Consideration of Long Course Radiation for Patients With Rectal Cancer

At Great Debates and Updates in Gastrointestinal Malignancies in New York, New York, Jennifer Wo, MD, Massachusetts General Hospital, Boston, Massachusetts, discussed use of long course neoadjuvant radiation therapy for the treatment of patients with rectal cancer. 

Transcript: 

Hi my name is Jennifer Wo and I am a GI radiation oncologist at Mass General Hospital. I'm here today with Great Debates and Updates in GI cancers to talk about my stance and why I'm arguing today for the consideration of long course radiation in the setting of locally advanced rectal cancer. 

For those of you who don’t regularly treat rectal cancer, radiation is an important component for many patients with locally advanced rectal cancer. There are 2 forms of radiation that have been published in the literature, one which is long course chemoradiation, typically administered over a 5 to 5 ½ week period, Monday through Friday, with concurrent chemotherapy, either 5-fluorouracil or capecitabine. Alternatively, another regimen that has emerged in the published randomized trials is short course radiation which is 5 doses of 5 Gy per day without chemotherapy. Both of these regimens have been utilized in randomized trials that have defined our field and the role of radiation, and therefore whether to consider  long course or short course is a very relevant question. There are randomized trials to date comparing those two directly, although those in and of themselves have some limitations. My stance was to argue for long course radiation. 

Pelvic radiation is critical to rectal cancer for 3 main reasons: to improve R0 resections, to decrease the likelihood of local recurrences within the pelvis, because local recurrences can be quite morbid and associated with a significant decrement in quality of life, and there's emerging data that has really pushed the envelope as to whether or not we could potentially even drop local therapy of surgical resection, for patients that have very low line rectal cancers surgical resection may require a permanent colostomy which can negatively impact patient's quality of life. In that era where we're trying to move away or treatment deescalate at large for rectal cancer, radiation can play a very important role for non-operative management. So I'm going to tackle each one in terms of why I think long course is a more effective treatment. 

For local recurrence, there's recent RAPIDO data that has shown that short course radiation followed by chemotherapy improved disease treatment related failures compared to the standard long course that has traditionally existed in the setting of German rectal, which is chemoradiation followed by surgery followed by chemotherapy. With that data alone it seems like short course would win, an argument I'm sure my counterparts will make, however with longer term follow-up and a secondary analysis of the RAPIDO study it actually has now come out that in patients that receive the short course local regional failures are increased in short course. As we circle back, one of the main purposes of radiation to the pelvis for rectal cancer is to decrease risk of local regional recurrence, short course now in a randomized setting, in the modern setting, has been shown to not as effectively control the pelvis as long course chemoradiation. I think if we're not meeting one of our fundamental primary endpoints to the best of our capability, that long course chemoradiation should remain standard of care and preferred standard of care.

The second argument is that actually in this era of total neoadjuvant therapy, where we're doing chemotherapy and radiation prior to surgery, there's also the emergence of the PRODIGE study. The PRODIGE study was looking at folfirinox followed by long course chemoradiation compared to the German rectal, which is what we had just talked about, neoadjuvant chemoradiation surgery, and then chemotherapy out back. With longer term follow-up, there is now an overall survival benefit with the PRODIGE approach, doing folfirinox, long course chemoradiation, and then surgery. There does not exist an overall survival benefit data  in RAPIDO which is the TNT approach that we just described. To date, PRODIGE is the best high level randomized phase 3 study in the modern day era that has shown a distinct overall survival benefit compared to our previous standard of the German rectal. That is the second reason I feel that  long course chemoradiation should remain standard of care to optimize maximally our outcomes for our patients. 

Lastly, in the setting of non-operative management, the far lion's share of data that exists for having patients achieve a clinical complete response with good durability without surgery exists in the setting of long course chemoradiation. Most recently, the OPRA study, total neoadjuvant approach, whether or not to do chemo first or radiation first, had very high impressive rates of TME-free survival showing that long course chemoradiation done first followed by adjuvant or consolidative chemotherapy offered the best chance of a TME-free survival. There is emerging data for a short course for non-operative management, but the outcomes are still early at two years and once again, extrapolating from our initial point that local recurrences seem not as quite well controlled I would hesitate to jump to short course without long term follow-up for non-operative management. This is a setting which we're already dose deescalating, we want to make sure that we do that safely.

For all of those reasons, I think long course chemoradiation should remain the preferred approach for the far majority of our patients.

Source: 

Wo J. Debate: Short-course vs. long-course neoadjuvant radiation therapy in rectal cancer. Presented at Great Debates and Updates in Gastrointestinal Malignancies. May 17-18, 2024. New York, NY.