OFFICIAL JOURNAL OF THE SOCIETY OF SURGICAL ONCOLOGY
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Implications of Conversion during Attempted Minimally Invasive Adrenalectomy for Adrenocortical Carcinoma
Olivia M. Delozier, MD, Zachary E. Stiles, DO, Benjamin W. Deschner, MD, Justin A. Drake, MD, Jeremiah L. Deneve, DO, Evan S. Glazer, MD, PhD, Miriam W. Tsao, MD, Danny Yakoub, MD, PhD, and Paxton V. Dickson, MD, FACS
Department of Surgery, Division of Surgical Oncology, University of Tennessee Health Science Center, Memphis, TN
ABSTRACT
Background. Although advocated by some, minimally invasive adrenalectomy (MIA) for adrenocortical carci- noma (ACC) is controversial. Moreover, the oncologic implications for patients requiring conversion to an open procedure during attempted MIA for ACC are not exten- sively reported.
Patients and Methods. The National Cancer Database was queried for patients undergoing resection for ACC. Overall survival (OS) for patients undergoing successful MIA was compared with those requiring conversion, and additionally evaluated with a multivariable Cox regression analysis including other factors associated with OS. After propensity matching, those experiencing conversion were further compared with patients who underwent planned open resection.
Results. Among 196 patients undergoing attempted MIA for ACC, 38 (19.4%) required conversion. Independent of 90-day postoperative mortality, conversion was associated with significantly reduced OS compared with successful MIA (median 27.9 months versus not reached, p = 0.002). Even for tumors confined to the adrenal, conversion was associated with worse median OS compared with suc- cessful MIA (median 34.2 months versus not reached,
p = 0.003). After propensity matching for clinicopatho- logic covariates to establish well-balanced cohorts (N = 38 per group), patients requiring conversion during MIA had significantly worse OS than those having planned open resection (27.9 months versus 50.5 months, p = 0.020). On multivariable analysis for predictors of OS, conversion during MIA (HR 2.32, p = 0.003) was independently associated with mortality.
Conclusions. ACC is a rare tumor for which adequate oncologic resection is the only chance for cure. Given the relatively high rate of conversion and its associated inferior survival, open resection should be considered standard of care for known or suspected ACC.
Since initially reported in 19921, minimally invasive adrenalectomy (MIA) has proven to be safe and effective as the recommended operative approach for small benign adrenal tumors.2-5 However, the use of MIA for patients with known or suspected adrenocortical carcinoma (ACC) remains controversial. ACC is a rare and highly aggressive malignancy for which en bloc margin negative resection is critical for potential cure. Concerns regarding MIA for ACC arise from studies reporting increased rates of tumor spillage, margin positive resection, increased peritoneal recurrence, and inferior survival when compared with open adrenalectomy (OA).6-10 However, several studies have reported equivalent outcomes between MIA and OA in select patients.1
In addition to conflicting conclusions from the afore- mentioned studies, there is some variability among guideline statements from several well-recognized organi- zations. The National Comprehensive Cancer Network (NCCN) states, “Open adrenalectomy is preferred for tumors with a high risk of being malignant because of
Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-020-08824-9) contains supplementary material, which is available to authorized users.
