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Risk Criteria and Prognostic Factors for Predicting Recurrences After Resection of Primary Gastrointestinal Stromal Tumor

Piotr Rutkowski, MD, PhD¹, Zbigniew I. Nowecki, MD, PhD¹, Wanda Michej, MD², Maria Dbiec-Rychter, MD, PhD³, Agnieszka Woniak, PhD⁴, Janusz Limon, PhD⁴, Janusz Siedlecki, PhD⁵, Urszula Grzesiakowska, MD, PhD⁶, Micha Kkol, MD⁷, Czesaw Osuch, MD, PhD⁸, Marcin Polkowski, MD, PhD⁹, Stanisaw Guszek, MD, PhD¹⁰, Zbigniew urawski, MD¹ and Wodzimierz Ruka, MD, PhD¹

¹ Department of Soft Tissue/Bone Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland
² Department of Pathology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland
³ Center for Human Genetics, University of Leuven, O&N Gasthuisberg Herestraat 49, 3000, Leuven, Belgium
⁴ Department of Biology and Genetics, Medical University of Gdansk, Debinki 1, 80-211, Gdansk, Poland
⁵ Department of Molecular Biology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland
⁶ Department of Radiology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland
⁷ Regional Oncological Center, Marii C. Sklodowskiej 2, 80-210, Gdansk, Poland
⁸ Department of General Surgery, Jagiellonian University, Kopernika 40, 31-501, Cracow, Poland
⁹ Department of Gastroenterology, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland
¹⁰ City Hospital, Grunwaldzka 45, 25-736, Kielce, Poland

Correspondence: Address correspondence and reprint requests to: Piotr Rutkowski, MD, PhD; E-mail: rutkowskip{at}coi.waw.pl.

Background: The introduction of adjuvant imatinib in gastrointestinal stromal tumors (GISTs) raised debate over the accuracy of National Institutes of Health risk criteria and the significance of other prognostic factors in GIST.

Methods: Tumor aggressiveness and other clinicopathological factors influencing disease-free survival (DFS) were assessed in 335 patients with primary resectable CD117-immuno-positive GISTs (median follow-up, 31 months after primary tumor resection) from a prospectively collected tumor registry.

Results: Overall median DFS was 37 months, and estimated 5-year DFS was 37.8 %. In univariate analysis, high or intermediate risk group (P < .000001), mitotic index >5/50 high-power field (P < .00001), primary tumor size >5 cm (P < .00001), nongastric primary location (P = .0001), male sex (P = .01), R1 resection/tumor rupture (P = .0003), and epithelioid cell or mixed cell pathological subtype (P = .05) negatively affected DFS. In multivariate analysis, statistically significant factors negatively influencing DFS for model 1 were mitotic index >5/50 high-power field (P = .004), primary tumor size >5 cm (P = .001), male sex (P = .003), R1 resection/tumor rupture (P = .04), and nongastric primary tumor location (P = .02), and for model 2 were high/intermediate risk primary tumor (P < .0001 and P = .008, respectively), male sex (P = .007), resection R1/tumor rupture (P = .01), and nongastric primary tumor location (P = .02). Five-year DFS for high, intermediate, and low/very low risk group was 20%, 54%, and 96%, respectively.

Conclusions: The risk criteria for assessing the natural course of primary GISTs were validated, but additional independent prognostic factors—primary tumor location and sex—were also identified.

Key Words: Gastrointestinal stromal tumor • Surgery • Prognosis