Local Ablation and Multimodal Recurrence Control in ACC

Management of Recurrent Disease

Local ablation and multimodal recurrence control in adrenocortical carcinoma (ACC) refers to the use of focal or regional treatments for recurrent or metastatic disease beyond systemic therapy alone. Within ACC management, these approaches sit under recurrent-disease care and commonly include repeat surgery, metastasectomy, thermal ablation, external-beam or stereotactic radiotherapy, and selected regional procedures such as embolization-based treatment.¹²³ They are most often considered in patients with isolated locoregional relapse, oligometastatic disease, or symptomatic lesions that are technically amenable to local control.¹⁴⁵

Recurrent ACC is biologically and anatomically heterogeneous. Patterns of failure include operative-bed recurrence, liver and lung metastases, peritoneal spread, and less common bone or central nervous system involvement, and these patterns strongly influence whether treatment is pursued with curative, disease-controlling, or palliative intent.¹⁶⁷⁵ Across retrospective series, better outcomes are repeatedly associated with longer disease-free interval, lower metastatic burden, and the possibility of controlling all evident sites of disease.⁸⁴³

The supporting evidence remains limited. Most published data come from retrospective single-center cohorts, multicenter observational series, reviews, and case reports, often mixing surgery, radiotherapy, ablation, mitotane, and cytotoxic therapy in the same patients.⁸⁹³⁵ As a result, reported survival advantages may partly reflect patient selection, referral patterns, and more favorable tumor biology rather than the independent effect of any one local modality.¹³ Comparative evidence against systemic therapy alone, or among different local approaches, is sparse.

Even with these limitations, the literature suggests that selected patients may derive meaningful benefit from metastasis-directed or locoregional treatment as part of multidisciplinary care. In practice, local therapy is generally viewed as complementary to systemic assessment and longitudinal surveillance rather than as a routine substitute for medical therapy in disseminated disease.¹⁹⁵

Diagnostic and clinical context

After initial resection, recurrence is common and may present as isolated local relapse, single-organ metastatic recurrence, or multiorgan progression.¹⁴⁵ This distinction is clinically important because isolated or oligometastatic recurrence may permit an attempt at complete local control, whereas diffuse progression more often shifts treatment toward systemic therapy with focal procedures reserved for palliation or prevention of complications.¹⁴

The most reliable conclusion is that recurrence pattern and disease tempo are central determinants of management. What remains less reliable is the degree to which local intervention itself improves survival once these baseline prognostic differences are taken into account.⁸⁵

Major treatment phenotypes

Repeat surgery and salvage resection

Repeat surgery remains the best-established local option for recurrent ACC when complete resection appears technically feasible and physiologically appropriate.¹⁹ Salvage surgery may involve isolated metastasectomy, resection of local recurrence, or selected multivisceral procedures for locoregionally advanced relapse.¹⁰ Retrospective studies suggest that complete resection is associated with longer survival, especially in patients with limited recurrence and a longer interval from primary treatment to relapse.¹¹⁴

What is relatively reliable is that carefully selected patients can achieve prolonged disease control after salvage resection. What is less reliable is any inference that surgery overcomes aggressive tumor biology in early, multifocal, or rapidly progressive recurrence.¹⁹ Clinically, surgery is usually favored when all visible disease appears resectable and the expected morbidity is acceptable.

Thermal ablation and image-guided focal therapy

Thermal ablation has emerged as a less invasive metastasis-directed option, particularly for discrete lesions such as liver metastases or for patients in whom repeated surgery would be disproportionate or technically difficult.²³ Multicenter retrospective data suggest that completely treated lesions may achieve durable local control, and some series report favorable lesion-level time to progression compared with other local approaches.³

The most dependable evidence supports ablation as a means of controlling individual targets in selected oligometastatic disease. It is not yet clear whether ablation improves overall survival relative to surgery or systemic treatment alone, and out-of-field recurrence remains common.⁸³ The practical implication is that ablation may be useful as part of staged multimodal management rather than as a stand-alone oncologic strategy.

