John L. Marshall, MD: Let’s shift gears a little bit and talk about rectal cancer. In my opinion, we went from a very sort of stodgy, everybody had to be treated the same way to what I now think of as the wild west. Everybody’s got their own idea of how to manage rectal cancer now. There is some evidence to support what we’re doing, but a lot of people are making moves without a lot of evidence. And we only want to spend some time with you guys much smarter than I am about this subject to talk about that data. Gabby, let me pick on you first to kind of set the stage for us. Where are we today? Would you say there’s a standard of care today for the management of rectal cancer? And let’s make it T3 and node-positive rectal cancers.

Gabriela Chiorean, MD: Yes. So, I think that among all the colorectal cancers, a plethora of tumors that arise from right to left and to the bottom of it, rectal cancer is among the most controversial because we talk even among our peers, and every institution sometimes has a little bit of a different practice. Having said that, I believe that still a standard, so to speak, of care in the United States today is to do the chemotherapy with radiation for the 5.5 weeks followed by surgery followed by adjuvant therapy. Now again, this has been the same for the past 15, 20 years, and all we’ve really accomplished with neoadjuvant chemoradiation is reducing the chance of local recurrence. And we are currently doing quite a bit of research to try to shift the paradigm—does everybody need radiation? Can we implement chemotherapy sooner to reduce distal metastases and improve survival? So, there are a lot of questions that we’re trying to address in different clinical trials, but I wouldn’t say that we have changed really the tradition of neoadjuvant chemoradiation, surgery, and adjuvant at this point.

John L. Marshall, MD: So, we don’t have anything new that you know of that’s really shifting that to where that’s no longer correct as at least as one of the options?

Gabriela Chiorean, MD: We have a lot of clinical trials that I think we’re trying to answer questions, whether can we substitute radiation with chemotherapy and improve survival. Can we potentially even not do surgery for certain patients who have amazing responses? We still haven’t addressed the question: Are we overtreating many patients with adjuvant therapy? But I don’t think that overall we have changed standard of practice.

John L. Marshall, MD: If we dial back even 10 years or more, isn’t it the British who sort of invented the mesorectal excision? And radiation to me has always been, “Well, I’m making up for ‘bad’ surgery.” And so if I’m now doing a mesorectal excision, Marwan, does that really mean I need mini radiation even as a primary therapy? And I think the British, although they of course try to trim every budget they can trim, they don’t do a lot of radiation there because their surgeons say we did a better job. What’s your take on that? Because our United States surgeons are all doing mesorectal excisions too.

Marwan Fakih, MD: Right, we are. But even when you look at the British data and you look at some of the studies, clearly some of the tumors that are close to the circumferential margin that are threatening the outside margin of the mesorectum have a high risk of recurrence. And you’re more likely to have a positive margin even with a total mesorectal excision. I think where we have not moved forward in the field is really individualizing who needs radiation.

There’s clearly a subgroup of patients who will need radiation, and we’re going to see some decrease in local relapse even with a TME, especially these distal tumors, where even with the standard total mesorectal excision, you may still have a close radial margin. So, until we standardize a way to prognosticate or predict who’s going to relapse more, unfortunately, I think we’re stuck with radiation for now, even though it doesn’t clearly move the overall survival much. For the higher-up rectal cancers, I think the local relapse rate is so low—or if you have a good MRI and know that it’s an early T3—I think it’s fair to have a very good discussion with the patient and say their benefit may not be that significant, based on the studies, and to consider sometimes foregoing radiation. I don’t think it’s one size fits all.

John L. Marshall, MD: Bert, let me kind of pick on you for a second. We’ve got this trimodality therapy, the chemoradiation surgery, and we do OK, right? Survival is not great, but they’re OK. Where I see this science really pushing us is to try to minimize the post-treatment morbidity. Maybe talk a little bit about how you discuss with a patient. What are the consequences of pelvic radiation? What are the consequences of a rectal resection on your bowel function and just your quality of life? We’re glad they’re not dead, but what’s their quality of life like after a traditional rectal cancer treatment?

Bert H. O’Neil, MD: Sure. Well, this is a very complex discussion and obviously depends on things, like are they going to have an APR? Are they going to have a low anterior resection? It is very important. It is very important to discuss potential long-term radiation complications, pelvic insufficiency fractures, urinary problems, long-term incontinence issues.

John L. Marshall, MD: Well, I’ve been thinking lately, too, that with the younger people and their more commonly distal tumors, you have fertility issues for women that come into play now.

Bert H. O’Neil, MD: Absolutely. And then, obviously, the major fear of all patients is to be left with a colostomy permanently.

John L. Marshall, MD: They don’t like that, do they?

Bert H. O’Neil, MD: They don’t like that idea. Even when the alternative is to have a high risk of recurrence, many patients are resistant to that.

John L. Marshall, MD: Well, 10 bowel movements a day. That’s sort of the trade-off sometimes, the very frequent bowel movements and knowing where every Starbucks …is that you can use. Wells, what are your thoughts on this?

Wells A. Messersmith, MD, FACP: I agree. Just to tie it back to your discussion of fertility, at least our radiation oncologists don’t recommend delivering a baby or even carrying a baby to a radiated uterus afterward, exactly. We often have to do a surgery to move the ovaries out of the way. So, as this becomes more common in your people, I think the issues become even more acute. There’s also long-term sexual dysfunction. That can be an uncomfortable topic for people but really needs to be brought up. Luckily, we have this PROSPECT trial that’s being done across the United Sates that’s enrolling well—and certainly we appreciate all the participation of the community sites in that—that will be looking at if you give chemotherapy, and you have a good response, can you forego radiation? So, I look forward to seeing the results of that, and we’ve been putting patients on that study.

Transcript Edited for Clarity