Preoperative radiochemotherapy is widely used in locally advanced rectal cancer. It can improve local control of rectal cancer. However, some researchers believe it increases the incidence of surgical complications. They doubt its safety. Patients with locally advanced rectal cancer receive three different treatments in our hospital, including long-course radiochemotherapy, short-course radiotherapy, and surgery directly. We can compare their differences in postoperative complications.

To investigate surgical complications caused by different preoperative radiotherapy regimens.

We retrospectively analyzed 1197 patients admitted between 2008 and 2010 with locally advanced rectal cancer. Three hundred and forty-six patients were treated with preoperative long-course radiochemotherapy (25 × 2 Gy) followed by total mesorectal excision (TME) 6–8 wk later, and 259 patients received short-course radiotherapy (10 × 3 Gy) and subsequently TME 7–10 d later. The remaining 592 patients underwent TME alone without neoadjuvant therapy. According to Clavien–Dindo classification, surgical complications were evaluated for up to 30 d after discharge from hospital.

There were no deaths in 30 d in all groups after treatment. The major complications were anastomotic leakage and perineal wound complications. The results suggested that both long-course [odds ratio (OR) = 3.624, 95% confidence interval (CI): 1.689–7.775, P = 0.001] and short-course (OR = 5.150, 95%CI: 1.828–14.515, P = 0.002) radiotherapy were associated with anastomotic leakage. Temporary ileostomy was a protective factor for anastomotic leakage (OR = 6.211, 95%CI: 2.525–15.385, P < 0.001). The severity of anastomotic leakage did not increase in patients following preoperative radiotherapy (P = 0.411). Compared with TME alone, short-course radiotherapy was associated with an increase in perineal wound complications (OR = 5.565, 95%CI: 2.203–14.057, P < 0.001), but long-course radiotherapy seemed safe regarding this complication (OR = 1.692, 95%CI: 0.651–4.394, P = 0.280). Although the severity of perineal wound complications increased in patients following short-course radiotherapy (P < 0.001), additional intervention was not necessary.

Radiotherapy increased the incidence but not severity of anastomotic leakage. Short-course radiotherapy was also accompanied with perineal wound complications, but intervention appeared unnecessary to ameliorate the complications.

Patients with locally advanced rectal cancer were recommended to receive neoadju-vant radiochemotherapy, especially for those with positive circumferential resection margin or extensive nodal involvement. It can improve local control for these patients. The rate of local recurrence has decreased significantly as a result of neoadjuvant radiochemotherapy. Some researchers believe that preoperative radiotherapy can improve survival of patients with resectable rectal cancer. It is suggested that patients who are sensitive to radiotherapy can achieve better prognosis. Approximately 15% of patients can achieve complete response after long-course neoadjuvant radioche-motherapy[1]. Different protocols for short-course radiotherapy that consists of 30 Gy in 10 fractions are recommended by the Chinese Anti-Cancer Association[2]. The biological equivalent dose of the short-course radiotherapy is similar to the commonly used regimen (5 × 5 Gy). Although the tumor regression is not as good as with long-course radiochemotherapy, with < 5% complete response rate, the advantages are no surgical delay, reduced toxicity from capecitabine, and avoidance of overtreatment of non-responders. However, some surgeons believe that preoperative radioche-motherapy increases surgical complications. Anastomotic leakage is thought to be associated with malnutrition resulting from radiotherapy[3]. Perineal wound complications after abdominoperineal resection (APR) are also considered to be associated with tissue edema and infection caused by radiotherapy. In addition, toxicity of radiochemotherapy may decrease patients’ tolerance to surgery.

The aim of this study was to evaluate surgical complications of patients with locally advanced rectal cancer following different neoadjuvant therapy and radical surgery. We compared the incidence and severity of surgical complications at 30 d after sur-gery in different groups and the contribution of neoadjuvant therapy to surgical complications.

Neoadjuvant radiochemotherapy has become important to reduce local recurrence of locally advanced rectal cancer. In China, an increasing number of patients have been recommended to receive radiotherapy before surgery, but an increase in postoperative complications if patients receive preoperative radiation has been a major concern[4]. The present study compared the major postoperative complications associated with long-course and short-course radiotherapy followed by TME in a large series of patients with locally advanced rectal cancer. Compared to those without radiotherapy, the increase in surgical complications caused by two different preoperative radiotherapy regimens was acceptable, and postoperative mortality did not increase. No patients died within 30 d after surgery, although preoperative radiotherapy might have been associated with anastomotic leakage and perineal wound complications. Temporary ileostomy prevented the occurrence and severity of anastomotic leakage. The grade of surgical complications did not differ significantly, except for perineal wounds, which did not always require surgical reintervention.

