AIM: To investigate the long-term oncologic outcomes and prognostic factors in patients with obstructive colorectal cancer (CRC) at multiple Japanese institutions.

METHODS: We identified 362 patients diagnosed with obstructive colorectal cancer from January 1, 2002 to December 31, 2012 in Yokohama Clinical Oncology Group’s department of gastroenterological surgery. Among them, 234 patients with stage II/III disease who had undergone surgical resection of their primary lesions were analyzed, retrospectively. We report the long-term outcomes, the risk factors for recurrence, and the prognostic factors.

RESULTS: The five-year disease free survival and cancer-specific survival were 50.6% and 80.3%, respectively. A multivariate analysis showed the ASA-PS (HR = 2.23, P = 0.026), serum Albumin ≤ 4.0 g/dL (HR = 2.96, P = 0.007), T4 tumor (HR = 2.73, P = 0.002) and R1 resection (HR = 6.56, P = 0.02) to be independent risk factors for recurrence. Furthermore, poorly differentiated cancers (HR = 6.28, P = 0.009), a T4 tumor (HR = 3.46, P = 0.011) and R1 resection (HR = 6.16, P = 0.006) were independent prognostic factors in patients with obstructive CRC.

CONCLUSION: The outcomes of patients with obstructive CRC was poor. T4 tumor and R1 resection were found to be independent prognostic factors for both recurrence and survival in patients with obstructive CRC.

Colorectal cancer (CRC) is the third most common cancer in Japan, and the incidence of CRC has been increasing rapidly. CRC is difficult to diagnose due to it early atypical symptoms and signs. Around 7%-16% of patients with colorectal malignancy present with acute colorectal obstruction[1-3]. It is generally accepted that right sided obstructive CRC can best be treated by right hemicolectomy with ileocolic anastomosis. On the other hand, the optimal treatment for left-sided obstructive CRC remains controversial[4-7]. The treatment options range from an emergency radical operation, such as Hartmann’s procedure, to bowel decompression using metallic stents or transanal tube or proximal diversion with a subsequent staged resection. The choices of surgical intervention for obstructive CRC vary greatly, according to the tumor location, general condition of the patients, and the experience level of the surgeons[8]. Therefore, It has been reported that CRC patients with obstruction have an advanced stage and worse long-term survival compared to non-obstructive CRC[3,9-11]. Although the negative impact of obstruction on the postoperative outcomes has been well documented, few studies have examined the outcomes of obstructive CRC patients in Japan[11-13]. Furthermore, the risk factors for recurrence and the prognostic factors are unclear owing to the small number of patients in previous study.

The aim of this study is to investigate the long-term oncologic outcomes and prognostic factors in patients with obstructive CRC at multiple Japanese institutions.

Three hundred and sixty-two patients who were diagnosed to have obstructive colorectal cancer from January 2002 to December 2012 at the Yokohama Clinical Oncology Group’s Department of Gastroenterological Surgery (10 institutions) were enrolled. Obstructive CRC was diagnosed based on medical history, physical examination, abdominal computed tomography (CT), and colonoscopy, and the surgical findings. We first performed emergency decompression of bowel obstruction by ileostomy/colostomy or the insertion of a decompression tube, or emergency resection of the primary lesion. The type of decompression method was chosen according to the surgeon’s judgment and preference. Patients with distant metastatic lesions (n = 103), who only underwent stoma creation and best supportive care (n = 23), stage I (n = 2) were excluded from this study. As a result, 234 patients who underwent surgical resection were analyzed retrospectively (Figure 1). The prognostic factors influencing survival and risk factors for recurrence were analyzed.

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Figure 1 Study flowchart.

Clinicopathological information was obtained from the medical records of the patients including gender, age, The American Society of Anesthesiologists (ASA)-physical status (PS), serum albumin, CEA, preoperative decompression, location of the tumor, tumor size, differentiation of the tumor, depth of the tumor, intramural lymphatic invasion, intramural vascular invasion, lymph node dissection, number of lymph nodes harvested, lymph node involvement, postoperative complication, anastomotic leakage, curability, and adjuvant chemotherapy. There were missing values for BMI in 13 patients, for serum albumin in 14 patients, for CEA in 19 patients, for tumor size in 4 patients, for lymphatic invasion in one patient and for harvested lymph nodes in 10 patients because this was a retrospective study.

Japanese D3 lymphadenectomy is equivalent to complete mesocolic excision (CME) with central vascular ligation (CVL)[14]. D2 lymphadectomy includes pericolic and intermediate nodes region, and D0-1 includes only pericolic nodes region.

In the present study, we evaluated the long-term oncologic outcomes and prognostic factors in patients with obstructive CRC in multiple Japanese institutions. Most previous studies have reported that patients with obstructive CRC have significantly poorer oncologic outcomes than patients with nonobstructive CRC[9,11,12,17]. Obstructive tumors have been reported to have a more advanced stage than nonobstructive tumors[11,18]. The reported 5-year survival ranges between 36% to 64.6% in patients with obstructive CRC[11,17,19,20]. Our retrospective data showed 5-year CSS to be 80.3%, which was higher than the previously reported findings. One reason for the good outcomes might be that Japanese standard surgical procedures include complete tumor resection and extended D2/D3 lymph node dissection, including the pericolic, intermediate and most central lymph nodes. West et al reported that the Japanese surgical procedures as well as CME with CVL eradicates tumors more effectively than the conventional procedures[14]. In our study, D2/D3 lymph node dissection was performed in about 70% of all patients.