@ Society of Surgical Oncology 2020
First Received: 8 May 2020 Accepted: 21 June 2020
P. V. Dickson, MD, FACS e-mail: pdickso1@uthsc.edu
increased risk for local recurrence and peritoneal spread when performed laparoscopically”.3 The American Asso- ciation of Clinical Endocrinologists and American Association of Endocrine Surgeons guidelines state “Open adrenalectomy by an experienced surgeon is the procedure of choice”.5 However, a positional statement of the Euro- pean Society of Endocrine Surgeons on malignant adrenal tumors states “Laparoscopic resection of ACC/potentially malignant tumors, which includes removal of surrounding periadrenal fat and results in an R0 resection without tumor capsule rupture, may be performed for pre-and intraoper- ative stage I-II ACC and tumors with diameter < 10 cm”.17 Finally, the Society of Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines for treatment of adrenal pathology recommend OA for patients with known or probable primary ACC. However, this is further quali- fied with the statement “If a laparoscopic approach is chosen due to an unknown malignancy status preopera- tively or suspected early-stage ACC, conversion to open surgery is strongly recommended when difficult dissection is encountered due to tumor adhesion or invasion or enlarged lymph nodes are seen”.4
Given the controversy regarding the appropriateness of MIA for ACC, some have suggested beginning laparo- scopically with a plan to convert if the dissection is difficult.18,19 The short-term implications of conversion are expected to include greater length of stay and increased postoperative pain. However, the long-term outcomes for patients who require conversion during attempted MIA for ACC are not extensively reported. Furthermore, some studies evaluating MIA versus OA for ACC have included patients requiring conversion in the MIA “intent-to-treat” group,7,20 some have included them in the OA group,21 and some have excluded them from analysis altogether.13 The purpose of the current study is to investigate the oncologic implications of conversion to an open procedure during attempted MIA for ACC.
PATIENTS AND METHODS
Patients with ICD-O-3 histologic codes corresponding to a diagnosis of ACC were selected from the 2000-2014 National Cancer Data Base (NCDB) dataset. As the NCDB contains appropriately deidentified patient data, this study was deemed exempt by the University of Tennessee Health Science Center institutional review board. Because the NCDB has only more recently included information regarding unplanned conversion, only cases from 2010 to 2014 were analyzed. Resections were stratified by opera- tive approach: those undergoing successful MIA, those requiring conversion to an open procedure during attemp- ted MIA, and those having planned OA. Patients
undergoing nonsurgical local therapies, those with distant metastases at diagnosis or M1 designation on pathology, those treated with neoadjuvant therapy, those with incomplete data regarding surgical approach, tumor size, vital status, and 90-day mortality data, those treated for other malignancies, and those with a medullary tumor were excluded from the analysis (Supplementary Fig. 1).
Factors Associated with Conversion
Patients undergoing successful MIA were compared with those requiring conversion during attempted MIA. Characteristics including age, gender, race, treatment facility, insurance status, distance traveled to treatment facility, comorbidities, tumor size, tumor extent, tumor laterality, extent of resection, minimally invasive approach (laparoscopic or robotic), and receipt of adjuvant therapy were compared in univariate analysis. Factors approaching significance on univariate comparison were included in a multivariable analysis to determine their independent association with conversion.
Short- and Long-Term Outcomes
Groups were compared with regard to length of stay (LOS), resection margins, readmission, and 90-day mor- tality. Overall survival (OS) was defined as the time from diagnosis to death or censoring and was evaluated for both groups and further substratified based on tumor extension (confined to or extending beyond the adrenal gland). Fac- tors potentially associated with OS, including conversion, were evaluated within a Cox proportional hazards model to determine their independent effect on survival.
Comparison with Open Adrenalectomy
Following similar selection criteria, patients experienc- ing conversion during attempted MIA were compared with those undergoing planned open adrenalectomy after propensity score matching to account for differences. Propensity scores were generated on the basis of a logistic regression model accounting for key covariates, including age, gender, race, facility type, insurance status, distance traveled to treatment facility, comorbidities, tumor size, tumor grade, tumor laterality, and extent of resec- tion. Groups were matched 1:1 based on generated propensity scores. Covariates were analyzed and compared before and after matching to assess the balance of groups. Unplanned conversion and planned open adrenalectomy were then compared with regard to short- and long-term outcomes as described above.
