Bowel GISTs Show Distinct Outcomes by Anatomic Site

Location, location, location. The adage doesn’t just apply to real estate. It’s also a factor in understanding the clinical characteristics, treatment patterns, and survival outcomes of patients with gastrointestinal stromal tumors (GISTs) – specifically bowel GISTs – say researchers with Cleveland Clinic in Florida.

The team conducted a retrospective population-based cohort study to determine whether tumors arising in the small intestine, colon and rectum exhibit distinct characteristics and survival patterns. Their analysis included 5,760 patients with bowel GISTs identified in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2022.

“GISTs are often categorized in the literature as gastric or non-gastric, but our study demonstrates that bowel GISTs are a heterogeneous group of tumors with distinct clinical profiles based on anatomical location,” explains Sameh Rizkalla, MBBCh, MSc, MD, FACS, a project scientist with the Digestive Disease Institute at Cleveland Clinic Weston Hospital and senior author of the study.

Rare tumors with varying prognoses

GISTs account for fewer than 2% of primary gastrointestinal malignancies, with approximately 6,000 cases diagnosed annually in the United States. About 60% occur in the stomach and 30% in the small intestine, while fewer than 10% arise in the colon or rectum.

Among the non-gastric tumors included in the analysis, most originated in the small bowel (85%), followed by the rectum (8.5%) and colon (6.6%).

The investigators observed marked differences in survival according to tumor location. Rectal GISTs demonstrated the most favorable outcomes, with a 5-year cancer-specific survival (CSS) rate of 86.5%, compared with 81.0% for small bowel tumors and 67.2% for colonic tumors.

Similarly, patients with rectal GISTs had a 5-year overall survival (OS) rate of 78.1%, compared with 73.7% among those with small intestinal tumors and 59.8% with colonic lesions.

“The favorable outcomes we observed in rectal tumors likely reflect earlier detection and differences in tumor biology and treatment patterns,” states Noam Kahana, MD, a general surgeon at Cleveland Clinic Weston Hospital and the study’s first author.

Symptoms such as hematochezia and anal pain may result in diagnosis at an earlier stage, and rectal tumors in the study showed the lowest proportion of T4 and metastatic disease.

Treatment modalities for GISTs

Surgical resection remains the primary treatment for GISTs. Of the 5,760 patients analyzed, 4,880 (84.8%) underwent surgery and 2,643 (45.9%) received systemic therapy, which consists primarily of tyrosine kinase inhibitors (TKIs), such as imatinib and sunitinib.

“GISTs are generally insensitive to traditional chemotherapy, and radiation therapy is also infrequently used,” notes Dr. Kahana.

The study found that surgical resection, with or without systemic therapy, was associated with improved survival across most anatomic sites.

Rectal GISTs, however, appeared to represent a unique therapeutic subgroup. Patients treated with systemic therapy alone achieved a 5-year CSS of 77.7%, substantially higher than those with colonic (25.0%) or small bowel disease (59.2%). Moreover, no statistically significant difference in survival was observed between surgery-only and systemic therapy-only approaches in rectal tumors.

The researchers point out that avoiding surgery could have meaningful implications, particularly for younger patients, since rectal resections may result in sexual dysfunction and bowel incontinence. “We need further research to know if some of these patients can avoid surgery, as we showed in the study,” says Dr. Kahana.

Biological and demographic distinctions

Because most GISTs are driven by activating mutations in KIT or PDGFRA genes, molecularly targeted therapy with TKIs has become a cornerstone treatment for unresectable, recurrent or metastatic disease, with efficacy varying by mutation subtype.

Several studies have suggested that rectal GISTs frequently harbor KIT exon 11 mutations, which tend to respond favorably to imatinib, whereas colonic tumors may more frequently exhibit KIT exon 9 mutations, a subtype associated with comparatively less favorable outcomes.

“This may help explain the promising survival rates for rectal GISTs and the poorer outcomes associated with colonic GISTs in our study,” suggests Dr. Kahana. “Unfortunately, the SEER database does not capture molecular or biochemical data, limiting the ability to analyze mutation-specific outcomes.”

The researchers also found patients with colonic tumors were older and had a markedly higher proportion of Black patients than those with tumors in other locations. Black patients accounted for 29.1% of colonic GISTs, compared with 8.6% of small bowel tumors and 13.6% of rectal tumors.

“Our results underscore the importance of site-specific risk stratification and highlight the need for additional molecular and epidemiological research for this type of tumor,” says Dr. Rizkalla.

Call for a national registry

Because GISTs are uncommon, randomized trials are difficult to conduct, making large observational datasets essential for understanding treatment patterns and outcomes.

Drs. Rizkalla and Kahana are advocating for a national registry that would capture granular molecular and biochemical data and enable prospective analyses.

“We need a mechanism for clinicians across the country to report their cases of small bowel, colonic and rectal GISTs in order to have enough patients to study treatment patterns prospectively,” says Dr. Rizkalla.

The need for more comprehensive data may become increasingly important as the incidence of GISTs has risen over the past two decades, due in part to improved imaging and diagnostic recognition. Yet bowel GISTs – particularly those arising in the colon and rectum – remain extremely rare, limiting opportunities for prospective studies and molecular characterization.

“While our study adds meaningful data to the current literature, additional molecularly stratified studies are needed to improve prognostication and optimize management,” concludes Dr. Kahana. “A national registry could provide the foundation needed to better understand these tumors and advance more personalized approaches to care.”