Abstract

Despite the lack of supporting data, it is a common practice to use adjuvant chemotherapy (ACT) in high-grade appendiceal cancer patients with peritoneal metastases (stage IVA/B) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Low incidence precludes conducting randomized clinical trials; therefore, many oncologists extrapolate from node-positive colon cancer studies demonstrating benefits of ACT. We aimed to evaluate ACT efficacy after CRS/HIPEC in patients with stage IVA/B appendiceal cancer. A single-institution retrospective cohort study using a prospective database was conducted. Stage IVA/B high-grade appendiceal cancer patients who underwent CRS/HIPEC with CC-0/1/2 were included. Survival outcomes were compared between patients receiving ACT and those under observation. Subgroup analysis was performed based on histopathologic subtype, neoadjuvant chemotherapy (NACT), lymph node (LN) status, and peritoneal cancer index (PCI) ≥20. We identified 196 patients: 84 with ACT and 112 with no adjuvant chemotherapy (NoCT). There was no significant difference between groups in age, preoperative tumor markers, NACT frequency, PCI, as well as complete cytoreduction (CC-0/1) and postoperative major complication rates. ACT group had more patients with signet ring cell carcinoma (SRC) (51% vs 31%, p=0.022) and positive LN (56% vs 34%, p=0.002). ACT regimens included 5-FU/capecitabine in 11 (13%), FOLFOX in 53 (63%), FOLFIRI in 17 (20%), with/without bevacizumab. Regimens were unknown in 3 (4%) patients. Median number of cycles was 8 (IQR: 4-12) and median time between CRS/HIPEC and ACT was 12 (IQR: 8-15) weeks. Median follow-up was 68 months. Overall survival (OS) did not significantly differ between groups (54 months in ACT vs 66 in NoCT, p=0.894). Subgroup analysis showed no OS benefit of ACT compared to NoCT for patients with NACT (median OS: 40 vs 33 months, p=0.284) or without NACT (53 vs 82 months, p=0.457), with SRC (39 vs 33 months, p=0.389) or without SRC (54 vs 89 months, p=0.583), positive LNs (39 vs 33 months, p=0.894), or PCI ≥20 (39 vs 24 months, p=0.356), respectively. Additionally, ACT did not impact OS after adjusting for other factors in the multivariable Cox regression model. In our patient cohort, colorectal-type ACT did not improve OS in stage IVA/B appendiceal cancer treated with CRS/HIPEC, even when adjusting for confounding factors. This may be due to differences in tumor biology compared to colon cancer or the inability to detect differences in a small sample size. Data from prospective collaborative clinical trials are needed.

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