Data Analysis
Categorical variables were listed as counts with relative frequencies and contrasted using the Chi square test or Fisher’s exact test as appropriate. Continuous variables were expressed as the median with the interquartile range (IQR) and analyzed with the Wilcoxon rank-sum test. Univariate survival analysis was performed with Kaplan- Meier curves, and hypothesis testing performed with the log-rank test. A p value < 0.2 was used to select variables for initial inclusion in the logistic regression model. Logistic regression model fit was assessed with the Hos- mer-Lemeshow goodness-of-fit test. For Cox regression analysis, factors were chosen de novo based on known or suspected impact on survival, and unplanned conversion was included in all model variations. Hazard ratios (HR) were generated and reported with 95% confidence intervals (CI). All statistical analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC).
RESULTS
Comparisons of Successful MIA to Conversion
Among 196 patients who underwent attempted MIA for ACC, 38 (19.4%) were converted to an open procedure. As shown in Table 1a, there were no differences in the sociodemographic characteristics when patients undergo- ing successful MIA were compared with those that required conversion. Resections that required conversion were associated with a larger median tumor size (9 cm versus 7.5 cm, p = 0.007) and right-sided tumors (27.2% con- version rate for right-sided versus 12.6% for left-sided, p = 0.033). Rates of conversion relative to tumor size are shown in Fig. 1. Conversion tended to be less likely in patients undergoing a robotic procedure as compared with a laparoscopic procedure (10.9% versus 22.0%, p = 0.095). On multivariable analysis (Table 1b), tumor size ≥ 6 cm (HR 3.19, 95% CI 1.22-8.35, p = 0.018) and right-sided tumor location (HR 2.79, 95% CI 1.28-6.07, p = 0.010) were independent predictors of conversion. In addition, when controlling for other covariates, robotic adrenalec- tomy was associated with a significant reduction in the odds of conversion compared with a laparoscopic approach (HR 0.33, 95% CI 0.11-0.98, p = 0.046).
Measures of short-term postoperative outcomes and pathology are presented in Table 2. Conversion was asso- ciated with a significantly increased LOS (4 versus 2 days, p < 0.001) and, although not statistically significant, a three-fold increased rate of 90-day mortality (7.9% versus 2.5%, p = 0.134). With regard to important measures of pathology, rates of R1 resection were nearly doubled (29.0% versus 17.1%, p = 0.159) in patients who required
conversion compared with successful MIA, although this was not statistically significant. The rate of lymph node evaluation for both successful MIA and conversion was low at 6.3% and 7.9%, respectively (p = 0.720).
Median follow-up for patients having successful MIA and those requiring conversion were 29.9 and 20.9 months, respectively. Median OS for patients requiring conversion was significantly lower at 26.4 months compared with successful MIA for which the median was not reached (p ≤ 0.001) (Fig. 2a). Even after excluding patients with 90-day mortality, median OS remained significantly diminished in patients who required conversion (27.9 months) compared with those that underwent suc- cessful MIA (median not reached), p = 0.002 (Fig. 2b). Upon further substratification for tumor extent, median OS among patients requiring conversion was significantly lower than successful MIA regardless of whether tumors were reported as confined to (34.2 months versus median not reached, p = 0.025) or extending beyond (19.9 months versus 56.2 months, p = 0.046) the adrenal gland (Fig. 2c, d). On multivariable Cox regression analysis, among patients who underwent attempted MIA, increasing age (HR 1.02, 95% CI 1.0-1.03, p = 0.025), positive resection margin (HR 3.23, 95% CI 1.81-5.75, p < 0.001), and conversion to an open procedure (HR 2.32, 95% CI 1.34-4.03, p = 0.003) were each independently associated with increased risk of death (Table 3).
Comparisons of Planned OA to Attempted MIA with Conversion
Within the dataset, 384 patients who underwent OA were identified. There were several patient and tumor related differences between this group of patients and those who had attempted MIA (Supplementary Table 1). Given these differences, propensity matching was performed to establish well-balanced demographic and clinicopathologic cohorts who underwent planned OA versus those that required conversion (n = 38 per group) (Table 4).
