The use of systemic chemotherapy for patients with poorly differentiated and signet cell adenocarcinoma of the appendix

The present study evaluated the effects of systemic chemotherapy and cytoreductive surgery (CRS) on survival in patients with aggressive types of cancer of the appendix (poorly differentiated and signet ring cell adenocarcinoma). The main findings were that systemic chemotherapy appears to be a viable treatment option for these types of cancer and that CRS provides survival benefit in patients with complete removal of the cancer. 

The appendix is a 10 cm pouch-like tube attached to the beginning of the large intestine and is considered part of the digestive tract. Therefore, cancers of the appendix are grouped together with colorectal cancers. Appendix cancer occurs when cells in the appendix become abnormal and multiply without control. Cancer of the appendix is very rare and has different subtypes, depending of the type of cells affected. Poorly differentiated and signet ring cell adenocarcinoma of the appendix are subtypes of appendiceal (of the appendix) cancer which have a generally poor prognosis. The primary treatment for these types of cancer is CRS.  This surgery aims to remove as much cancer burden as possible (when the tumor cannot be resected completely) and is frequently followed by hyerthermic intraperitoneal chemotherapy (HIPEC). This is where warm chemotherapy drugs (usually mitomycin-C and Cisplatin) are used to wash the abdominal cavity. The benefit of this treatment is however unclear. 

This review gathered information from previous studies and found 142 patients with poorly differentiated or signet ring cell carcinomas of the appendix. 123 of these patients had cancers that had spread to other parts of the body (metastatic). 78 of these patients with metastatic disease received at least one cycle of whole body (systemic) chemotherapy. 

Results show that patients who had complete removal of the cancer via CRS (15 patients) had a significantly longer overall survival time of 10.4 years compared to 2.3 years in patients whose tumor was only reduced in size (11 patients). There was also a significant increase in relapse-free survival time (survival without return of the cancer) from 0.9 years to 2.2 years. Among the chemotherapy group, cancer response (assessed by whole body scans) was seen in 44% of patients. The median survival without progression of the disease was 6.9 months. However, patients who received second-line chemotherapy (treatment tried when the first one failed) appeared to have less benefit from systemic chemotherapy. The choice of chemotherapeutic drug did not seem to affect survival.

In conclusion, systemic chemotherapy appears to be a valid treatment option for these types of cancer. Treatment is most effective after CRS, especially in patients in whom a complete tumor resection is achieved. In these cases, the combined treatment offers a substantial survival benefit. 

However, part of this benefit likely reflects the selection of patients with less aggressive tumors. If complete tumor resection is not possible, attempts to shrink it to <2.5mm should be done.