Study Explores Benefits of Watch-and-Wait Approach in Rectal Cancer

Fahima Dossa, MD

Fahima Dossa, MD

Physicians should consider a watch-and-wait approach for patients with rectal cancer who have a clinical complete response to neoadjuvant chemoradiation, findings from a recent study suggest. Although the safety of this approach is unclear, it could potentially save patients from the morbidity of conventional surgery, which may affect their bowel and sexual function.

MEDLINE, Embase, and the grey literature were searched for studies of patients who had been managed by the watch-and-wait approach. Through this process, it was determined that among 867 patients across 23 studies, the pooled 2-year local regrowth was 15.7% (95% CI, 11.8-20.1).

No significant difference in overall survival was found between patients managed with watch-and-wait and patients who had undergone surgery (HR, 0.73; 95% CI, 0.35-1.51). Additionally, no significant difference was found in nongrowth recurrence (risk ratio [RR], 0.58; 95% CI, 0.18-1.90), cancer-specific mortality (RR, 0.58; 95% CI, 0.06-5.84), disease-free survival (HR, 0.56; 95% CI, 0.20-1.60), or overall survival (HR, 3.91; 95% CI, 0.57-26.72). Although, the rate of disease-free survival in the surgery group was better than in the watch-and-wait group, (HR, 0.47; 95% CI, 0.28-0.78).

In an interview withTargeted Oncology, study authors Fahima Dossa, MD, surgical resident, St. Michael’s Hospital, and Nancy Baxter, MD, PhD, chief of the General Surgery Department, St. Michael’s Hospital, discussed the potential of using a watch-and-wait approach in the management of patients with rectal cancer.

TARGETED ONCOLOGY:What was the intent behind this study?

Dossa:

The reason why this study was done dates back to 2004. A group from Brazil decided to try to treat patients with rectal cancer differently than the convention. Previously, the convention would have been neoadjuvant chemoradiation surgery and then adjuvant therapy after that with chemotherapy.

As we mentioned in the paper, there is a minority of patients that have an excellent response to neoadjuvant treatment, and when they are taken for surgery, there is no sign of the tumor. So, this group from Brazil decided that it was worth looking at whether these patients really benefitted from surgery at all. Unfortunately, we cannot identify these patients, except for at the time of surgery when their pathology is looked at.

This group developed a set of clinical parameters that they used to see who was likely to have a complete pathologic response. They took those patients and offered them the option of watching and waiting, rather than surgery. Essentially, it is close follow-up with regular endoscopy and regular imaging and regular clinic visits. And they had pretty good results. They had very good long-term survivals and low rates of tumor recurrence. But there were some questions of will these tumors come back and what happens to these patients when their tumors do come back. A lot of other groups have tried to investigate this but most of the studies are quite small, so it is hard to draw conclusions from them.

TARGETED ONCOLOGY:Could you provide an overview of the study that you conducted?

Dossa:

The study is designed as a systematic review and meta-analysis. We searched 3 common databases as well as a series of grey literature to try to find any studies by which any patients were managed by this watch-and-wait approach. We looked at studies in which any patients were treated by this approach, and then we looked at studies where patients were treated by a watch-and-wait approach versus patients that were treated with surgery, and we compared outcomes in those groups. All of the patients had locally advanced rectal cancer and the ones who were treated with watch-and-wait were identified as having a complete response based on clinical parameters. The surgical group was divided between those that had a clinical complete response and those who had a pathologic complete response.

TARGETED ONCOLOGY:What were the significant findings?

Dossa:

The primary outcome for our study was the rate of regrowth. So, how often the tumor regrew in the lumen of the rectum. Specifically, we looked at the 2-year rate of regrowth. Previous studies have shown that within the first 2 years are when the patient has the highest risk for the tumor to regrow. What we found that was that the rate of regrowth was 15%, so 15% of patients have their tumor come back, but the rest of the patients were spared from surgery.

One of the important findings of our study was that of those 15% that did have regrowth, almost all of them were able to undergo further therapy at the time of the regrowth. So that outweighs some of the concerns of when you delay surgery in these patients.