Measures of short-term perioperative outcomes and pathology in these matched groups are shown in Table 5. Although not reaching significance, the rate of R1 resection in patients requiring conversion was over two times that of those who had planned OA (29% versus 13.2%, p = 0.080). In the matched cohorts, rates of lymph node evaluation were 15.8% for those undergoing planned OA and 7.9% for those requiring conversion (p = 0.480).
Median follow-up for the matched OA and conversion groups were 35.4 and 20.9 months, respectively. Patients that underwent OA had a median OS of 50.5 months (95% CI 29.3-not reached) compared with 26.4 months (95% CI, 14.0-47.0) for patients requiring conversion (p = 0.020) (Fig. 3a). The difference in OS remained significant, even
| Variable | MIA (N = 158) | Conversion (N = 38) | p-Value |
|---|---|---|---|
| (a) Univariate comparison | |||
| Age, median (IQR) (years) | 56 (45-67) | 57 (45-65) | 0.783 |
| Gender, n (%) | 0.171 | ||
| Male | 52 (32.9) | 17 (44.7) | |
| Female | 106 (67.1) | 21 (55.3) | |
| Race, n (%) | 0.915 | ||
| White | 142 (89.9) | 35 (92.1) | |
| Black | 11 (7.0) | 2 (5.3) | |
| Other | 5 (3.2) | 1 (2.6) | |
| Facility type, n (%) | 0.646 | ||
| Community cancer program | 4 (2.5) | 2 (5.3) | |
| Comprehensive community program | 41 (26.0) | 11 (29.0) | |
| Academic/research program | 73 (46.2) | 15 (39.5) | |
| Integrated network cancer program | 20 (12.7) | 3 (7.9) | |
| Unknown | 20 (12.7) | 7 (18.4) | |
| Primary payer, n (%) | 0.920 | ||
| Uninsured | 6 (3.8) | 2 (5.3) | |
| Private insurance | 88 (55.7) | 21 (55.3) | |
| Medicaid | 9 (5.7) | 2 (5.3) | |
| Medicare | 50 (31.7) | 13 (34.2) | |
| Other government | 2 (1.3) | 0 (0.0) | |
| Unknown | 3 (1.9) | 0 (0.0) | |
| Distance traveled, median (IQR) | 11.9 (5.3-40.5) | 13.7 (5.6-40.1) | 0.856 |
| Comorbidity index, n (%) | 0.692 | ||
| 0 | 107 (67.7) | 27 (71.1) | |
| 1 or greater | 51 (32.3) | 11 (29.0) | |
| Tumor size (cm), median (IQR) | 7.5 (5-10) | 9 (7-12) | 0.007 |
| Tumor extent, n (%) | 0.835 | ||
| Confined to adrenal | 107 (67.7) | 27 (71.1) | |
| Extends beyond adrenal | 50 (31.7) | 11 (29.0) | |
| Unknown | 1 (0.6) | 0 (0.0) | |
| Tumor grade, n (%) | 0.363 | ||
| Well/moderately differentiated | 10 (6.3) | 4 (10.5) | |
| Poorly differentiated/undifferentiated | 23 (14.6) | 8 (21.1) | |
| Not determined | 125 (79.1) | 26 (68.4) | |
| Laterality, n (%) | 0.033 | ||
| Right | 67 (42.4) | 25 (65.8) | |
| Left | 90 (57.0) | 13 (34.2) | |
| Unknown | 1 (0.6) | 0 (0.0) | |
| Multivisceral resection n (%) | 5 (3.2) | 3 (7.9) | 0.186 |
| Modality, n (%) | 0.095 | ||
| Laparoscopic | 117 (74.1) | 33 (86.8) | |
| Robotic | 41 (26.0) | 5 (13.2) | |
| (b) Multivariable comparison | |||
| Male sex (versus female) | 1.39 | 0.65-3.00 | 0.399 |
| Tumor size ≥ 6 cm (versus < 6 cm) | 3.19 | 1.22-8.35 | 0.018 |
| Right adrenalectomy (versus left) | 2.79 | 1.28-6.07 | 0.010 |
Conversion during MIA for ACC
| Variable | MIA (N = 158) | Conversion (N = 38) | p-Value |
|---|---|---|---|
