A Prospective Observational Study Comparing Long-Course Conventional Neoadjuvant Chemoradiotherapy with Short-Course Radiotherapy Followed by Consolidation Chemotherapy with Delayed Surgery in Locally Advanced Rectal Cancer

Abstract

Background Polish and Australian randomized studies compared short-course radiotherapy (RT) with immediate surgery and long-course chemoradiotherapy (CRT) with delayed surgery. In these studies, similar long-term survival and local control have been reported for both these approaches, but pathological complete response (pCR) is not better with short-course RT. Moreover, studies have shown better tumor downstaging with delayed surgery. In this context, the use of short-course RT with delayed surgery may have some advantages and needs to be tested in clinical trials. Patients and Methods This was a two-arm, prospective, observational study, in which preoperative short-course RT followed by two cycles of chemotherapy was compared with the conventional neoadjuvant CRT in locally advanced rectal cancer. The primary end points were the rate of complete response and toxicity profile. The secondary end points were the rate of R0 resection, overall survival, and progression-free survival. The data obtained from the two arms were analyzed using Pearson’s chi-square test to determine the statistical significance between the two treatment arms. Results The pCR rate was 6.7% in the study arm and 0 in the control arm (p = 0.343). The RO resection rates were 92.8 and 92.3% in the study and control arms, respectively. The rates of grade 3and 4 acute toxicity in the study and control arms were 14.2 and 61.5%, respectively (p = 0.011). The rates of grade 3 and 4 late toxicity in the study and control arms were 21.4 and 15.3%, respectively (p = 0.686). Conclusions The pCR rates and the late toxicities in both arms are comparable. The major advantages of the 5 × 5 Gy regimen with chemotherapy in a neoadjuvant setting are a significant reduction in acute toxicities and better patient compliance along with similar efficacy as that of the standard regimen.

Total neoadjuvant therapy versus standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis of 15 trials

“…Fig 1 shows the selection of relevant studies for inclusion in the meta-analysis. A total of 8 nRCTs with 1502 and 7 RCTs with 2077 enrolled patients enrolled patients were included for this meta-analysis [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] (Fig 1), there were 1812 patients in the TNT group and 1767 patients in the nCRT group. The main characteristics of the included studies are summarized in Table 1.…”

Preoperative short-course radiotherapy followed by consolidation chemotherapy for treatment with locally advanced rectal cancer: a meta-analysis

“…1 ). Four of these studies were RCTs [ 9 , 17 – 19 ], and the other three were non-RCTs [ 20 – 22 ].

Fig.

…”

“…2, which demonstrated risk of bias graph and risk of bias summary). The three non-RCTs were all cohort studies including two prospective study [ 20 , 22 ] and one retrospective study [ 21 ]. All three cohort studies scored at least 6 based on the Newcastle–Ottawa criteria (Additional file 1 : Table 1).…”

Neoadjuvant Short-Course Radiotherapy Followed by Consolidation Chemotherapy before Surgery for Treating Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis

“…Seventeen studies enrolling 7507 rectal cancer patients from 13 cohorts were included in this meta-analysis [13][14][15][16][20][21][22][23][24][25][26][27][28][29][30][31][32]. Of these, two studies reported different parameters of the same cohort [28,29], four studies reported survival outcomes at different time points [13,14,20,24], and one study reported an expanded enrollment including the preliminary cohort [31].…”

“…All studies were published between 2015 and 2022; of these, ten were RCTs, two were prospective studies, and five were retrospective studies. In summary, four cohorts from five studies compared SCRT with delayed surgery (n = 803) and conventional CRT (n = 4075) [13,[20][21][22][23], and nine cohorts from 12 studies compared SCRT followed by consolidation chemotherapy with delayed surgery (n = 1452) and conventional CRT (n = 1452) [14][15][16][24][25][26][27][28][29][30][31][32]. The characteristics of the included studies are summarized in Table 1.…”