Dr. Liaw shares the role disease burden and other factors play in treatment selection.
Bobby Liaw, MD: There's a lot of variability in how oncologists and urologists are selecting treatment options for metastatic castrate-sensitive prostate cancer these days. A lot of the variabilities likely are due the fact that we have multiple agents that have all demonstrated in their own individual studies to had significant overall survival benefit. But unfortunately, there were only placebo-controlled studies, none were compared to each other, which is why there's a lot of controversy as to what's necessarily the best drug to use when, where. I tend to individualize treatment selections based on a couple of factors of like some of it is going to be based on performance status and patient comorbidities, but symptomatology, disease burden, sites of metastasis also play a big role in our decision-making process. Then there's always going to be the issue of trying to find ways to integrate a patient's personal preference. Now, docetaxel tends to be the option that might fall off a little bit easier due to issues with performance status, anticipated tolerance, or just plain old patient preference. Chemotherapy still has like a fair amount of stigma with patients. I can't think of anyone who was entirely enthused about getting chemotherapy. However, in patients who are actively symptomatic with a high-volume metastatic disease, I do usually give stronger preference or consideration for chemotherapy because this is the area where the CHAARTED data really supports its use. We don't see the same OS benefit readout in patients with low volume disease for the long-term fall of that study. Now, while LATITUDE, the abiraterone study was designed as a study for high-risk prostate cancer, it didn't use like the same criteria as CHAARTED which has been adopted for a lot of the other studies going forward, but there was a post-hoc reevaluation of the study, of the LATITUDE study using CHAARTED criteria separating out for high and low volume disease. And it still suggests that it maintains a good benefit in both low and high-volume diseases. Enrollment on the TITAN and ENZAMET studies actually saw about one-third of study participants having low volume disease. And we're very happy to see that the treatment effect on overall survival actually on both studies were favorably consistent across multiple pre-specified subgroups. And that was also consistent across like the high volume versus low volume disease patients. But I'll editorialize a little bit. Currently, the way that we define high volume disease, it's simply a yes or no. Do you have high-volume disease, yes or no? It doesn't actually more accurately quantify the amount of disease that you have. It doesn't really speak towards locations of disease involvement. I think we all can agree that deep down a patient with a Gleason 7 prostate cancer with 4 spots of bone metastases does not have like the same prognosis as a patient with Gleason 10 disease with diffuse bone disease, as well as liver metastases. Yet if we go strictly by tried criteria, they both would fall into the category of high-volume disease. A recent abstract that was actually presented at AUA by Jardel at all actually really tries to drive this point home using data from like the TITAN study, they actually found that the risk of worse outcomes was significantly increased with increased number of metastatic locations, and that multiple metastatic locations at baseline were significantly associated with a higher risk of worse outcomes as compared to people who had bone-only metastases. That makes a lot of sense to me, and I think a lot of people also feel the same way. I think more studies are going to be needed to further stratify and prognosticate because I think for all of us, the question is going to be how best to optimize treatment in these patients who are at the highest risk of poor outcomes.
Transcript edited for clarity.