SERVICES . USA \\TMENT OF HEALTH & HOME
Published in final edited form as: Clin Genitourin Cancer. 2022 October ; 20(5): 497.e1-497.e7. doi:10.1016/j.clgc.2022.04.011.
Association of Surgical Approach with Treatment Burden, Oncological Effectiveness, and Perioperative Morbidity in Adrenocortical Carcinoma
Kevin B. Ginsburg, MD, MS1,2, Akhil A. Chandra, BS1, Elizabeth A. Handorf, PhD3, Jared P. Schober, MD1, Ali Mahmoud, MD2, Marc C. Smaldone, MD, MSHP1, Rosalia Viterbo, MD1, Robert G. Uzzo, MD1, Richard E. Greenberg, MD1, David YT Chen, MD1, Alexander Kutikov, MD1, Andres F. Correa, MD1
1Department of Surgical Oncology, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA
2Wayne State University Department of Urology, Detroit, MI
3Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia PA
Abstract
Introduction/Background: We investigated the cumulative treatment burden, oncological effectiveness, and perioperative morbidity in patients undergo minimally invasive adrenalectomy (MIA) compared with open adrenalectomy (OA) for patients with adrenocortical carcinoma (ACC).
Corresponding Author: Kevin B. Ginsburg, MD, MS, Department of Surgical Oncology, Division of Urologic Oncology Fox Chase Cancer Center, Temple University Health System, 333 Cottman Avenue, Philadelphia, PA 19111, kevin.ginsburg@fccc.edu, Tel: 215 728 4300.
Authors Contributions statement:
Kevin B. Ginsburg: conceptualization, formal analysis, methodology, validation, visualization, writing - original draft Akhil A. Chandrea: conceptualization, visualization, writing - original draft
Elizabeth A. Handorf: formal analysis, methodology, supervision, validation, visualization Jared P Schober: conceptualization, methodology, writing - review and editing Ali Mahmoud: visualization, writing - original draft, writing - review and editing Marc C. Smaldone: conceptualization, methodology, writing - review and editing Rosalia Viterbo: conceptualization, methodology, writing - review and editing Robert G. Uzzo: conceptualization, methodology, writing - review and editing
Richard E. Greenberg: conceptualization, methodology, writing - review and editing
David YT Chen: conceptualization, methodology, writing - review and editing Alexander Kutikov: conceptualization, methodology, supervision, writing - review and editing Andres F. Correa: conceptualization, methodology, supervision, writing - review and editing
Conflicts of Interest: Kevin B. Ginsburg - None Akhil A. Chandra - None Elizabeth A. Handorf - None Jared P. Schober - None Ali Mahmoud - None Marc C. Smaldone - None Rosalia Viterbo - None Robert G. Uzzo - None Richard E. Greenberg - None David YT. Chen - None Alexander Kutikov - None Andres F. Correa - None
Patients and Methods: We reviewed the NCDB for patients undergoing surgical resection (MIA vs. OA) for ACC from 2010 to 2017. Inverse probability of treatment weighted logistic regression, negative binomial, and Cox proportional hazards models were fit to assess for an association of surgical approach with cumulative treatment burden (any adjuvant therapy, radiation therapy (RT), and systemic therapy), oncological effectiveness (positive surgical margins (PSM), lymph node yield (LNY), and overall survival (OS)), and perioperative morbidity (length of stay (LOS) and readmission) as appropriate.
Results: We identified 776 patients that underwent adrenalectomy for ACC, of which 307 underwent MIA. We noted patients with larger tumors (OR 0.82, 95% CI 0.78-0.86, p<0.001) were less likely to have MIA prior to IPTW. We did not appreciate a significant association of MIA with cumulative treatment burden or the use of any adjuvant therapy (OR 0.85, 95% CI 0.60-1.21, p=0.375), adjuvant RT (OR 0.94, 95% CI 0.59-1.50, p=0.801), or adjuvant systemic therapy (OR 0.84, 95% CI 0.58-1.21, p=0.352). Patients undergoing MIA had similar oncological effectiveness of surgery and OS when compared with patients which underwent OA. Patients that underwent MIA had a significantly shorter LOS (IRR: 0.74, 95% CI 0.62-0.88, p=0.001) and lower odds of readmission (OR 0.46, 95% CI 0.23-0.91, p=0.026).
