The non-responding adrenal metastasis in melanoma: The case for minimally invasive adrenalectomy in the age of modern therapies

Zippel, Douglas; Yalon, Tal; Nevo, Yehonatan; Markel, Gal; Asher, Nethanel; Schachter, Jacob; Goitein, David; Segal, Tamar Abramovich; Nissan, Aviram; Hazzan, David

doi:10.1016/j.amjsurg.2019.11.033

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…In 1991, Branum et al 18 was the first to report a potential survival benefit for patients with metastatic melanoma to one or both adrenal glands who underwent a surgical intervention compared with nonsurgical treatment. This finding is further supported by a report from Zippel et al 23 showing that minimally invasive adrenalectomy is safe and improves survival compared with conservative management in a selected group of patients with metastatic melanoma with operable AGMs. Moreover, a recent review from Spartalis et al 24 that included studies from patients with different primary tumors, including melanoma, concludes that an adrenalectomy should be performed when the lesion is isolated in the adrenal gland and the site of primary cancer has or can be resected, because this procedure has the potential to offer prolonged survival.…”

Section: Discussionsupporting

confidence: 70%

“…However, as previous case reports and studies have shown, AGMs may present an obstacle for successful treatment of patients with advanced-stage disease. 11,18,23,24 We and others have hypothesized that the adrenal gland may serve as a so-called sanctuary site, as defined by their inherent immunosuppressive microenvironment, allowing the tumor to grow in an immunologically permissive milieu and limiting the efficacy of ICIs. To further investigate this, we performed a large, single-center, retrospective analysis of all patients with stage IV melanoma with and without an AGM who were treated with ICIs.…”

Section: Discussionmentioning

confidence: 99%

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Melanoma Metastases to the Adrenal Gland Are Highly Resistant to Immune Checkpoint Inhibitors

Borgers

Tobin

Torphy

et al. 2021

Journal of the National Comprehensive Cancer Network

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Background: Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites. We sought to investigate whether having an AGM is associated with altered outcomes and whether ICI responses are dampened in the adrenal glands. Patients and Methods: We retrospectively compared ICI responses and overall survival (OS) in 68 patients with melanoma who were diagnosed with an AGM and a control group of 100 patients without AGMs at a single institution. Response was determined using RECIST 1.1. OS was calculated from time of ICI initiation, anti–PD-1 initiation, initial melanoma diagnosis, and stage IV disease diagnosis. Tumor-infiltrating immune cells were characterized in 9 resected AGMs using immunohistochemical analysis. Results: Response rates of AGMs were significantly lower compared with other metastatic sites in patients with AGMs (16% vs 22%) and compared with those without AGMs (55%). Patients with AGMs also had significantly lower median OS compared with those without AGMs (3.1 years vs not reached, respectively). We further observed that despite this, AGMs exhibited high levels of tumor-infiltrating immune cells. Conclusions: In this cohort of patients with melanoma, those diagnosed with an AGM had lower ICI response rates and OS. These results suggest that tissue-specific microenvironments of AGMs present unique challenges that may require novel, adrenal gland–directed therapies or surgical resection.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Melanoma Metastases to the Adrenal Gland Are Highly Resistant to Immune Checkpoint Inhibitors

Borgers

Tobin

Torphy

et al. 2021

Journal of the National Comprehensive Cancer Network

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“…The choice of operative approach should consider tumor size and the potential need for concomitant organ resection. The lower overall morbidity and more rapid recovery associated with minimally invasive adrenalectomy suggest that this approach should generally be favored in patients with melanoma adrenal metastasis when technically feasible and otherwise indicated 23,33 . When the adrenal metastasis is modest in size (e.g., ≤6 cm), adrenalectomy can commonly be performed as a minimally invasive operation, either transabdominally (laparoscopic) or from the back (retroperitoneoscopic).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we found that patients selected for adrenalectomy experienced a considerably longer survival duration following development of adrenal metastasis compared to patients treated with systemic therapy alone (116.9 vs. 11.0 months, p < 0.001). 23,33 When the adrenal metastasis is modest in size (e.g., ≤6 cm), adrenalectomy can commonly be performed as a minimally invasive operation, either transabdominally (laparoscopic) or from the back (retroperitoneoscopic). The low associated morbidity and rapid recovery facilitates expedient resumption of any indicated postoperative systemic therapy.…”