| Multivisceral resection | 2.60 | 0.52-12.87 | 0.243 |
| Robotic approach (versus laparoscopic) | 0.33 | 0.11-0.98 | 0.046 |
MIA minimally invasive adrenalectomy, IQR interquartile range, OR odds ratio, CI confidence interval
35
30
Rate of Conversion
25
20
15
10
5
0
< 4 cm
4 - 6 cm
6 - 8 cm
8 - 10 cm
>= 10 cm
Tumor Size
| Variable | MIA (N = 158) | Conversion (N = 38) | p-Value |
|---|---|---|---|
| LOS, median (IQR) | 2 (1-4) | 4 (3-6) | < 0.001 |
| Unplanned readmission, n (%) | 6 (3.8) | 1 (2.6) | 0.785 |
| 90-day mortality, n (%) | 4 (2.5) | 3 (7.9) | 0.134 |
| R1 Resection, n (%) | 27 (17.1) | 11 (29.0) | 0.159 |
| Lymph node evaluation, n (%) | 10 (6.3) | 3 (7.9) | 0.720 |
MIA minimally invasive adrenalectomy, LOS length of stay, IQR interquartile range
when excluding patients that experienced 90-day mortality: 50.5 (95% CI 34.8-not reached) months for OA compared with 27.9 (95% CI 19.9-47.0) months for patients requiring conversion (p = 0.035) (Fig. 3b).
DISCUSSION
Historically, OA has been considered the gold standard operation for ACC. However, over the last few decades there has been growing debate regarding the appropriate- ness of MIA for this disease.22 This has led some to consider starting with a minimally invasive approach with
a plan to convert if the operation is difficult.18,19 The results of the current study, however, demonstrate that conversion during attempted MIA for ACC results in inferior survival compared with both successful MIA as well as planned OA. These findings were exclusive of 90-day postoperative mortality, demonstrating the negative long-term oncologic impact of conversion. Among patients undergoing attempted MIA, conversion was independently associated with decreased survival when controlling for other factors on multivariable analysis. Unique to this report is the matched evaluation of patients undergoing planned OA versus those requiring conversion during
A 1.0
B 1.0
p < 0.001
p = 0.002
0.8
0.8
Survival probability
Survival probability
0.6
0.6
0.4
0.4
0.2
1. MIA
0.2
1. MIA
2. Conversion
2. Conversion
0.0
0.0
1
2
158
110
154
110
57
23
38
20
57
23
0
1
0
6
1
0
2
35
20
6
1
0
0
20
40
60
80
0
20
40
60
80
Months from diagnosis
Months from diagnosis
C 1.0
p = 0.025
D
1.0
5
p = 0.046
0.8
0.8
Survival probability
Survival probability
0.6
0.6
0.4
0.4
0.2
1. MIA
0.2
1. MIA
2. Conversion
2. Conversion
0.0
0.0
1
2
105
25
80
42
17
0
1
48
29
14
0
6
1
0
2
6
16
10
4
0
0
20
40
60
80
0
20
40
60
80
Months from diagnosis
Months from diagnosis
| Variable | HR | 95% CI | p-Value |
|---|---|---|---|
| Age | 1.02 | 1.00-1.03 | 0.025 |
| Comorbidity index ≥ 1 | 0.83 | 0.47-1.46 | 0.515 |
| Tumor size | 1.01 | 0.97-1.05 | 0.703 |
| R1 resection | 3.23 | 1.81-5.75 | < 0.001 |
| Conversion | 2.32 | 1.34-4.03 | 0.003 |
| Tumor extension beyond adrenal | 1.31 | 0.74-2.31 | 0.348 |
| Adjuvant therapy | 1.21 | 0.97-2.12 | 0.493 |
HR hazard ratio, CI confidence interval
attempted MIA. This revealed that patients having planned OA had a survival nearly double that of patients requiring conversion during attempted MIA.