Conclusions: Although the standard of care for adrenal lesions suspicious for ACC remains OA, in appropriately selected patients, MIA may offer similar oncological effectiveness and cumulative treatment burden, with less morbidity, than OA.
Microabstract
In the National Cancer Database, patients treated with minimally invasive adrenalectomy for adrenocortical carcinoma had similar oncological outcomes and cumulative treatment burden with less morbidity compared with open adrenalectomy. Although open adrenalectomy remains the standard of care for adrenal lesions concern for malignancy, minimally invasive adrenalectomy in appropriately selected patients may offer equivalent oncological outcomes.
Keywords
Adrenalectomy; Minimally Invasive Surgery; Open Surgical Therapy; Adjuvant Radiotherapy; Adjuvant Chemotherapy
Introduction:
Adrenocortical carcinoma (ACC) is a rare malignancy with an annual incidence of approximately 0.72 to 2 cases per million people in the United States1. Patients with metastatic ACC have a generally poor prognosis with a 5-year survival of approximately 37%1. As a result, complete surgical resection remains the preferred therapy for patients with localized diease.2, 3 With the rise of laparoscopy in the late 20th century and robotic surgery in the 21st century, minimally invasive adrenalectomy (MIA) has become an attractive option in effort to limit the morbidity of open adrenalectomy (OA). Currently, the NCCN guidelines state that both MIA (robotic and laparoscopic) and OA may be utilized for adrenal lesions depending on “tumor size and degree of concern regarding potential malignancy, and local surgical expertise”2 while the European Society of Endocrinology/
European Network for the Study of Adrenal Tumors (ESE/ENSAT) state that “open adrenalectomy is the standard surgical approach for confirmed or higly suspected ACC.”3
However, the utilization of MIA approaches have been questioned by early reports of increased local recurrence and peritoneal carcinomatosis in patients treated with MIA as compared with OA.4-7 Furthermore, previous research has shown that patients undergoing MIA are more likely to have incomplete resection and positive surgical margin, which strongly correlates with recurrence, progression and worse survival.8-11 Despite the concern of increased risk of PSM and local recurrence, certain groups have shown comparable survival outcomes between patients treated with MIA vs. OA.12, 13 It remains unknown if patients that undergo MIA incur a cumulative higher treatment burden by utilizing more adjuvant radiation and systemic therapy, which may in turn impact quality of life, in order to provide equivalent survival outcomes as compared with patients undergoing OA. Herein, we describe the use of adjuvant therapies and cumulative treatment burden, oncological effectiveness, and perioperative morbidity in patients undergoing MIA and OA.
Patients and Methods
Study Design
We conducted a retrospective review of patients undergoing extirpative surgery for adrenocortical carcinoma (ACC) in the National Cancer Database (NCDB) from 2010 to 2017. The NCDB, a hospital-based registry, obtains clinical data from more than 1,500 Commission on Cancer (CoC) accredited institutions in the United States and Puerto Rico. Approximately 70% of all new cancer diagnoses in the United States are captured in the NCDB.14-17 The NCDB is a joint project of the CoC of the American College of Surgeons and the American Cancer Society. The data analyzed in the study was obtained from a de- identified NCDB file. The American College of Surgeons and the CoC have not verified and are not responsible for the analytic or statistical methodology employed nor the conclusions drawn from this data by the investigators. This study was deemed exempt from IRB review by the Fox Chase Cancer Center Institutional Review Board.
Study Population
Patients from the NCDB were included in this study if they underwent adrenalectomy for ACC (histology code 8370) during the period 2010 to 2017. Patients were excluded if there was clinical evidence of nodal (cN+) or metastatic disease (cM+ or clinical stage IV disease). Patients with missing or incomplete information regarding surgical approach were excluded. Patients which received preoperative RT or systemic therapy were excluded. Furthermore, we excluded patients with T4 tumors or masses larger than 20 cm in size as most would agree that these patients should not be treated with a minimally invasive surgical approach.18 The final analytic cohort consisted of 776 patients.
