Neoadjuvant treatment before radical prostatectomy: Current situation

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Published: 8 May 2019
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Prof Nicolas Mottet - University Hospital St Etienne, St Etienne, France

Prof Nicolas Mottet speaks to ecancer at the 2019 International Gastrointestinal, Liver and Uro-Oncology Conference (IGILUC) in Cairo about the neoadjuvant treatment prior to surgery in patients with prostate cancer.

Prof Mottet describes the types of neoadjuvant therapy which consists of either oral treatment or a combination of oral treatment plus chemotherapy.
The use of bicalutamide as an oral therapy has shown little added value, however newer drugs such as enzalutamide and abiraterone have shown limited data thus far.

In regard to the combination of docetaxel and ADT along with local treatment, Prof Mottet notes one French trial which achieved an improvement in progression-free survival, however this did not translate with metastasis-free or overall survival.

Prof Mottet also emphasises that this data is purely experimental at this stage and that neoadjuvant ADT should not be used prior to surgery - as stated in the recommended guidelines.

 

The discussion was about neoadjuvant treatment before surgery and only before surgery because before radiotherapy it’s proven it’s worth doing. Before surgery we have two main classes of drugs that are considered – hormonal treatment or a combination of hormonal treatment plus chemo. Regarding hormonal treatment we have old data, old randomised trials with bicalutamide, that’s an old-fashioned non-steroidal. Both trials showed the same thing – less margins, less pT3, that is more pT2, sounds attractive except that the relapse rate in terms of PSA was absolutely unchanged. So it sounds to be attractive without any added value.

The second group of drugs from hormonal treatment are the new ones, that is abiraterone, enzalutamide or a combination of abiraterone and enzalutamide. All the data we have so far are very limited, always less than 100 patients; the largest one is something like 80 men. They all showed the same thing – some complete response, histologically speaking, some near complete response, that is a minimal amount of disease still in the specimen when the prostate is taken out, all these belong to patients that are high risk. The problem with that is we have absolutely no data in terms of outcome regarding PSA relapse or further relapse; we have absolutely nothing. So it sounds to be attractive, is it linked to a better survival or a better outcome? At least a better PSA relapse free survival? Nobody knows, the data are still not there.

On top of that, giving that form of treatment is probably not so trivial, we might increase the rate of surgical side effects. When it’s reported sometimes, very often, it is said there is no change. Sometimes it’s said that there might be more fibrosis and there might be more bleeding so we do not know very well if, yes or no, it changed something in terms of surgery. It’s also not trivial because it’s been shown in a small subgroup of patients that, genetically speaking, there are some modifications. We see much more splice variants like AR-V7. We see some induction of genes that are involved with the neuroendocrine pathway. So it might be that using neoadjuvant changes the disease, and we know that every time we use something we change the disease, but we might make the disease more aggressive. That was for ADT.

With chemo we have a little bit more data, some very exotic regimens using docetaxel every week that are almost all negative. We have one large randomised controlled trial, a French one, the GETUG-12, who considered ADT with docetaxel estramustine versus ADT monotherapy on top of local treatment that might be either surgery or radiotherapy. The primary objective of this trial was progression free survival, there was a huge difference with twelve years’ follow up. The problem is that progression free survival did not yet translate, neither in met free survival nor specific nor overall survival. So if you consider progression free survival is important, there is a benefit and there are level 1 evidence for that. If you consider only survival, or at least met free survival, is needed so far the trials are negative. We are awaiting a CALGB trial on docetaxel plus ADT, pure docetaxel every three weeks, standard regimen. No data is available yet. So that’s where we are with neoadjuvant.

Is there anything you’d like to add?

Yes, based on that it should be considered as purely experimental and guideline based again, we strongly said, and it’s a strong recommendation, do not use neoadjuvant ADT before surgery because we don’t know what the outcome is. It might be beneficial, it might be deleterious, it might be completely useless. So don’t use it outside a trial. Trials are worth doing but they are experimental.