Radiotherapy and stereotactic approaches

Radiotherapy is used in recurrent ACC for postoperative consolidation, palliation, and treatment of sites where surgery is difficult or hazardous, including bone, spine, skull, and orbital metastases.⁶⁷¹²¹³ Stereotactic techniques may also support repeated focal treatment in selected oligometastatic patients.¹⁴

The strongest and most consistent role for radiotherapy is symptom relief and local stabilization, particularly when neurologic or structural complications are threatened.¹²¹³¹⁵ Evidence for a direct survival benefit is limited and heavily influenced by case reports and small retrospective series.⁶⁷ In practice, radiotherapy is often used when resection is not feasible or when local palliation is the primary objective.

Other regional approaches

Other regional strategies, including embolization-based liver therapy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, have been reported in highly selected situations.¹¹¹⁶ These approaches illustrate that recurrence control in ACC may sometimes require organ-specific or compartment-specific treatment planning, especially in liver-dominant or peritoneal disease.

However, the evidence for these methods is narrow and largely anecdotal. Their current role is investigational or highly specialized rather than standard, and routine use is not supported by comparative data.¹¹¹⁶

Selection factors and expected outcomes

Across modalities, outcomes appear to be driven more by patient selection than by local technique alone. Longer disease-free interval, fewer metastatic sites, single-lesion or single-organ recurrence, and the ability to eradicate all evident disease are the factors most consistently associated with more favorable outcomes.⁸⁴³ Some studies also suggest that nonfunctioning primaries, lower prior treatment burden, and effective concomitant mitotane exposure may correlate with better local control.⁸³

These findings support a practical distinction between potentially controllable oligometastatic relapse and biologically aggressive disseminated progression. What is reliable is that selected patients may achieve prolonged progression-free intervals and occasional repeated no-evidence-of-disease states; what is not reliable is the expectation of durable cure for most patients with recurrent ACC.⁹⁵ Rare long-term survivors treated with repeated metastasis-directed therapy demonstrate possibility rather than typical prognosis.¹⁴

Limitations and role in management

Interpretation of the literature is constrained by small sample sizes, retrospective design, referral bias, and heterogeneous combinations of surgery, ablation, radiotherapy, and systemic therapy.⁸⁹⁵ Case reports remain useful for demonstrating technical feasibility at unusual metastatic sites, but they offer weak evidence for general treatment effectiveness or modality comparison.⁶⁷¹²

Treatment burden also differs substantially across modalities. Repeat surgery and multivisceral salvage procedures may carry considerable morbidity, while radiotherapy and spine-directed interventions must account for neurologic risk, structural stability, and prior local treatment.¹³¹⁵¹⁰ Ablation is generally less invasive but does not address occult systemic disease and therefore depends on careful whole-patient selection.²³

Overall, local ablation and multimodal recurrence control have a selective role in recurrent ACC. Retrospective evidence supports their use most strongly in isolated locoregional relapse, oligometastatic progression, or symptomatic focal disease within multidisciplinary care, often alongside mitotane, chemotherapy, or planned salvage surgery.¹⁷¹⁹ By contrast, there is limited evidence that any focal modality alone substantially alters the course of rapidly progressive or widely disseminated ACC.

Included Articles

• PMID 11388389: This case report describes recurrent metastatic ACC with a rare orbital metastasis causing pain, diplopia, ptosis, edema, proptosis, and intracranial extension. It highlights use of radiotherapy for symptom relief and palliative resection for locally progressive orbital disease when further irradiation was not advisable.⁶

• PMID 12887367: A case report describes repeatedly recurrent ACC in which initially unresectable psoas and rib metastases were downsized with radiotherapy plus platinum-etoposide chemotherapy, enabling wide resection and resulting in 5-year disease-free survival. The report emphasizes complete resection after multimodal therapy as a potential strategy in selected recurrent metastatic disease.¹⁷

• PMID 19322014: This small single-institution series suggests that long-term survival in ACC recurrence may be associated with aggressive radical treatment, including metastasectomy, radiotherapy, systemic therapy, and transcatheter arterial embolization for liver metastases. Patients who did not undergo surgical treatment for recurrent or metastatic disease died of progressive disease.¹¹

• PMID 19375918: This case report describes exceptionally rare skull and leptomeningeal metastasis from adrenocortical carcinoma after resection of a nonfunctioning primary tumor. In a large symptomatic cranial recurrence that progressed despite chemotherapy, complete surgical excision followed by whole-brain radiotherapy achieved local neurological and radiographic control, although systemic disease later progressed.⁷

