Pattern of Recurrence in Adrenocortical Carcinoma
Adrenocortical carcinoma recurs in approximately 64-70% of patients after curative-intent resection, with the majority of recurrences occurring within the first 2 years, particularly within the first 11-18 months post-resection. 1, 2
Temporal Pattern of Recurrence
The greatest frequency of disease recurrence occurs within the first 2 years after surgery, which is why adjuvant mitotane is recommended for at least 2 years in high-risk patients 3. The median recurrence-free interval after primary resection is approximately 11 months, though this varies significantly based on tumor characteristics and site of recurrence 1.
- Few ACC recurrences occur after 5 years, which is why continuing adjuvant mitotane beyond 5 years is not advised 3
- The shortest time to recurrence is associated with lung metastases or multiple site metastases 1
Spatial Pattern of Recurrence
Initial Recurrence Sites
The most common sites of initial recurrence are the lungs and the tumor bed (locoregional) 1. Among patients who experience recurrence:
- Distant-only recurrence: 45.1% of recurrent cases 2
- Locoregional-only recurrence: 36.3% of recurrent cases 2
- Combined locoregional and distant recurrence: 18.6% of recurrent cases 2
Systemic Recurrence Patterns
Systemic recurrence most often involves the liver, lungs, and bone 4. When distant metastases occur, they frequently involve multiple organs 1.
Sequential Recurrence Pattern
Recurrence is often a sequential process rather than a single event:
- Of patients who develop initial recurrence, 57% (142 of 249) develop one or more additional sites of recurrence, with a median time of 5 months between first and second recurrence 1
- The lungs are the most common site for subsequent recurrences 1
- A subset of patients (20 in one series) develop a third site of recurrence 1
Risk Factors for Different Recurrence Patterns
Locoregional Recurrence Risk Factors
Left-sided ACC location (OR 2.71) and T3/T4 disease (OR 3.04) are associated with increased locoregional recurrence 2.
Distant Recurrence Risk Factors
Larger tumor size (OR 1.11 per cm) and T3/T4 disease (OR 5.23) are associated with distant recurrence 2.
Prognostic Implications by Recurrence Pattern
The pattern of recurrence significantly impacts survival:
- Locoregional-only recurrence: Best prognosis with 3-year survival of 81.4% and 5-year survival of 64.1% 2
- Distant-only recurrence: Intermediate prognosis with 3-year survival of 55.1% and 5-year survival of 43.3% 2
- Combined locoregional and distant recurrence: Worst prognosis with 3-year survival of 39.5% and 5-year survival of 19.7% 2
Recurrences to the peritoneal cavity or to multiple sites are associated with worse survival compared to lung metastases, despite lung metastases occurring earlier 1.
Clinical Implications for Surveillance
Based on the temporal pattern of recurrence, radiological imaging should be performed:
- Every 3 months for the first 2 years after complete resection 3
- Every 3-6 months for at least another 3 years (years 3-5) 3
This intensive surveillance schedule is justified because the highest risk period is within the first 2 years, and early detection of recurrence may allow for potentially curative repeat resection in selected patients 5.
Pattern After Repeat Resection
Among patients who undergo reoperation or metastasectomy, 79% experience recurrence again 1. Importantly, same organ or site recurrence is common after reoperation, occurring in 67% of cases 1. This high rate of same-site recurrence suggests that microscopic disease often remains despite apparently complete resection.
Metastasectomy beyond three total operations does not improve overall survival, indicating diminishing returns with repeated surgical interventions 1.