Expert Discusses Surgical Intervention in Metastatic CRC

Dominik P. Modest, MD

In a central evaluation for surgical treatment options in the FIRE-3 study results, investigators set out to determine the number of patients with metastatic colorectal cancer who had resectable disease during systemic first-line therapy.

A panel of 8 surgeons and 3 medical oncologists served as reviewers of 448 patients, defining resectability as at least 50% of the reviewers recommending surgical intervention.

Results showed that resectability increased from 22% prior to treatment, to 53% at best response. Patients who had a secondary resection demonstrated a better outcome compared to those who did not undergo surgical intervention, or those with unresectable disease.

In an interview with OncLive, Dominik P. Modest, MD, University of Munich, discussed the evaluation of resection in patients with colorectal cancer.

Could you provide some background of this evaluation?

The FIRE-3 study was a phase III study in untreated metastatic CRC. It started without any restricting for biological markers and KRAS mutations were introduced as secondary information after a few years of recruitment. The study was fully published in 2014 and the results showed that first-line FOLFIRI chemotherapy in combination with either cetuximab (Erbitux) or bevacizumab (Avastin) invokes differences in outcome with the main difference in overall survival in favor of the cetuximab arm.

What methods were used in your evaluation?

We did not really care about the treatment arms—we took all of the patients that we could have CT of and we homogenized them, which was really difficult. And then we took a pair of scans for each patient—a treatment-naïve scan before treatment, and then a scan at best response, which was when we knew the tumor was at the smallest diameter. We ask a panel of 8 surgeons and 3 medical oncologists whether this patient would have been a candidate for resection. So, we offer different algorithms before treatment and we offer resection or chemotherapy at best response.

The outcome was intact that before treatment, roughly 20% of the population would have been a candidate for surgical intervention and at best response, it was a little more than 50%—which was higher than expected.

What are the significance of these findings in everyday practice?

I think what we have to understand is that the central review always will overestimate numbers. I think this is important to know—people will miss information if the patient is not sitting in front of them—you don’t know preferences, experiences, etc. You may also miss a little information on comorbidities and disease spread. New lesions or lymph nodes are not really clear on the CT, but if you have a laparoscopy done at site, you get additional information which is extremely valuable to make any decision, and you don’t get that in the central review. We have overestimated what could have been done.

The main message we found is that systemic treatment increases resectability and never forget that you have uncertainties in terms of spread. The most important thing in CRC with this focus is that you have a reassessment after treatment—that is the main thing. If you miss the assessment before treatment, that isn’t good, but you should absolutely never miss this reassessment after treatment. And you should not exclude any treatment based off of the baseline CT scan—even if you initially think they won’t be a candidate, have a reassessment and a dedicated surgeon to check on that.

What do you hope community oncologists took away from these findings?

You have to remember, that if you resect all lesions, the vast majority of patients stay in the palliative treatment setting. So, the chance of relapse is much higher, unfortunately, than of cure. These oncologists don’t lose anything if they send the patient to be resected, they add a modality to it that we know is associated with improved survival. For me, there is no reason to not do it, or to have any concerns about it. What you have to have is a high-volume surgeon who can provide safe intervention with low rates of morbidity and mortality, that is important. The more modalities you can offer, the better it is.

Modest DP, Denecke T, Pratschke J, et al. Central evaluation for surgical treatment options in FIRE-3- updated results and impact on overall Survival. Ann Oncol 2017; 28 (suppl_3): mdx262.029. doi: 10.1093/annonc/mdx262.02.

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