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    • br Neoadjuvant chemotherapy regimens infusional fluorouracil

    2018-10-22


    Neoadjuvant chemotherapy regimens (infusional 5-fluorouracil, oral 5-fluorouracil, and other agents) Adding 5-fluorouracil (5-FU) CT to RT in gastrointestinal cancer treatment to improve overall survival (compared with RT alone) was approved in 1969. To determine the effect of neoadjuvant CT, the European Organization for Research and Treatment of Cancer 22921 randomized controlled trial reported that combining CT with RT preoperatively could improve pathologic response rates and the downsizing effects. Therefore, to decrease the tumor bulk to improve the likelihood of sphincter preservation, using long-course instead of short-course CRT is a more rational choice, which is similar to a finding reported in the German Rectal Cancer Study trial. Regarding the choice of CT, infusional 5-FU/leucovorin with RT is currently the gold standard. Oral 5-FU (uracil, tegafur, and capecitabine) with RT has been proven to have therapeutic effects similar to those of infusional 5-FU. The addition of other chemotherapeutic or target therapy agents, including oxaliplatin, irinotecan, bevacizumab, and cetuximab, is currently being investigated in randomized controlled trials, but it is not considered in standard treatment plans because of higher toxicities, despite similar pathologic complete response (PCR) rates. Notably, in 2015, the German Rectal Cancer Study Group published remarkable results for a randomized controlled trial, stating that if oxaliplatin were incorporated into both neoadjuvant 5-FU-based CRT and adjuvant CT for patients with locally advanced rectal cancer, better disease-free survival could be achieved with acceptable treatment-related toxicity and death. Because this large randomized controlled trial was performed by an acclaimed study group, we believe that more oxaliplatin-related neoadjuvant trials will be reported by surgical and oncological tubulin in the future. Accordingly, based on our personal series, the use of infusional 5-FU and a concomitant RT protocol can be expected to lower treatment toxicity without compromising the desirable treatment effects of neoadjuvant CRT in standard low rectal cancer patients. Finally, the choice of whether postoperative adjuvant CT should be given is controversial, particularly for ypT0-2N0 patients. A meta-analysis of the Cochrane review demonstrated that adjuvant CT after rectal cancer resection improved local control of the disease but not specifically under the premise of neoadjuvant CRT. To date, randomized trials targeting this issue do not support the use of postoperative CT after neoadjuvant CRT for operable rectal cancer. Additional appropriately designed studies are necessary to address this concern in the future.
    Total mesorectal excision, minimally invasive surgery, and pelvic lymph node dissection TME is the cornerstone of curative treatment for low rectal cancer patients. The natural barriers of the bony structure and pelvic organs render low pelvic dissection difficult, even in open surgery. With rapid advancements in technology, higher magnification and a clearer optic view can be obtained in minimally invasive surgery (MIS). In addition, faster tissue-dividing and safer vessel-sealing ability could be achieved with new ultrasonic or bipolar energy equipment. Thus, currently, TME with MIS in a narrow male pelvis can be performed safely with low risk of morbidity. Although relatively new, the prevalence of MIS in rectal cancer surgery has increased rapidly worldwide. Randomized controlled trials and many retrospective studies have confirmed that MIS, either laparoscopic or robotic, can achieve comparable surgical quality with similar morbidity and mortality to open surgery. Another aspect of surgery is about pelvic lateral lymph node dissection, which is an essential part of surgery for low rectal cancer in Japan, although it is not frequently performed in Taiwan. According to reports from both Western societies and Japan, lateral lymph node dissection is equivalent to CRT in terms of local control of the disease. A noninferiority trial (JCOG0212) was conducted in Japan to examine the effectiveness of TME and lateral lymph node dissection compared with TME alone. The results of that study are expected to clarify the therapeutic benefits and long-term outcomes of this surgical procedure. By contrast, rectal cancer surgery has included the so-called “down-to-up” approach since the first report of transanal TME (or reverse TME) in 2010, which claimed it to be an easier surgical approach with shorter operation time for low rectal cancer. Increasingly more medical facilities have published reports of the short-term outcomes of this reversed procedure regarding specimen quality and operative morbidities; basically, perioperative outcomes are comparable with those of traditional laparoscopic surgery. More studies are currently underway to confirm the safety and feasibility of this procedure.