Study Outcomes
The aim of this study was to assess treatment burden in patients undergoing MIA or OA for ACC. We tested for an association between surgical approach and use of any postoperative adjuvant therapy (RT or systemic therapy). The NCDB records all treatments administered
Clin Genitourin Cancer. Author manuscript; available in PMC 2023 October 01.
before recurrence or progression. Therefore, salvage therapies that were administered after recurrence or progression are not included in these outcomes. Patients which underwent a robotic or laparoscopic surgery were classified in the MIA group. Robotic or laparoscopic surgeries which were converted to OA were classified as MIA to account for the potential morbidity of MIA utilizing the intention to treat principle. Additional objectives were to assess for the association of surgical approach (MIA vs OA) with measures of oncological effectiveness: overall survival (OS), positive surgical margins, and lymph node yield and perioperative morbidity: readmission and length of stay (LOS). OS was calculated from the date of diagnosis to the date of death for patients which died or the date of last clinical contact for patients which remained alive at last follow up. Sensitivity analysis was performed by excluding patients with missing information regarding clinical T stage.
Statistical Analysis
Clinical, demographic, and oncological parameters were compared between patients treated with MIA vs OA with mean standardized differences. A multivariable logistic regression model was fit to calculate the adjusted odds ratio of factors associated with MIA vs OA. Variables included in the model were clinical T stage (cT1 vs. cT2 vs. cT3 vs. missing), tumor size (continuous in cm), age (continuous per year), race (white vs. non-white), sex (male vs. female), comorbidity score (0 vs. 1 vs. ≥2), and insurance type (private vs. public vs. uninsured/unknown). The multivariable logistic regression model was used to calculate the probability of MIA vs OA. Model fit was assessed with AUC and Hosmer-Lemeshow Goodness of Fit test. Inverse probability of treatment weighting (IPTW) was then used to adjust for measurable difference in the above covariates between patients treated with MIA vs OA. Balance between covariates was assessed in the weighted sample using mean standardized differences.19 We then fit IPTW logistic regression models to assess for the association of surgical approach with adjuvant therapies. The Kaplan-Meier method was used to graph IPTW survival curves and an IPTW Cox proportional hazards model was fit to assess for an association between surgical approach with survival. IPTW logistic regression models were fit to test for an association of surgical approach with positive surgical margins (PSM) and readmission. IPTW negative binomial regression models were fit for an association of surgical approach with length of stay and lymph node yield. All regression models had robust standard errors which were clustered by hospital. Statistical analysis was performed with Stata version 15.1 with statistical significance set at a threshold of 0.05.
Results
Demographics
From 2010 to 2017, we identified 776 patients that underwent surgical resection for ACC in the NCDB. Median follow up for the entire cohort was 38.9 months (IQR: 18.1-61.7). Median age of the cohort was 57 (IQR: 45-67) and most patients (73%) were healthy (CCI=0). 469 patients underwent an OA (60%) compared with 307 (40%) which underwent MIA. Clinical and demographic parameters for patients with MIA and OA disease are shown in Table 1.
Inverse probability of treatment weighting
We fit a multivariable logistic regression model to identify clinical, demographic, and oncological factors associated with MIA (Supplemental Table 1). The model had modest predictive capability (AUC: 0.74, Supplemental Figure 1) and good fit (Hosmer-Lemeshow Goodness of Fit, p=0.327). We noted patients with larger tumors (OR 0.82, 95% CI 0.78- 0.86, p<0.001) were less likely to have MIA.