Several authors have suggested preoperative obstruction to be a prognostic factor in CRC[12,17]. However, there are few data concerning the prognostic factors associated with obstructive CRC patients[4,19]. Jiang et al[4] reported a delayed resection to provide a better oncologic outcome than a primary resection for obstructive left-sided colorectal cancer. Other authors have showed that decompression followed surgery is better than emergency surgery in terms of the primary anastomosis rate, the stoma rate, the morbidity rate, the successful treatment of the patient’s comorbidities, and preparation for elective surgery[21,22]. According to our results, however, no difference in the prognosis was found in regard to whether patients underwent preoperative decompression or not, It therefore remains inconclusive as to which approach may be superior to the other.

Malignant obstruction can occur in any part of the colon and rectum, however, the risk varies at different locations. In present study, 70.5% of the obstructive CRC occurred in the left-sided colon and most of them occurred in the sigmoid colon. This tumor distribution is similar to what has been reported by other series[11,19]. Our results showed that the prognosis was not different between right-sided and left-sided obstructive CRC.

Obstructive tumors are reported to be associated with a more advanced stage than nonobstruction[11,18]. Our data showed 53.4% to have T4 tumors, and 51.7% had positive lymph nodes. This is one of the reasons why obstructive CRC has a worse prognosis. In present study, especially, a T4 tumor was found to be a risk factor for recurrence in patients with obstructive CRC.

Seventy-one patients had a recurrence of the disease as the first event in our study. The distant metastasis rate is significantly higher in obstructed patients when compared with nonobstructed patients[17]. The common sites of recurrence were the liver (11.5%) and lung (9.4%), which were similar to previous reports[23]. An interesting finding in the present study is that patients with obstructive CRC showed a higher rate of peritoneal dissemination (9.0%) than previously reported (1.9%-3.5%) in nonobstructive CRC[24,25]. These findings suggested that obstructive CRC was locally advanced cancer consisting of T4 tumors and which may be unexpectedly exposed during R1 resection. Therefore, reducing the rate of performing R1 resection might be a key to achieving improved surgical results.

In our study, patients with stage II disease and those with stage III disease had similar poor outcomes in terms of the 5-year DFS and CSS. This finding suggests that lymph node involvement, which is a well-known prognostic factor, does not have any significant impact on the outcomes in patients with obstructive CRC. One of the reasons for this finding is due to the fact that Japanese standard lymph node dissection procedures for advanced colorectal cancer include D2/D3 lymph node dissection, which is nearly the same method as that performed for CME and CVL[14]. In our clinical oncology group, lymphadenectomy for colorectal cancer was routinely performed during the study period. Therefore, a T4 tumor was identified as the most important prognostic factor, in which the 5-year DFS and OS were 38.7% and 60%, respectively.

In the present study, a lower level of albumin was also a predictive factor for survival. The serum albumin levels have recently been studied as the Glasgow Prognostic Score (GPS), based on a combination of albumin and C-reactive protein (CRP). Several authors have revealed the GPS to have prognostic value in patients with advanced colorectal cancer[26,27]. However, we failed to collect data of CRP because this was a retrospective analysis. It is estimated that low albumin levels are associated with a decreased survival time because a low albumin level likely reflects some type of systemic compromise[28].

Our results demonstrated that poorly differentiated tumors or mucinous differentiated tumors are also predictive factors for survival. Histologically, poorly differentiated CRC represents from 4.8% to 23.2% of all colorectal cancers[29]. The rate of poorly differentiated tumors was not higher than that described in previous reports. Poorly differentiated cancers have been linked to adverse prognoses in many studies[30].

Recently, several authors have suggested the feasibility of performing preoperative chemotherapy without the routine use of radiation therapy for locally advanced rectal cancer and a high R0 resection rate[31,32]. Furthermore, the FOxTROT Collaborative Group demonstrated the feasibility of performing preoperative chemotherapy for locally advanced colon cancer[33]. Our result suggested that obstructive colorectal cancer is also locally advanced cancer. Therefore, preoperative chemotherapy after the decompression of bowel obstruction may also be useful for the management of obstructive colorectal cancer.

Our retrospective study had several important limitations. First, there were several missing data and we could not obtain the clinical course related to the treatment of patients after recurrence. Second, the adjuvant therapy, which affects the outcome, was not uniform.

In conclusion, in addition to generally accepted knowledge, we found that T4 tumor and R1 resection were prognostic factors for both recurrence and survival. These results suggested that a curative resection of the tumor is very important and that systemic treatment for preventing distant metastasis, such as peritoneal dissemination associated with T4 tumors, is necessary in patients with obstructive colorectal cancer.

We are grateful to the many members of the Yokohama Clinical Oncology Group and Dr. Mari S Oba (Department of Biostatistics, Yokohama City University) whose comments were extremely valuable throughout the course of our study.