Clinical and molecular diagnosis of pathologic complete response in rectal cancer

Abstract

The current standard approach to locally advanced rectal cancer involves pre-operative chemoradiotherapy followed by total mesorectal excision. This practice is supported by several studies that have demonstrated superior local control with this approach. This strategy, leads to a pathologic complete response (pCR) in a substantial proportion of patients treated with neoadjuvant therapy. Furthermore, pCR has been shown to be a reliable predictor of improved oncologic outcomes. This observation has led to an increased interest in the pursuit of identifying clinical, radiographic, pathologic and biochemical predictors of pCR. This review discusses the promising approaches to and most recent advancements in predicting pCR in rectal cancer.

Keywords:

• abdominoperineal resection
• chemoradiation
• clinical complete response
• ionizing radiation
• low anterior resection
• lymphocyte to monocyte ratio
• radiation therapy
• tumor regression grade

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Neoadjuvant chemoradiation (CRT) can help downstage rectal tumors before patients undergo surgery. Patients have a range of responses. While some patients may not respond to this treatment at all, others go on to achieve a pathological complete response (pCR). Determining where a patient falls in this spectrum can allow for a more efficient and effective treatment plan.

• Investigations into proteins and factors involved in cell cycle repair and apoptosis as predictors of pCR have been mostly unyielding. Levels of some proteins such as Ku protein and p21 have been associated with achieving pCR, further investigation is needed to determine the sensitivity and specificity of their predictive capacity in clinical practice. miRNAs are emerging as potential molecular predictors of pCR.

• Other clinical and biological features of the tumor can provide additional information about how tumors will respond to CRT.

• Host environment as measured by inflammatory markers also influences tumor response and, therefore, is an important consideration in creating a predictive model.

• The most promising predictive model is likely to be a combination of modalities. Together, tumor features, host environment, imaging results and clinical data may be able to capture the group of patients who will achieve pCR following CRT.

• The optimal time interval between completion of CRT and surgery has yet to be determined, but can play an important role in pCR rates.

• Currently, most studies carry substantial bias as a result of the heterogeneity of the patient population, tumors, treatment modalities and interval between CRT and surgery. An attempt at standardizing these factors would allow for a more accurate set of predictors of pCR.

Notes