Hoehn 2021 - Appendiceal Neoplasms

Hoehn 2021 — Current Management of Appendiceal Neoplasms

Citation: Hoehn RS, Rieser CJ, Choudry MH, Melnitchouk N, Hechtman J, Bahary N. Current Management of Appendiceal Neoplasms. 2021 ASCO Educational Book. 2021:118-132. doi:10.1200/EDBK_321009.

Type of source

Review article (ASCO Educational Book), covering diagnosis, staging, and management of all five histopathologic subtypes of appendiceal neoplasms, plus a dedicated controversies section on CRS/HIPEC.

Scope

Appendiceal neoplasms are rare (age-adjusted incidence ~6/1,000,000/year), found in ~1% of appendectomy specimens, usually diagnosed postoperatively after presenting like acute appendicitis. Prognosis depends heavily on tumor type and grade (long-term survival 10-90%). Five subtypes, covered in full on Appendiceal Neoplasms:

1. Mucinous appendiceal neoplasms (MANs) / pseudomyxoma peritonei (PMP)
2. Neuroendocrine neoplasms (NENs)
3. Goblet cell adenocarcinoma (GCA)
4. Colonic-type (nonmucinous) adenocarcinoma
5. Signet ring cell adenocarcinoma

Key reference tables in this source

• Table 1: AJCC 8th edition TNM staging for appendiceal tumors (includes the LAMN-specific Tis(LAMN) category, and M1a/M1b/M1c distinguishing acellular mucin vs. cellular peritoneal deposits vs. extraperitoneal metastasis).
• Table 2: PSOGI classification of primary MANs and metastatic PMP (LAMN → high-grade mucinous neoplasm → mucinous adenocarcinoma; PMP graded low-grade / high-grade / signet-ring).
• Table 3: outcomes of CRS/HIPEC for PMP across 10 published series (1,000+ patients in the largest) — median OS 51-196 months, 5-year OS 39-98% depending on selection and completeness of cytoreduction.
• Table 4: WHO 2019 grading for GI/hepatobiliary neuroendocrine neoplasms (NET G1-G3 by mitotic rate and Ki-67 index, vs. poorly-differentiated NEC).

Key findings by subtype

• MANs/PMP: low-grade (grade 1) MAN confined to appendix, non-perforated → appendectomy alone with surveillance may suffice; grade 2/3 or any node involvement → right hemicolectomy. Lymph node positivity rates: grade 1 ~1%, grade 2 ~17%, grade 3 ~72% (5-yr survival 91%/61%/23% respectively). PMP → CRS/HIPEC in well-selected patients; no role for systemic chemo in low-grade MAN/PMP.
• NENs: management driven mainly by size — <1cm appendectomy alone sufficient; >2cm right hemicolectomy generally recommended; 1-2cm zone individualized by other risk features. LN involvement scales sharply with size (15% / 47% / 86% for <1cm / 1-2cm / >2cm). Advanced/metastatic disease: somatostatin analogs (octreotide — PROMID trial; lanreotide — CLARINET trial), everolimus (RADIANT-2/4), peptide receptor radionuclide therapy with Lu-177-DOTATATE (NETTER-1 trial) for somatostatin-receptor-positive disease.
• GCA: renamed from “goblet cell carcinoid” because the neuroendocrine component is now understood to be minor; more aggressive than typical NETs (frequent transmural invasion, nodal and peritoneal spread); treated like adenocarcinoma — right hemicolectomy recommended for essentially all (small series suggesting appendectomy alone might suffice for <1cm tumors are not strong enough to change consensus guidance). CRS/HIPEC used for peritoneal spread; grade 3 tumors (>50% high-grade histologic pattern) have markedly worse survival (23% vs 54% 5-yr OS for grade 3 vs grade 1/2 in one series).
• Colonic-type (nonmucinous) and signet ring adenocarcinomas: treated per colon cancer algorithms; right hemicolectomy recommended even for small tumors given real nodal risk (19% for

  1cm tumors, similar to primary colon adenocarcinoma). Signet ring cell tumors are markedly worse — median survival 24 months vs. 48 months for standard appendiceal adenocarcinoma — despite similar T-stage distribution; genetically distinct from typical colorectal cancer despite similar prognosis-worsening behavior.

Controversies (CRS/HIPEC)

• PRODIGE 7 (French phase III, colorectal peritoneal metastases) found no OS benefit from adding HIPEC to CRS — but the trial used a short-duration (30min) oxaliplatin-based protocol on patients mostly already exposed to IV oxaliplatin, and is not appendiceal-specific; conclusions don’t clearly transfer to appendiceal neoplasms.
• COLOPEC (Dutch phase III, T4/perforated colon cancer) found no benefit from prophylactic adjuvant HIPEC — again not appendiceal-specific.
• PCI (Peritoneal Carcinomatosis Index, 0-39) cutoffs for who benefits from CRS/HIPEC are inconsistent across studies (proposed thresholds range 12-20); completeness of cytoreduction (CC-0) is the more reproducible predictor of survival than PCI itself — some patients with high PCI and high-grade tumors still benefit if CC-0 is achievable.
• Mitomycin vs. oxaliplatin as the HIPEC agent: one large US multicenter RCT found oxaliplatin associated with less hematologic toxicity and better QoL scores than mitomycin, with similar OS.

Relevance

Establishes Appendiceal Neoplasms as a new condition page (fifth distinct entity family requiring its own staging and management logic — very different from diverticulitis and rectal cancer) and Cytoreductive Surgery and HIPEC as a reusable concept page, since CRS/HIPEC will likely recur in future sources on peritoneal disease from colorectal primaries too.