Assessment of clinical and pathological complete response after neoadjuvant chemoradiotherapy in rectal adenocarcinoma and its therapeutic implications

Because almost one fourth of patients with rectal adenocarcinoma (RC) achieve pathological complete response (pCR) after neoadjuvant chemoradiation therapy (CRT), having significantly higher survival rates than those without pCR, the assessment of pCR represents a highly important challenge nowadays. Moreover, recent studies revealed that organ-sparing approaches could represent a reasonable alternative to radical surgery (RS) in patients with pCR, achieving similar long-term outcomes with lower morbidity rates and improved quality of life. Unfortunately, the decision of a rectum-sparing approach should be based only on clinical, endoscopic (with or without biopsy) and radiological methods, that must accurately predict the pCR after neoadjuvant CRT, in the absence of the pathological examination of the RS specimen. Thus, a surrogate parameter called clinical complete response (cCR) emerged, to assess the results of neoadjuvant CRT. The evolving accuracy of recent endoscopic and imaging methods in assessment of cCR and their predictive value for estimation of pCR achievement are presented. The usefulness of combining the results of these evaluation methods (resulting in the development of few nomograms) for a more accurate estimation of pCR, as well as the predictive factors for pCR achievement are also debated. Moreover, the changing landscape of therapeutic approaches based on cCR assessment is discussed, emphasizing the advantages and pitfalls of rectum-sparing approaches, compared to RS. Because there are no reliable methods to estimate with 100% accuracy the pCR, the only way to decrease as much as possible the risk of misleading treatment choices is the multidisciplinary team-based decision.