This study aimed to determine the efficacy and safety of treatment of obstructing left-sided colon cancer with SEMS followed by neoadjuvant chemotherapy and elective surgery. The findings suggest that this approach is feasible and safe, and does not increase postoperative morbidity.
An important concern with neoadjuvant chemotherapy, especially when administered after SEMS for obstructive colorectal cancer, is the toxicity of the drugs used.22 In our series, only one (9.1%) patient had a grade 3 toxicity (diarrhea). Neoadjuvant chemotherapy was generally well tolerated, and all patients were able to undergo surgery after completion of chemotherapy. Thus, two or three cycles of neoadjuvant chemotherapy after SEMS insertion appears to be safe.
A previous study reported a significant fall in serum albumin level despite sufficient nutritional intake when surgery was performed 2 weeks after stenting in patients with obstructive colorectal cancer; the authors suggested that SEMS insertion might increase the risk of anastomotic leakage.23 Hosono et al24 also reported decrease in serum albumin level in the interval between admission and surgery in 75% of patients treated with SEMS. In the present study, the serum albumin level decreased slightly after SEMS insertion, but then increased significantly in the interval between neoadjuvant chemotherapy and surgery. The hemoglobin level also increased significantly before surgery. Thus, it appears that the relatively longer interval before surgery allows improvement of the nutritional status of patients. This improvement probably contributes to the lower rate of postoperative complications.
The hypothesis driving the growing interest in the use of SEMS in colonic obstruction is that it can convert an emergency surgery into an elective one, and thus help minimize perioperative morbidity, aid restoration of bowel function, and decrease the need for a stoma.15,23,24 However, the temporary stoma rate was much higher in patients treated with SEMS followed by elective surgery than in those treated directly with elective surgery (11% vs. 1%).15 The authors suggested that this may have been because the surgeons choose to make a stoma for preserving anastomotic integrity in patients with intraoperative intestinal wall edema as a result of previous colonic obstruction.15 Preoperative evaluation of mucosal edema may help prevent anastomotic leakage.23 We evaluated colonic wall thickness 10 cm proximal to the tumor and found that the thickness increased significantly 1 week after SEMS placement (before chemotherapy), and decreased significantly after chemotherapy. None of our patients required stoma creation, probably because of the improvement in physical condition and reduction of intestinal wall edema during the prolonged interval between SEMS and surgery.
Among patients receiving SEMS placement, 43.5%–91% were successfully treated by laparoscopic surgery; this high success rate is partly attributable to intestinal decompression, which allows more efficient performance of laparoscopic surgery.23,25 As laparoscopic surgery is minimally invasive, short-term surgical outcomes are better.26 In our study, laparoscopic surgery was successfully performed in nine (81.8%) patients. We suggest that neoadjuvant chemotherapy administered in the interval between SEMS placement and surgery does not decrease the possibility of success laparoscopic surgery; on the contrary, it might actually increase the chances of success.
Although neoadjuvant chemotherapy is not routinely administered in locally advanced colorectal cancer patients, several authors have demonstrated benefits with a neoadjuvant chemotherapy-alone approach.22,27–29 A single-center phase II study conducted at Memorial Sloan-Kettering Cancer Center evaluated neoadjuvant chemotherapy with six cycles of FOLFOX plus bevacizumab in locally advanced rectal cancer patients and showed that neoadjuvant chemotherapy was relatively safe and capable of inducing major tumor regression.27 Four cycles of neoadjuvant mFOLFOX6 chemotherapy-alone approach has also shown promising efficacy for locally advanced rectal cancer in the FOWARC study.28 Other studies have shown that neoadjuvant chemotherapy with CAPOX or FOLFOX is effective and safe in patients with locally advanced colon cancers.22,29 All patients in our study completed neoadjuvant chemotherapy without experiencing any major toxicities. Although no patient achieved complete pathologic response in our study, tumor reduction was achieved in all patients.
It was reported that tumor recurrence was more frequent in patients treated with SEMS.30 Gorissen et al25 found that among patients ages, the local recurrence rate was higher in those treated with SEMS and elective surgery than in those treated with emergency surgery. The poor outcomes may be related to the significantly increased levels of CK20 mRNA that have been detected in the peripheral circulation of colorectal cancer patients after endoscopic insertion of colonic stents; it is probably caused by tumor manipulation during guidewire insertion, dilatation, and stent deployment.31 One of the disadvantages of colonic stenting is that it increases the risk of PNI. Kim et al18 found PNI of the primary tumor to be significantly more frequent in patients treated with SEMS than in those treated with emergency surgery (76% vs. 51.4%, p = 0.033). Similarly, Haraguchi et al23 found significantly higher incidence of PNI in patients treated with SEMS than in those treated with emergency surgery (59.1% vs. 18.2%, p = 0.005). PNI is associated with decreased survival and is an independent predictor of poor outcome in colorectal cancer patients.32 In our study, no patient had PNI. Moreover, no patient had local recurrence or metastases during follow-up. There were no tumor-related deaths during follow-up of 44 months. Therefore, we suggest that neoadjuvant chemotherapy after SEMS might lower the risk of PNI and thus help improve survival.
This study has some limitations. First, this was a single-center study with a small sample. Second, there was no comparison of patients treated with SEMS plus neoadjuvant chemotherapy and those treated with conventional SEMS. The comparison might reveal the real effect of new treatment on patients’ general conditions, operational variables and oncologic results compare with conventional SEMS treatment. Third, this was a retrospective case series, and a selection bias is therefore inevitable.