• PMID 23776337: This review outlines management of recurrent ACC after complete resection, emphasizing specialist-center multidisciplinary care, selection for repeat surgery based on disease-free interval and resectability, and use of mitotane with or without chemotherapy for systemic relapse. It also notes controversial radiotherapy, possible use of radiofrequency ablation in selected cases, and the importance of hormone control and clinical trials.¹

• PMID 26765762: This case report describes rare spinal metastatic recurrence of ACC to the T12 vertebra with epidural extension and suggests that, in selected symptomatic oligometastatic spinal disease, complete vertebrectomy with stabilization plus radiotherapy may provide more durable local control than decompression alone or radiation alone.¹²

• PMID 27716880: This case report describes extensive peritoneal and local recurrent ACC managed with cytoreductive surgery plus HIPEC using melphalan, achieving complete visible resection and short-term palliation. It proposes selection factors for repeat locoregional intervention, including relative sparing of small bowel and mesentery, no extra-abdominal disease, and limited high-grade burden.¹⁶

• PMID 31447392: In patients undergoing resection or ablation for ACC liver metastases, longer disease-free interval and nonfunctioning primary tumors were independently associated with prolonged survival. These factors may help select candidates for invasive local treatment in recurrent metastatic disease, despite high recurrence and morbidity rates.⁸

• PMID 31804360: This case report and literature review addresses spinal metastatic ACC causing pain, fracture, and neurologic compromise, highlighting multimodal management with vertebral cement augmentation, radiotherapy, radiofrequency ablation, and PD-1 therapy. It suggests posterior surgical decompression or excision may be considered for neurologic deficits, while emphasizing the absence of standardized management.¹³

• PMID 33741778: This review describes thermal ablation as an emerging local treatment option for metastatic ACC, noting that localised therapy is recommended for metastatic tumour bulk and citing a small case series of CT-guided radiofrequency ablation for oligometastatic disease with high complete ablation rates and low local progression.²

• PMID 36629278: In recurrent ACC after initial surgery, this retrospective single-center series suggests that selected patients can achieve prolonged survival with multimodal salvage therapy, particularly when recurrent disease is limited, shows response or stable disease on chemotherapy or chemoradiotherapy, and appears completely resectable for salvage surgery.⁹

• PMID 36655273: In a retrospective single-center cohort of 106 patients with postoperative ACC recurrence, prognosis was better when recurrence presented as a single lesion rather than multiple organs, and locoregional treatment frequently achieved no evidence of disease. Longer time to first recurrence favored survival, whereas multiorgan recurrence predicted worse outcomes.⁴

• PMID 36776311: This retrospective series of malignant adrenal tumor spinal metastases, including two ACC cases, describes surgery for symptomatic spinal recurrence causing pain, weakness, or cord compression. Early radical resection with preoperative embolization was associated with symptom relief and neurological improvement, while prognosis remained generally poor.¹⁵

• PMID 38398097: A multicentre retrospective cohort of 66 patients with advanced metastatic ACC found that local therapies can provide substantial lesion-level control, with local thermal ablation showing the longest time to progression and all complete responses. Longer interval from diagnosis to local therapy, fewer prior treatments, and mitotane levels above 14 mg/L were associated with better local control.³

• PMID 39221851: This retrospective series of recurrent ENSAT stage I-III ACC found that recurrence was managed with repeat surgery, mitotane, chemotherapy, radiotherapy, or other locoregional therapies based on recurrence pattern and timing. Despite frequent second progression after local treatment, multimodal management was associated with median progression-free survival of 17 months, while older age and shorter time to recurrence predicted higher mortality.⁵

• PMID 40845750: In selected patients with multifocal locoregionally recurrent left-sided ACC, a standardized left upper quadrant en bloc multivisceral resection achieved R0 resection in a small single-center cohort, with no perioperative mortality, limited major morbidity, and median locoregional recurrence-free survival of 22.1 months.¹⁰

• PMID 41340776: This case series describes four patients with recurrent low-tumor-burden metastatic ACC who achieved 11.5 to 20 years of survival through repeated metastasis-directed local therapies combined with prolonged mitotane, remaining radiologically disease-free at last follow-up. Recurrences were mainly in liver and lung and were managed with resections, ablations, and stereotactic radiotherapy within multidisciplinary care.¹⁴

