Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

Abstract

The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm.

Prognostic Significance of Tumor Regression in Locally Advanced Rectal Cancer after Preoperative Radiochemotherapy

“…10,14 Complete pathologic response (pCR), which means stage ypT0N0 or in other words no tumor cells in resected surgical specimen, can be detected in 7-30% of patients with locally advanced rectal cancer, treated with neoadjuvant therapy. 2,7,8 Our results are comparable with those studies, as we detected 14.8% of pCR. Using statistical analysis, we found out that pCR means excellent prognosis, as 5-year survival rate turned out to be >90% (p = 0.001).…”

“…Using statistical analysis, we found out that pCR means excellent prognosis, as 5-year survival rate turned out to be >90% (p = 0.001). Meta analysis of 12 larger studies worldwide reports 90.2% 5-year survival rate in pCR patients (p = 0.0001) 15 ; similar percentage (90% or more) is mentioned in various other studies 2,4,16 , while others failed to prove relation between pCR and better survival. 15 In the literature, strong evidence exists that patients with pCR have very few local recurrences (2-5% in 5 years) and that there are statistically significant differences, if groups of patients with pCR are compared to those who failed to respond to preoperative treatment.…”

“…Various trials tried to find possible biological markers for pCR. 2,11,19 Considering data exist about excellent prognosis in patients with pCR but a question about most appropriate therapy in patients with pCR is still unanswered. Could neoadjuvant radiochemotherapy without surgery suffice or might less extensive operation, for example transanal local excision be a better option for them?…”

“…Moreover, patients with complete pathologic response to neoadjuvant treatment have much better prognosis than patients with less or no response. 2 The rate of response is better in neoadjuvant CRT compared with long course RT, and possibly absent in short course RT with immediate surgery. In fact, maximal response of the radiation occurs only several weeks after its end.…”

Organ Saving Treatment of Rectal Cancer

“…Таким образом, целесообразность выполнения хирургического вмешательства у пациентов с полной клинической регрессией опухоли является спорной [7]. Альтернативой этому, по немногочисленным дан-ным литературы, является выжидательная тактика с активным динамическим наблюдением (watch and wait approach) [8].…”