Recent advances of neoadjuvant chemoradiotherapy in rectal cancer: Future treatment perspectives

Abstract

Neoadjuvant chemoradiotherapy (nCRT) has been widely used as a multidisciplinary approach for stage II/III rectal cancer. However, its safety and efficacy are controversial because previous studies have shown conflicting outcomes. The present review aimed to elucidate the benefits and limitations of nCRT for patients with rectal cancer. Future perspectives of nCRT are also described. No recent randomized trials have been able to show a survival benefit, although many studies have demonstrated good local control with the use of fluoropyrimidine (e.g. 5‐fluorouracil [FU] or capecitabine)‐based nCRT. Addition of oxaliplatin (OX) to FU‐based nCRT might improve overall survival by preventing distant metastasis, as shown in recent meta‐analyses. However, control of adverse effects is an important concern with this treatment. New treatment strategies such as nonoperative management (watch and wait policy) and total neoadjuvant therapy (TNT) are promising, but the establishment of reliable diagnostic methods of metastasis is essential. Development of new biomarkers is also necessary to select patients who are more likely to benefit from nCRT.

Intratumoural-infiltrating CD4 + and FOXP3 + T cells as strong positive predictive markers for the prognosis of resectable colorectal cancer

“…Cancer tissue specimens were obtained from a consecutive series of 342 patients who underwent curative resections for CRC at the Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Japan, from 1993 to 2012. Patients with a tumour below the peritoneal reflection were excluded from the study to exclude lower rectal cancer patients, whose preoperative treatment as neoadjuvant chemo-(radiation) therapy has been differ from colon cancer upper the peritoneal reflection, 27 and those who died from other diseases or stopped follow-up within 5 years after resection were excluded to determine the 5-year disease-specific survival (DSS) and relapse-free survival (RFS). The patient demographics and baseline characteristics are listed in Table 1.…”

Evaluation and Predictive Factors of Complete Response in Rectal Cancer after Neoadjuvant Chemoradiation Therapy

“…In their research, tumors with KRAS codon 13 mutations didn't achieve pCR and also had a higher incidence of the TP53 mutation compared with tumors with other KRAS mutations. These results suggested that mutations in different KRAS codons may have different effects on the resistance of rectal cancer to nCRT and that the rectal cancers carrying TP53 and KRAS mutations have a lower opportunity to respond to nCRT compared with wild-type tumors [83,112].…”

“…Thus far, the optimal interval is considered to be 6-8 weeks. The rationale for this interval is that it is expected to increase the pCR rate and reduce postoperative complications [82][83][84].…”

“…Several researches have assessed the association of neutrophil-to-lymphocyte ratio (NLR) with response to nCRT [83,105,138]. Caputo et al in 2016 assessed NLR and derived neutrophil-to-lymphocyte ratio (d-NLR) before and after nCRT in rectal cancer patients.…”

Molecular and Kinetic Analyses of Circulating Tumor Cells as Predictive Markers of Treatment Response in Locally Advanced Rectal Cancer Patients

“…In addition, considering that the majority of patients will not respond to NCRT, it is extremely important to identify these patients, in an attempt to optimize the response to these patients. As there are no randomized phase-III studies to date, comparing this strategy with isolated induction chemoradiotherapy, it becomes fundamental to identify a biomarker capable of selecting patients for these approach [12,13,14].…”