Workup and Treatment of Appendix Cancer
Initial Workup and Diagnosis
Most appendiceal cancers are discovered incidentally during appendectomy for suspected appendicitis, requiring immediate histopathological classification to determine the appropriate surgical approach. 1
The workup must distinguish between the major histologic subtypes, as management differs dramatically:
- Neuroendocrine (carcinoid) tumors: Most common appendiceal malignancy, typically well-differentiated with favorable prognosis 1
- Adenocarcinomas: Including mucinous cystadenocarcinoma, colonic-type adenocarcinoma, and goblet cell carcinoid (adenocarcinoid) 1, 2
Staging Evaluation
For any appendiceal cancer diagnosed on initial pathology, perform:
- Abdominal/pelvic CT or MRI with IV contrast (maximum 5mm collimation) to assess for distant metastases and peritoneal involvement 1, 3
- Chest CT to exclude pulmonary metastases 1
- Baseline CEA level for adenocarcinomas 1
- Chromogranin A level (category 3) for neuroendocrine tumors 1, 3
- Complete colonoscopy to exclude synchronous lesions, particularly important given higher rates of concomitant GI malignancies 2
Treatment Algorithm by Histologic Type
Neuroendocrine (Carcinoid) Tumors
Tumors ≤2 cm WITHOUT High-Risk Features
Simple appendectomy alone is sufficient and curative for well-differentiated appendiceal carcinoid tumors ≤2 cm confined to the appendix without adverse features. 1, 3
- No additional surgery required if margins are clear 1
- Follow-up as clinically indicated; some institutions recommend evaluation at 1 year then with decreasing frequency 1, 3
Tumors >2 cm OR High-Risk Features Present
Right hemicolectomy with regional lymphadenectomy is mandatory for appendiceal carcinoids >2 cm or those with any high-risk features, regardless of size. 1, 3
High-risk features requiring right hemicolectomy include:
- Tumor size 1-2 cm with lymphovascular invasion 1
- Mesoappendiceal invasion >3 mm 1, 3
- Tumor at the base of appendix 3
- Serosal breach 3
- Atypical histologic features 1
- Incomplete initial resection 1
Critical pitfall: The NCCN guidelines note controversy exists for 1-2 cm tumors, as SEER database analysis revealed lymph node metastases can develop even in tumors ≤2 cm with aggressive features. 1
Goblet Cell Carcinoid (Adenocarcinoid)
Goblet cell carcinoids must be managed according to colon cancer protocols, not neuroendocrine tumor protocols, due to their adenocarcinoma component. 1
- Requires right hemicolectomy regardless of size 1
- Consider adjuvant chemotherapy per colon cancer guidelines if node-positive 1
Adenocarcinomas of the Appendix
Right hemicolectomy with regional lymphadenectomy is the standard treatment for all appendiceal adenocarcinomas, as appendectomy alone results in inferior survival. 2, 4, 5
Surgical Approach
- Right hemicolectomy with lymphadenectomy is required for T2 or higher stage disease due to high risk of lymph node metastases 6, 4, 5
- Minimum of 12 lymph nodes should be examined in the specimen 7
- T1 tumors may be managed with appendectomy alone ONLY if the base is completely free and no lymphadenopathy is present 6
Adjuvant Chemotherapy
Adjuvant chemotherapy is indicated for node-positive disease or peritoneal seeding, though optimal regimens remain poorly defined as appendiceal cancers respond less favorably than colorectal cancers to standard regimens. 8, 4
- Extrapolated from colorectal cancer protocols (FOLFOX or similar) 8
- Evidence base is weak due to rarity and lack of randomized trials 8, 4
- Consider for Duke's C disease (node-positive) 9
Important caveat: Research demonstrates that appendiceal adenocarcinomas have different biology than colorectal cancers and show inferior outcomes with standard colorectal chemotherapy regimens, highlighting the need for novel tailored strategies. 8
Advanced/Metastatic Disease
Peritoneal Metastases
For mucinous cystadenocarcinomas with peritoneal dissemination (pseudomyxoma peritonei), cytoreductive surgery combined with heated intraperitoneal chemotherapy (HIPEC) is the established treatment achieving long-term survival in selected patients. 8, 2
- Aggressive surgical debulking is essential 2
- Can achieve prolonged survival despite extensive peritoneal involvement 2
Hepatic Metastases
For limited hepatic metastases from neuroendocrine tumors:
- Complete resection of primary and metastases can achieve 50.4% 10-year overall survival 1
- Resection of primary in setting of unresectable metastases is generally NOT indicated 1
Surveillance Protocol
For Resected Neuroendocrine Tumors
- H&P and imaging (CT or MRI abdominal/pelvic) at 3-12 months post-resection, then every 6-12 months 1, 3
- Chromogranin A levels may be monitored (category 3), though can be falsely elevated with PPI use, renal/hepatic insufficiency 1, 3
- 24-hour urine 5-HIAA for small intestinal carcinoids with carcinoid syndrome 1
- Octreoscan not routinely recommended but may assess disease burden if recurrence suspected 1
Exception: Appendiceal carcinoids ≤2 cm without aggressive features require only clinical follow-up as indicated 1, 3
For Resected Adenocarcinomas
- Follow colorectal cancer surveillance protocols 1
- CEA monitoring 1
- Colonoscopy at appropriate intervals 1
Key Clinical Pitfalls to Avoid
Performing only appendectomy for tumors >2 cm or with high-risk features leads to inadequate oncologic resection and higher recurrence rates 1, 3, 5
Failing to obtain adequate staging imaging before declaring a patient has localized disease 1, 3
Treating goblet cell carcinoids as typical neuroendocrine tumors rather than adenocarcinomas results in undertreatment 1
Not examining the entire bowel during surgery for neuroendocrine tumors, as synchronous lesions are common 1
Relying on chromogranin A alone without recognizing false elevations from PPIs or organ dysfunction 1
Assuming colorectal chemotherapy regimens will be equally effective for appendiceal adenocarcinomas, when evidence shows inferior outcomes 8