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Purpose <p>To evaluate overall and site-specific cancer risk in a large Turkish acromegaly cohort and assess the contribution of surveillance bias.</p> Methods <p>We retrospectively analyzed 393 acromegaly patients followed at a single tertiary center (1980–2023). Standardized incidence ratios (SIRs) were calculated against Turkish national cancer rates. Sensitivity analyses included thyroid exclusion, graded landmarks (1, 2, 5 years), temporal restrictions, and reference rate variation (± 20%). Multivariable logistic regression assessed predictors of cancer, including cumulative IGF-1 exposure (time-weighted average, TWAvg×ULN).</p> Results <p>Sixty-four patients (16.3%) developed cancer over a median follow-up of 9 years. The overall cancer SIR was 5.48 (95% CI: 4.15–7.10), driven by thyroid (46.25), renal/urinary (7.38), and breast cancer (3.75; all <i>p</i> &lt; 0.001 except breast <i>p</i> = 0.006). The non-thyroid SIR remained significant at 2.76 (1.86–3.94, <i>p</i> &lt; 0.001) and stable across graded landmarks (range 2.42–2.53; all <i>p</i> &lt; 0.001) and other sensitivity analyses. TWAvg IGF-1 was higher in the cancer group (1.26 vs. 0.97 ×ULN; <i>p</i> = 0.002) and independently predicted cancer (OR: 1.80; 95% CI: 1.21–2.69; <i>p</i> = 0.004).</p> Conclusions <p>In this large single-center Turkish acromegaly cohort, the overall SIR (5.48) exceeded the pooled population-based estimate of 1.45. The non-thyroid SIR remained significant across all sensitivity analyses (range 2.22–3.45), indicating multi-site predisposition beyond surveillance bias. Cumulative IGF-1 exposure independently predicted cancer, supporting sustained hormonal excess as a driver of oncogenesis. These findings support systematic thyroid screening and heightened vigilance for non-thyroid malignancies in tertiary-managed acromegaly.</p>

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Cancer risk in a large acromegaly cohort: a standardized incidence ratio analysis

  • 期刊论文

  • 发表日期：

    2026年6月16日

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  • Polat Ercan,
  • Busra Firlatan Yazgan,
  • Suleyman Nahit Sendur,
  • Selcuk Dagdelen,
  • Tomris Erbas

摘要

Purpose

To evaluate overall and site-specific cancer risk in a large Turkish acromegaly cohort and assess the contribution of surveillance bias.

Methods

We retrospectively analyzed 393 acromegaly patients followed at a single tertiary center (1980–2023). Standardized incidence ratios (SIRs) were calculated against Turkish national cancer rates. Sensitivity analyses included thyroid exclusion, graded landmarks (1, 2, 5 years), temporal restrictions, and reference rate variation (± 20%). Multivariable logistic regression assessed predictors of cancer, including cumulative IGF-1 exposure (time-weighted average, TWAvg×ULN).

Results

Sixty-four patients (16.3%) developed cancer over a median follow-up of 9 years. The overall cancer SIR was 5.48 (95% CI: 4.15–7.10), driven by thyroid (46.25), renal/urinary (7.38), and breast cancer (3.75; all p < 0.001 except breast p = 0.006). The non-thyroid SIR remained significant at 2.76 (1.86–3.94, p < 0.001) and stable across graded landmarks (range 2.42–2.53; all p < 0.001) and other sensitivity analyses. TWAvg IGF-1 was higher in the cancer group (1.26 vs. 0.97 ×ULN; p = 0.002) and independently predicted cancer (OR: 1.80; 95% CI: 1.21–2.69; p = 0.004).

Conclusions

In this large single-center Turkish acromegaly cohort, the overall SIR (5.48) exceeded the pooled population-based estimate of 1.45. The non-thyroid SIR remained significant across all sensitivity analyses (range 2.22–3.45), indicating multi-site predisposition beyond surveillance bias. Cumulative IGF-1 exposure independently predicted cancer, supporting sustained hormonal excess as a driver of oncogenesis. These findings support systematic thyroid screening and heightened vigilance for non-thyroid malignancies in tertiary-managed acromegaly.