Tumor deposits in rectal adenocarcinoma after neoadjuvant chemoradiation are associated with poor prognosis

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Abstract

Although tumor deposits have been associated with poor prognosis in colorectal carcinoma, the prevalence and clinical significance of tumor deposits in rectal adenocarcinoma following neoadjuvant chemoradiation are relatively unexplored. The aims of this study are to assess the clinical significance of tumor deposits in rectal adenocarcinoma patients, including those receiving neoadjuvant therapy. Pathology slides and medical records from 205 consecutive patients who underwent resection for rectal adenocarcinoma between 1990 and 2010 at a single tertiary care center were reviewed. Patients with tumor deposits had higher tumor grade (P=0.006) and worse tumor stage (P<0.001) at presentation than patients without tumor deposits. Among 110 patients who underwent neoadjuvant chemoradiation, tumor deposits were associated with higher rates of lymph node involvement (P=0.035) and distant metastases (P=0.006), and decreased survival (P=0.027). These patients had a trend toward lower treatment response scores (P=0.285) and higher local recurrence (P=0.092). Of 52 patients with tumor deposits, those who underwent neoadjuvant chemoradiation had significantly worse pretreatment stage by endoscopic ultrasound (P<0.001) but interestingly had significantly lower rates of lymphovascular invasion on resection (P<0.001) compared with those who had not received neoadjuvant chemoradiation. Despite treatment with neoadjuvant chemoradiation, tumor deposits were present in over one-fifth of rectal adenocarcinoma patients. Overall, the outcome of patients with tumor deposits in treated and untreated patients were similar, however the association of tumor deposits with deeply invasive tumors and less tumor regression when comparing with treated patients without tumor deposits raises the possibility that these tumors could have a more aggressive biology, possibly explaining the association of tumor deposits with higher rates of recurrence and lower survival after neoadjuvant chemoradiation. Overall, tumor deposits appear to be a poor prognostic marker among rectal adenocarcinoma patients following neoadjuvant chemoradiation and may identify a subset of patients who require aggressive adjuvant therapy to prevent recurrence.

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Most cited references 15

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A Proportional Hazards Model for the Subdistribution of a Competing Risk

Jason P. Fine, Robert J Gray (1999)

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Colorectal tumour deposits in the mesorectum and pericolon; a critical review.

Phil Quirke, Iris Nagtegaal (2007)

Although tumour deposits (TD) in the pericolic and mesorectal fat have been recognized since 1935, incorporation in the Tumour Node Metastasis (TNM)/American Joint Committee on Cancer (AJCC) system took place in 1997. The 3-mm rule classified TD as lymph node metastases. This rule was changed in 2002, when the contour of the deposit became the diagnostic feature. This review has evaluated the 3714 patients described in the literature. The incidence of TD varies from 5 to 45%. Their origin has been shown to be heterogeneous; however, their presence indicates a poorer survival. The hazard ratio for death due to disease is 1.96. Various studies have tried to determine the importance of types of TD, based on contour, size and origin, but all fail to provide an evidence base to substantiate its use in the TNM system. To classify TD as positive lymph nodes after neoadjuvant therapy is a misconception, since the presence of tumour microfoci after therapy can be a sign of good response to treatment and indicative of a good prognosis. In conclusion, we did not find adequate evidence for the inclusion of TD in TNM/AJCC staging systems. Moreover, the current directives are confusing, and the definitions should not be used after neoadjuvant therapy.

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Pathological assessment of pericolonic tumor deposits in advanced colonic carcinoma: relevance to prognosis and tumor staging.

Marco Chilosi, Michele Masullo, Giuseppe Viale … (2007)

The current TNM classification considers a tumor nodule in the pericolic/perirectal adipose tissue as venous invasion if the nodule has an irregular contour and as regional lymph node metastasis if the nodule has the form and smooth contour of a lymph node. However, detailed studies on the clinico-pathological implications of pericolonic tumor deposits and of extranodal extension are still lacking. We investigated the impact of these metastatic deposits in the pericolic fat in a series of 228 patients with advanced colon cancer. The pericolonic tumor deposits were characterized by their appearance, size, distance from the primary tumor and by their relation with the lymphatic tissue not organized in lymph nodes. These features were then compared with the clinico-pathological characteristics of the tumors and with the patients' survival. All these lesions were associated with reduced disease-free and overall survivals in a univariate analysis, but only pericolonic tumor deposits retained an independent prognostic role in the multivariate analysis. Our findings suggest that pericolonic tumor deposits are a destructive type of venous invasion different from other types of vessel involvement, and that these lesions may rather be included in the M category for staging purposes.