Treatments for Anal Cancer.
What about the results? The standard therapy for anal cancer, before 20 years ago -18-20 years ago – was abdominoperineal resection. Obviously abdominoperineal resection is something that can’t be taken too lightly since you are removing the whole anorectal mechanism and you leave a patient with a permanent colostomy. In a review of some 460 patients this was done with, what I consider as relatively high – and of course these were patients treated in the 60’s and 70’s – with relatively high operative mortality. The cure rate was about 50% with this procedure. So it’s important in one sense to be absolutely sure – particularly in the context of taking the Boards – that you never want to do an abdominoperineal resection as the first line therapy for a patient with anal cancer. But the other thing is to keep abdominoperineal resection in your back pocket, because as I’ll show you, it’s still an effective salvage rate for patients who recur or who don’t respond.
Looking at radiation therapy alone in the treatment of patients with anal cancer, and you get a local control rate of somewhere from 60-70% and a five year survival rate of somewhere around 50-65%. So radiation alone has some benefit. Now the radiation therapists are in a sense like chemotherapists in that if a little radiation is good someone is always going to say, “Well, a lot of radiation is better.” These are data from France from Papillion, and what he did was to do brachytherapy or interstitial radiation in patients with anal cancer, and he had some 64 patients and he was able to render about two-thirds of them without any evidence of disease. However, there was a significant incidence of radionecrosis that occurred. And the other thing that is not mentioned in this slide, which I think is an important consideration to keep, what we are talking about is the potential for sphincter-sparing surgery here. Now if you spare the sphincter but it doesn’t work, you haven’t done the patient any favors really. So you need to look at functional benefit in these patients, after whatever sphincter-sparing approach you are going to use. With this much radiation many people would agree, we would be very concerned about the function of the residual sphincter.
Well, when the modern era arrived where data, using the combination of mitomycin, 5-FU and radiation in patients with basaloid and squamous cancers of the anus. The original work was done at Wayne State University by Dr. Nigro and his colleagues. Many people picked up on it and initially the combination of 5-FU, mitomycin and radiation was used in patients with larger anal cancers, or patients who were thought to be very poor surgical risks, or patients who refused to have abdominoperineal resections. What was found was that this tended to be very effective therapy. The way it’s given, and the way it’s given still, is interesting because there are all kinds of innovations in combined modality therapy and people are constantly looking at how best to modulate the radiation-chemotherapy, for example in esophageal cancer. What’s happened is that in the early 1980’s, late 1970’s, we stumbled upon this and it works real well and people are reluctant to leave it. I’ll show you that we are looking at new approaches but it’s like MOP chemotherapy in Hodgkin’s disease. You have to have a real good reason to want to change it. This therapy is really quite simple to give. You give a gram per M2 (meter square) per day for 96 hours of 5-FU by continuous infusion, and most people do this now with a pump as an outpatient. It used to be that the patient would come to the hospital. Mitomycin C is given on the first day, either 10 or 15 mg. For many people 10 mg is probably plenty. Radiation has changed somewhat in that the radiation dose has been increased. Most radiation oncologists give about 5,000 centigray. In this original study, one of these studies from San Francisco by Flamm et all, there were 11 patients who were treated and they ran ED and had a very good response; essentially 100% response rate.