To adjust for the clinical, demographic, and oncological differences between patients undergoing MIA and OA, we conducted inverse probability of treatment weighting (IPTW). The multivariable logistic regression model was used to estimate each patient’s probability of having an MIA which was then used to weight the sample by the inverse probability of the treatment each patient received. The weighted demographics for the cohort are shown in Table 1. The standardized difference was used to assess for balance in the weighted cohort. All standardized differences after IPTW were less than the absolute value of 0.1, suggesting that the IPTW cohort was well balanced with regard to measured variables.19
Cumulative Treatment Burden
Of the 776 patients included in the study, 325 underwent any adjuvant treatment (RT, systemic, or both), 149 underwent adjuvant RT, and 265 underwent adjuvant systemic therapy. To test for an association of total treatment burden and surgical approach, we fit IPTW logistic regression models for the outcomes of the use of any adjuvant therapy, adjuvant RT, or adjuvant systemic therapy. We did not appreciate a significant association with MIA and the use of any adjuvant therapy (OR 0.85, 95% CI 0.60-1.21, p=0.375), adjuvant RT (OR 0.94, 95% CI 0.59-1.50, p=0.801), or adjuvant systemic therapy (OR 0.84, 95% CI 0.58-1.21, p=0.352) compared with patients that underwent OA (Figure 1).
Oncological Effectiveness
The distribution of pathologic T stage was similar among patients undergoing MIA (pT1: 12%; pT2: 49%; pT3: 30%; pT4: 4.2%; and unknown: 4.0%) and OA (pT1: 7.6%; pT2: 51% pT3: 29%; pT4: 5.3%; and unknown: 6.4%). To assess the oncological quality of surgery, we tested for an association between surgical approach with positive surgical margins, lymph node yield, and overall survival (Table 2). There were 125 patients with a PSM. We did not appreciate a significant association between surgical approach with PSM (OR 1.39, 95% CI 0.90-2.15, p=0.143). The median lymph node yield (LNY) in patients which underwent a lymphadenectomy was 3 nodes (IQR:1-7). We did not appreciate a significant difference in LNY between patients which underwent MIA and OA (IRR 0.90, 95% CI 0.46-1.76, p=0.753). There were 360 deaths during follow up. We did not appreciate a significant association between surgical approach and overall survival (HR 1.14, 95% CI 0.90-1.46, p=0.260, Figure 2 and Table 2).
Perioperative Morbidity
To assess for the morbidity of surgery, we tested for an association between surgical approach with LOS and readmission (Table 2). The median postoperative LOS in the cohort was 4 days (IQR 2-6) and 54 patients were readmitted. Patients that underwent MIA had a significantly shorter postoperative LOS (IRR: 0.74, 95% CI 0.62-0.88, p=0.001) and
Clin Genitourin Cancer. Author manuscript; available in PMC 2023 October 01.
significantly lower odds of readmission (OR 0.46, 95% CI 0.23-0.91, p=0.026) compared with patient which underwent OA.
Sensitivity Analysis
Due to concern of the potential influence of missing information regarding clinical T stage, we excluded 228 patients that were missing a clinical T stage. We refit a logistic regression model for factors associated with MIA vs. OA and reweighted the cohort by the inverse probability of the predicted treatment. The interpretation of the results of the models as well as the point estimates, confidence intervals, and statistical significance were nearly equivalent between the sensitivity analysis and analysis of the whole cohort. We did note that MIA was associated with lower lymph node yield (IRR 0.43, 95% CI 0.27-0.70, p=0.001) compared with OA and MIA was no longer associated with a reduction in readmissions (OR: 0.54, 95% CI 0.23-1.30, p=0.17) in the sensitivity analysis (Supplemental Table 2).
Discussion
As with most solid malignancies, assimilation to minimally invasive surgical technologies has been swift in the care of patients with adrenal masses due to reduction in postoperative morbidity. In ACC, there was initial concern that MIA was associated with inferior oncological outcomes compared with OA, yet emerging data have suggested equivalent OS in patients undergoing OA and MIA.12, 20, 21 Despite the increased risk of PSM and tumor spillage, it remains unknown if patients which undergo MIA may demonstrate equivalent outcomes at the expense of increase treatment burden and utilization of adjuvant therapies (chemotherapy or radiotherapy). In the present analyses, we demonstrated that patients with ACC undergoing MIA for non-metastatic ACC in the NCDB had similar cumulative treatment burden and use of any adjuvant therapy, adjuvant RT, and adjuvant systemic therapy as patients undergoing OA. Furthermore, we found similar oncological effectiveness of surgery (positive surgical margins and overall survival) in patients undergoing MIA and OA, with less morbidity in the MIA group as evident by the shorter LOS and lower odds of readmission.