• PMID 11829767: A mixed hepatobiliary surgical series reported one patient with liver involvement from right adrenocortical carcinoma treated with caudate lobectomy, illustrating that technically demanding hepatic salvage resection can be performed in selected cases but offering only indirect and very limited ACC-specific outcome data.¹⁸

References

Footnotes

1. Current management options for recurrent adrenocortical carcinoma.. Onco Targets Ther. 2013. PMID: 23776337. Local full text: 23776337.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹

2. Thermal ablation in adrenal disorders: a discussion of the technology, the clinical evidence and the future.. Curr Opin Endocrinol Diabetes Obes. 2021. PMID: 33741778. Local full text: 33741778.md ↩ ↩² ↩³ ↩⁴

3. The Value of Local Therapies in Advanced Adrenocortical Carcinoma.. Cancers (Basel). 2024. PMID: 38398097. Local full text: 38398097.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹

4. The management of postoperative disease recurrence in patients with adrenocortical carcinoma: a retrospective study in 106 patients.. Eur J Endocrinol. 2023. PMID: 36655273. Local full text: 36655273.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷

5. Treatment Outcomes in Patients with Recurrent Adrenocortical Carcinoma.. Endocr Res. 2025. PMID: 39221851. Local full text: 39221851.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹

6. Adrenocortical carcinoma metastatic to the orbit.. Ophthalmic Plast Reconstr Surg. 2001. PMID: 11388389. Local full text: 11388389.md ↩ ↩² ↩³ ↩⁴ ↩⁵

7. A rare bone-leptomeningeal metastasis from an adrenal cortical carcinoma.. J Clin Neurosci. 2009. PMID: 19375918. Local full text: 19375918.md ↩ ↩² ↩³ ↩⁴ ↩⁵

8. Disease-free interval and tumor functional status can be used to select patients for resection/ablation of liver metastases from adrenocortical carcinoma: insights from a multi-institutional study.. HPB (Oxford). 2020. PMID: 31447392. Local full text: 31447392.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸

9. The role of multimodal salvage therapy in the management of recurrent adrenocortical carcinoma.. Jpn J Clin Oncol. 2023. PMID: 36629278. Local full text: 36629278.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸

10. A standardized surgical approach to multifocal locoregionally recurrent left-sided adrenocortical carcinoma.. Eur J Surg Oncol. 2025. PMID: 40845750. Local full text: 40845750.md ↩ ↩² ↩³

11. A twelve-year experience with adrenal cortical carcinoma in a single institution: long-term survival after surgical treatment and transcatheter arterial embolization.. Urol Int. 2009. PMID: 19322014. Local full text: 19322014.md ↩ ↩² ↩³ ↩⁴

12. Metastatic adrenal cortical carcinoma to T12 vertebrae.. J Clin Neurosci. 2016. PMID: 26765762. Local full text: 26765762.md ↩ ↩² ↩³ ↩⁴

13. Successful treatment of metastatic adrenocortical carcinoma in the spine: A case report and literature review.. Medicine (Baltimore). 2019. PMID: 31804360. Local full text: 31804360.md ↩ ↩² ↩³ ↩⁴

14. Prolonged Mitotane Administration in Metastatic Adrenocortical Carcinoma With Over a Decade of Survival: A Case Series.. Case Rep Endocrinol. 2025. PMID: 41340776. Local full text: 41340776.md ↩ ↩² ↩³

15. Surgical management and outcomes of spinal metastasis of malignant adrenal tumor: A retrospective study of six cases and literature review.. Front Oncol. 2023. PMID: 36776311. Local full text: 36776311.md ↩ ↩² ↩³

16. Peritoneal metastases from adrenal cortical carcinoma treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.. Tumori. 2016. PMID: 27716880. Local full text: 27716880.md ↩ ↩² ↩³

17. Successful long-term disease-free survival following multimodal treatments in a patient with a repeatedly recurrent refractory adrenal cortical carcinoma.. Int J Urol. 2003. PMID: 12887367. Local full text: 12887367.md ↩ ↩²

18. [Resection of caudate lobe of liver: report of 26 cases].. Zhonghua Wai Ke Za Zhi. 1999. PMID: 11829767. Local full text: 11829767.md ↩