Surveillance After Curative-Intent Therapy

ACC overview

Surveillance after curative-intent therapy in adrenocortical carcinoma (ACC) refers to structured post-treatment monitoring for recurrent local, regional, or metastatic disease after apparently complete resection. It is a core component of ACC management because recurrence is common even after R0 resection, often occurs early, and may present through either imaging abnormalities or return of hormone excess in functioning tumors.¹² Surveillance typically combines cross-sectional imaging with clinical and biochemical assessment, but the optimal intensity and duration remain uncertain because most evidence comes from retrospective series, institutional practice patterns, and case-based observations rather than randomized or prospective comparative studies.³⁴

Within the broader ACC care pathway, surveillance sits between primary local therapy and treatment of relapse, with the practical aim of detecting potentially resectable recurrence, monitoring endocrine syndromes, and identifying progression that would alter systemic or locoregional management. Available data consistently suggest that the highest risk period is the first 2 years after surgery, but late recurrences also occur, supporting longer-term follow-up in selected patients.¹²⁵ What is reliable is that recurrence risk remains substantial after curative-intent therapy; what is less reliable is the exact schedule or modality that improves survival, since comparative effectiveness data are limited.

Surveillance in ACC is also constrained by tumor heterogeneity. Functional tumors may recur with biochemical changes before lesions become radiographically evident, whereas nonfunctioning tumors may be detected only on imaging.³⁶⁴ Risk-adapted strategies based on stage, tumor burden, proliferative markers such as Ki-67, and composite clinicopathologic scores are increasingly used in practice, but these approaches are still supported mainly by retrospective prognostic associations rather than validated surveillance trials.¹⁷²

Diagnostic and Clinical Context

Postoperative follow-up in ACC is intended to detect recurrence at a stage when repeat surgery, metastasectomy, local ablative treatment, or a change in systemic therapy may still be considered. In most series, surveillance relies on periodic clinical review and cross-sectional imaging of the chest, abdomen, and pelvis, reflecting the predominance of local relapse, pulmonary metastases, and hepatic metastases.¹² This anatomic pattern is reasonably consistent across retrospective cohorts, so focusing imaging on these sites is well supported; however, unusual metastatic distributions can occur, especially in children or rare pathologic subtypes, limiting the sensitivity of narrowly targeted follow-up alone.⁸⁷

Biochemical surveillance adds a complementary layer when the primary tumor was hormonally active or produced measurable steroid abnormalities. Serial hormone assessment may provide an early signal of recurrence, particularly when recurrence reproduces the secretory pattern of the original tumor.³⁶⁹ The clinical implication is that postoperative surveillance should usually be aligned with the biology of the original tumor rather than relying on imaging alone.

Recurrence Timing and Patterns

The dominant epidemiologic feature of resected ACC is a high recurrence rate, with many relapses occurring within months to 2 years of surgery.¹² Median recurrence-free survival in retrospective surgical cohorts has been reported at well under 2 years, and the lungs and liver are common sites of distant failure.¹² This timing signal is among the more reliable findings in the literature and supports intensified early surveillance after curative-intent treatment.

At the same time, recurrence is not confined to the early postoperative period. Late relapse has been described, and not every new lesion identified during surveillance is ACC recurrence.⁵ The practical consequence is that clinicians may need to maintain long-term vigilance while also confirming the nature of suspicious findings rather than assuming all interval abnormalities represent metastatic ACC.

Imaging-Based Surveillance

Cross-sectional imaging remains the mainstay of ACC surveillance after surgery. CT-based follow-up is the most commonly described approach in the available literature, often performed at shorter intervals during the first postoperative years and then spaced out over time.³¹⁰ Although this strategy is widely used, the exact interval schedule is not standardized by high-level comparative evidence, so recommendations are generally extrapolated from recurrence timing rather than proven by outcome trials.

MRI may be used in selected contexts, particularly when repeated radiation exposure is a concern or when local abdominal evaluation is prioritized, but available evidence does not clearly establish superiority over CT for routine surveillance.⁸ Functional imaging such as FDG-PET may help clarify equivocal findings or evaluate suspected recurrence outside the usual pattern, yet its role appears complementary rather than primary in routine follow-up.⁶⁸ Thus, imaging is reliable for anatomic detection of established disease, but less reliable for very early biologic recurrence, which is one reason endocrine monitoring remains relevant.

Biochemical and Steroid-Based Follow-up

Hormonal follow-up is most clearly relevant for functioning ACC, where recurrence may manifest through return of a prior endocrine syndrome such as hypercortisolism, androgen excess, or rarer secretory phenotypes.⁶⁹ Older and contemporary reports suggest that serial urinary or serum steroid assessment can sometimes indicate relapse before conventional imaging becomes definitively positive.³⁴ This supports integrating endocrine testing into surveillance for patients whose tumors were hormonally active at diagnosis.

