Research focus: New cervical cancer treatment programme

The BBC has reported on new research into cervical cancer treatment – Biggest cervical cancer drug advance in 20 years hailed.

We have looked at the original research - LBA8 A randomised phase III trial of induction chemotherapy followed by chemoradiation compared with chemoradiation alone in locally advanced cervical cancer: The GCIG INTERLACE trial - and written a simplified explanation for you below. If you are studying BTEC National Unit 4 Enquiries into Current Research, you will find this blog post is very helpful.

At the end of the post is a list of key terms used.

What was the research question/investigation?

It is typical to treat locally advanced cervical cancer (LACC) with chemoradiation treatment (CRT). The INTERLACE trial wanted to test whether a short course of weekly induction chemotherapy (IC) before the standard CRT, would improve progression free survival (PFS) and overall survival (OS) for individuals with LACC.

Who did the research?

20 researchers contributed to this trial, from several NHS Trusts and cancer treatment centres, as well as universities and research centres. University College London was the trial sponsor and Cancer Research UK funded the trial. This adds credence to the research findings, as the researchers are experts in the field, the sponsor is an academic institution, and the funding was providing by a leading cancer research charity. None of these groups would gain financially from the results, therefore we can conclude that researcher bias towards a particular result would not be financially driven.

What research method(s) did they use?

This was a randomised controlled trial (RCT), which is an experimental method used to test medical treatments. Patients recruited to the trial were randomised (1:1) to either receive the standard CRT (the control group) or IC followed by standard CRT (the test group). 1:1 randomisation means that for every one person randomised to conventional (control) treatment, one person was randomised to the test treatment.

RCTs are considered the ‘gold standard’ when investigating the effectiveness of a treatment or intervention.

The advantages of RCTs:

• Randomised selection (see below).
• The use of a control group against which the differences in outcome for the test group can be compared against. Without a control group it is impossible to confidently determine which changes or outcomes are due to the intervention as opposed to being due to some other variable.
• The trial follows scientific principles, such as a standard operating procedures (SOPs). In this case, this would ensure that the control and test treatments were carried out in exactly the same way, using the same dosages and over the same time period. Moreover, the performance measure is clearly established – PFS and OS are standardised measures used throughout clinical research into disease treatment effectiveness. This increases the validity of the study – the accuracy of what is being measured, as well as the reliability – the consistency of what is being measured. Together, this improves the generalisability of the research findings to the wider population.

The disadvantages of RCTs:

• Costly – in this case Cancer Research UK provided the funding, their primary aim is to discover new treatments for cancer
• Time consuming
• Complex – require thorough quality control
• Need large sample sizes – 500 participants took part from 5 different countries
• Ethical approval needed – in this case the participants have cancer and they were randomised to either receive a proven treatment, or an experimental one. All treatments have side effects and adding an additional round of chemotherapy (the IC) would increase these. On the other hand, the researchers hypothesised that the test treatment would extend the life of participants, so being randomised to the control group could be disappointing for participants, who might feel denied the possibility of a longer life. Therefore, participants needed to be thoroughly informed about the trial so they could give their complete consent.

How were participants selected?

500 patients were recruited to the trial, based on eligibility criteria linked to the stage of their cervical cancer and other possible variables. Whether each participant received the standard (control) treatment or the test treatment, was entirely random.

Randomisation is important, as it avoids ‘selection bias’, because each participant has an equal chance of being randomised to either the control or test group. This means that any confounding variables which are known, or unknown, are equally distributed. This increases the validity of the study – the accuracy of what is being measured.

Why is this research important?

1 in 142 UK females will be diagnosed with cervical cancer in their lifetime. Finding ways to improve survival rates from cervical cancer is extremely important for those affected individuals. It is also important to their loved ones and families. Improving treatments for cancer also offers significant benefits to society. For example, individuals affected by cancer may become economically inactive. Individuals with advanced cancers require a range of treatments and care packages, which is costly and uses both physical and human resources.

What were the findings?

The test treatment was found to improve both the length of time that affected individuals lived cancer free (PFS), as well as the length of their life overall (OS), compared to the standard treatment.

What can be done differently in future considering the findings?

The researchers recommend that induction chemotherapy (IC) followed by chemoradiation (CRT) becomes the new standard treatment for individuals with locally advanced cervical cancer (LACC).

As this trial was successfully run in five countries, in a range of different health settings, it was also found to be feasible to offer this treatment in different geographical locations with different health systems.

Key terms explained

Cervical cancer: cancer of the cervix, which is the structure that connects the uterus and vagina.

Locally advanced cervical cancer (LACC): where there is a large tumour (of more than 4cm) or the cancer has spread into the tissues surrounding the cervix. However, no other organs are involved.

Chemotherapy: the use of cytotoxic drugs to destroy cancer cells. Usually given intravenously, the chemotherapy is a systemic treatment, meaning it can destroy cancer cells anywhere in the body.

Induction chemotherapy (IC): an initial course of chemotherapy given to an individual with the aim of destroying as many cancer cells as possible.

Radiotherapy: the use of ionising radiation (high energy) that destroys the cancer cells in the treatment area by damaging the DNA of these cells.

Chemoradiation treatment (CRT): treatment that combines chemotherapy and radiotherapy. Usually these treatments are given in two separate time periods, consecutively (one after the other). However, to treat some cancers they are given concurrently (at the same time), so for example a chemotherapy infusion in the morning radiotherapy in the afternoon. The chemotherapy drugs can make cancer cells more sensitive to radiotherapy, so combining these treatments can make it more successful.

Progression free survival (PFS): the time between treatment aimed at shrinking or controlling cancer, and signs that it has started to grow again.

Overall survival (OS): how long people live after treatment.

Selection bias: sample selection that does not accurately reflect the target population.