Reports regarding the early use of MIA for treatment of ACC have served as a cautionary note. Miller at al. reported on 88 patients undergoing adrenalectomy from 2003-2008, 17 of which were MIA, noting MIA was associated with shorter recurrence free survival (9.6 months) and increase in local recurrences (25%) compared with patients undergoing OA (19.2 months and 20%, respectively).7 A follow up study from the same group included 217 patients undergoing adrenalectomy for ACC from 2005 to 2011, reporting 30% of patients undergoing laparoscopic adrenalectomy (LA) had PSM or tumor spillage as compared with 16% of patients undergoing OA.4 Cooper et al. (n=302) found similar results and noted an increased risk of PSM (28% vs.17%) and local/peritoneal recurrence (54% vs. 26%) for patients undergoing LA vs. OA, respectively 22. Both of these groups reported worse recurrence-free survival and overall survival for patients undergoing LA as compared with OA. However, other groups have suggested equivalent oncological outcomes for patients undergoing LA and OA. Studying patients with adrenal masses ≤10 cm in the
German ACC registry, Brix et al. reported similar risk of PSM/tumor spillage, recurrence- free, and overall survival in patients that underwent LA and OA.21 Utilizing the NCDB, Maurice and colleagues reported similar OS in patients undergoing MIA and OA, yet MIA was associated with increased odds of PSM in their multivariable model.12 Herein, we sought to comprehensively investigate if patients undergoing MIA incurred a higher treatment burden and utilize more adjuvant therapies in order to achieve equivalent OS when compared with patients undergoing OA. In our study, we found similar use of any adjuvant therapy, adjuvant RT, and adjuvant systemic therapy in patients undergoing MIA and OA. Additionally, we found similar OS and similar odds of PSM for patients undergoing MIA and OA.
Furthermore, MIA was associated with shorter LOS and less readmission in our study compared with OA. Congruent with our results, utilizing the National Surgery Quality Improvement Project database, Elfenbein et al. demonstrated less 30-day readmission, 30-day mortality, and shorter LOS in patients undergoing LA vs. OA for patients with and without ACC.23 Using a cohort of national claims data, Faiena et al. demonstrated a reduction in morbidity (LOS and major complications) with MIA in patients undergoing adrenalectomy for benign and malignant disease.24 We expand upon previously published reports by utilizing comparative effectiveness techniques and IPTW to demonstrate similar uses of adjuvant therapies, similar oncological outcomes (PSM, LNY, OS) and improved morbidity of surgery in patients undergoing MIA and OA in the NCDB.
There are several limitations inherent to a retrospective registry study. First, details which lead to the medical decision-making process to receive adjuvant therapies or surgical approach are not available within the dataset, allowing for an element of selection bias. Second, the NCDB includes therapies in a patient’s first treatment course up to recurrence or progression. Therefore, the use of salvage RT or salvage systemic therapies after recurrence or the development of metastasis were not captured in this analysis. Third, despite inverse probability of treatment weighting and balance among measurable covariates, there remains the potential for residual and unmeasured confounding. Forth, certain parameters of potential interest, including pathologic grade, had a significant degree of missing data and could not be included for analysis. Small sample size among specific subgroups, notably patients with clinical T3 disease, limits the ability to do subgroup analysis for these select patients. As a results, these results should be applied cautiously to patients with clinical T3 disease. Despite these limitations, our study adds to the limited data regarding cumulative treatment burden and oncological effectiveness of MIA vs. OA in patients with ACC.
