Surgery Plus Systemic Therapy Improves Outcomes in Stage IV GIST

Surgery in combination with systemic therapy improves outcomes for patients with stage IV gastrointestinal stromal tumors (GIST), according to a study being presented by Johannes Uhlig, MD, MPH, Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen, Goettingen, Germany, at the 2021 ASCO Gastrointestinal Cancers Symposium (J Clin Oncol. 2021;39[suppl 3):abstr 462]). 

Dr Uhlig and colleagues wanted to evaluate the epidemiology, treatment, and outcomes of stage 4 GIST. To do so, they explored the 2010-2016 United States National Cancer database for adult patients with invasive GIST at AJCC stage 4, without prior malignant disease. They used the Cox proportional hazards regression, accounting for potential confounders in multivariable models to evaluate overall survival (OS).

The study included a total of 1,578 patients with stage 4 GIST (13.3% of all GIST), the male: female ratio was 1.38:1. The most common cancer sites were the stomach (55.4%) and small intestine (40%), and the median age at diagnosis was 62 years with a median tumor diameter of 10cm. 58.7% reported distant organ metastases, with hepatic being the most frequent (n = 801, 50.8% of stage 4 GIST). 

The majority of patients received systemic therapy (78.6%), either alone or combined with surgery (35.4%; 43.3%, respectively); systemic therapy was administered neoadjuvant in 6.9% of patients, adjuvant in 32%, and neoadjuvant+adjuvant in 5.1% of surgically resected patients. Furthermore, 12.9% of patients were treated with surgical resection alone.

The OS rates were 88%, 77%, 67%, and 51% at 1, 2, 3, and 5 years, respectively. However, multivariable COX proportional hazard models found that primary GIST treatment independently affected OS, compared to combined surgery and systemic therapy. The OS was shorter in patients who received systemic therapy alone (HR, 2.77; 95% CI: 2.12-3.61; P <.001) or no treatment (HR, 4.2; 95% CI, 2.75-6.43; P <.001). 

Additionally, Dr Uhlig and his team found no significant difference in OS when comparing surgery combined with system therapy to surgery alone  (HR, 1.23; 95% CI, 0.88-1.72; P = .227). However, treatment at non-academic vs. academic centers was linked to a shorter OS (multivariable HR, 1.36; 95% CI, 1.1-1.69; P = .005]). Other independent OS predictors included male versus female (HR, 1.28; 95% CI, 1.03-1.59; P = .023), older age, higher comorbidities, higher cancer grade, and larger cancer.

“Stage IV GIST is a rare gastrointestinal malignancy that most commonly manifests in the stomach and small intestine in male patients, with frequent hepatic metastases and excellent 5-year OS rates of up to 51%. Combined surgery plus systemic therapy demonstrates best outcomes, although surgical resection alone might yield comparable results in selected patients,” concluded Dr Uhlig et al. —Alexandra Graziano

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