This study established three main findings. First, perforation was found in approximately 4% of the patients diagnosed with stage IV CRC. Furthermore, approximately 80% of the patients underwent resection as a treatment for the primary tumor, and approximately 55% underwent chemotherapy as a treatment for distant metastases. Second, the prognosis was not associated with perforation in stage IV CRC. Third, the presence of peritoneal dissemination was a poor prognostic factor in patients with perforated stage IV CRC.
The incidence of perforation in CRC is reported to be 2.6–10% in all stages [10-13]. When limited to stage IV cases, perforation was observed in 3.2% of the cases reported in a study by Chen et al. [14]. In our study, perforation was observed in 3.7% of the patients, and the percentage of patients with stage IV CRC having colon perforation was not higher than that of those with the other stages.
The treatment of primary lesions includes primary tumor resection or colostomy. Takesue et al. noted that intestinal contents from the colostomy site could invade the perforation area, causing a persistent focus of infection, indicating that colostomy alone may not be sufficient to control intraperitoneal infection [15]. The rate of primary resection was high in this study similar to that in previous studies. However, although the principles of oncologic resection should usually be followed, medical comorbidities and septic status should be taken into account while selecting a technique aimed at enabling the initiation of postoperative chemotherapy as soon as possible, and there is no clear evidence as to which technique to choose [16].
Few comprehensive studies have provided details on chemotherapy for perforated cases of stage IV CRC. In a study by Gao et al., chemotherapy was introduced for distant metastases in approximately 65% of the cases [17]. In a study by Onozawa et al., chemotherapy was introduced in 64% of the cases, with oxaliplatin as the treatment of choice in all cases [18]. Our study was not significantly different from existing studies regarding the incidence of perforation in CRC, the rate of primary tumor resection, and the chemotherapy regimens. However, this study can be considered more inclusive because it collected data from all nine designated cancer hospitals across Fukushima, Japan.
The presence or absence of perforation did not affect the prognosis of patients with stage IV CRC. Previous studies have indicated that patients with CRC and perforation have a poor prognosis. For example, Onozawa et al. reported a median survival time of approximately 22 months [18], and Tan et al. reported a median survival time of approximately 13 months [19]. In comparison to these studies, our cohort included a relatively high number of patients who received systemic chemotherapy, resulting in a similar or better overall prognosis. The median survival time of patients for whom chemotherapy induction was possible was 24 months, which was significantly longer than that of the patients who received the best supportive care. Although there was no difference in survival according to the timing of induction of postoperative chemotherapy in this study, patients with stage IV CRC and colon perforation who can receive postoperative chemotherapy may have a survival rate comparable to that of patients without perforation.
We observed that patients with CRC with peritoneal metastases had a relatively poor prognoses. This is in line with the findings of previous studies [20-22]. It is relatively rare for simultaneous metastases with peritoneal dissemination to occur at the time of the diagnosis of perforation. Even if postoperative chemotherapy is administered in these cases, the prognosis will still be poor, with a median survival time of 11.5 months.
The present study has some limitations. First, the sample size was relatively small, and the confidence interval was relatively large due to the number of perforated cases. However, this study had the largest sample size compared to that in previously reported studies. However, further large cohort studies are needed to analyze the prognostic factors in patients with stage IV CRC and perforation. Second, this study included cases from 2008 to 2015, and chemotherapy selection was not based on the results of genetic tests for RAS and BRAF or any other markers. Therefore, further studies with a comparatively large number of cases that would consider chemotherapy selection and gene outcomes are required.
In conclusion, we examined cases of patients with stage IV CRC to determine their survival and treatment details and found that perforation does not seem to affect their prognosis. Once the acute phase of treatment is overcome, surgery and systemic chemotherapy may lead to a long-term prognosis similar to that of patients with normal CRC. The results of this study may assist clinicians engaged in the treatment of CRC with perforation in their practice.