In the absence of more definitive evidence, OA remains the standard of care for most patients with adrenal lesions concerning for ACC, as recommended by guideline statements.2,3 In appropriately selected patients, MIA may offer equivalent oncological efficacy with less morbidity as OA. The similar use of adjuvant treatments, survival, and oncological outcomes presented in this study would suggest that surgeons are appropriately selecting patients which are appropriate for MIA and utilizing this technology cautiously.
Conclusions
In the NCDB, patients undergoing MIA with clinically localized ACC had similar cumulative treatment burden (any adjuvant treatment, adjuvant radiation and adjuvant systemic therapy) compared with patients undergoing OA but had less morbidity as evident by shorter LOS and lower odds of readmission. Although the standard of care for adrenal lesions suspicious for ACC remains OA, in appropriately selected patients, MIA may offer equivalent oncological efficacy with less morbidity than OA.
Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
Data Sharing:
Per the NCDB DUA, data sharing is not permissible.
References:
1. Rodgers SE, Evans DB, Lee JE et al .: Adrenocortical carcinoma. Surg Oncol Clin N Am, 15: 535, 2006 [PubMed: 16882496]
2. Shah MH, Goldner WS, Halfdanarson TR et al. : NCCN Guidelines Insights: Neuroendocrine and Adrenal Tumors, Version 2.2018. J Natl Compr Canc Netw, 16: 693, 2018 [PubMed: 29891520]
3. 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, 179: G1, 2018 [PubMed: 30299884]
4. Miller BS, Gauger PG, Hammer GD et al. : Resection of adrenocortical carcinoma is less complete and local recurrence occurs sooner and more often after laparoscopic adrenalectomy than after open adrenalectomy. Surgery, 152: 1150, 2012 [PubMed: 23158185]
5. Huynh KT, Lee DY, Lau BJ et al. : Impact of Laparoscopic Adrenalectomy on Overall Survival in Patients with Nonmetastatic Adrenocortical Carcinoma. J Am Coll Surg, 223: 485, 2016 [PubMed: 27238874]
6. Payabyab EC, Balasubramaniam S, Edgerly M et al. : Adrenocortical Cancer: A Molecularly Complex Disease Where Surgery Matters. Clin Cancer Res, 22: 4989, 2016 [PubMed: 27742785]
7. Miller BS, Ammori JB, Gauger PG et al. : Laparoscopic Resection is Inappropriate in Patients with Known or Suspected Adrenocortical Carcinoma. World Journal of Surgery, 34: 1380, 2010 [PubMed: 20372905]
8. Margonis GA, Kim Y, Prescott JD et al. : Adrenocortical Carcinoma: Impact of Surgical Margin Status on Long-Term Outcomes. Ann Surg Oncol, 23: 134, 2016 [PubMed: 26286195]
9. Bedrose S, Daher M, Altameemi L et al. : Adjuvant Therapy in Adrenocortical Carcinoma: Reflections and Future Directions. Cancers (Basel), 12, 2020 [PubMed: 32718075]
10. Anderson KL Jr., Adam MA, Thomas SM et al. : Impact of Micro- and Macroscopically Positive Surgical Margins on Survival after Resection of Adrenocortical Carcinoma. Ann Surg Oncol, 25: 1425, 2018 [PubMed: 29500765]
11. Ayala-Ramirez M, Jasim S, Feng L et al. : Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center. Eur J Endocrinol, 169: 891, 2013 [PubMed: 24086089]
12. Maurice MJ, Bream MJ, Kim SP et al. : Surgical quality of minimally invasive adrenalectomy for adrenocortical carcinoma: a contemporary analysis using the National Cancer Database. BJU Int, 119: 436, 2017 [PubMed: 27488744]
13. Hu X, Yang WX, Shao YX et al. : Minimally Invasive Versus Open Adrenalectomy in Patients with Adrenocortical Carcinoma: A Meta-analysis. Ann Surg Oncol, 27: 3858, 2020 [PubMed: 32277316]
14. Mohanty S, Bilimoria KY: Comparing national cancer registries: The National Cancer Data Base (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) program. J Surg Oncol, 109: 629, 2014 [PubMed: 24464362]
