Adjuvant Chemo for Rectal Cancer Patients?


Hello. I am David Kerr, Professor of Cancer Medicine at the University of Oxford. I am interested in the management of gastrointestinal cancer, particularly colorectal cancer.

A good friend of mine, Jean-Francois Bosset, who led a large EORTC study to look at the effect of adjuvant chemotherapy in rectal cancer, just published some long-term results in Lancet Oncology. These results raise some controversy as to whether we should be using adjuvant systemic treatment for the management of rectal cancer. In their clever factorial trial design, they looked at a long course of radiotherapy plus or minus chemotherapy. They showed unequivocally that the addition of [preoperative] chemotherapy significantly reduces local recurrence rates.

This is an important study, quite an old one, and it took place before the depth of quality in modern rectal cancer surgery. But the addition of preoperative chemotherapy to radiotherapy is a good thing.

It was disappointing that the use of adjuvant postoperative chemotherapy for rectal cancer seemed to have no benefit at all. The chemotherapy was rather old-fashioned. It was bolus 5-fluorocuracil (5-FU), low-dose leucovorin given daily for 5 days and repeated every 3 weeks, with a planned delivery of 4 cycles of postoperative treatment.

Of interest, fewer than half of the patients got the planned course of treatment, so there is no doubt that these are pretty vulnerable patients. They have had a lot of pretreatment, a lot of radiotherapy, and they may be somewhat sensitized to the 5-FU, and a significant portion of the patients didn't get through the treatment.

What are we to make of this? We know now that because of the fantastic effort made by our colleagues in surgery and radiation oncology that local recurrence rates are now down to a manageable and respectable 5%-10%. When I first started in oncology, local recurrence rates for rectal cancer were 20%-30%, so it is a great step forward. But our attention has shifted, of course, to those 25%-30% of rectal cancer patients who relapse with metastatic and systemic disease.

What do the guidelines tell us? They are confusing. Different guidelines say different things. Under the auspices of the European Society for Medical Oncology (ESMO), we held a series of guideline meetings in which we tried to come to some consensus about the use of adjuvant treatment for rectal cancer, and it proved difficult because the evidence base is weak. In our QUASAR-1 study, rectal cancer patients were randomized along with the colon cancer patients. We saw a definite benefit for chemotherapy, and the size of the chemotherapy benefit for rectal cancer was the same as for colon cancer. We didn't differentiate in terms of chemosensitivity, advanced or metastatic disease, or whether it was colon or rectal cancer.

For those of us who offer adjuvant chemotherapy, should these long-term results (very well-reported by Jean-Francois) change practice? I, for one, will not be changing my practice. We tend to offer 3-4 months of treatment, usually with single-agent capecitabine. We are not in the habit of using oxaliplatin but instead use a fluoropyrimidine in some size, shape, or form. It seems a reasonable thing to do, and we have our own QUASAR trial backing it up.

In that setting, using the QUASAR chemotherapy (5-FU, low-dose leucovorin), it was pretty well-tolerated and we managed to deliver it to most of our patients. So our recommendation would be to continue, but it is controversial. I would be very interested to see what you think of this, and whether you think the long-term results of this study are practice-changing. Perhaps your practice is different; perhaps you don't give adjuvant chemotherapy for rectal cancer. I would be very interested to know your thoughts on this and would be grateful if you posted any comments online. Have a look at the article and see what you think, and perhaps we can discuss this later.