Prognostic value of tumor shrinkage versus fragmentation following radiochemotherapy and surgery for rectal cancer

Abstract

Most patients with rectal cancer receive neoadjuvant radiochemotherapy (RCT), causing a variable decrease in tumor mass. We evaluated the prognostic impact of pathologic parameters reflecting tumor response to RCT, either directly or indirectly. Seventy-six rectal cancer patients receiving neoadjuvant RCT between 2006 and 2009 were included. We studied the association between disease-free survival (DFS) and the "classical" clinicopathologic features as well as tumor deposits, circumferential resection margin (CRM), Dworak regression grade, and tumor and nodal downstaging. Patients with tumor downstaging had a longer DFS (p = 0.05), indicating a more favorable prognosis when regression was accompanied by a decrease in tumor infiltrative depth, referred to as tumor shrinkage. Moreover, tumor downstaging was significantly associated with larger CRM and nodal downstaging (p = 0.02), suggesting that shrinkage of the primary tumor was associated with a decreased nodal tumor load. Higher Dworak grade did not correlate with tumor downstaging, nor with higher CRM or prolonged DFS. This implies that tumor mass decrease was sometimes due to fragmentation rather than shrinkage of the primary tumor. Lastly, the presence of tumor deposits was clearly associated with reduced DFS (p = 0.01). Assessment of tumor shrinkage after RCT via tumor downstaging and CRM is a good way of predicting DFS in rectal cancer, and shrinkage of the primary tumor is associated with a decreased nodal tumor load. Assessing regression based on the amount of tumor in relation to stromal fibrosis does not accurately discern tumor fragmentation from tumor shrinkage, which is most likely the reason why Dworak grade had less prognostic relevance.

How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement

“…The limited size of the fragments is below the power of resolution on imaging and surgical treatment might be irradical, resulting in local recurrences. Three recent studies (289 patients with locally advanced rectal cancer) [68][69][70] showed that fragmentation was present in 40% of cases, while in a study of 45 cT3 patients from Cleveland [44] 80% of cases showed fragmented response. Fragmentation or scattering of tumour cells also causes a clear discrepancy between macroscopy and microscopy [71].…”

“…In a careful description of the findings in 27 patients (49%), it was shown that fragments could be found up to 3 cm from the ulcer, in all directions (proximal, distal and lateral). Fragmentation is associated with more frequent residual lymph node metastases, less downstaging, positive resection margins and a poor outcome [68][69][70]. When TRG was applied to these cases [69], there was no prognostic impact.…”

“…Fragmentation is associated with more frequent residual lymph node metastases, less downstaging, positive resection margins and a poor outcome [68][69][70]. When TRG was applied to these cases [69], there was no prognostic impact. However, one could argue that these were cases with intermediate TRG grades.…”

“…Local regrowth in smaller tumours (cT1/T2) was significantly lower, 19%. In the five series [44,[68][69][70][71] that describe fragmentation as a response mechanism (total number of patients 460), only limited information is presented about stage in relation to response mechanism. Early stage tumours (cT2) show fragmentation in 25% compared to 44% in cT3 tumours [68].…”

Prognostic influence of histopathological regression patterns in rectal adenocarcinoma receiving neoadjuvant therapy

“…We feel that the explanation for this apparent discordance between MRI estimation of response and histopathological regression can be the pattern of regression. A recent report by Hav et al (17) has evaluated this issue in a sample of 76 rectal carcinoma patients receiving CRT. These authors concluded that tumor shrinkage is prognostically different from tumor fragmentation and this can explain the worse predictive power of regression compared to down-staging.…”