Malignant Neoplasms of the Small Intestine Guidelines

Updated: May 18, 2022
  • Author: Ponnandai S Somasundar, MD, MPH, FACS; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Guidelines Summary

Guidelines on small bowel adenocarcinoma (SBA) from the National Comprehensive Cancer Network are summarized below. [31]


Patients with SBA require a complete staging workup, including the following:

  • Biopsy (if appropriate)
  • Pathologic tissue review
  • Imaging studies
  • Complete blood count
  • Chemistry profile
  • Carbohydrate antigen 19-9
  • Carcinoembryonic antigen
  • Studies for celiac disease or inflammatory bowel disease (depending on tumor location and patient history)
  • DNA mismatch repair (MMR) or microsatellite instability (MSI) testing

Imaging studies may include the following:

  • Esophagogastroduodenoscopy with endoscopic ultrasound is recommended when a duodenal malignancy is suspected.
  • Double balloon endoscopy may be of particular benefit for patients with small bowel strictures.
  • CT or MRI may be used to evaluate the extent of local tumor invasion and to assess for distant metastases; CT or MR enterography or enteroclysis may be used when conventional CT or MRI with contrast have failed to show a tumor.
  • PET/CT is not routinely indicated, but may be considered when CT or MR results are equivocal.

Treatment of Stage I–III Small Bowel Adenocarcinoma

Primary treatment for local (stage I–III) SBA consists of surgical resection with en bloc removal of at least 8 regional lymph nodes.

The type of resection used to treat localized SBA depends on the location of the primary tumor, as follows:

  • Segmental resection of the small bowel is often the mainstay of treatment.
  • Duodenal tumors may require either pancreaticoduodenectomy (Whipple procedure) or segmental duodenal resection.  Experienced surgeons may consider minimally invasive procedures (eg, laparoscopic surgery) for pancreaticoduodenectomy.
  • For tumors of the jejunum or ileum, segmentectomy is the preferred method of resection.

Participation in a clinical trial is preferred for all patients with SBA who are considering adjuvant therapy, as the optimal approach is unknown.

Observation is recommended after surgical treatment of all stage I SBA tumors and stage II tumors that have high MSI (MSI-H) or deficient MMR (dMMR).

Observation or 6 months of adjuvant treatment with 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine is recommended for T3, N0, M0 (stage IIA) tumors that are microsatellite stable (MSS) or MMR proficient (pMMR) and have no high-risk features.

Observation or 6 months of adjuvant treatment with 5-FU/LV/oxaliplatin (FOLFOX), capecitabine plus oxaliplatin (CAPEOX), 5-FU/LV, or capecitabine is recommended for stage II tumors that are MSS or pMMR and have high-risk features (eg, T4 stage, close or positive surgical margins, few lymph nodes examined)

Six months of adjuvant treatment with FOLFOX, CAPEOX, 5-FU/LV, or capecitabine is recommended for any locally advanced SBA with positive lymph nodes (stage III).

Chemoradiation with capecitabine or infusional 5-FU is another option for stage III duodenal cancer that is margin-positive after resection.

Patients with locally unresectable or medically inoperable SBA may undergo neoadjuvant therapy, with routine monitoring for conversion to resectable disease. I in cases where conversion to resectable disease is not feasible, palliative chemotherapy may be considered.

Treatment of Advanced or Metastatic (Stage IV) Small Bowel Adenocarcinoma

Recommended first-line chemotherapy regimens are FOLFOX, CAPEOX, FOLFOXIRI (infusional 5-FU, LV, oxaliplatin, irinotecan), or FOLFIRINOX (same drugs as FOLFOXIRI, but with bolus 5-FU and higher irinotecan dose) any of which may be combined with bevacizumab. Patients with dMMR/MSI-H tumors may be treated with nivolumab with or without ipilimumab. Patients who are not appropriate candidates for intensive therapy may receive these regimens with the more toxic components excluded (ie, 5-FU/LV or capecitabine with or without bevacizumab), or with nivolumab with or without ipilimumab if their tumor is dMMR/MSI-H

For intensive subsequent lines of therapy, recommended regimens include the following:

  • FOLFOX ± bevacizumab
  • CAPEOX d ± bevacizumab
  • FOLFIRI ± bevacizumab
  • Taxane-based chemotherapy
  • In patients with dMMR/MSI-H tumors and no previous checkpoint inhibitor exposure: nivolumab ± ipilimumab; pembrolizumab; or dostarlimab-gxly
  • In patients with metastatic SBA with NTRK gene fusion and no satisfactory alternative treatments: Larotrectinib

Treatment with trifluridine-tipiracil or regorafenib is not recommended.

Certain patients with SBA and limited metastasis to visceral organs may be candidates for metastasectomy.

For resectable peritoneal carcinomatosis, surgical cytoreduction may be considered. With unresectable peritoneal metastases, treatment is palliative and primarily consists of systemic therapy

Posttreatment Surveillance

Due to the lack of data regarding optimal surveillance following curative-intent treatment of SBA, an approach similar to that for colorectal cancer is recommended. This includes regular history and physical examination; carcinoembryonic antigen and/or carbohydrate antigen 19-9 measurement; and CT of the chest, abdomen, and pelvis.

Patients with Crohn disease or familial syndromes (eg, Lynch syndrome, familial adenomatous polyposis, Peutz-Jeghers syndrome) may require more intensive surveillance (eg, with endoscopy/enteroscopy).