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The American Journal of Surgery
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AJS The American Journal of Surgery”
Invited Commentary
Commentary: Locoregional metastasis of adrenocortical carcinoma and lymphadenectomy - Disease clearance or identification of high-risk features?
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Given the increased options for systemic treatment of adrenocortical carcinoma (ACC), attention has returned to focus on more effective control of the primary tumor and locoregional disease via development of best practices for surgical management. In ‘Informing Therapeutic Lymphadenectomy: Location of Regional Metastatic Lymph Nodes in Adrenocortical Carcinoma’,1 the authors document locoregional lymph node involvement by ACC from operations performed at a single insti- tution over a 20 year period. While adding to the existing literature, we are reminded of the difficulty in examining this type of data. In addition to overall treatment heterogeneity affecting outcomes (both medical and surgical), the study results are dependent on lymph nodes being both resected by the surgeon and detected by pathology; thus, the true numerator and denominator for nodal involvement are likely different than reported. We must consider this in interpreting the results and making future treatment recommendations; however, the reader is provided with valuable information.
What constitutes an adequate lymphadenectomy for ACC has yet to be entirely defined and accepted. Do the 3.5 lymph nodes retrieved in the Sada et al. study equate to adequate resection for a therapeutic lymphadenectomy? There are few nodes adjacent to the adrenal glands in the paracaval and para-aortic regions, so this number could be real- istic but could also be inadequate. Some studies have arbitrarily created cut-offs for the number of lymph nodes to be resected, but these were based on the mean number retrieved to perform a binary analysis.2-4 Reports of nodal involvement solely based on lymph node size or FDG avidity could be false positives as these nodes could be enlarged or FDG avid for other reasons, and small foci of FDG avid disease may instead be small tumor deposits resulting from the initial surgical resection instead of lymph nodes.3 5 Depending on timing of follow-up imaging, one must be wary of studies reporting lymph node involvement later in the disease process where nodal involvement reflects secondary and tertiary sites of metastasis within the lymphatic system.2 4,6-8 These examples drive home the importance of developing a standardized operative approach for ACC and critically assessing the methodology of existing literature.
Understanding presence of nodal involvement more likely provides information about aggressiveness of disease rather than being of direct value by removing all microscopic disease and preventing recurrence. Upstaging leads to additional early treatment in some centers, as pa- tients would be more likely to receive adjuvant mitotane normally reserved for high-risk features (frank lymphovascular invasion, micro- scopic peritumoral lymphovascular invasion, high grade, Stage III tu- mors with invasion into the periadrenal soft tissue, adjacent organs, cortisol producing tumors, etc.). It has already been shown that micro- scopic peritumoral lymphovascular invasion (the small vessels and
lymphatics in and immediately surrounding the tumor as opposed to lymph nodes and tumor within named vessels) provides enough infor- mation to denote an increased risk of distant metastasis to change rec- ommendations for more aggressive adjuvant therapy; therefore, prophylactic nodal dissection may not be necessary for informational purposes to drive treatment recommendations for adjuvant therapy.9 Adjuvant external beam radiation, as given in some centers based on risk for locoregional recurrence, may provide adequate locoregional control for microscopic disease in lymph nodes most commonly involved by ACC.
While thorough preoperative evaluation combined with oncologi- cally sound surgical resection and guideline adherent follow-up and treatment are critical to optimal outcomes for patients with ACC, these necessary elements of care are lacking far too often. The forthcoming American College of Surgeons Operative Standards for Cancer Surgery Volume 3 provides recommendations for the critical technical steps of surgical resection of ACC to better standardize initial treatment. As part of this work, the working group reviewed as a ‘key question’ the advisability of pursuing prophylactic locoregional nodal dissection at the time of resection of the primary tumor. After comprehensive review of the literature, the group determined prophylactic nodal dissection for ACC was unnecessary given lack of definition of an adequate number of nodes to examine pathologically, which nodal stations to remove, and methodologic concerns impacting reported outcomes from most studies on the topic.2,3,6-8 Prospective studies are needed to better understand the potential utility of prophylactic nodal dissection for ACC.
References
1. Sada A, Glasgow AE, Lyden ML, Dy BM, Foster TR, Habermann EB, Bancos I, Mckenzie TJ. Informing therapeutic lymphadenectomy: Location of regional meta- static lymph nodes in adrenocortical carcinoma. Am J Surg. 2022;223(6):1042-1045.
2. Nilubol N, Patel D, Kebebew E. Does lymphadenectomy improve survival in patients with adrenocortical carcinoma? A population-based study. World J Surg. 2016;40(3): 697-705. https://doi.org/10.1007/s00268-015-3283-2.
3. Reibetanz J, Jurowich C, Erdogan I, Nies C, et al. Impact of lymphadenectomy on the oncologic outcome of patients with adrenocortical carcinoma. Ann Surg Feb. 2012;255 (2):363-369. https://doi.org/10.1097/SLA.0b013e3182367ac3.
4. Reibetanz J, Rinn B, Kunz AS, Flemming S, et al. Patterns of lymph node recurrence in adrenocortical carcinoma: possible implications for primary surgical treatment. Ann Surg Oncol. 2019 Feb;26(2):531-538.
5. Miller BS, Doherty GM. Regional lymphadenectomy for adrenocortical carcinoma. Ann Surg. 2013 Apr;257(4):e13-e14.
6. Panjwani S, Moore MD, Gray KD, Finnerty BM, et al. The impact of nodal dissection on staging in adrenocortical carcinoma. Ann Surg Oncol Nov. 2017;24(12): 3617-3623.
7. Saade N, Sadler C, Goldfarb M. Impact of regional lymph node dissection on disease specific survival in adrenal cortical carcinoma. Horm Metab Res. Oct 2015;47(11): 820-825.
https://doi.org/10.1016/j.amjsurg.2021.12.004
8. Tran TB, Postlewait LM, Maithel SK, Prescott JD, et al. Actual 10-year survivors following resection of adrenocortical carcinoma. J Surg Oncol Dec. 2016;114(8): 971-976.
9. Glenn JA, Else T, Hughes DT, Cohen MS, et al. Longitudinal patterns of recurrence in patients with adrenocortical carcinoma. Surgery. 2019 Jan;165(1):186-195.
Sarah C. Oltmann
Division of Endocrine Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA
E-mail address: Sarah.Oltmann@utsouthwestern.edu. Barbra S. Miller Division of Surgical Oncology, The Ohio State University Wexner Medical Center, N924 Doan Hall, 410 W. 10th Street, Columbus, OH, 43210, USA
*
Corresponding author.
E-mail address: Barbra.Miller@osumc.edu (B.S. Miller).