Paolo Zaurito: Thank you so much for the introduction.
Neeraj Agarwal: First of all, congratulations for presenting at the 2026 annual American Urology Association meeting. We are in Washington, DC, and we really enjoy your presentation on doublet versus triplet therapy in patients with metastatic hormone-sensitive prostate cancer.
So Paolo, how do you approach doublet versus triplet versus monotherapy if there is any role of monotherapy? So we'll start with monotherapy first. Are there any candidates for monotherapy? Do you use monotherapy with ADT in anyone?
Paolo Zaurito: Okay. So thank you for the introduction. The use of ADT in monotherapy is still an ongoing debate since because we have some recent data from trial that suggests that in men with metastatic castration sensitive prostate cancer to start intensifying them with using ADT with ARPI or also triplet therapy for men with advanced cancer characteristics. So ADT, ARPI, docetaxel. So what could be the role of ADT only? Probably the role of ADT only, it should be reserved. And this is what we observed also in our abstract that now it's going also to be a paper. It's possibly only older men with some comorbidities, still maybe some oncologists at the nationwide population level in Sweden where our data came from. They hesitate to do maybe the intensification treatment and so on. It's for maybe these men with cardiovascular also some kind of comorbidity that they consider although to treat them with ADT.
Neeraj Agarwal: And if you see 100 patients with metastatic castration sensitive or hormone-sensitive prostate cancer, how many patients do you think would be candidate for ADT only?
Paolo Zaurito: I think it will be less than 20% because right now, and this is what we report in our abstract, are really nationwide population data. So it's what like all the oncologists treat in all the country. And what we have seen is that less than 20% of patients receive kind of ADT monotherapy where we have mostly patients that receive the combination treatment with ADT plus ARPI while the use of ADT plus docetaxel was reduced and the use in comparison of triplet therapy has reached approximately the 17% of the population. And these are what type of patients that are younger men with more advanced prostate cancer, high release and higher T-stage.
Neeraj Agarwal: So that's a very meaningful study I think looking at the real-world data. That's where we get a lot of information from. And in your database, real world database, how many patients were there?
Paolo Zaurito: There were 9,000 of patients.
Neeraj Agarwal: So large number of patients with metastatic hormone-sensitive prostate cancer and you found less than 20% patients of these patients are treated with ADT monotherapy, which is great news. It's very good news actually because we saw just recently until two years ago, about 50% of patients were not getting ADT plus ARPI, at least about 50% of patients were getting ADT monotherapy alone. So I think this is a big, great news, big jump in the patient number of patients who are getting doublet or triplet therapy.
And then you showed that about 17% of these patients are getting triplet therapy with ADT plus docetaxel plus ARPI who are likely younger, high-volume disease, maybe visceral metastasis, but fortunately 80% of patients are getting doublet or triplet. Is that correct?
Paolo Zaurito: Is this correct? Exactly. And I agree with you that the fact that we are moving from clinical trial setting to real world setting. So the paradigm is changing. We looked for patients from 2016 to 2024 and the trends are improving and this has reflect also an improved three-year overall survival for these patients at a nationwide level led by the intensification treatment.
Neeraj Agarwal: Any other aspect of treatment you interrogated in your study. For example, side effect, cardiovascular side effects, something we are really concerned about as patients are living longer, especially exceptional responders who are about 60% of these patients who achieve a PSA level of less than 0.2. Their median survival is going to be in many, many years and they are living so long with low testosterone. So any of those things you are looking or you plan to look?
Paolo Zaurito: We are planning to look. At the moment in the current form of the paper we have not looked for adverse events of intensification treatment. We just looked for survival outcomes. But of course we are looking at true data. We observed that older patients, of course, had less percentage of treatment compared to younger one. This may be related to the comorbidities and also to an higher risk of adverse events.
Neeraj Agarwal: And we are coming to the survival outcomes in a moment. So what was the outcomes in your database?
Paolo Zaurito: The outcome was trying randomized control trials, so was overall survival.
Neeraj Agarwal: And what did you find?
Paolo Zaurito: We observed that patients that were intensificated over time had higher three-year overall survival. In particular, the three-year overall survival for patients diagnosed in 2016 and treated at the time with ADT only or also with ADT plus docetaxel was lower compared to the overall survival of more recent here where ARPI and also triple therapy came and also led to have better overall survival for more recently treated patients.
Neeraj Agarwal: And are these overall survival data similar to what we have seen from the randomized control trial?
Paolo Zaurito: Yes, they are pretty similar. Of course, they are a bit lower, but I think it was approximately a five or 6%, but this is of course due to the fact that sometimes patients in randomized trial may be a bit fitter than population.
Neeraj Agarwal: Always. They're always fitter. They don't represent the sometimes many a times the real world patients we see are much older with much more, many comorbidities and I agree with you. But overall, the good news is in your database from 2016 to 2024, there is consistent increase in overall survival, pretty close to what we have seen with randomized control trials and which is great news for our patients.
Paolo Zaurito: Of course it is.
Neeraj Agarwal: Anything future looking? You said you're looking into the cardiovascular side effects, other side effects. Any other studies you are planning to undertake using this robust database?
Paolo Zaurito: Yes. Thank you for the question. I think of course next step will be to prolongate then follow up data for overall survival because prostate cancer is a long-term disease also for metastatic patients, a relatively long-term disease also for metastatic patients. So we need to have five, 10-year overall survival estimates. And of course second point will be to look in adverse events of treatment. And we can do this in the Swedish prostate cancer register where we have all the ICD codes with complication occurred even if the patients came back in the hospital, even if the patients see his physicians in his office. So I think that next step will be to look in long-term follow-up hospital outcomes and also adverse events.
Neeraj Agarwal: First of all, congratulations for taking on this meaningful research as a urology resident and I'm sure great things will come in the coming years from you and from your group and thank you for taking the time to come and present here. Talk about yourself.
Paolo Zaurito: Thank you very much for your time and for the communication.