Neoadjuvant Treatment in Upper Rectal Cancer Does Not Improve Oncologic Outcomes But Increases Postoperative Morbidity

Abstract

Background/Aim: Neoadjuvant chemoradiation/ radiation therapy in locally advanced (LA) upper rectal adenocarcinoma management remains unclear. The aim of this study was to compare outcomes between neoadjuvant chemoradiation therapy (CRT) and upfront surgery (US). Patients and Methods: A total of 127 patients were retrospectively included from 5 centers (79 treated with US and 48 with CRT). CRT and US groups were compared in terms of postoperative complications and long-term oncological and functional results. Results: Total mesorectal excision (TME) was more frequent in CRT (58% vs. 20% in US, p<0.001). CRT was associated with more overall and severe postoperative complications (60% vs. 30%, p<0.001 and 17% vs. 1%, p=0.002, respectively), and was the only risk 2), p=0.007]. Five-year overall survival and 5-year recurrence-free survival were similar between CRT and US (96% vs. 91% p=0.256 and 85.4% vs. 85%, p=0.495). The functional results were similar between the two groups. Conclusion: CRT did not improve long-term oncological outcomes in patients with LA upper rectal adenocarcinoma, but increased postoperative complications compared with US.Management of locally advanced (LA) rectal cancer is based on a multimodal approach including radiation therapy, chemotherapy followed by total (TME) or partial mesorectal excision (PME) (1-5). Although management of low and mid LA rectal cancer is now well established and standardized, upper rectal cancer management remains debated. To date, very few studies have analyzed the impact of neoadjuvant treatment in patients with upper rectal cancer, and conflicting results have been reported (6)(7)(8)(9)(10)(11). The main reasons are: 1) most of the trials reporting the effectiveness of TME and neoadjuvant treatment have included upper rectal cancer along with mid and low rectal tumors. Consequently, there is a lack of evidence regarding possible benefit of neoadjuvant treatment specifically in patients with LA upper rectal cancer (2, 12); 2) Most of the retrospective studies have compared long-term outcomes of sigmoid and/or upper rectal cancer to mid and/or low rectal cancer. This comparison could be considered irrelevant, because rectal cancer location is known to significantly affect oncological outcomes (13). Because of the great heterogeneity of the reported series, the ESMO Society for Medical Oncology states that upper rectal cancers do not benefit from preoperative neoadjuvant treatment and should be treated as colon cancer. However, many authors disagree and consider that patients with cT4 tumors of the upper rectum could 3579

Efficacy&nbsp;of&nbsp;Neoadjuvant&nbsp;Therapy&nbsp;in&nbsp;Improving&nbsp;Long-Term&nbsp;Survival&nbsp;of&nbsp;Patients&nbsp;with&nbsp;Resectable&nbsp;Rectal&nbsp;Cancer: a&nbsp;Meta-Analysis

“…In terms of tumor location, the data of our study showed that compared with the control group, patients with resectable mid/low rectal cancer had better 5-year OS and DFS after neoadjuvant therapy, whereas the resectable upper rectal cancer showed no bene t in the 5-year OS (HR: 0.95, 95% Cl: 0.87-1.02). The conclusion that neoadjuvant CRT and neoadjuvant SCRT may not be suitable for the treatment of upper rectal cancer was consistent with the views of Tabchouri et al [49] and Rades et al [38]. The possible reason for this is that the location of mid/low rectal cancer was relatively xed, whereas upper rectal cancer was more active and had poor therapeutic effect.…”

Efficacy&nbsp;of&nbsp;Neoadjuvant&nbsp;Therapy&nbsp;in&nbsp;Improving&nbsp;Long-Term&nbsp;Survival&nbsp;of&nbsp;Patients&nbsp;With&nbsp;Resectable&nbsp;Rectal&nbsp;Cancer: A&nbsp;Meta-Analysis

“…In terms of tumor location, the data of our study showed that compared with the control group, patients with resectable mid/low rectal cancer had better 5-year OS and DFS after neoadjuvant therapy, whereas the resectable upper rectal cancer showed no bene t in the 5-year OS (HR: 0.95, 95% Cl: 0.87-1.02). The conclusion that neoadjuvant CRT and neoadjuvant SCRT may not be suitable for the treatment of upper rectal cancer was consistent with the views of Tabchouri et al [49] and Rades et al [38]. The possible reason for this is that the location of mid/low rectal cancer was relatively xed, whereas upper rectal cancer was more active and had poor therapeutic effect.…”

The oncological outcomes of postoperative radiotherapy in patients with stage II and III upper rectal cancer

“…Moreover, although statistical significance was not attained, local recurrence was prevented by RT > 50 Gy (5-year local recurrence-free rate: 85.7% vs. 92.4%). Tabchouri et al, found that neoadjuvant CRT did not improve the long-term oncological outcomes of patients with locally advanced upper rectal adenocarcinoma and, in fact, increased postoperative complications [27]. Our postoperative CRT complication rates were very low.…”