In an interview with Oncology Learning Network, Arthur Sun Myint, FRCP, FFRCS, FRCR, FICS, Lead Clinician in Papillon, Clatterbridge Cancer Centre, University of Liverpool, United Kingdom, discussed the clinical significance of a trial evaluating the role of contact X-ray brachytherapy (CXB) after external beam radiotherapy (EBRT) or external beam chemo radiotherapy (EBCRT) in patients with rectal cancer ineligible for surgery.

What existing data led you and your co-investigators to conduct this research?

I am based in the United Kingdom and work as a Co-Chief Investigator for the European phase 3 randomized clinical trial OPERA [Organ Preservation for Early Rectal Adenocarcinoma] in collaboration with my mentor and my senior colleague, Jean-Pierre Gerard, MD, Department of Radiotherapy, Centre Antoine-Lacassagne, Nice, France, who is the Chief Investigator of this trial.

Dr Gerard and I have published a number of peer-reviewed papers on CXB (also known as Papillon treatment, which is named after its pioneer, Jean Papillon, MD, Professor of Radiotherapy, University of Lyon and Head of Radiotherapy Department at the Centre Léon Bérard, France).

Papillon is a kind of radiation technique which uses low energy X-rays (50KeV) to treat rectal adenocarcinoma. This type of treatment is mainly used for older and frailer patients with multiple medical comorbidities who are not suitable for surgery which is the Gold Standard of care for rectal cancer.

Please briefly describe your study and its findings.

Over the years we have observed that CXB can actually cure a high proportion of cases with rectal cancer without needing surgery or a stoma bag. These are mainly small (<3cm) rectal cancer cases in the early stages cT1 or cT2 with no obvious lymph node spread (cN0).

However, a proportion of cases with more advanced cancer cT3a and cT3b up to 5cm in size can also be treated and cured using this technique. These cases need EBRT or EBCRT first to downsize which also down stage the tumors to cT2 or less.

In a small proportion of cases, there is no trace of residual cancer either on endoscopy, digital rectal examination or on radiological examination, using magnetic resonance imaging technique (MRI). This is known as clinical complete response (cCR). However, the proportion of patients achieving cCR is usually less than 30% when external radiotherapy is use alone. If CXB is added after EBCRT or EBRT the proportion of patients achieving cCR is much higher at 70-90% depending on the stage (cT1) and size (<3 cm) of the initial tumor. Moreover, the addition of CXB to EBCRT or EBRT can also reduce the proportion of patients with local regrowth after achieving cCR.

If EBCRT or EBRT are used in isolation about 25-30% of patients can develop local regrowth, whereas in our experience, we found that if CXB is added the number of cases of local regrowth can be lowered to less than 11%. This finding has led us to set up a randomised trial to evaluate the role of CXB after EBCRT or EBRT in order to establish this as a standard of care in patients with rectal cancer not suitable for surgery or in younger patients not keen on surgery.

What are the possible real-world applications of these findings in clinical practice?

In the real world, population is ageing not just in Western countries but in other countries as well. There is published evidence of surgical harm in term of increase in surgical mortality and complications in older patients. In addition, a number of western countries have started bowel cancer screening programs which have increased the pickup rate of early stage rectal cancer. These cases should not be treated with extirpative surgery designed a century ago to treat more advanced rectal cancers.

We should personalize rectal cancer treatment and give patients a choice of treatment after full discussion with all the information regarding treatment options before consenting them for their treatment. Most patients would prefer to avoid surgery if they are given a choice, even when they know that the chance of cure is reduced. In any case, we have shown that surgery can be offered at a later date if the patient has residual cancer or a recurrence following treatment without compromising their chance of cure in those who need it.

Do you and your co-investigators intend to expand upon this research?

Yes, we would like to expand our research to more advanced rectal cancer (cT3 c and cT3d with lymph node spread cN1 or cN2), where the standard of care is still surgery. A proportion of these patients will respond and be able to avoid surgery.

Obviously, the chance of response will be less than in those with early rectal cancer and we would like to explore the addition of chemotherapy with or without immunotherapy to EBCRT or EBRT and CXB boost.

Is there anything else pertaining to your research and findings that you would like to add?

Our goal in cancer treatment is not just to cure the cancer. We need to consider the quality of life after treatment as the patient has to live with its consequence for the rest of their lives. The quality of life will be much better if one can avoid surgery.

We need to explore the quality-of-life studies in parallel in all our research trials. In addition, we need to do full Health Economic Assessments as the cost to healthcare providers will be much less if we can avoid surgery, as there is no need for hospital admission, or surgical procedure cost and time of 6 to 8 hours in theatre and no intensive care stay.

We also need a patient satisfaction survey and be mindful that some patients may prefer surgery as they do not want any uncertainty during their intensive follow up in the watch and wait period.