p < 0.002; c for patients with tumors confined to the adrenal gland median, OS in months for MIA was not reached (95% CI 59.5-not reached) versus 34.2 (95% CI 20.8-not reached), p < 0.025; and d for patients with tumors extending beyond the adrenal gland median OS in months for MIA was 56.2 (95% CI 21.5-not reached) versus 19.9 (95% CI 5.5-32.8), p < 0.046
While the exact reasons for worse OS observed in patients requiring conversion are not entirely clear, they may be accounted for by some of the study findings. Although not statistically significant, the rate of R1 resection for patients who required conversion (29%) was higher than that of those who underwent successful MIA (17%) and was over double that of those who underwent successful OA (13.2%). Margin negative resection has been clearly established as critical for potentially curative treatment of localized ACC.23-26 Consistent with this, positive resection margin was the strongest independent predictor of worse OS among patients undergoing attempted MIA in this study.
Another potential reason for the worse survival among patients requiring conversion is the risk of increased tumor abrasion or spillage, which has been documented as a poor prognostic factor for patients undergoing resection of ACC.27 Although the NCDB does not account for this variable, conversion during any minimally invasive oper- ation is typically prompted by technical problems such as bleeding, poor visibility, or difficulty in developing proper
Conversion during MIA for ACC
| Variable | Open (N = 38) | Conversion (N = 38) | p-Value |
|---|---|---|---|
| Age, median (IQR) (years) | 55.5 (41-67) | 57 (45-65) | 0.901 |
| Gender, n (%) | 1.000 | ||
| Male | 17 (44.7) | 17 (44.7) | |
| Female | 21 (55.3) | 21 (55.3) | |
| Race, n (%) | 0.841 | ||
| White | 36 (94.7) | 35 (92.1) | |
| Black | 1 (2.6) | 2 (5.3) | |
| Other | 1 (2.6) | 1 (2.6) | |
| Facility type, n (%) | 0.734 | ||
| Community cancer program | 2 (5.3) | 2 (5.3) | |
| Comprehensive community program | 8 (21.1) | 11 (29.0) | |
| Academic/research program | 19 (50.0) | 15 (39.5) | |
| Integrated network cancer program | 1 (2.6) | 3 (7.9) | |
| Unknown | 8 (21.1) | 7 (18.4) | |
| Primary payer, n (%) | 0.534 | ||
| Uninsured | 3 (7.9) | 2 (5.3) | |
| Private insurance | 18 (47.4) | 21 (55.3) | |
| Medicaid | 5 (13.2) | 2 (5.3) | |
| Medicare | 10 (26.3) | 13 (34.2) | |
| Other government | 1 (2.6) | 0 (0.0) | |
| Unknown | 1 (2.6) | 0 (0.0) | |
| Comorbidity index, n (%) | 1.000 | ||
| 0 | 27 (71.1) | 27 (71.1) | |
| 1 or greater | 11 (29.0) | 11 (29.0) | |
| Tumor size (cm), median (IQR) | 9 (7-12.5) | 9 (7-12) | 0.843 |
| Tumor extent, n (%) | 0.803 | ||
| Confined to adrenal | 26 (68.4) | 27 (71.1) | |
| Extends beyond adrenal | 12 (31.6) | 11 (29.0) | |
| Tumor grade, n (%) | 0.689 | ||
| Well/moderately differentiated | 2 (5.3) | 4 (10.5) | |
| Poorly differentiated/undifferentiated | 9 (23.7) | 8 (21.1) | |
| Not determined | 27 (71.1) | 26 (68.4) | |
| Laterality, n (%) | 0.135 | ||
| Right | 17 (44.7) | 25 (65.8) | |
| Left | 20 (52.6) | 13 (34.2) | |