Emerging evidence also suggests that LC-MS/MS steroid profiling may complement routine imaging more broadly by identifying “endocrine progression” before radiographic progression in a subset of patients.⁴ However, these data remain retrospective, the lead time is modest, and generalizability across laboratories and surveillance settings is uncertain. The practical implication is that steroid profiling may be useful as an adjunct in experienced centers, but it does not replace imaging or clinical assessment.

Risk Stratification and Follow-up Intensity

Because recurrence risk is heterogeneous, surveillance intensity is often individualized using pathologic and clinical risk factors. Higher stage, larger primary tumor size, capsular invasion, and proliferative activity have all been associated with greater recurrence risk after resection.¹⁷² ENSAT stage III, in particular, has been linked to early recurrence in small retrospective cohorts.² These associations are sufficiently consistent to support more intensive early imaging in higher-risk patients.

More complex risk-adapted frameworks, including use of Ki-67 and composite systems such as S-GRAS-style factors, are clinically attractive because they fit the biologic variability of ACC. Still, evidence for how these tools should change surveillance intervals is indirect, since they predict recurrence risk more readily than they define an optimal surveillance protocol.⁷ In practice, risk stratification appears useful for tailoring follow-up intensity, but it should be understood as prognostic rather than definitively prescriptive.

Limitations and Pitfalls

The surveillance literature for ACC is limited by small sample sizes, referral-center bias, heterogeneous imaging schedules, and frequent reliance on retrospective designs.¹⁴² Case reports are valuable for illustrating uncommon presentations, delayed recurrence, and endocrine clues, but they do not establish population-level performance of a surveillance strategy.⁵⁶⁸ Therefore, broad conclusions are strongest for recurrence frequency and timing, and weaker for specific modality comparisons or exact interval recommendations.

Another practical pitfall is diagnostic overattribution: new lesions detected during follow-up may not always represent ACC recurrence, and unusual pathology or competing malignancy remains possible.⁵ Conversely, recurrence may be underestimated if surveillance is inconsistent or omits biochemical monitoring in previously functional disease.⁹ The clinical implication is that surveillance findings should be interpreted within the original tumor phenotype, current risk profile, and the differential diagnosis of new abnormalities.

Role in Management and Research

In current practice, surveillance after curative-intent therapy is primarily a management tool for early recognition of relapse and selection of patients for further intervention. Compared with waiting for symptoms, structured follow-up may identify clinically occult recurrence during the period when local or metastasis-directed treatment is still feasible, although a direct survival advantage from any one schedule has not been conclusively demonstrated.¹² For functioning tumors, surveillance also helps detect re-emergent hormone excess that can itself require treatment.⁶⁹

Future research is likely to focus on validating risk-adapted schedules, clarifying the incremental value of steroid metabolomics, and determining whether earlier detection of recurrence translates into improved outcomes. Until then, the most defensible approach remains multimodal and individualized: intensified surveillance in the first 2 postoperative years, continued longer-term follow-up for selected patients, and integration of biochemical testing when the primary ACC was hormonally active or biochemically trackable.³¹⁴²

Included Articles

• PMID 9597936: In a single-center ACC series, postoperative follow-up used clinical assessment, CT, and serial urinary steroid profiling, with some recurrences suggested by steroid abnormalities despite normal imaging. The report also describes a structured surveillance schedule with visits every 3 months in year 1 and CT every 6 months.³

• PMID 16619572: This case report describes unusually long survival after complete resection of a nonfunctional ACC and two local recurrences, followed 15 years later by mediastinal lymphadenopathy that proved to be mantle cell lymphoma rather than ACC metastasis. It emphasizes the need for close long-term follow-up and careful reassessment of new thoracic findings during surveillance.⁵

• PMID 17954420: A case of initially resected adrenal nodule later recognized as ACC highlights that malignancy can be missed despite biochemical, imaging, and histologic assessment. The authors recommend postoperative abdominal imaging every 3 months in the first year and every 6 months in the second year for selected resected adrenal nodules with residual suspicion.¹⁰

• PMID 18489644: This case report describes a rare renin-producing ACC in which blood pressure, plasma renin activity, and aldosterone normalized after adrenalectomy, then rose again before FDG PET-CT confirmed early local recurrence at 4 months. It suggests blood pressure monitoring may aid surveillance in hormonally active renin-secreting ACC.⁶