15. Merkow RP, Rademaker AW, Bilimoria KY: Practical Guide to Surgical Data Sets: National Cancer Database (NCDB). JAMA Surg, 153: 850, 2018 [PubMed: 29617542]
16. Bilimoria KY, Stewart AK, Winchester DP et al. : The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol, 15: 683, 2008 [PubMed: 18183467]
17. Boffa DJ, Rosen JE, Mallin K et al. : Using the National Cancer Database for Outcomes Research: A Review. JAMA Oncol, 3: 1722, 2017 [PubMed: 28241198]
18. Zografos GN, Vasiliadis G, Farfaras AN et al. : Laparoscopic surgery for malignant adrenal tumors. JSLS, 13: 196, 2009 [PubMed: 19660215]
19. Austin PC: Using the Standardized Difference to Compare the Prevalence of a Binary Variable Between Two Groups in Observational Research. Communications in Statistics - Simulation and Computation, 38: 1228, 2009
20. Porpiglia F, Fiori C, Daffara F et al. : Retrospective evaluation of the outcome of open versus laparoscopic adrenalectomy for stage I and II adrenocortical cancer. Eur Urol, 57: 873, 2010 [PubMed: 20137850]
21. Brix D, Allolio B, Fenske W et al. : Laparoscopic versus open adrenalectomy for adrenocortical carcinoma: surgical and oncologic outcome in 152 patients. Eur Urol, 58: 609, 2010 [PubMed: 20580485]
22. Cooper AB, Habra MA, Grubbs EG et al. : Does laparoscopic adrenalectomy jeopardize oncologic outcomes for patients with adrenocortical carcinoma? Surg Endosc, 27: 4026, 2013 [PubMed: 23765427]
23. Elfenbein DM, Scarborough JE, Speicher PJ et al. : Comparison of laparoscopic versus open adrenalectomy: results from American College of Surgeons-National Surgery Quality Improvement Project. J Surg Res, 184: 216, 2013 [PubMed: 23664532]
24. Faiena I, Tabakin A, Leow J et al. : Adrenalectomy for benign and malignant disease: utilization and outcomes by surgeon specialty and surgical approach from 2003-2013. Can J Urol, 24: 8990, 2017 [PubMed: 28971785]
Key Points
· We tested if minimally invasive adrenalectomy was associated with worse outcomes compared with open adrenalectomy.
· In the NCDB, we noted patients treated with minimally invasive adrenalectomy had similar cumulative treatment burden (use of any adjuvant treatment) and similar oncological effectiveness (positive surgical margins, lymph node yield, and overall survival) compared with open adrenalectomy.
· Although the standard of care remains open surgery, in appropriately selected patients, MIA may offer equivalent oncological efficacy with less morbidity than OA.
Clinical Practice Points
Previous reports raised concerns that minimally invasive adrenalectomy for patients with adrenocortical carcinoma was associated with higher incidence of positive surgical margins, local recurrence, and worse overall survival. Using the comparative effectiveness technique of inverse probability of treatment weighting to adjust for measurable differences between patients undergoing minimally invasive and open adrenalectomy, we investigated the oncological effectiveness, cumulative treatment burden, and morbidity of surgery for patients undergoing minimally invasive adrenalectomy compared with open adrenalectomy. We found patients treated with minimally invasive adrenalectomy had similar oncological outcomes (positive surgical margins and overall survival) and similar cumulative treatment burden (use of adjuvant radiation therapy or systemic therapy) compared with patients treated with open adrenalectomy. Additionally, minimally invasive adrenalectomy was associated with a shorter length of stay and less readmissions compared with open adrenalectomy. Although the standard of care for adrenal lesions suspicious for adrenocortical carcinoma remains open adrenalectomy, in appropriately selected patients, minimally invasive adrenalectomy may offer similar oncological effectiveness and cumulative treatment burden, with less morbidity than open adrenalectomy.
