Necessity of neoadjuvant chemoradiation therapy in extremely low rectal cancer initially requiring abdominoperineal resection retrospective study in Korea

Article information

Korean Journal of Clinical Oncology. 2025;21(2):98-104

Publication date (electronic) : 2025 August 31

doi : https://doi.org/10.14216/kjco.24316

Go Woon Park, Na Hyeon Park, Dae Ro Lim, Jung Cheol Kuk, Eung Jin Shin

Division of Colon and Rectal Surgery, Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea

Correspondence to: Dae Ro Lim, Division of Colon and Rectal Surgery, Department of Surgery, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon 14584, Korea, Tel: +82-32-621-6267, Fax: +82-32-621-6950, E-mail: limdaero@schmc.ac.kr

Received 2024 October 16; Revised 2025 February 13; Accepted 2025 February 18.

Abstract

INTRODUCTION

In rectal cancer, radical resection of the rectum with mesorectal excision along the mesorectal fascia has been performed to remove mesentery, lymphatics, and tumor deposits, which improves local recurrence rate, postoperative bleeding, and injury of the autonomic nerves [1]. However, it is hard to achieve the negative circumferential margin in locally advanced rectal cancer, in which the tumor extends beyond the fascia propria of rectum. Tumor involvement of the circumferential resection margin (<1 mm) is an independent prognostic factor associated with local recurrence and overall survival in rectal cancer [2]. To achieve the circumferential resection margin, chemoradiation therapy (CRT) has been developed since the late 1980s. In the latest consensus, neoadjuvant CRT (nCRT) is accepted for standard treatment in clinical stage II/III rectal cancer [3].

The nCRT reduces the local recurrence rate in advanced rectal cancer compared to postoperative CRT (6%–13%) [4,5]. Also, nCRT is known as increasing the rate of the anal sphincter saving surgery (39% vs. 19%) [6]. However, nCRT leads to acute toxicities such as diarrhea and skin problems due to radiation. There are long-term toxicities as radiation enteritis, anastomotic stricture, and urinary or sexual dysfunction [7].

Low rectal cancer is defined as tumors located less than 5 cm from the anal verge. The type of surgery for low rectal cancer is chosen by the location and clinical stage of the tumor according to the distance from the anal verge and relation to the anal sphincter. Ultra-low anterior resection, intersphincteric resection, or abdominoperineal resection (APR) are the surgical options for low rectal cancer. The tumor extended to the external anal sphincter or involved below or at the anal verge should be treated with APR [8,9]. And also, extremely low rectal cancer should achieve the oncologic satisfaction of the distal and circumferential resection margin by performing APR with cylindrical en-bloc resection of the tumor with removal of the levator ani muscle and external anal sphincter [10].

The study was designed from the question that the patient of extremely low rectal cancer requiring APR when initially diagnosed is really necessary for the nCRT, because this group of the patients can achieve curative resection margins with APR and there is no need to save the anal sphincter, which is the advantage of nCRT. Also, acute and long-term complications of radiation could impact the lifetime of the patients. This study aimed to analysis the oncological outcomes and postoperative morbidity of the patients with clinical stage II and III extremely low rectal cancer (<4 cm from the anal verge) requiring APR when initially diagnosed by dividing into two groups (nCRT group: patients who received nCRT; adjuvant chemotherapy alone group: patient who received adjuvant chemotherapy alone without nCRT after surgery).

METHODS

RESULTS

Patient characteristics

All patients were clinical stage II and III (clinical T3/4, N −/+). Patient characteristics were analyzed through a comparison of the adjuvant chemotherapy alone group (n=68) and nCRT group (n=20) (Table 1). Mean age, sex ratio, height, weight, body mass index (BMI), and American Society of Anesthesiologists scores, as well as initial carcinoembryonic antigen level, show significant differences between the two groups. Operation time, time to sips of water, time to liquid diet, time to soft diet, also did not significant different between the two groups. The blood loss was significantly higher in adjuvant chemo group compared to nCRT group (P=0.029). Total morbidity rate was 22.1% (n=15) in adjuvant chemotherapy alone group and 10.0% (n=2) in CRT group (P=0.095).

Table 1

Patient characteristics (n=88)

Pathologic results

The TNM stage, pT stage, pN stage, and pM stage were classified according to the American Joint Committee on Cancer (AJCC, 7th edition) [11]. In the distribution of TNM stage, complete response rate after nCRT was 20.0% (n=4) in nCRT group. The histological grades of differentiation, lymphovascular invasion rate, perineural invasion rate and harvested number of lymph nodes were not significantly different between the two groups. Proximal resection margin, distal resection margin and circumferential resection margin were not significantly different between the two groups (Table 2).

