Discussion
We retrospectively analyzed the postoperative course of patients with rectal cancer subjected to intensified neoadjuvant RCT in comparison with patients who were not treated before surgery. The question was, whether patients treated before surgery had a higher rate of morbidity and mortality compared with the group that did not receive a neoadjuvant treatment. The main finding of this study is that intensified neoadjuvant radiochemotherapy resulted in a significantly higher surgical morbidity rate. To rule out known risk factors, this study was designed as matched pair analysis with matching patients 1 to 1 in decreasing priority for tumor height, discontinuous resection, tumor infiltration, dividing stoma and UICC stage. Patients in the neoadjuvantly treated group were younger and had less comorbidities without affecting the average ASA score. The number of examined lymph nodes was lower after intensified neoadjuvant RCT complying with previous reports. Some patients had a total reduction of the tumor and had therefore an ypT0 and/or UICC 0 classification. In conclusion, matching was successful and the groups were comparable.
Patients without neoadjuvant RCT were older and had a higher rate of comorbidities. This propably was the reason for an increased non-surgical morbidity. The group without neoadjuvant treatment had a leakage rate of 9.7% and was comparable with the results of other institutions. But nevertheless the overall surgical morbidity after intensified neoadjuvant treatment (especially anastomotic leakage of 26.6% and perineal wound infection rate of 42.2%) in our series is rather high compared to other groups as shown in Table 3 ranging between 0% and 25.9%. The quality of surgery appears to be comparable with other groups represented by the number of lymph nodes harvested. Other groups reported that there was no increase of surgical morbidity after applying non-intensified neoadjuvant radiochemotherapy (Table 3). By adding an extra agent, surgical results seem to be influenced in a negative way. If there was a benefit in oncologic outcome and if this potential benefit would compensate the increased surgical morbidity, it remains yet uncertain.
Taking the literature into account as shown in Table 3, the intensivation of neoadjuvant RCT according to Horisberger et al. appears to be even more aggressive compared to a neoadjuvant treatment without intensivation and results in a higher surgical complication rate. On the other hand, Gollins et al., Aschele et al., Sato et al. as well as Voelter et al. report rather low anastomotic leakage rates of 6.4%, 2%, 0% and 6% respectively from a group of 31, 747, 67 and 21 patients with sphincter sparing surgery. All studies concerning an intensified neoadjuvant RCT regime lack either a substantial number of patients and are basically series without a control group or do not focus on the surgical outcome. So far, there has been no explanation, how an additional chemotherapeutic agent could influence surgical morbidity of a subsequent operation which usually takes place 6 weeks after termination of radiochemotherapy. Horisberger et al. found a relationship between tumor response to intensified neoadjuvant therapy and major complications. The rate of anastomotic leakages was 25.9% in the group with a major response comparing to 0% in the group with a minor response to the neoadjuvant treatment. The authors suggest that collagen deposition, the depressing effect on the blood cells and other essential elements of wound healing as well as different definitions of anastomotic dehiscence and the irritation of bowel mucosa could have influenced this result. While the large multicenter studies on the oncological impact of radio(chemo)therapy do not show differences in the anastomotic leakage rate with or without pre- or postoperative radio-(chemo)-therapy, we demonstrate in our study the results of a single center institution with a standardized and reproducible treatment concept surgically as well as perioperatively. It should be pointed out, that surgical morbidity and mortality was not the main focus of the studies mentioned above whereas surgical complications were the main aim of our investigation. However, in a retrospective multicenter study Garlipp et al. focused on the effect of neoadjuvant radiochemotherapy on the anastomotic leak rate and did not find any differences between groups, even though the tumor location was significantly lower in patients subjected to neoadjuvant treatment. Weiss et al. report pooled data from three trials administering neoadjuvant RCT with capecitabine and oxaliplatin with or without cetuximab. The leakage rate is reported to be 11 per cent of all included patients without stating the fractions of patients with anterior resection or exstirpation of the rectum. Gerard et al. report low anastomotic leakage rates of 6.2% (12 out of 195 patients) administering only capecitabine and 4,9% (10 out of 205 patients) using capecitabine and oxaliplatin in the neoadjuvant RCT regime. Aschele et al. and Sato et al. report extremely low anastomotic leakage rates of 2% and 0%. This is noteworthy since the generally accepted leakage rate after rectal resection reported from leading surgical departments ranges from 5.5% to 37.5%. Also, a recent study showed a threefold higher anastomotic leakage rate in males in comparison to females after laparoscopic rectal resections. This correlation was somewhat debatable in the past. In our study, there was also a difference between males and females, but due to smaller patient numbers, we did not reach significant differences.
There are only few studies addressing perineal wound infection rate after neoadjuvant treatment in the literature. Data from Gollins et al. as well as Voelter et al. show a higher rate of perineal wound infections after an intensified regime (22.2 and 58%) compared with 10% and 26% after conventional preoperative radiochemotherapy. Our study confirms a high incidence of perineal wound infection following intensified neoadjuvant radiochemotherapy.