Section: Discussionmentioning

confidence: 99%

Melanoma metastatic to the adrenal gland: An update on the role of adrenalectomy in multidisciplinary management

Asare

Fisher

Chiang

et al. 2023

Journal of Surgical Oncology

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Background and Objectives: Modern systemic therapy (immune checkpoint blockade [ICB], targeted therapy) has improved survival for patients with metastatic melanoma. The role of adrenal metastasectomy is not well characterized in this setting.Methods: Consecutive patients treated with adrenalectomy 1/1/2007-1/1/2019 were retrospectively compared to patients treated with systemic therapy alone in the same time period. Overall survival and survival after adrenal metastasis were compared, prognostic factors associated with survival after adrenal metastasis development were evaluated.Results: A total of 74 patients underwent adrenalectomy and were compared to 69 treated with systemic therapy alone. The most common indications for adrenalectomy were to render the patient disease-free in the setting of isolated adrenal metastasis (n = 32, 43.2%) or treatment of isolated progression in the setting of other stable/responding metastases (n = 32, 43.2%). Patients treated surgically had longer survival (116.9 vs. 11.0 months after adrenal metastasis diagnosis, p < 0.001). On multivariate analysis, receipt of ICB (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: [0.40-0.95]) and selection for adrenalectomy (HR: 0.27, 95% CI: [0.17-0.42])were the strongest factors associated with improved survival after adrenal metastasis diagnosis.Conclusions: Selective application of adrenal metastasectomy is associated with prolonged survival benefit and remains an important consideration in the multidisciplinary management of patients with metastatic melanoma.

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“…Resection of resistant adrenal metastases has been facilitated by minimally invasive adrenalectomy [ 88 ]. Despite systemic therapy, the adrenal gland may function as a sanctuary for metastatic growth.…”

Section: Main Findings Of the Literature (Review) Questmentioning

confidence: 99%

Intra-Abdominal Malignant Melanoma: Challenging Aspects of Epidemiology, Clinical and Paraclinical Diagnosis and Optimal Treatment—A Literature Review

et al. 2022

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According to European consensus-based interdisciplinary guidelines for melanoma, cutaneous melanoma (CM) is the most deadly form of dermatological malignancy, accounting for 90% of the deaths of skin cancer patients. In addition to cutaneous melanoma, mucosal melanoma occurs in four major anatomical sites, including the upper respiratory tract, the conjunctiva, the anorectal region, and the urogenital area. As this cancer type metastasizes, a classification used in the current medical literature is the distinction between secondary lesions and primary malignant melanoma of the abdominal cavity. Given that malignant melanoma is the most common cancer that spreads to the gastrointestinal tract, different imaging modalities compete to diagnose the phenomenon correctly and to measure its extension. Treatment is primarily surgery-based, supported by immunotherapy, and prolongs survival, even when performed at stage IV illness. In the end, special forms of malignant melanoma are discussed, such as melanoma of the genito-urinary tract and amelanotic/achromic melanoma. The importance of this present literature review relies on yielding and grouping consistent and relevant, updated information on the many aspects and challenges that a clinician might encounter during the diagnosis and treatment of a patient with intra-abdominal melanoma.

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The non-responding adrenal metastasis in melanoma: The case for minimally invasive adrenalectomy in the age of modern therapies

Cited by 9 publications

References 36 publications

Melanoma Metastases to the Adrenal Gland Are Highly Resistant to Immune Checkpoint Inhibitors

Melanoma Metastases to the Adrenal Gland Are Highly Resistant to Immune Checkpoint Inhibitors

Melanoma metastatic to the adrenal gland: An update on the role of adrenalectomy in multidisciplinary management

Intra-Abdominal Malignant Melanoma: Challenging Aspects of Epidemiology, Clinical and Paraclinical Diagnosis and Optimal Treatment—A Literature Review

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