| Unknown | 1 (2.6) | 0 (0.0) | |
| Multivisceral resection, n (%) | 3 (7.9) | 3 (7.9) | 1.000 |
IQR interquartile range
| Variable | Open (N = 38) | Conversion (N = 38) | p-Value |
|---|---|---|---|
| LOS, median (IQR) | 5 (4-6) | 4 (3-6) | 0.373 |
| Unplanned readmission, n (%) | 2 (5.3) | 1 (2.6) | 1.000 |
| 90-day mortality, n (%) | 1 (2.6) | 3 (7.9) | 0.615 |
| R1 resection, n (%) | 5 (13.2) | 11 (29.0) | 0.080 |
| Lymph node evaluation, n (%) | 6 (15.8) | 3 (7.9) | 0.480 |
LOS length of stay, IQU interquartile range
A
1.0
p = 0.020
0.8
Survival probability
0.6
0.4
1. MIA
0.2
2. Conversion
0.0
1
2
38
25
38
20
18
2
6
1
0
20
40
60
Months from diagnosis
B 1.0
p = 0.035
Survival probability
0.8
0.6
0.4
1. MIA
0.2
2. Conversion
0.0
1
2
37
25
18
35
20
2
6
1
0
20
40
60
Months from diagnosis
tissue planes and working space, any of which may potentiate tumor disruption. When operating on malig- nancies that are confined within an intestinal lumen or deeply seeded within the parenchyma of the parent organ, risk of tumor rupture or margin compromise may be less likely if conversion is required. However, in ACC, the entire gland is often replaced by tumor, and dissection may take place along the surface of the tumor capsule. Wide exposure and the ability to detect malignant adhesions or involvement of surrounding viscera without violating such planes are critical to avoid tumor disruption. An interesting finding in the current study is that conversion resulted in worse OS even for patients with tumors reported as con- fined to the adrenal gland. It is possible that this is at least partially related to unappreciated or delayed recognition tumor disruption.
In prior studies, conversion during attempted MIA for ACC has been reported to occur at rates of 0-34%.6,9,11,12,20,28,29 However, few studies have described the reasons or examined predictors of conversion in these cases. An analysis from the German ACC registry reported
that conversion was required in 12/35 (34%) laparoscopic resections because of bleeding (4), adhesions (4), bowel perforation (1), other “technical problems” (2), and intra- operative evidence of malignancy (1).11 In a multiinstitutional review from 13 US centers, conversion occurred in 9/47 (19%) cases and was significantly asso- ciated with increased BMI (34 kg/m2 versus 24 kg/m2), larger tumor size (11 cm versus 6.5 cm), increased blood loss (800 mL versus 100 mL), and longer operative time (358 min versus 156 min).20 However, in these two stud- ies, conversion was not associated with worse survival compared with successful MIA. In a previous NCDB study, Calcatera et al.30 identified a tumor size of > 5 cm as the only predictor of conversion, and patients requiring con- version had lower OS than successful MIA and OA patients. In the current study, a size cut-off of 6 cm was selected a priori based on prior reporting that this threshold carries a 25% risk of ACC in adrenocortical tumors.31 On multivariable Cox regression analysis, tumor size ≥ 6 cm and right-sided location were each independent predictors of conversion during attempted MIA.
