Ask the Experts - Preoperative Chemoradiation for Stage T3 Rectal...
Ask the Experts - Preoperative Chemoradiation for Stage T3 Rectal...
An 80-year-old man in excellent health found blood in his stool. Exam showed a tumor in the rectum. The distal tumor margin was 4.5 cm from the anal verge, about 3 cm in circumference, occupying about 1/4 of the rectum wall circumference. It was freely movable, just to the left and superior to the prostate, which felt normal. By magnetic resonance imaging (MRI) rectal coil, it was diagnosed as a T3 lesion. No nodes were noted on MRI or abdomino-pelvic CT. Moderately differentiated adenocarcinoma was found on biopsy.
If this was your father, what would you advise: preoperative 5-fluorouracil (5-FU) plus radiotherapy or postoperative chemotherapy and radiotherapy? If preoperative therapy is chosen, what would be the best radiotherapy dose? Is preoperative capecitabine plus radiotherapy warranted? Would the choice of agents change if a T2 lesion was noted on rectal coil MRI?
There are essentially 2 therapeutic options for this patient: surgical resection followed by adjuvant chemoradiation if a T3-4 or N positive tumor is found, or, preoperative chemoradiation plus additional chemotherapy based on the pathologic findings from the resected specimen. The superiority of one strategy over the other with regard to the incidence of recurrence and survival is presently unknown, but is the subject of ongoing randomized clinical trials.
With this consideration in mind, each of these strategies has potential advantages and disadvantages. The main disadvantage of upfront surgical resection is that, given the distal location of the tumor, the resection will most likely include an abdominoperineal resection (APR) and, consequently, a permanent colostomy. The principal benefit of this strategy is that if the resected tumor is a T2 lesion, no additional therapy is needed. The probability that this occurs, however, is low, since rectal coil MRI is quite accurate in predicting the T stage of the tumor.
The alternative approach, which is the one I would recommend, is preoperative chemoradiation with continuous infusion of 5-FU and external beam radiotherapy to a total dose of 5400-5900 cGy over 5 weeks. The principal advantage of this approach is that in approximately 70% of patients, there is sufficient tumor reduction to avoid an APR and a permanent colostomy. This regimen should then be followed by 4-6 cycles of 5-FU chemotherapy. The principal disadvantage is that if the tumor stage is T2 instead of T3, the patient is essentially being overtreated. However, given the high specificity of rectal coil MRI for assessing T staging, the likelihood that this will occur is low.
Considering the higher probability of downstaging the tumor to allow for a sphincter-sparing procedure vs the smaller probability that the final stage will be a T2 tumor that will not require additional therapy, coupled with the relatively good tolerability of the 5-FU and pelvic radiation, provided the patient is followed closely and appropriate dose modifications are made, I would recommend preoperative chemoradiation followed by surgical resection. Regarding the role of capecitabine, although it has demonstrated equal efficacy to 5-FU in patients with advanced colorectal cancer, its use in adjuvant therapy remains investigational and is not a standard regimen.
An 80-year-old man in excellent health found blood in his stool. Exam showed a tumor in the rectum. The distal tumor margin was 4.5 cm from the anal verge, about 3 cm in circumference, occupying about 1/4 of the rectum wall circumference. It was freely movable, just to the left and superior to the prostate, which felt normal. By magnetic resonance imaging (MRI) rectal coil, it was diagnosed as a T3 lesion. No nodes were noted on MRI or abdomino-pelvic CT. Moderately differentiated adenocarcinoma was found on biopsy.
If this was your father, what would you advise: preoperative 5-fluorouracil (5-FU) plus radiotherapy or postoperative chemotherapy and radiotherapy? If preoperative therapy is chosen, what would be the best radiotherapy dose? Is preoperative capecitabine plus radiotherapy warranted? Would the choice of agents change if a T2 lesion was noted on rectal coil MRI?
There are essentially 2 therapeutic options for this patient: surgical resection followed by adjuvant chemoradiation if a T3-4 or N positive tumor is found, or, preoperative chemoradiation plus additional chemotherapy based on the pathologic findings from the resected specimen. The superiority of one strategy over the other with regard to the incidence of recurrence and survival is presently unknown, but is the subject of ongoing randomized clinical trials.
With this consideration in mind, each of these strategies has potential advantages and disadvantages. The main disadvantage of upfront surgical resection is that, given the distal location of the tumor, the resection will most likely include an abdominoperineal resection (APR) and, consequently, a permanent colostomy. The principal benefit of this strategy is that if the resected tumor is a T2 lesion, no additional therapy is needed. The probability that this occurs, however, is low, since rectal coil MRI is quite accurate in predicting the T stage of the tumor.
The alternative approach, which is the one I would recommend, is preoperative chemoradiation with continuous infusion of 5-FU and external beam radiotherapy to a total dose of 5400-5900 cGy over 5 weeks. The principal advantage of this approach is that in approximately 70% of patients, there is sufficient tumor reduction to avoid an APR and a permanent colostomy. This regimen should then be followed by 4-6 cycles of 5-FU chemotherapy. The principal disadvantage is that if the tumor stage is T2 instead of T3, the patient is essentially being overtreated. However, given the high specificity of rectal coil MRI for assessing T staging, the likelihood that this will occur is low.
Considering the higher probability of downstaging the tumor to allow for a sphincter-sparing procedure vs the smaller probability that the final stage will be a T2 tumor that will not require additional therapy, coupled with the relatively good tolerability of the 5-FU and pelvic radiation, provided the patient is followed closely and appropriate dose modifications are made, I would recommend preoperative chemoradiation followed by surgical resection. Regarding the role of capecitabine, although it has demonstrated equal efficacy to 5-FU in patients with advanced colorectal cancer, its use in adjuvant therapy remains investigational and is not a standard regimen.