• PMID 19542759: In a prospective cohort of adrenal incidentalomas followed a median of 24 months, radiologic enlargement and new subclinical cortisol secretion were uncommon, but one patient developed adrenocortical carcinoma during follow-up. The authors therefore support serial imaging and hormonal reassessment, while noting that optimal long-term follow-up schedules remain uncertain.¹¹

• PMID 21851499: This pediatric ACC case highlights that recurrence can occur within seven months after apparently complete resection of stage II functional disease, with unusual contralateral pleural dissemination despite scheduled abdominal MRI and hormonal follow-up. The report argues for early whole-body radiologic surveillance after surgery and notes potential utility of FDG-PET.⁸

• PMID 26282907: After curative-intent resection of ACC, recurrence occurred in 64.4% of patients, with median recurrence-free survival of 18.8 months and distant relapse often involving lung or liver. Higher T stage, larger tumor size, and capsular invasion were linked to recurrence risk, supporting vigilant early postoperative surveillance.¹

• PMID 34804891: This case highlights that after primary adrenalectomy for ACC, absence of serial follow-up was associated with delayed detection of hormonally active liver metastases. The report emphasizes postoperative surveillance with hormonal assessment and cross-sectional imaging because recurrence can occur within years and prognosis after metastasectomy remains poor.⁹

• PMID 38248823: A retrospective study suggests serum LC-MS/MS steroid profiling can complement routine imaging during ACC follow-up, identifying recurrence or progression earlier in a subset of patients. Endocrine progress, defined as elevation of at least three steroids, preceded radiologic detection by a median of 32 days in 20 of 89 progression events, with 11-deoxycortisol and testosterone the most sensitive markers.⁴

• PMID 39434371: In pure oncocytic adrenal neoplasms, lesions of uncertain malignant potential can recur after complete resection as distant metastatic adrenocortical carcinoma, including within 11 to 25 months. Higher Ki-67 at initial resection was associated with recurrence, supporting judicious periodic follow-up after surgery.⁷

• PMID 40726586: In a small retrospective cohort of resected non-metastatic ACC, recurrence occurred in 60% of patients, with a median recurrence-free survival of seven months and all recurrences within 24 months, predominantly in the lungs or liver. ENSAT stage III was the only significant predictor of recurrence, supporting intensive early postoperative CT-based surveillance focused on these organs.²

References

Footnotes

1. Curative Resection of Adrenocortical Carcinoma: Rates and Patterns of Postoperative Recurrence.. Ann Surg Oncol. 2016. PMID: 26282907. Local full text: 26282907.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹

2. Prognostic Factors Among Patients with Non-metastatic Adrenocortical Carcinoma.. Int J Endocrinol Metab. 2025. PMID: 40726586. Local full text: 40726586.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹²

3. Adrenocortical carcinoma: surgery and mitotane for treatment and steroid profiles for follow-up.. World J Surg. 1998. PMID: 9597936. Local full text: 9597936.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷

4. Early Detection of Recurrence and Progress Using Serum Steroid Profiling by LC-MS/MS in Patients with Adrenocortical Carcinoma.. Metabolites. 2023. PMID: 38248823. Local full text: 38248823.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷

5. Development of mantle cell lymphoma in a patient with adrenocortical carcinoma and an 18-year survival after complete removal of the primary cancer and resection of local recurrences.. Anticancer Res. 2006. PMID: 16619572. Local full text: 16619572.md ↩ ↩² ↩³ ↩⁴ ↩⁵

6. Newly developed hypertension as an early marker of recurrence of adrenocortical carcinoma with high renin expression.. Int J Urol. 2008. PMID: 18489644. Local full text: 18489644.md ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷

7. Oncocytic Adrenal Neoplasms: Clinical Profiles and Long-Term Outcomes.. Am Surg. 2025. PMID: 39434371. Local full text: 39434371.md ↩ ↩² ↩³ ↩⁴ ↩⁵

8. Contralateral pleural recurrence of adrenocortical carcinoma after surgical resection.. Pediatr Int. 2011. PMID: 21851499. Local full text: 21851499.md ↩ ↩² ↩³ ↩⁴ ↩⁵

9. Metastatic liver cancer with hormone secretion: a case report.. Gland Surg. 2021. PMID: 34804891. Local full text: 34804891.md ↩ ↩² ↩³ ↩⁴ ↩⁵

10. Diagnostic challenges in adrenocortical carcinoma: recommendations for surveillance after surgical resection of selected adrenal nodules.. Endocr Pract. 2007. PMID: 17954420. Local full text: 17954420.md ↩ ↩²

11. Prospective evaluation of tumor size and hormonal status in adrenal incidentalomas.. J Endocrinol Invest. 2010. PMID: 19542759. Local full text: 19542759.md ↩