Impact of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal adenocarcinoma

Abstract

AimPeritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well‐recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective.MethodA prospective database of 294 patients with advanced appendiceal primary tumors undergoing CRS ± HIPEC between June 2009 and December 2020 was reviewed. Baseline characteristics and long‐term outcomes were compared between patients with adenocarcinoma who received neoadjuvant chemotherapy or upfront surgery.ResultsEighty‐six (29%) patients were histologically diagnosed with an appendiceal cancer. These included intestinal‐type adenocarcinoma (11.6%), mucinous adenocarcinoma (43%), and goblet cell adenocarcinoma (GCA) or signet ring cell adenocarcinoma (SRCA) (45.4%). Twenty‐five (29%) of these underwent NAC, of which eight (32%) exhibited some degree of radiological response. There was no statistical difference in OS at 3 years between the NAC and upfront surgery groups (47.3% vs. 75.8%, p = 0.372). Appendiceal histology subtypes, particularly GCA and SRCA (p = 0.039) and peritoneal carcinomatosis index >10 (p = 0.009), were factors independently associated with worse OS.ConclusionAdministration of NAC did not appear to prolong OS in the operative management of disseminated appendiceal adenocarcinomas. GCA and SRCA subtypes display a more aggressive biological phenotype.

Incidental diagnosis of primary appendiceal signet-ring cell adenocarcinoma after appendectomy for acute appendicitis, a case report

“…The role of radiotherapy in ASCA is uncertain. For appendiceal tumor spreading to peritoneum, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are considered the standard treatments 21 . Yet, it remains controversial in peritoneal dissemination from signet-ring cell carcinoma from the appendix 22 .…”

Consensus guideline for the management of patients with appendiceal tumors Part 1: Appendiceal tumors without peritoneal involvement

“…Outcomes were overall and disease-free survival, and adverse events. Seventeen studies reported on preoperative or neoadjuvant chemotherapy ( [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] ), 6 reported on postoperative or adjuvant chemotherapy ( [47][48][49][50][51] ), 9 reported on both ( [52][53][54][55][56][57][58][59][60] ), and 2 reported on other or unspecified regimens ( 61,62 ). These studies are summarized in Table 2, addressed qualitatively in Principles of Systemic Therapy, and applied in blocks 3 and 6 of the Appendiceal Adenocarcinoma pathway.…”

“…48,53,54,59,60,[71][72][73]78 Others studies have shown minimal benefit or even detriment after adjuvant therapy; it is unclear how much of this variation reflects selection bias, as the patients who are most likely to undergo adjuvant therapy are those who are well enough to do so. 47,49,51,52,56 To our knowledge, no studies have comprehensively evaluated the role of modern neoadjuvant therapy for resectable appendix tumors without peritoneal involvement; at present expert consensus opinion is not in favor of neoadjuvant therapy in that setting, as it would delay definitive resection.…”

“…[31][32][33][34]37,39,61 However, this may not translate to cohort-wide overall-, recurrence-free, or progression-free survival, as a number of observational studies suggest a lack of benefit of preoperative chemotherapy in one or all of those domains. 31,33,34,36,41,42,44,47,50,52,54,56,57,83 Overall and disease-free survival is still poor even with definitive cytoreduction; a large study of the US HIPEC collaborative estimates 23.2% five-year disease-free survival and 43.8% overall survival for high-grade appendiceal tumors with peritoneal involvement. 84 Some studies show a survival benefit from postoperative therapy as well, but there is conflicting data regarding its role or benefit.…”

Appendiceal Signet Ring Cell Carcinoma: An Atypical Cause of Acute Appendicitis—A Case Study and Review of Current Knowledge

“…The role of adjuvant radiotherapy in appendiceal adenocarcinoma, particularly in ASRCC, is uncertain. Systemic chemotherapy is a viable option for patients with metastatic disease, while cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are the standard treatments for peritoneal dissemination from appendiceal cancer [36,37]. However, the benefit of CRS/HIPEC in cases of peritoneal dissemination from ASRCC remains controversial [38].…”