It is recognized that, in some cases, the diagnosis of ACC is not known preoperatively. Increasing tumor size is a well-documented predictor for an adrenocortical tumor being malignant. In a 2002 National Institutes of Health (NIH) state-of-the-science statement, the risk of ACC for tumors < 4 cm, 4-6 cm, and > 6 cm was reported to be 2%, 6%, and 25%, respectively.31 With a Surveillance, Epidemiology, and End Results (SEER) database of 457 ACCs and an institutional dataset of 47 benign adrenal adenomas, Sturgeon et al.18 examined the relationship between tumor size and risk of malignancy. Using a pretest probability of 5%, they reported the posttest probability of an adrenocortical tumor ≥ 8 cm being malignant as 47%. This size threshold had a sensitivity of 77% and a speci- ficity of 95%. In a subsequent report by Abdel-Aziz et al., examination of an institutional database revealed that 31 of 37 (84%) adrenocortical tumors > 8 cm were ACC.32 In the current study, the median tumor size of patients undergoing attempted MIA was 7.9 cm, with an interquartile range of 5.1-10.8 (Supplementary Table 1). Given the likelihood of an 8 cm cortical tumor representing ACC, and most US guideline statements advocating OA for ACC [NCCN, American Association of Clinical Endocri- nologists (AACE)/American Association of Endocrine Surgeons (AAES)], this was a somewhat surprising and concerning finding.
Given the very low risk of maligancy for tumors < 6 cm and low rates of conversion for tumors this size, it is hard to justify not offering MIA to these patients, in particular for “incidentalomas”. However, this dilemma emphasizes the need for surgeons to obtain appropriate preoperative imaging and consider features other than size when
determining the need for operation as well as the operative approach. Imaging characteristics, such as internal hetero- geneity, irregular or infiltrative borders, a measurement of > 10 Hounsfield units on unenhanced computed tomog- raphy (CT), delayed washout on adrenal protocol CT, and an increase in tumor size during serial imaging, should raise concern for malignancy.33-35 Additionally, in the case of a functional tumor, if biochemical evaluation reveals a combination of glucocorticoid and androgen hypersecre- tion, the diagnosis of ACC should be suspected.36 Given the rarity and aggressive nature of ACC, if the diagnosis is suspected based on tumor size or other concerning features, referral to a team or center with expertise in the surgical and medical management of the disease is recommended16,25,37-44
Several groups have reported similar outcomes between MIA and OA for select patients and concluded that MIA is appropriate for those with tumors < 10 cm and confined to the adrenal gland.11,13,20,28 However, a close look at these studies reveals that, for patients undergoing MIA, median tumor sizes were 6.2 cm,11 5.5 cm,28 9 cm,13 and 5.5 cm.20 The current data do not contend that successful MIA for ACC can lead to excellent survival in patients with smaller tumors, but the relatively high rates of conversion observed for tumors measuring > 6 cm should be noted. Ultimately, what is most important when operating for ACC is en bloc margin negative resection and regional lymphadenectomy. This allows for best outcomes and appropriate staging. The high rate of R1 resection, low rate of lymph node evalua- tion, and inferior survival for patients requiring conversion in the current study should give pause before pursuing MIA if ACC is known or suspected. Although the short-term benefits of minimally invasive resection are well recog- nized, they should not come at the expense of possible cure or gained years of life in patients with this rare and aggressive tumor. Moreover, a decision to convert because of technical difficulties when operating for possible ACC is likely a decision made too late.
There are limitations to the current study that warrant mention. These include its retrospective nature as well as the absence of many relevant data points within the NCDB. Specific to the current study, the database does not include surgeon volume, specific reasons for conversion, intraop- erative tumor disruption or spillage, or blood loss and transfusion requirements. Tumor-related factors such as hormone production and Ki-67 index are not captured. In addition, the type and duration of adjuvant therapy (e.g., mitotane dosing and levels) are not detailed. Finally, while OS is reported, disease-recurrence and disease-specific survival are not.
CONCLUSIONS
Analysis of a large national dataset demonstrated that, among patients undergoing attempted MIA for ACC, conversion was required in nearly 20% and was an inde- pendent predictor of worse OS. Moreover, when compared with a matched cohort of patients undergoing OA, con- version during attempted MIA resulted in significantly lower OS. The current findings raise caution about the pursuit of MIA in patients with known or suspected ACC and challenge a philosophy of starting laparoscopically with plans to convert if the operation is difficult.
DISCLOSURES None.
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