1. Disease-free survival was not impacted by the order in which chemoradiotherapy CRT and systemic chemotherapy is provided

2. Higher rectum preservation rate was found when providing CRT before systemic chemotherapy

Evidence Rating Level: 1 (Excellent)

Study Rundown: The treatment for locally advanced rectal adenocarcinoma includes total mesorectal excision (TME), which is invasive and can result in a decreased quality of life. Previous studies imply that variable neoadjuvant chemoradiotherapy treatment may permit organ preservation. This study aimed to determine whether patients who were treated with total neoadjuvant therapy (TNT) and either subsequent TME or selective watch-and-wait (WW) had an improved disease-free survival (DFS) when compared to the historical DFS associated with standard therapy (chemoradiotherapy (CRT), TME, post-operative adjuvant chemotherapy). Additionally, this study examined the difference in organ preservation rates between patients receiving either induction chemotherapy (INCT) followed by CRT or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). The DFS at 3 years for each of the two groups did not differ compared to the historical 3 year DFS rate (76% for both groups, compared to 75% for historical rate). Distant metastasis-free survival was 84% for the INCT group, and 82% for the CNCT group, while local recurrence-free survival was 94% for both groups. Rectum preservation rates (TME-free survival) were 47% for the INCT group and 60% for the CNCT group. Limitations to this study include the lack of a non-surgical arm as a comparator (likely owing to low accrual rates if there was) and comparison to historical DFS which is cautiously interpreted compared to direct comparison. Overall, a higher rectum preservation rate was found when providing CRT before systemic chemotherapy in patients receiving treatment for stage II or III rectal adenocarcinoma and cautiously comparable to historical DFS which may represent a potential non-surgical option for patients.

Click to read the study in The Journal of Clinical Oncology

Relevant Reading: Quality of life after sphincter preservation surgery or abdominoperineal resection for low rectal cancer (ASPIRE): A long-term prospective, multicentre, cohort study

In-Depth [randomized controlled trial]: This prospective, multi-centre, randomized and nonblinded clinical trial randomly assigned 324 adult patients who had stage II or III rectal adenocarcinoma to receive either induction chemotherapy (INCT) followed by chemoradiotherapy (CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT). The INCT-CRT group was comprised of 158 patients, while the CRT-CNCT group had 166. The treatments were either oral capecitabine or continuous infusion fluorouracil during radiotherapy. An additional treatment of either 8 cycles of fluorouracil, leucovorin, and oxaliplatin or 5 cycles of capecitabine and oxaliplatin were provided before or after CRT. Tumour response was determined at 8 +/- 4 weeks post-TNT. The 3-year DFS rates were 76% for both groups and did not differ from the historical rate; 95% confidence interval (CI), 69% to 84% for the INCT-CRT group and 95% CI, 69% to 83% for the CRT-CNCT group. The historical DFS was 75%. Local recurrence-free survival was 94% for both the INCT and CNCT groups (95%CIs are 89% to 99% and 90% to 98%, respectively). Distant metastasis-free survival was 84% for the INCT group (95% CI, 77% to 91%), and 82% for the CNCT group (95% CI, 75% to 89%). Rectum preservation rates were 47% for the INCT group (95% CI, 39% to 56%) and 60% for the CNCT group (95% CI, 52% to 68%).

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