PROSPECT: Neoadjuvant Therapy for Locally Advanced Rectal Cancer


Muhammad Shaalan Beg, MD, joins the Oncology Brothers, Rohit Gosain, MD, and Rahul Gosain, MD, to discuss recent data from the PROSPECT trial investigating neoadjuvant therapy regimens for the treatment of locally advanced rectal cancer.

Rahul Gosain, MD: Hello, everyone, I am Rahul Gosain.

Rohit Gosain, MD: And I'm Rohit Gosain.

Rahul Gosain, MD: And we are Oncology Brothers. So, a lot of data was presented at ASCO [American Society of Clinical Oncology] 2023. As community medical oncologists, there are a few key studies that we need to get comfortable with. Today we'll focus on four important studies in GI malignancies presented at the annual ASCO 2023 meeting. We'll start off with the PROSPECT trial, followed by two studies, NORPACT-1, and NAPOLI-3 in pancreatic cancer. And then IMbrave050 in adjuvant hepatocellular carcinoma. To walk us through these critical studies we're joined by Dr Shaalan Beg from Texas. Dr Beg, thank you so much for joining us.

Muhammad Shaalan Beg, MD: Thank you so much for having me.

Rohit Gosain, MD: Dr Beg, welcome. Let's start off with the first study prospect trial. Before we dive into the study itself, just to reiterate the current standard of care that has been a multidisciplinary approach mainly involving total neoadjuvant therapy, chemoradiation or chemotherapy vice versa followed by surgery or chemoradiation up front, followed by surgery and then adjuvant chemotherapy. Radiation here has multiple side effects that patients have to battle in long-term settings. The PROSPECT trial is an attempt to see if in some patients, can we successfully avoid neoadjuvant radiation. Diving into this trial further, could you please walk us through the study design?

Muhammad Shaalan Beg, MD: Yes, well, I talk about the study design, let's take one second and understand how we got where we- where we are for rectal cancer. When we look at the large German neoadjuvant rectal cancer study that evaluated chemoradiation, surgery followed by chemotherapy for rectal cancer and became our standard of care for decades. It did so by showing a reduction in public recurrence rates and sphincter preservation. So, on this trial, they wanted to see how they can systematically exclude radiation for a defined group of people. They took people who had T3 and zero rectal cancer, who were not candidates who did not require sphincter surgery. So, these were higher rectal tumors, not the rectal tumors that would require an APR. And they randomized those folks into getting the conventional pelvic chemoradiation followed by surgery and adjuvant chemo or upfront chemotherapy and emitting radiation in people who have a good response. So, if people started off with chemotherapy, they got three months of chemotherapy, if they had more than 20% response they went straight to surgery, then adjuvant chemotherapy. But if they didn't have a response, they got radiation like they would have otherwise, then this was a way to really cherry-pick a group of patients say hey, will we still do fine by emitting radiation in this group of patients, in order to avoid both some short term side effects around the radiation as well as long term side effects that can take place, and that's what led to this clinical trial that was presented at ASCO this year. When we look at the results, they compared disease-free survival at five years. And we see that the disease-free survival for chemoradiation, which is the way quote unquote, we've always been doing it so the disease-free survival with 78% with chemoradiation, when we deploy upfront chemotherapy, followed by radiation in just the non-responders, we don't see a reduction in disease-free survival. This was a non-inferiority clinical trial, and you can see the overlapping Kaplan-Meier curves. Really- I was really impressed with the median follow-up that they've had of 58 months as well for the study, which tells us this is a fairly mature result. And we've already been starting to receive questions from patient advocacy groups, practicing oncologists, this is one of those trials on Monday after ASCO you can apply the results. And for me, the take-home here is that all rectal cancer tumors do not necessarily need to be managed the same. If you have a mid to high rectal tumor, which we start with chemotherapy, and they have a good response, I think it's worth a conversation with the patient on whether they can forego radiation for that group of patients.

Rahul Gosain, MD: Thanks for going over that. But it's amazing to see how fast this field is evolving with- like you started off by TNT, the short course, or the long course of radiation. So, when we're looking at this data, it's also important to keep that in mind, and I don't want our community oncologists to walk away or our patients to walk away with this broad blanket that no one needs radiation. A selected few to what Dr Beg you've mentioned perhaps can omit radiation here.

Muhammad Shaalan Beg, MD: I think for me, this trial gives us a reason to pause when someone has started on the treatment for neoadjuvant therapy and not to just set someone up on a specific path and not reevaluate until they're six, nine months into their treatment. And if we see that there are certain aspects of the tumor location and the response that we consider whether someone should have chemoradiation or not. So yes, the standard of care treatment options especially in terms of the delivery of radiation has evolved, but I think it's made it even more clear that rectal cancer is one of those diseases where you really need to have your radiation oncologist, medical oncologist and surgeon on the same page and having these discussions throughout the course of someone's treated.

Rohit Gosain, MD: It just adds to the multidisciplinary approach that we need for this tumor or other tumors as well. And it is important to stress how quality of life is taking a front seat in addition to the survival data. We've seen that with MSI-High tumors, it's all aware it has responded so well to immunotherapy where other modalities have been avoided, and same thing here where one could avoid radiation to avoid short and long-term side effects.

Rahul Gosain, MD: Absolutely, Dr Beg; thank you for covering that.

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