When we compared surgery to a watch-and-wait approach, one of the things that we noticed right away was that there were very few studies that were looking at this, so it was hard to make any definitive conclusions from the data. What it looks like is that there is no clear difference in survival between patients who are treated by surgery and those who are not.

TARGETED ONCOLOGY:What would you like community oncologists to take away from these findings?

Baxter:

I think that many of us that treat rectal cancer have had patients who refused surgery and actually did relatively well. So, many of us have had some experience with this approach, but not actually offering it to patients. I think it is a big leap to go from the standard tried-and-true therapy to this, which is novel and we do not actually know what the outcomes are going to be long term.

I think what we have done is that we have gotten the best evidence together so that can give more informed advice and patients can make more informed choices, if they have a complete clinical response.

I think that it is important that this is a choice that is at least discussed with patients, because it does seem like it is a viable option for many patients. We must include the fact that we do not have anything close to the evidence that we have for standard neoadjuvant therapies and surgery, which we know gives excellent curative results—but that have a major impact on people's quality of life and long-term psychosocial sexual outcomes.

It is a balance, and I think this study helps us understand this balance a little bit better.

TARGETED ONCOLOGY:How would you like to see this information used in further studies?

Baxter:

Well, we definitely need to work together to get more studies done on this. We need to follow patients closely and commit to following these patients who choose the watch-and-wait approach in a way that allows us to gather information for future patients—to engage people in protocols versus just having patients opt for watchful waiting.

Also, we need to develop some decision-making tools to help patients work through this decision because there are a lot of pros and cons and I think we need a better way of articulating that.

TARGETED ONCOLOGY:Do you have any advice on how physicians should approach this conversation with patients?

Baxter: Many patients are open to not having surgery. That is—many patients do not want surgery. They are anxious to hear information like this because they do not want an operation. How this is framed and discussed with patients is very important—1 experimental option versus 1 standard option. I think you do need to describe that there is this possibility of watch-and-wait. Patients are becoming more aware of it, as well.

We clearly need more research, to find ways to predict people who will have local regrowth, and we also have to have a better understanding when we should start introducing this to more and more patients. Many of these patients that were in the study were patients who were high risk of complications for other reasons—so, people with a lot of comorbidities that surgeons perhaps did not want to operate on, or patients that want to preserve their rectum. So, when you start introducing it to a broader population, you might not end up having the same results.

TARGETED ONCOLOGY:What do you feel is the biggest current challenge in the management of rectal cancer?

Baxter:

Right now, we have these 2 diametrically opposed movements in terms of management. There is the watch-and-wait approach, where there is almost a push to treat more people with preoperative chemoradiation. If you get a higher rate of complete response, you could potentially manage more people without surgery and without the need to remove people’s rectum and effect their long-term bowel, bladder, and sexual function.

Then there is the other push to decrease the use of radiation so that you can improve people’s function long-term. With good surgery in patients who have stage II disease, but not particularly high-risk stage II disease, we may well be able to avoid radiation entirely.

So, you have these two approaches to rectal cancer that are frankly in opposition. It is hard to know which way to go forward with your patients in terms of achieving the best result possible for them in terms of survival as well as their quality of life.

TARGETED ONCOLOGY:Is there anything else that you would like to emphasize about the study?

Baxter:

Again, I think we really need larger groups of patients treated this way. We need people to start to treat patients on protocol so that we have results. I’d also really like to emphasize that these patients need to be followed extremely closely, and that is a challenge both for the patients and the providers. If someone develops a regrowth and it is identified early and treated, that seems to be—at least from what we see here—a “no harm, no foul” type of thing. It does not seem to have a major negative consequence for the patients.

If you do not follow these patients very closely, and they develop a regrowth that progresses, you may have taken someone who was curable and put them into a situation where they cannot be cured of their disease and may die of a local regrowth, which is horrible. I cannot emphasize enough the need to follow these patients closely—and that is not a simple task.

Reference:

Dossa F, Chesney TR, Acuna SA, Baxter NN. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis [published online May 4, 2017].Lancet Gastroenterol Hepatol. doi: 10.1016/S2468-1253(17)30074-2.