Denis, it’s great to get you in this interim period between being in Quebec and Toulouse, I think you’re actually in Toulouse now, aren’t you?

Back to France, yes.

So you’ve been giving everybody here in Liverpool the benefit of your extensive knowledge about the sort of unresolved issues in cervical cancer. First of all, what’s the state of the art with advanced cervical cancer? It is quite a successful one, isn’t it?

It is more successful than is usually thought because the majority of patients, over 50%, can be cured, even with advanced cervical cancer, using modern techniques and state of the art techniques.

That’s chemoradiation and surgery.

That is, in most countries, especially in Northern America and many countries in Europe, chemoradiation – concomitant use of chemotherapy and radiation therapy.

There are, of course, toxicities. What are the unresolved issues that you’ve been tackling?

Toxicity is not such a big issue knowing that radiation therapy has improved tremendously during these last years. The unsolved issues, one is is this standard therapy really the best therapy because it is challenged by another option which is using neoadjuvant chemotherapy followed by surgery. This alternative option is being explored in a randomised study so we will soon hopefully know the results of this study. There is a European study that is on-going and has accrued 600 patients, the target being 680, so in the next few years we’ll have the answer.

Because neoadjuvant therapy before surgery is actually quite commonly done in other clinical situation, other cancers, isn’t it?

It is probably less used than chemoradiation but this is back to history. The struggle between surgeons and radiation therapists has been sold on the basis of one finding, a common finding, that patients that get up-front surgery with advanced cervical cancer generally need additional radiation therapy. That’s the reason why up-front radiation therapy probably is better if it is definitive with no surgery at all. But in countries where surgeons do not believe in radiation therapy, there are countries like this, and where radiation therapy facilities are not available, you have to find another solution. And surgery only is not a good solution and adding neoadjuvant chemotherapy definitely adds to the outcome.

But it’s not one size fits all because some patients will be easier to resect, presumably.

Generally advanced cervical cancers are divided into two sets of patients; one part of patients have really extensive disease that are not amenable for surgery but your question is excellent for the less extended advanced cervical cancer which are called 1B2 or early 2B and that’s the situation where there is still a controversy about surgery versus radiation therapy.

And although radiation therapy is a main plank of treatment for these patients, there is resistance to it, isn’t there, to contend with?

We observe failures and the failures are mainly related to resistance to radiation but these same patients are generally chemosensitive. But biological features of these tumours are probably unique, whatever the treatment and we have no idea, at the moment, of what is really prognostic.

How much optimism do you have about pushing this success further? Because you’ve reached quite a good level already, how near to improving it are you?

There is still a lot of space for improvement. We can improve the radiation therapy techniques, there are a lot of new techniques – modulation arc therapy, tomotherapy, so many, many techniques. Also brachytherapy, which is part of the radiation therapy management is tremendously improving with image guided brachytherapy so the local treatment can be improved. Also in the future maybe we’ll be able to use new drugs in addition with radiation therapy, not only cisplatin which is the usual mainstay but some trials are on the way. Finally, some hopes are coming from other trials with adjuvant chemotherapy which means giving additional chemotherapy after completion of radiation and chemo and there are retrospective arguments to think that it can help the patient. So there are two randomised trials, one from the International RTOG and one in Australia and New Zealand on this topic.

Are any of the molecularly targeted drugs of any use here, do you think?

There are really a few of them. One drug is directed against human papilloma virus antigen but not a lot of the new antibodies, for the moment they are not extensively used but in one situation recurrence of cervical cancer where we recently have found that adding Avastin, bevacizumab, improves the results of therapy with recurrent cervical cancer. So it’s a new development.

Is there any point at this stage of targeting the HPV itself?

For the moment there are only a few drugs that can do this. Knowing that in addition there is a lot of research about different genotypes of HPV, some of them have a better prognosis, some of them have a worse prognosis. So probably that’s a field for future research.

So what do you recommend doctors to make of all of this fascinating but quite diverse research that’s going on now?

One, organise as much as possible the process of management which is radiation, concurrent chemotherapy, then brachytherapy and, in some cases, additional surgery. This is an organisation within cancer centres. I think that structuring the treatment is probably the first goal but in the future probably in some cases adding chemotherapy in addition can be advised in patients with very bad prognoses, especially with this. In addition, there is another research about surgical staging. It’s still a pending issue – do we surgically stage or not. There are new techniques to surgically stage patients, laparoscopic techniques, patients can stay only over night or as a day surgery, on a day surgery basis so we can assess the status of nodes. But again there is a randomised study to explore the real usefulness of this technique in clinical practice.

So could you sum this all up into a few words that need to be remembered about the important progress in advanced cervical cancer?

Radiation and chemo but good radiation with the latest techniques is probably the best way to do things. For the radiation therapy to work as a team with surgeons who are able to surgically stage the patient when necessary and to do the proper surgery after, if it is necessary because some patients resist radiation therapy. In a few words that, I think, is the standard of today.

And the importance of a multidisciplinary approach?

Yes, definitely. Definitely.

Thank you very much, Denis.

Thank you.