EAU prostate cancer guidelines 2019: What changed and why?

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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 changes made to the EAU prostate cancer guidelines.

Prof Mottet summarises the main changes which include performing an MRI prior to a biopsy, the redefinition of a relapse, the use of enzalutamide, apalutamide and darolutamide for the treatment of non-metastatic castration-resistant prostate cancer and the addition of radiotherapy to the prostate in patients with low-volume prostate cancer.

 

The EAU guidelines update yearly so there are several topics that were changed in the 2019 version based on the available literature. To summarise the main changes, let’s say, the first one was for up-front MRI before biopsy. We came to the conclusion that before biopsy an MRI is needed to be done every time but every time not for screening, every time a biopsy is considered, based on risks. Then the decision to take with the MRI depending on where we are. If it’s a first biopsy we strongly suggest to perform if the MRI is abnormal, that is a PI-RADS lesion 3 or above, to biopsy the lesion plus to perform a systematic biopsy. We do not believe we have enough data yet to avoid these systematic biopsies. On the other side if the MRI is negative, that is PI-RADS 2, 1 or normal, we have to think about doing a biopsy, yes or no, based on the risk of the patient based on a DRE and the PSA and the family history, that is a risk calculator that might be used. It must be a shared decision not to go for biopsy with the patient, that’s for the pre-biopsy MRI for the first time.

If the patient already had a normal MRI and a normal biopsy before then it’s a little bit different. If the MRI is positive we strongly suggest to go for biopsy and probably targeted biopsies are enough and probably it’s safe to avoid a systematic biopsy on top of them. On the opposite, if the MRI is normal, the same definition as before, again it’s a shared decision based on the risk factors using a risk factor calculation tool, there are several that might be useful. They are the main changes we had, the first one.

The second we had is about the definition of relapse and how to deal with a relapse. This is based on nothing special that was published but on a formal systematic review that was conducted at the guideline office on that. We tried to answer two questions that transferred into the guidelines. The first one is if there’s a link between survival and relapse, which sounds to be trivial but it’s far from being so trivial. The answer is yes but the link is very heterogeneous. You have some relapses where the relative risk of death is something around 1.03, meaning almost no increased risk of death. And there are some other relapses where the relative risk is more than two point something, 2.3 or 2.4 if I remember well, meaning that these relapses are at a very high risk of death if not treated. This has led us to the second question – can we stratify those relapses at risk and those at very low risk. Yes we can, again based on the evidence. For the high risk, the relapse at high risk, it’s a patient that had an early relapse, that is a relapse between 12-18 months after the end of the local treatment, or have an ISUP score above 4 or equal to 4, that is Gleason 8-10, or probably even more important is a PSA doubling time that is less than twelve months. This is correct even for surgery or radiotherapy and for those relapses they are high risk relapses and they should be treated.

On the opposite, the low risk relapses are those that relapse late, who have an ISUP score of less than 4, that is Gleason 7 and below, and, even more important again, is the PSA doubling time with a doubling time of more than twelve months. In this case the link between relapse and death is marginal, if any, and the added value of any form of salvage treatment must be balanced by the side effects you create when you use it and the very long-term benefit that so far is purely hypothetical, suggesting that for those relapses of low risk the need to receive salvage form of treatment is marginal. That’s the second major point I want to highlight regarding guidelines.

The third one is a non-metastatic CRPC, something completely new, and this is a major change based on two randomised trials that are available before we finalise the text. Later on a third one appeared and now we have three trials showing exactly the same thing. For the patient with M0 CRPC and a very rapidly growing PSA, that is a PSA doubling time of less than ten months, adding either enzalutamide or apalutamide or darolutamide, the third one that just was published a few weeks ago, we clearly postponed mets for at least more than one and a half years, close to two years. This is also linked to a decrease to postpone side effects of mets, patients needing some form of treatment for painful or symptomatic metastasis. Based on these trials we suggested that for those men who are M0 CRPC one of these three drugs is an absolutely valid option and a strong recommendation to consider. On that I want to highlight the fact that M0 is defined by bone scan and CT scan only and that PET PSMA or PET choline has absolutely no place there. We have nothing regarding any data on survival and outcome based on that.

The very last major change comes from the newly diagnosed M1 disease. Probably you remember last year we had two new things, that is adding docetaxel on top of ADT or adding abiraterone on top of ADT for newly diagnosed M1 disease. Now with a third arm to consider that is adding radiotherapy that comes from a subgroup analysis in STAMPEDE that was pre-planned so it’s correct to analyse it independently. Therefore patients with low volume disease based on the CHAARTED definition adding radiotherapy to the prostate adds survival. So we have now three standards for low volume disease – adding radiotherapy, adding abiraterone but also adding docetaxel which still is a standard of care even for the low risk disease. Low volume disease means no visceral metastases and no bone metastases outside the actual skeleton. So this is the definition of low volume disease.

That’s the four main points that are new in the guidelines.