimally invasive surgery for resectable adrenocor- tical carcinoma: a nationwide analysis. J Surg Res. 2022;279: 200-207. https://linkinghub.elsevier.com/retrieve/pii/ S0022480422003201
15. Datrice NM, Langan RC, Ripley RT, et al. Operative management for recurrent and metastatic adrenocortical carcinoma. J Surg Oncol. 2012;105(7):709-713.
16. 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(5):1238-1245.
17. Gaujoux S, Mihai R, Carnaille B, et al. European society of endocrine surgeons (ESES) and european network for the study of adrenal tumours (ENSAT) recommendations for the surgical management of adrenocortical carcinoma. Br J Surg. 2017;104(4):358-376.
18. Glenn JA, Else T, Hughes DT, et al. Longitudinal patterns of recurrence in patients with adrenocortical carcinoma. Surgery. 2019;165(1):186-195.
19. Anderson KL, Adam MA, Thomas SM, et al. Impact of micro- and macroscopically positive surgical margins on survival after resection
of adrenocortical carcinoma. Ann Surg Oncol. 2018;25(5): 1425-1431. https://pubmed.ncbi.nlm.nih.gov/29500765/
SUPPORTING INFORMATION
Additional supporting information can be found online in the Supporting Information section at the end of this article.
How to cite this article: Carlisle K, Blackburn KW, Japp EA, et al. Laparoscopic surgery for adrenocortical carcinoma: Estimating the risk of margin-positive resection. J Surg Oncol. 2024;129:691-699. doi:10.1002/jso.27544