Table 2

Pathologic results of rectal cancer patient with requiring abdominoperineal resection

Oncologic outcomes and recurrent patterns of APR for low rectal cancer

The mean follow-up period was 59.7 months. The 5-year overall survival rate was 58.2% in adjuvant chemotherapy alone group and 85.5% in nCRT group (P=0.022). The 5-year disease-free survival rate was 60.0% in adjuvant chemotherapy alone group and 79.6% in nCRT group (P=0.042) (Fig. 1). Total recurrence rate was 45.6% (n=31) in adjuvant chemotherapy alone group and 15.0% (n=3) in nCRT group (P=0.010). The local recurrence rate was 10.3% (n=7) in adjuvant chemotherapy alone group and 5.0% (n=1) in nCRT group (P=0.469). The systemic recurrence rate was 35.3% (n=24) in adjuvant chemotherapy alone group and 10.0% (n=2) in nCRT alone group (P=0.029) (Table 3).

Fig. 1

Five-year oncologic outcomes of patient with rectal cancer requiring abdominoperineal resection: (A) disease-free survival rate and (B) overall survival rate. nCRT, neoadjuvant chemoradiation therapy.

Table 3

Recurrence patterns of abdominoperineal resection for rectal cancer

Univaiate and multicariate analysis of prognostic factors for DFS

In univariate analysis, advanced BMI (<25 kg/m²), N(+) stage, lymphovascular invasion, and circumferential resection margin invasion were analyzed as prognostic factors for disease-free survival. And nCRT was also analyzed as a prognostic factor in univariate analysis (hazard ratio, 0.22; 95% confidence interval, 0.05–0.93; P=0.039). In multivariate analysis, N(+) stage was a prognostic factor for disease-free survival (Table 4).

Table 4

Univariate and multivariate analysis of prognostic factor for 5-year disease-free survival of rectal cancer patient with requiring abdominoperineal resection

DISCUSSION

The CRT affects favorable to oncologic outcome in advanced rectal cancer referred as previous studies [12–14]. The Dutch Colorectal Cancer Group studied the preoperative radiotherapy versus surgery alone which showed the lower local recurrence rate in preoperative radiotherapy group compared to surgery alone group (2.4% vs. 8.4%, P<0.001) [15,16]. “Long-course” chemoradiotherapy was introduced in the German Rectal Cancer trial (CAO/ARO/AIO9). In this trial, it was reported that preoperative chemoradiation group had a low local recurrence rate of 6% and a high sphincter sparing operation of 39% [6,17].

Various complications of radiation therapy have been reported, including radiation-induced tissue damage, perineal wound complication, fecal incontinence, sexual dysfunction, radiation enteritis and anastomosis site adverse effects [18–21]. However, in the present study, the postoperative complication rate is not statistically different between nCRT group (10%, n=2) and adjuvant chemo group (22.1%, n=15). The nCRT group had just ileus (n=1) and wound infection (n=1). Since rectal cancer surgery must be performed in a narrow pelvic cavity, the risk of blood loss is somewhat high. It is generally believed that radiation therapy can increase the risk of bleeding during surgery [18–21], but in present study, the blood loss was higher in the adjuvant chemo group compared to nCRT group.

One of the important goals of nCRT in the treatment of rectal cancer is to improve oncologic outcomes through downstaging [12–14]. However, it was questionable whether nCRT would be effective in patients who need APR when initially diagnosed because this group of the patients can achieve curative resection margins with APR and is no need for saving the anal sphincter. Recently, one of the studies reported that not all patients with clinical stage II/III rectal cancer require the nCRT as the guideline of rectal cancer. This study reported that a subset group of clinical T3 rectal adenocarcinoma with good prognosis (distance to the mesorectal fascia greater than 1mm, T3 with less than 5 mm of extramural depth of invasion) could be treated by surgery alone rather than receiving the nCRT [22]. In other words, radiation therapy can be overtreatment in the treatment of rectal cancer. In another study, there was no difference in 5-year oncological outcomes between patients with clinical T3N0 rectal adenocarcinoma that need an APR who received nCRT and those who are not receiving nCRT [23].

However, the present study revealed significant the better oncologic outcome of nCRT group compared to adjuvant chemotherapy alone group (79.6% vs. 60.0%, P=0.042). The recurrence rate also was significantly different between the two groups (45.6% in adjuvant chemotherapy alone group vs. 15.0% in nCRT group, P=0.010). This is similar to the results of an existing large-scale study that showed that the received radiation had better oncologic outcomes than the group that did not receive radiation [24–27]. The adjuvant chemotherapy alone group has a high T stage and nCRT group has a relatively low T stage, it is thought that this is a radiation effect. Even if the clinical T stage is the same, receiving radiation before surgery will lower the T stage after surgery. Although T stage was not analyzed as an effect factor on disease-free survival in present study, it is thought to be a factor that has the potential to effect oncological outcomes. This also applied to N stage. The N stage is relatively high in the adjuvant chemotherapy alone group in the present study and is analyzed to effect factor on disease-free survival.

The present study is designed retrospectively, the patient’s selection bias could be affected to the results and small sized sample, single institution study is a limitation of present study. Nevertheless, the present study can be meaningful, considering that it was limited to patients requiring APR, and there are very few studies. Based on present data, the oncologic outcomes are better in nCRT compared to adjuvant chemotherapy alone after surgery in patients with extremely low rectal cancer requiring APR initially diagnosed, even if curative surgery is possible. It seems that more and large-scale study is needed on this.

Article information Continued