Rectal cancer (RC) is one of the main causes of cancer-related mortality worldwide, accounting for approximately 860,000 deaths annually1). In Japan, the standard treatment for locally advanced RC without distant metastasis has been total mesorectal excision (TME)2), plus postoperative adjuvant chemotherapy without preoperative treatment. On the other hand, preoperative CRT followed by surgery for rectal cancer has been the standard treatment in the Western countries for a long time, a position supported by the Swedish Rectal Cancer Trial, which showed that preoperative short course radiotherapy (SCRT) was more effective than surgery alone3) and clinical trial data from Sauer et al. showing fewer adverse events and better local control (LC) in the preoperative chemoradiotherapy group compared to the postoperative group CRT group4). However, there is still debate over improvement in overall survival (OS) with the addition of SCRT or CRT compared to surgery alone4-7).
In recent years, advances in systemic chemotherapy for colorectal cancer have significantly improved local tumor reduction as well as overall survival. Preoperative reduction of tumor size may increase the rate of R0 resection and the likelihood of securing an adequate circumferential resection margin (CRM). In addition, compliance with NAC may be better than with conventional adjuvant chemotherapy8). With this in mind, the concept of using chemotherapy as a preoperative treatment could be considered an acceptable strategy for poor risk RC treatment in Japan, where preoperative treatment has not been commonly used. However, in Western countries, preoperative (neoadjuvant) chemotherapy (NAC) without radiotherapy (RT)/CRT for poor-risk RC is considered unacceptable.
Combinations of capecitabine and oxaliplatin, known as the CAPOX regimen, have been established for the treatment of unresectable/metastatic RC and are used as adjuvant chemotherapy for colorectal cancer. According to a previous report, the CAPOX response rate for metastatic RC was approximately 47.0% and progression-free survival was 8.0 months9). CAPOX is one of the main first-line regimens for advanced/recurrent rectal cancer and is valued as a port-less regimen10), thus it is suitable for NAC with a limited treatment period. The main adverse event (AE) is peripheral neuropathy, which may persist after treatment, leading to questions about the acceptability for NAC. Therefore, NAC with CAPOX for locally advanced RC in Japan may be a potentially therapeutic option to improve OS and the LC of locally advanced RC. However, there are two unresolved issues with NAC:1) The possibility of the tumor becoming unresectable due to tumor growth during NAC, and 2) The possibility that surgery cannot be performed safely in time due to NAC-associated AEs. In order to address these issues, we retrospectively reviewed the consecutive NAC cases performed at our hospital, with the aim of examining the safety and short-term results of NAC for locally advanced RC.