# Persistent Long-Term Risk After Primary Surgery for Head and Neck Adenoid Cystic Carcinoma: Competing-Risk and Conditional Estimates

## TL;DR

This study shows that head and neck adenoid cystic carcinoma has a long-term risk of recurrence and death, even decades after surgery, requiring lifelong monitoring.

## Contribution

The study provides conditional and RMST-based risk estimates for long-term outcomes in HNAdCC patients, emphasizing the need for lifelong follow-up.

## Key findings

- About one-third of patients experienced recurrence or metastasis, with some events occurring more than 5 years after surgery.
- Lung metastases were the most common site of cancer spread, and disease-related deaths remained high over decades.
- Older age, advanced tumor stage, and nerve invasion were linked to worse survival outcomes.

## Abstract

Head and neck adenoid cystic carcinoma is uncommon and often grows slowly, but it can return or spread many years after treatment. We reviewed 57 patients treated with curative surgery at our hospital between 1984 and 2020 and followed them for up to 40 years. We found that about one in three patients developed a first recurrence or metastasis, and more than one in three of these events happened later than 5 years after surgery. When the cancer spread, it most often involved the lungs. Over a very long follow-up, deaths caused by cancer remained frequent, while deaths from other (non-cancer) causes also accumulated and needed to be considered when estimating long-term risk. Older age, more advanced local tumor stage, and tumor spread along nerves were associated with worse outcomes. These results show that patients cannot be considered “out of danger” after 5 years and support lifelong, risk-adapted follow-up, with particular attention to detecting lung metastases.

Background/Objectives: Head and neck adenoid cystic carcinoma (HNAdCC) is characterized by indolent growth but sustained long-term risk of late recurrence and disease-related mortality. Data describing very long-term outcomes using analytic approaches that explicitly account for competing mortality remain limited. We aimed to characterize late failures, competing causes of death, and clinically interpretable long-horizon risk estimates after primary surgery for HNAdCC. Methods: We performed a retrospective single-center cohort study of patients with HNAdCC treated with curative-intent surgery between 1984 and 2020. Overall survival (OS) and cancer-specific survival (CSS) were estimated using Kaplan–Meier method. Competing risks of disease-related and other-cause death, as well as first-failure patterns, were analyzed using cumulative incidence functions, including a 5-year landmark analysis. Conditional mortality and restricted mean survival time (RMST; τ = 25 years) were additionally assessed. Results: Fifty-seven patients were included (median age 54 years). Median follow-up was 133 months overall and 212 months among survivors. A first failure occurred in 19/57 (33.3%) of patients, with distant metastasis as the most common pattern; 7/19 (36.8%) of failures occurred beyond 5 years. OS at 5, 10, and 25 years was 68.4%, 64.9%, and 37.5%, respectively; corresponding CSS was 78.9%, 74.8%, and 51.7%. At 25 years, cumulative incidence of disease-related death was 41.7%, compared with 20.9% for other-cause death. Older age and advanced T category were independently associated with worse OS, while older age and perineural invasion predicted worse CSS. Among 5-year survivors, conditional risk of disease-related death by 25 years remained 32.7%. RMST analyses demonstrated substantial long-term life-years lost associated with perineural invasion and T3–4 disease. Conclusions: HNAdCC exhibits persistent long-term risk with clinically meaningful late failures and substantial competing mortality over decades. Conditional and RMST-based estimates provide patient-centered measures that support lifelong, risk-adapted surveillance, particularly focused on detection of distant metastases.