ASCO GI 2023 | Non-surgical treatment options for patients with rectal cancer
Surgery is the standard of care for rectal cancer, and radiotherapy is typically given in advanced rectal cancer. Arthur Myint, MBBS, FRRP, FFRCS, FRCR, FICS, The Clatterbridge Cancer Centre, Cambridge, UK, provides an overview of novel strategies that minimize the use of surgery. Previous research has determined that approximately half of patients receiving external beam radiotherapy (EBRT) alone will progress. Findings from the Phase III OPERA trial (NCT02505750) demonstrated that additional contact radiotherapy enhances organ preservation rates. This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Gastrointestinal Cancers (GI) Symposium in San Francisco, CA.
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Transcript (edited for clarity)
The standard of care for rectal cancer is to go for surgery, even for very early stage tumors. The only time radiation is used in rectal cancer is for very advanced tumors where the resection margins, circumferential resection margins are involved. They get chemoradiation or radiation to try and downstage them, to make them operable from inoperable situation. That’s the only time that radiation is indicated in the protocols and the guidelines...
The standard of care for rectal cancer is to go for surgery, even for very early stage tumors. The only time radiation is used in rectal cancer is for very advanced tumors where the resection margins, circumferential resection margins are involved. They get chemoradiation or radiation to try and downstage them, to make them operable from inoperable situation. That’s the only time that radiation is indicated in the protocols and the guidelines.
We are interested in early stage tumors, trying to avoid major surgery, especially for very early stage tumors, where they end up having a permanent stoma and major surgery that involves an eight-hour operation, staying in hospital for five to 10 days, and end up with a permanent stoma in over half the patients. For patients, when they’re not fit for major surgery, that is an option that we were using before, but more and more we’re seeing younger, fitter patients trying to avoid major surgery, because they don’t want a permanent stoma, and that’s where our story begins.
What we try to do is after the external beam chemo radiotherapy or radiation, there are people who responded very well and this is what we call clinical complete response. This strategy was led by Professor Habr-Gama from Sao Paulo in Brazil, where she’s just watched them in people who responded to treatment, and that was how we got our inspiration. But we were doing it on elderly patients who are not quite fit for major surgery giving this treatment, and we’re finding that if they respond well, we just watch them and they don’t need any surgery.
For younger, fitter patients who are fit for surgery and refusing it, they get external beam chemoradiation. In about half the patients, they do respond well. But then the patients who do respond well, in a quarter of these patients, the cancer started to grow and they needed surgery. The organ preservation rate, if you just give external beam alone, is less than half.
With dose escalation, using the contact radiation boost, after chemo radiation, we would boost with contact radiation, especially in patients who had a small residual tumor. We don’t boost it for people who achieve a clinical complete response, but only for people with small residual tumor. If you give additional dose of radiation with contact radiation boost, what we found was the local regrowth rates were almost halved, so only about 10% to 15% had a regrowth. Our organ preservation rate is quite high.
We have done this randomized trial called OPERA where we randomized chemo radiation toward 45 Gy in 25 fractions over five weeks with oral Capecitabine given, followed by external beam radiation boost, nine Gy in five fraction, so the total dose is 54 Gy in 30 fraction, which is what Habr-Gama was advocating. That is an arm A randomized against arm B, which is giving external beam chemo radiation, 45 Gy in 25 fractions over five weeks with Capecitabine, followed by contact radiation boost where we give 90 Gy, 30 Gy every two weeks for three fraction.
We are comparing nine Gy external beam versus 90 Gy contact, which is quite a high dose. What we found was in tumor less than three centimeters, if we give contact radiation boost upfront, the organ preservation rate at three years is 97% as opposed to 63% when we give external beam alone.
This is highly significant, and hopefully this data when published will be level one evidence, and that this will be practice-changing for patients with rectal cancer. Hopefully for younger fitter patient who wanted to avoid major surgery, or older patient who are fit but want to avoid surgery, this level one evidence will provide the evidence for them to avoid surgery and just give external beam radiation with contact radiation boost.
Hopefully this will be a practice-changing experience for people and a lot of young fit patients who want to avoid major surgery who will benefit from this trial.
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