Ginsburg et al.
| OR | 95% CI | p |
|---|---|---|
| 0.85 | 0.60-1.21 | 0.375 |
| 0.94 | 0.59-1.50 | 0.801 |
| 0.84 | 0.58-1.21 | 0.352 |
Model 1: Any Adjuvant Treatment
Model 2: Adjuvant RT
Model 3: Adjuvant Systemic Treatment
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
Weighted OR
Less Adjuvant Therapy
More Adjuvant Therapy
1.00
Kaplan-Meier Survival Estimates
0.75
Overall Survival
0.50
0.25
0.00
0
12
24
36
48
60
72
Time from Diagnosis (Months)
OA
MIA
Table 1. Clinical, demographic, and oncological factors associated with open and minimally invasive adrenalectomy (MIA) in the unweighted and inverse probability of treatment weighted cohort.
| Unadjusted IPTW | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Open (n=476) | MIA (n=309) | Open Percent/Mean | MIA | ||||||
| N/median | %/IQR | N/median | %/IQR | SD | Percent/Mean | SD | |||
| Clinical T stage | -0.168 | Clinical T stage | -0.013 | ||||||
| cT1 | 34 | 7.3% | 58 | 19% | cT1 | 11.6% | 11.7% | ||
| cT2 | 223 | 48% | 128 | 42% | cT2 | 45.2% | 45.9% | ||
| cT3 | 74 | 16% | 31 | 10% | cT3 | 14.3% | 13.8% | ||
| missing | 138 | 29% | 90 | 29% | missing | 28.9% | 28.6% | ||
| Size (cm, median) | 10.8 | 7.5-14.4 | 7 | 5-9.5 | -0.829 | Size (cm, mean) | 9.5 | 9.6 | 0.014 |
| Age (years) | 56 | 44-67 | 57 | 46-68 | 0.111 | Age (years) | 55.7 | 55.8 | 0.006 |
| Race | -0.080 | Race | 0.040 | ||||||
| White | 403 | 86% | 272 | 89% | White | 86.9% | 85.5% | ||
| Non-white | 66 | 14% | 35 | 11% | Non-white | 13.1% | 14.5% | ||
| Sex | -0.075 | Sex | 0.011 | ||||||
| Male | 185 | 39% | 110 | 36% | Male | 38.7% | 38.2% | ||
| Female | 284 | 61% | 197 | 64% | Female | 61.3% | 61.8% | ||
| Comorbidity Score | 0.232 | Comorbidity Score | -0.021 | ||||||
| 0 | 359 | 77% | 206 | 67% | 0 | 72.3% | 72.8% | ||
| 1 | 85 | 18% | 71 | 23% | 1 | 19.4% | 19.8% | ||
| ≥2 | 25 | 5.3% | 30 | 9.8% | ≥2 | 8.2% | 7.4% | ||
| Insurance Type | -0.116 | Insurance Type | -0.001 | ||||||
| Private | 242 | 52% | 168 | 55% | Private | 51.9% | 51.2% | ||
| Government | 185 | 39% | 124 | 40% | Government | 40.8% | 42.6% | ||
| Uninsured/unknown | 42 | 9.0% | 15 | 4.9% | Uninsured/unknown | 7.3% | 6.2% | ||
| OR/IRR/HR | 95% CI | p | |
|---|---|---|---|
| Positive Surgical Margin | |||
| Open | ref | ref | ref |
| MIA | 1.39 | 0.90-2.15 | 0.143 |
| Lymph Node Yield | |||
| Open | ref | ref | ref |
| MIA | 0.90 | 0.46-1.76 | 0.753 |
| Overall Survival | |||
| Open | ref | ref | Ref |
| MIA | 1.15 | 0.90-1.46 | 0.260 |
| Length of Stay | |||
| Open | ref | ref | ref |
| MIA | 0.74 | 0.62-0.88 | 0.001 |
| Readmission | |||
| Open | ref | ref | ref |
| MIA | 0.46 | 0.23-0.91 | 0.026 |
* Minimally Invasive Adrenalectomy (MIA)