Complete clinical response after preoperative chemoradiation in rectal cancer: is a "wait and see" policy justified?

PURPOSE: A proportion of patients, who receive preoperative chemoradiation for locally advanced (T3, T4, NX) rectal cancer achieve a complete clinical response and a pathologic complete response in the region of 15 to 30 percent. Support is growing in the United Kingdom for the concept of "waiting to see" and not proceeding to radical surgery when a complete clinical response is observed. The purpose of this review was to use a literature search to assess how often complete clinical response is achieved after neoadjuvant chemoradiation, the concordance of this finding with pathologic complete response, and to determine whether it is feasible to observe patients who achieve complete clinical response rather than proceed to surgery. RESULTS: In total, 218 Phase I/II or retrospective studies and 28 Phase III trials of preoperative radiotherapy or chemoradiation were identified: 96 percent of trials documented the pathologic complete response, but only 38 trials presented data on the achievement of a complete clinical response/partial clinical response. Only five studies were found in which patients with clinically staged T2/T3 tumors were treated with radiotherapy/chemoradiation and did not routinely proceed to surgery and also reported on the long-term outcome of a "wait and see" policy. DISCUSSION: It remains uncertain whether the degree of response to chemoradiation in terms of complete clinical response or pathologic complete response is a useful clinical end point. Studies that include T3 rectal cancer are associated with high local recurrence rates after nonsurgical treatment. Few studies report long-term outcome after achievement of a complete clinical response. CONCLUSIONS: The end point of complete clinical response is inconsistently defined and seems insufficiently robust with only partial concordance with pathologic complete response. The rationale of a "wait and see" policy when complete clinical response status is achieved relies on retrospective observations, which are currently insufficient to support this policy except in patients who are recognized to be unfit for or refuse radical surgery.

Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision?

INTRODUCTION: Local excision is considered inappropriate treatment for T3-T4 rectal adenocarcinomas, as it cannot provide prognostic information regarding lymph node involvement and has a high risk of pelvic recurrence. Preoperative chemoradiation (CRT) studies in rectal cancer suggest that a pathological complete response (pCR) in the primary tumour provides an excellent long-term outcome. If downstaging to stage pT0 predicts a tumour response within the perirectal and pelvic lymph nodes, this may allow local excision to be performed without increased risk of pelvic recurrence. This retrospective study aimed to determine the incidence of involved lymph nodes following pCR (ypT0) after preoperative CRT and total mesorectal excision. METHOD: The outcome and treatment details of 211 patients undergoing preoperative CRT for clinically staged T3-T4 unresectable rectal adenocarcinomas between 1993 and 2003 at Mount Vernon Hospital were reviewed. RESULTS: Data were recorded from the 143 patients who completed treatment with a median follow-up of 25 months. Twenty-three patients (18%) were found to have had a pCR. Four out of 23 patients (17%) had involved lymph nodes. No pelvic recurrences developed after a ypCR. Overall survival was similar for patients with ypT0 or residual tumour. CONCLUSION: Pathological complete response in the primary tumour failed to predict a response in the perirectal lymph nodes (p=0.08). The degree of response predicted a lymph node response (p=0.02). The detection of ypCR identified patients with a low rate of pelvic recurrence. This may in the future allow selection of patients for whom local excision can be performed without a higher risk of local relapse.

Metachronous stomal adenocarcinoma following abdominoperineal resection for rectal cancer.

Although metachronous colorectal tumours are relatively common, they seldom occur at stomasites. We present the case of a 57-year-old woman who developed a colostomy site malignancy. Possible associations and risk factors are discussed.

The reliability of lymph-node staging in rectal cancer after preoperative chemoradiotherapy.

AIMS: To determine the prognostic significance of the nodal stage and number of nodes recovered in the surgical specimen after preoperative synchronous chemoradiation (SCRT) and surgery for locally advanced or unresectable rectal cancer. MATERIALS AND METHODS: One hundred and eighty-two consecutive patients with locally advanced or unresectable (T3/T4) rectal carcinomas were entered on a prospective database and treated in this department with preoperative chemoradiation, followed 6-12 weeks later by surgical resection. Most patients received chemotherapy in the form of low-dose folinic acid and 5-fluorouracil (5-FU) 350 mg/m2 via a 60-min infusion on days 1-5 and 29-33 of a course of pelvic radiotherapy delivered at a dose of 45 Gy in 25 fractions over 33 days to a planned volume. After resection, patients with a positive circumferential margin (< or = 1 mm), extranodal deposits or Dukes' C histology received adjuvant 5-FU-based-chemotherapy (n = 40). RESULTS: After SCRT, 161 patients underwent resection. Twenty-one patients remained unresectable or refused an exenterative operation. Median follow-up is 36 months. Down-staging was achieved in most patients, with 19 having a complete pathological response (pT0). The median number of lymph nodes recovered for all patients was five (range 0-21). The 3-year survival rate for node-positive patients is 47%, for node-negative patients with less than three lymph nodes recovered is 62% and for node-negative patients with three or more lymph nodes recovered is 70%. Compared with node-positive patients, simple regression models revealed a reduced hazard ratio (HR) of 0.72 (0.36-1.43) for node-negative patients with less than three nodes recovered and 0.48 (0.26-0.89) for node-negative patients with three or more lymph nodes recovered. In a multivariate model, including nodal status, excision status, age and sex only positive excision margins significantly predicted a poor outcome: HR = 3.05 (1.55-5.97). CONCLUSIONS: The number of nodes found after preoperative chemoradiation is a significant prognostic factor by univariate analysis. In this study, patients with node-negative histology, and at least three nodes recovered, had better long-term survival than patients in whom two or less nodes were recovered or with positive nodes. This effect was attenuated by the inclusion of excision status in multivariate models.

Investigation of ranitidine 150 mg bd or 300 mg bd in the treatment of reflux disease.

Twenty patients with symptoms and endoscopic changes of gastro-oesophageal reflux were randomly allocated to treatment with either ranitidine 150 mg bd, or 300 mg bd for 8 weeks. Symptoms, endoscopic appearances, histopathology of oesophageal biopsies and 22-h intra-oesophageal pH profile in ambulant patients on standard diets were recorded before and at the end of the treatment period. Symptoms improved rapidly and markedly on either dose of ranitidine. Both doses produced significant improvement of the endoscopic appearances, but there were no differences in symptomatic and endoscopic improvement related to the dose. Biopsy appearances and the 22-h oesophageal pH profile remained unchanged on either dose of ranitidine.