14 It's important to refer to a genetic counsellor before you send patients testing as germline testing can have major implications when applying for life insurance or even a medical aid plan, as there are currently no laws in South Africa to prevent these companies from discriminating against these patients. This is clearly an issue that needs to be taken up with the industry and I know that The Prostate Cancer Foundation is looking into this. In the UK there is a voluntary code on genetic testing agreed between HM Government and the Association of British Insurers that prevents discrimination of patients who have germline mutations.. All the major society guidelines recommend that the new standard of care for metastatic hormone sensitive prostate cancer (mHSPC) is ADT plus an ARPI. So, when these patients progress to the castrate resistant stage, is there a rationale for continuing with the ARPI or using a combination PARP and ARPI or should they have PARP monotherapy? We still have many patients who become castrate resistant and who have been on ADT monotherapy, so for these patients who have the relevant mutations it makes sense to give a combination of a PARP inhibitor and an ARPI. For example, niraparib combined with abiraterone in a single tablet. The research shows that these patients have better outcomes than patients on only an ARPI. However, for patients who have been on ADT plus an ARPI and have progressed to the castrate resistant stage we know that there is not much activity of one ARPI over another. So, if these patients have the relevant genetic mutations, then PARP monotherapy is an option. We're looking at whether there is any benet to continuing with ADT, but that data is not out yet. There doesn't seem to be a lot of data about sequencing with chemotherapy for patients who have progressed to the castrate resistant stage and have relevant genetic mutations that would make them candidates for treatment with a PARP inhibitor. There are no head-to-head trials comparing the sequence of a taxane followed by a PARP inhibitor, or a PARP inhibitor followed by taxane, so we only have some subgroup analysis that was done in the randomized Phase 3 trials. It seems as though there may be a benet to using the PARP inhibitor before chemotherapy but more trials are needed to conrm this. What other developments do you anticipate in the future? There are trials underway looking at PARP inhibitors in combination with ARPIs in the hormone sensitive setting so it's possible that these drugs will be used earlier in the treatment pathway in the future. We should also remember that there are a lot of other drugs in our armamentarium and there's a lot of sequencing required based on various factors. We have to consider a patient's performance status when deciding on the rst-line treatment for mCRPC, because it's going to change and could affect what options are available as the disease progresses. For example, if you want to use radium223 for mCRPC patients, the criteria is that they have symptomatic bone mets and no visceral mets and that they have had docetaxel or couldn't have chemotherapy. If you wait too long to initiate treatment with radium-223, then patients could progress and develop visceral mets, in which case they cannot use this treatment so you lose one option that could have been highly benecial. Also, we have to constantly be aware of the costs of many of these new treatment options. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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