The effect of neoadjuvant short-course radiotherapy and delayed surgery versus chemoradiation on postoperative outcomes in locally advanced rectal cancer patients – A propensity score matched nationwide audit-based study

Abstract

Objective: To investigate differences in postoperative outcomes between short-course radiotherapy and delayed surgery (SCRT-delay) and chemoradiation (CRT) in patients with locally advanced rectal cancer (LARC). Background: Previous trials suggest that SCRT-delay could serve as an adequate neoadjuvant treatment for LARC. Therefore, in frail LARC patients SCRT-delay is recommended as an alternative to CRT. However, data on postoperative outcomes after SCRT-delay in comparison to CRT is scarce. Methods: This was an observational study with data from the Dutch ColoRectal Audit (DCRA). LARC patients who underwent surgery (2014e2017) after an interval of 6 weeks were included. Missing values were replaced by multiple imputation. Propensity score matching (PSM), using age, Charlson Comorbidity Index, cT-stage and surgical procedure, was applied to create comparable groups. Differences in postoperative outcomes were analyzed using Chi-square test for categorical variables, independent sample t-test for continuous variables and Mann-Whitney U test for non-parametric data. Results: 2926 patients were included. In total, 288 patients received SCRT-delay and 2638 patients underwent CRT. Patients in the SCRT-delay group were older and had more comorbidities. Also, ICUadmissions and permanent colostomies were more common, as well as pulmonic, cardiologic, infectious and neurologic complications. After PSM, both groups comprised 246 patients with equivalent age, comorbidities and tumor stage. There were no differences in postoperative complications. Conclusion: Postoperative complications were not increased in LARC patients undergoing SCRT-delay as neoadjuvant treatment. Regarding treatment-related complications, SCRT-delay is a safe alternative neoadjuvant treatment option for frail LARC patients.

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

“…In the Stockholm III trial, the experimental arm showed an increasing pCR rate if surgery was delayed for four to eight weeks after SCRT, and it could reach 11.8%, compared to 2.1% in the SCRT with the immediate surgery group [11]. According to previous studies, an increasing pathological response was observed after SCRT with delayed surgery; however, the pCR rate was not greater than after conventional CRT [13,[20][21][22][23]. Moreover, the pooled results in this meta-analysis showed a significantly lower pCR rate compared to conventional CRT in patients who underwent SCRT followed by delayed surgery without consolidation chemotherapy.…”

“…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.…”

Impact of Age on Multimodality Treatment and Survival in Locally Advanced Rectal Cancer Patients

“…Elderly patients more often have a comorbidity, disability, geriatric diseases and consequently physical impairment, and they tend to undergo abdominal surgery less often because of the higher risk of perioperative complications [ 4 , 9 ]. In order to reduce these complications, multimodal therapy modifications are often used in elderly rectal cancer patients, such as reduction of chemotherapy dose or choosing short-course radiotherapy (RT) with delayed surgery [ 7 , 10 , 11 , 12 ]. Moreover, resection with colostomy formation without an anastomosis is often used to reduce postoperative risks of anastomotic leakage [ 13 , 14 , 15 ].…”