Several studies have investigated whether preoperative radiotherapy increases surgical complications[5]. The conclusions were not in agreement. Most of these studies have suggested that preoperative radiotherapy does not increase postoperative morbidity[6]. However, the complications in patients with neoadjuvant radiotherapy seem to be more severe, as demonstrated by the need for more surgical reintervention to treat the complications[7]. Our study indicated that long-course and short-course chemoradiotherapy were not associated with increased incidence or grade of complications. Conservative measures do not have any benefit after radiotherapy[8]. Reintervention is more often used for patients who receive radiotherapy if anastomotic leakage cannot be healed. This was one of the major setbacks of radiotherapy.

Anastomotic leakage is the most serious surgical complication after LAR for rectal cancer. It occurs in 3.5%–25.0% of patients after surgery[9,10]. The rates reported varied according to different definitions being used. In some studies, anastomotic leakage was diagnosed by computed tomography, magnetic resonance imaging, or radio-graphy. The incidence rates were usually higher by imaging diagnosis than clinical observation. In this study, we defined leakage by the presence of gas or feces around the anastomosis in the drainage tubes. Radiology was used only when surgical reintervention was required. There were many risk factors believed to be associated with anastomotic leakage, such as male gender, lower location of the tumor, and preoperative radiotherapy[11,12]. Neoadjuvant radiotherapy has been implicated as a causative factor for the increased rate of anastomotic leakage[13]. It might be due to the local effect of radiation, and subsequently increased technical difficulty during the operation. Radiotherapy may also decrease the oxygen supply to the local tissue around the anastomosis. It can slow down the healing process and cause leakage. In our study, the rate for all these patients was 5.4%. It was a low incidence and within the acceptable range compared with other complications.

It is agreed that preoperative radiotherapy is associated with an increase in anastomotic leakage. Patients with radiotherapy may need a longer time for healing of leakage. As a result, a temporary defunctioning ileostomy was constructed during rectal surgery for patients who underwent preoperative radiotherapy, and it was reversed after 6 mo[14]. It is believed that ileostomy can reduce anastomotic leakage[15]. In the present study, more patients with radiotherapy had a defunctioning ileostomy than those who underwent surgery alone. Defunctioning ileostomy also decreases the grade of leakage as the feces are diverted[16]. This may be an effective approach to avoid surgical reintervention caused by anastomotic leakage.

Perineal wound complications are commonly seen after APR. Previously reported rates varied between 5.9% and 31.0%[17,18]. Most perineal wound complications, such as wound gaping, are mild and do not require a prolonged stay in hospital or surgical reintervention. However, severe wound complications can impair quality of life[19]. For example, patients with open wounds are usually accompanied with pain and movement limitation. They might also delay subsequent adjuvant chemotherapy, which may result in worse prognosis. Previous studies have shown that the rate of perineal wound complications increases in patients who receive preoperative radiotherapy[4,20]. Our study also showed a significant increase in perineal wound complications after short-course radiochemotherapy compared with patients who received long-course raidochemotherapy and those who did not receive neoadjuvant treatment. In addition, the grade of the complications was also higher in the short-course radiotherapy group. The grade of these complications was always 3a. However, no reintervention was required to manage these complications.

Although our study had a large patient cohort, it was limited by its retrospective nature. It is difficult to fully evaluate late complications for > 30 d after hospital discharge, and the incidence might have been underestimated.

The use of preoperative radiochemotherapy for rectal cancer has been debated for decades, including indications, methods, TRG, and so on. Preoperative chemora-diotherapy may be affected by several factors, such as carcinoembryonic antigen and histological regression score. Acellular mucin pools are also thought to be a useful predictor for complete response in several studies[21,22], but it is controversial. The association between postoperative complications and mucin pools is worth study. From 2008-2010, which is the recruitment period, we had not begun to detect routinely regression rate and mucin pool in our hospital. Therefore, these data were not collected for this study. It is one of the limitations of our study.

Since the sample includes more 1000 patients, we can compare the local control, survival, and quality of life among different groups. We can compare differences of clinical effect between different preoperative therapies, and additional studies are necessary in the future.

In conclusion, preoperative radiotherapy was associated with two major surgical complications: anastomotic leakage and perineal wound complications. There were no significant differences in other complications. Both long-course and short-course radiochemotherapy increased the incidence of anastomotic leakage, but the grade remained close to that in patients treated with surgery alone. A temporary defunctioning ileostomy seemed to be an effective method to reduce the risk of anastomotic leakage for patients who received radiotherapy. Short-course radiochemotherapy increased the incidence and grade of perineal wound complications. Reintervention may not be necessary to ameliorate the perineal wound complications as the damage is usually low grade.