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Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation.

Quah HM et al.

Cancer. 2008 Jul 01; 113(1):57-64

https://doi.org/10.1002/cncr.23516PMID:18442099

BACKGROUND: Preoperative chemoradiation is the standard treatment for locally advanced rectal cancer. However, it is uncertain whether pretreatment clinical stage, degree of response to neoadjuvant treatment, or pathologic stage is the most reliable predictor of outcome. This study compared various staging elements and treatment-related variables to identify which factors or combination of factors reliably prognosticates disease-free survival in rectal cancer patients receiving neoadjuvant combined modality therapy.

METHODS: From a prospectively maintained single institution database, 342 consecutive patients with locally advanced rectal cancer staged by endorectal ultrasound were identified. Patients underwent rectal resection 4 to 8 weeks after a 5.5-week course of pelvic radiotherapy/concurrent chemotherapy. The degree of tumor regression was histologically graded on each resected specimen using a previously reported response scale of 0% to 100%. Predictive models of disease-free survival were created utilizing available pretherapy and postoperative staging elements in addition to the degree of tumor regression noted histologically. Model accuracy was measured and compared by concordance index, with 95% confidence interval (CI).

RESULTS: Stratifying patients by degree of tumor regression predicted outcome with a concordance index of 0.65 (95% CI, 0.59-0.71), which was significantly better than models using preoperative stage elements (concordance index of 0.54; 95% CI, 0.50-0.58). However, the model found to be most predictive of disease-free survival stratified patients by final pathologic T classification and N classification elements, with a concordance index of 0.75 (95% CI, 0.70-0.80).

CONCLUSIONS: Tumor response to preoperative therapy is a strong predictor of disease-free survival. However, outcome is most accurately estimated by final pathologic stage, which is influenced by both preoperative stage and response to therapy.

(Copyright) 2008 American Cancer Society.

Quah HM¹,
Chou JF ,
Gonen M ,
Shia J ,
Schrag D ,
Saltz LB ,
Goodman KA ,
Minsky BD ,
Wong WD ,
Weiser MR

Affiliations

¹ Department of Colorectal Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA

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This article reinforces the thought that the final pathologic stage is the best predictor of disease-free survival for patients with rectal cancer. It has also revealed that tumor response to neoadjuvant therapy may play a role in prognosis.Rectal cancer affects >40,000 Americans annually. As we know, therapy is dictated by the extent of the disease on presentation defined by the TNM staging classification of malignant tumours. The standard of care for the treatment of locally advanced rectal cancer is a combination of chemoradiation and surgery.Through a prospectively maintained database of patients preoperatively staged with endorectal ultasound (ERUS) at the Memorial Sloan Kettering Cancer Center, 342 patients with advanced primary rectal cancer staged as T3/4 and/or N1/2 were identified. The purpose was to identify the staging elements and treatment-related variables that most reliably prognosticate disease-free survival in patients with rectal cancer receiving neoadjuvant therapy. All patients underwent the appropriate surgical resection. They were then followed every three to four months for two years, and then every six to twelve months thereafter. Various staging elements were examined to determine their reliability in predicting outcome. Postoperative pathology (T and N classification) was found to be the best predictor of outcome with a concordance index of 0.75. It was also found that clinical staging adds no predictive value to the pathologic staging model. Interestingly, this study showed a predictive role for the histological response to preoperative chemoradiation; however, it was not equal to the pathologic staging. Over time, the response to neoadjuvant therapy may be incorporated into staging systems if a way for standardization is found. However, it currently remains the standard of care to treat patients according to their preoperative clinical stage and use the postoperative pathologic stage to help determine the patient's prognosis.

The final pathologic stage in the evaluation of rectal cancer prognosis is, without any doubt, as fundamental as tumor response to neoadjuvant treatment. We use these data in our clinic, both in the preoperative and in postoperative setting, for evaluating prognosis. This study examined the role of final pathologic stage as a prognostic factor, comparing it to other variable elements from a prospectively maintained single-institution database. At the Sloan Kettering Cancer Center, 342 consecutive patients with advanced rectal cancer staged by EUS as T3 and T4 with N1/N2 were selected. The degree of tumor regression was histologically graded. The final pathological T and N classifications were demonstrated by the analysis to be most predictive of disease-free survival. In addition, tumor response to preoperative therapy was shown to remain a strong predictor.The study confirms a very common opinion regarding the main prognostic factors in the evaluation of disease-free survival following a combined standard treatment of locally advanced rectal cancer.