Unusual metastatic patterns in gastrointestinal stromal tumors: a multicenter analysis from the Dutch GIST Registry

Background In gastrointestinal stromal tumors (GISTs), metastases usually occur in the liver or peritoneum, typically at diagnosis or within 5 years. The prognostic impact of metastases at atypical sites or appearing later remains unclear. This study aimed to identify prognostic factors and assess survival outcomes in patients with GIST and unusual metastatic patterns. Methods Data were obtained from the Dutch GIST Registry, a nationwide prospective database. An unusual metastatic pattern was defined as metastases outside the liver or peritoneum and/or the first metastases diagnosed >5 years after curative-intent treatment. Patient and tumor characteristics were compared between unusual and usual metastatic patterns using univariate and multivariate logistic regression. Overall survival (OS) was measured from diagnosis to death, and metastatic-specific OS from first metastasis to death, using Kaplan–Meier analysis with log-rank testing. Results Among 713 patients (median follow-up 116.9 months), 151 (21%) showed an unusual metastatic pattern: 71 due to atypical site, 71 due to late onset, and 9 meeting both criteria. Only 2% initially presented with metastases at unusual sites. Primary rectal GIST was significantly associated with unusual metastatic patterns [odds ratio (OR) 2.67], especially bone metastases (OR 7.43). Unusual site metastases were linked to poorer OS (median 63.6 versus 126.1 months, P = 0.03), while late-onset metastases showed a trend toward improved metastasis-specific survival ( P = 0.06). Conclusion Metastases at unusual sites occur in advanced stages of disease and indicate a poorer prognosis. Primary rectal GIST was a prognostic factor for metastases at unusual sites. Patients with late-presenting metastases tended to have a more favorable metastatic-specific survival.