Does the addition of oxaliplatin to preoperative chemoradiation benefit cT4 or fixed cT3 rectal cancer treatment? A subgroup analysis from a prospective study.

BACKGROUND: Whether there is any benefit derived from adding oxaliplatin to fluoropyrimidine-based preoperative chemoradiation is currently unknown in cases of advanced cT3 or cT4 tumours. Our aim was to evaluate this issue by analysing a randomized trial, which compared two schedules of preoperative treatment (chemoradiation vs. 5 × 5 Gy with 3 cycles of consolidation chemotherapy) for cT4 or fixed cT3 rectal cancer. PATIENTS AND METHODS: Delivery of oxaliplatin was mandatory to the first part of the study. For the second part, its delivery in both treatment-assigned groups was left to the discretion of the local investigator. We analysed a subgroup of 272 patients (136 in the oxaliplatin group and 136 in the fluorouracil-only group) from institutions that had omitted oxaliplatin in the second part of the study. RESULTS: Circumferential resection margin negative (CRM-) status rate was 68% in the oxaliplatin group and 70% in the fluorouracil-only group, p = 0.72. The pathological complete response rate (pCR) was correspondingly 14% vs. 7%, p = 0.10. Following multivariable analysis, when comparing the CRM- status in the oxaliplatin group to the fluorouracil-only group, the odds ratio was 0.79 (95 CI 0.35-1.74), p = 0.54; there being no interaction between concomitant chemoradiation and 5 × 5 Gy with consolidation chemotherapy; pinteraction = 0.073. For pCR, the corresponding results were 0.47 (95 CI 0.19-1.16), p = 0.10, pinteraction = 0.84. CONCLUSION: No benefit was found of adding oxaliplatin in terms of CRM nor pCR rates for either concomitant or sequential settings in preoperative radiochemotherapy for very advanced rectal cancer.

Local excision after radio(chemo)therapy for rectal cancer: is it safe?

According to current opinion, local excision in rectal cancer should be limited to selected T1N0 tumours. Preoperative radio(chemo)therapy provides an opportunity for expanding the use of local excision for more advanced tumours. The key rationale of this approach is the correlation between the radiosensitivity and inherited low aggressiveness of rectal cancer and the correlation between the radiosensitivity of the primary tumour and the radiosensitivity of mesorectal nodal disease. This allows for a selection of local excision for radiosensitive tumours or conversion to abdominal surgery in radioresistant cases. Eleven reports including a total of 311 patients treated with preoperative radio(chemo)therapy and local excision have been published. In some series, the tumours were initially large and unresectable by the transanal approach. Pathological data suggest that local excision must involve all tissue invaded on pre-treatment examination with a margin, even in patients with a clinical complete response. The pooled analysis has shown a local recurrence rate of 1% (1/83) for patients achieving a pathological complete response, 8% (3/40) for ypT1, 11% (4/37) for ypT2 and 3/9 for ypT3. In conclusion, the results of preoperative radio(chemo)therapy and local excision are encouraging and warrant a population-based, multicentre controlled study.

Sphincter preservation after short-term preoperative radiotherapy for low rectal cancer--presentation of own data and a literature review.

This report is based on a series of 108 patients with clinically staged T2 (9), T3 (94) and T4 (5) rectal cancer treated with preoperative irradiation with 25 Gy, 5 Gy per fraction given for one week. In 77% of patients. the tumour was located within 7 cm of the anal verge and in 15% the anal canal was involved. Surgery was usually undertaken during the week after irradiation. For low tumours, total mesorectal excision was performed, and for middle and upper cancers, the whole circumference of the mesorectum was excised at least 2 cm below the lower pole of a tumour. Tumour was resected in 103 patients, and sphincter-preserving surgery was performed in 73% of them. In the subgroup where the tumour was located higher than 4 cm from the anal verge, sphincter-preserving surgery was performed in 95%. The follow-up period ranged from 10 to 49 months, with a median of 25 months. Local recurrences were observed in 4% of patients. Anorectal dysfunction caused impairment of social life in 40% of patients and 18% admitted that their quality of life was seriously affected however, none of them stated that they would have preferred a colostomy. These preliminary data suggest that following high dose per fraction short-term preoperative radiotherapy a high rate of sphincter-preserving surgery can be reached, with acceptable anorectal function and an acceptable rate of local failure and late complications. The results of our own data and literature review indicate the need for a randomized clinical trial comparing high dose per fraction preoperative radiotherapy with immediate surgery with conventional preoperative radiochemotherapy with delayed surgery.